This is the deposition of Dr. Gerhard Schrauzer, Ph.D., a retired chemistry professor. This is a very lengthy deposition, but in this excerpt, the professor discusses some of his research into whether Zicam or zinc nasal products can cause loss of smell. This deposition was taken in 2006 in the case of O’Hanlon v. Matrixx Initiatives, Inc., which was filed in the U.S. District Court for the Central District of California.
Q What scientific method have you employed to form your opinion that the actual cause of Dennis O'Hanlon's smell dysfunction was Zicam rather than a viral process or anything else?
A I have compared some of the other substances he was exposed to and eliminated those as possible causes of agents. Like he used a leather spray, Armor leather spray. I checked the Internet, for example, if there is any ever case of anosmia caused by Armor leather spray, which is a very popular spray. And I haven't found not one single evidence that ever anybody -- and this is an older product -- has ever reported loss of smell after using Armor leather spray. And when I looked up the Internet for Zicam, I got hundreds of cases. So that is how I based my evidence.
Q What other possible causes did you consider and rule out based on Internet research with respect to Dennis O'Hanlon's smell dysfunction?
A I was for a while thinking -- well, no. None other. No.
Q Putting aside the question of Internet research, what other possible causes did you consider and rule out as causes of Dennis O'Hanlon's smell dysfunction?
A I looked at his medical records. I was interested if he possibly suffered brain trauma at one time or had some other condition that -- or was on certain drugs that could cause changes in smell acuity, and I couldn't see any reason.
Q Prior to your involvement in this litigation, had you ever done any formal research into the causes of anosmia?
A Formal research, no.
Q Prior to your involvement in this litigation, had you ever done any research into the determination of whether intranasal zinc application can cause anosmia?
A No.
Q Prior to your involvement in this litigation, had you ever attempted to determine the cause of a specific individual's smell dysfunction?
A Yes.
Q Tell me what you did --
A Well, as a chemist, you see, there are certain substances that will result in temporary paralysis of the olfactory functions. Hydrogen sulfide is a good example. Hydrogen selenide is a good example. I worked close with hydrogen sulfide. S-u-i-f-i-d-e. And, you see, we chemists are exposed to such substances. We have students that may be exposed to such substances. So a knowledge of toxicology is very important. So we know that certain substances causes disturbances of smell function and taste function.
MR. LAZARUS: Move to strike as nonresponsive.
BY MR. LAZARUS:
Q Doctor, my question is whether you've ever, before your involvement in Zicam litigation, undertaken to determine whether an individual who has suffered smell dysfunction developed that condition as a result of any specific cause?
MR. WENZEL: As to his work on Zicam cases?
MR. LAZARUS: Prior to his involvement.
MR. WENZEL: Oh, prior to his -- sorry.
MR. LAZARUS: That's all right.
THE WITNESS: I'm not a medical doctor.
BY MR. LAZARUS:
Q I understand that and that's why I'm asking the question. Have you ever attempted to determine the specific cause of an individual's smell dysfunction prior to your involvement in this litigation?
A Right. And I have had one case of a person that lost his taste and smell following a viral infection. Yes.
Q Did you make a determination as to whether his smell and taste dysfunction was caused by a viral infection or some other potential cause?
A Based on his testimonial it was a viral infection.
Q Did you rule out other potential causes to determine that it was a viral infection in that instance?
A No.
Q Did you leave that to a medical doctor?
A Not even that. This was a person who had suffered permanent smell and taste function loss after a severe viral infection, and 30 years later he was still trying to sniff his food in order to get some taste sensation out of it. And he told me it was a viral infection, so -- that was one example.
Q Based on that, you concluded as a matter of scientific process that his smell dysfunction was caused by a viral infection?
A I concluded nothing. I just took the information.
Q Doctor, what is it in your professional background, training, and experience that qualifies you to offer opinions concerning what does and does not qualify under homeopathic medicine as a homeopathic remedy?
MR. WENZEL: Objection. Asked and answered and previously testified to.
MR. LAZARUS: I don't think so.
MR. WENZEL: He said he developed homeopathic products himself.
BY MR. LAZARUS:
Q Is that it?
A Yes.
Q And what homeopathic product did you develop?
A The selenium, for example, is a homeopathic product.
Q Did you develop selenium as a homeopathic product?
A I developed supplements, yes. And if you want to know, as an aside, I was even accused by our medical faculty that I was doing the big no-no in studying homeopathy at the University of California San Diego. Seriously, the levels -- and that is, of course, what separated me from the pharmacologists that -- and that is the real fundamental issue here also bordering on the Zicam case. My research has shown that levels very, very low can have profound effects, and that is basically what homeopathic practitioners have been preaching all along. But I've done that scientifically without using the terminology of homeopathy, eventually being damaging to my career.
Q When you say your research has shown that levels very, very low can have profound effects, are you talking about selenium?
A Not only selenium but also other metals. Cobalt, zinc, copper.
Q Is it fair to say that all the work that you've done to investigate whether intranasal application of zinc compounds can cause smell dysfunction has come since you began working with attorneys in cases against Matrixx and Quigley?
A Yes.
Q Were you aware that Robert Henkin is a member of the scientific advisory board of the Quigley Company, which is a maker of Cold-Eeze?
A I didn't know that.
Q Have you published in any scientific journal any of the opinions that are stated in or on the report in this case?
A No.
Q Have you made any effort to do so?
A Absolutely not.
Q Have you submitted any of the opinions stated in your report for any form of formal peer review?
A No.
Q Did you consider yourself an expert on the olfactory effects of intranasal zinc prior to being retained in the Zicam litigation?
A No. I was retained as a chemist.
Q Aside from the case reports by Drs. Jafek, Davidson and Hirsch, are you aware of any peer review publication of opinions that Zicam is the cause of anosmia?
A No.
Q Are you aware of any peer review publication of the opinion that Zicam can reach the olfactory epithelium in the absence of sniffing?
A Could you kindly repeat this.
Q Are you aware of any peer review publication which states the conclusion that Zicam can reach the olfactory epithelium in the absence of any sniffing?
A The only published paper I would consider is the paper by Davidson and Alexander.
Q And Davidson and Alexander concluded that ordinarily a sniff will be required to cause Zicam to reach the olfactory epithelium. Correct?
A I think so. Yes.
DEPOSITION of GERHARD SCHRAUZER, Ph.D., taken at 550 West C Street, Suite 1050, San Diego, California, commencing at 9:41 a.m., Thursday, August 24, 2006, before Jane Bramblett, CSR No. 7574.
San Diego, California, August 24, 2006, 9:41 a.m.
GERHARD SCHRAUZER, Ph.D., having been administered an oath, testified as follows:
EXAMINATION
BY MR. LAZARUS:
Q Good morning, Dr. Schrauzer.
A Good morning.
Q Doctor, you're under oath, and I have deposed you in the last couple of months, so you're familiar with the admonitions. Is there anything about this deposition process that's unclear to you or you would like me to explain?
A No.
Q You understand that if there's anything about my question that's unclear, even though I'm coming at this all from a lay perspective, you should bring that to my attention and I'll try to clarify the question?
A Yes.
Q Is that fair?
A Yes, sir.
(Exhibit 1 was marked for identification.)
BY MR. LAZARUS:
Q All right. Doctor, as a preliminary housekeeping matter, we've marked as Exhibit 1 the notice of taking your videotaped deposition. We're not taking this by videotape today. We're only taking it stenographically.
(Exhibit 2 was marked for identification.)
BY MR. LAZARUS:
Q As Exhibit 2, we've marked a copy of your report. Let me just show that to you and ask you to verify that that's a true and accurate document -- a true and accurate copy of the report that you produced here today. As a matter of fact, that is the report you produced here today. Correct?
A Correct.
Q Is that the second version of your report that you've prepared for this case?
A Yes.
(Exhibit 3 was marked for identification.)
BY MR. LAZARUS:
Q Doctor, I'm showing you what's been marked as Exhibit 3, and I'll ask you to identify what this stack of documents are. I can represent to you that these were loosely contained in the otherwise bound file that we've marked as Exhibit 4.
(Exhibit 4 was marked for identification.)
THE WITNESS: Yes. These were documents I found after I had sent off my collection of documents. And I thought maybe they could still be included. But they obviously have not been. I found a few more things that I had not seen. I found a few more things that I thought I should fax to Mr. Moses Libovits, which I did, and he obviously was able to give it to you.
BY MR. LAZARUS:
Q Doctor, actually, for the record, you gave this to me in that it was contained in the file that you produced today.
A Okay.
Q So it's true, is it not, then, that the documents that are marked Exhibit 3 are parts of your file in this case?
A Yes.
MR. WENZEL: Hang on a second.
BY MR. LAZARUS:
Q And showing you Exhibit 4, is Exhibit 4 a copy of a bound file being produced today?
A Yes.
Q Now, Doctor, you've seen what I've marked as Exhibit 1, which is the notice of deposition.
A Yes.
Q Have you brought the documents that were requested in the deposition notice?
A Yes.
Q Are there any documents or any requests for documents in the deposition notice that you have documents for which you have not produced here today?
A No.
Q There are no documents that you've withheld from production because of objections or because you haven't searched for documents responsive to this notice. Is that correct?
A To my knowledge, it is correct. Maybe I should give you these two pages. This could be redundant. And then I received --
Q Well, Doctor, before we go any further, are these pages that were from the stack of documents that are contained in Exhibit 3?
A I'm not sure. I don't think so.
MR. LAZARUS: Any objection to me adding these two --
MR. WENZEL: Can I take a look at them?
MR. LAZARUS: -- pieces of correspondence?
MR. WENZEL: I don't know if I've seen them.
THE WITNESS: Then I received the --
MR. LAZARUS: One second, Doctor.
MR. WENZEL: Okay. No problem.
MR. LAZARUS: For the record, this is an August 9 letter from Dr. Schrauzer to -- I'm sorry -- from Mark Wenzel to Dr. Schrauzer, and a July 14 letter from Elizabeth Livingston to Dr. Schrauzer, and we're going to include those by stipulation to Exhibit 3.
THE WITNESS: Then I only received very recently from Moses Libovits the testimonials by Dr. Davidson and Bruce Jafek in that O'Hanlon case.
BY MR. LAZARUS:
Q You've handed me the professional expert witness report of Terence Davidson dated May 23, 2006 and a letter report from Bruce Jafek, MD, to Mark Wenzel dated May 15, 2006. Correct?
A Correct.
Q And you said you received these recently. When exactly did you receive these documents?
A Along with the subpoena notice, so it is only a few days ago.
Q You received these in the last few days, correct?
A Yes.
MR. LAZARUS: I'm going to mark these two reports, the reports of Drs. Jafek and Davidson, as Exhibit 5 to your deposition.
(Exhibit 5 was marked for identification.)
BY MR. LAZARUS:
Q Doctor, have you reviewed the reports of any other experts in this case?
A Specifically to this case, no. These are the only two.
Q So I take it, then, you have not reviewed the reports of any of the defense experts in this case.
A No.
Q Have you reviewed reports of expert witnesses in other cases besides the Gillespie case?
A No.
Q Have you reviewed at any time any reports by Richard Dolby?
A Richard Dolby. I cannot recall right now.
Q Have you reviewed any deposition testimony by any individual who you understood was testifying as an expert for Matrixx?
A Not to my knowledge.
Q To make this short, let me ask it this way: Have you reviewed an expert report from any individual who was testifying or designated as an expert for Matrixx in any case?
A He was testifying for Matrixx.
Q The question is whether you've reviewed the reports of any expert witness for Matrixx in any case?
A That -- could you clarify “for Matrixx”? That means an expert witness for the defendant.
MR. WENZEL: Yes.
BY MR. LAZARUS:
Q Yes.
A Where there were reports from the Scientific Advisory -- Scientific Advisory Board of Matrixx. Those I reviewed.
Q I understand. What you're referring to are the documents that are contained in your file --
A Yes.
Q -- Which are seCurities and exChange coMmission filings --
A Yes.
Q -- That were made to report the findings of the scIentific adVisory boArd. Correct?
A Correct.
Q Aside from those two documents, have you reviewed the reports of any experts for Matrixx?
A No.
Q Just to sum that up, Doctor, to this date, you have not reviewed the reports or deposition testimony of any of the experts for Matrixx. Correct?
A Yes.
Q Doctor, referring you to Exhibit 2 to your deposition, which I believe you have in front of you, are all the opinions you plan to testify to in this litigation contained and described in Exhibit 2?
A Excuse me. Repeat this question.
Q Are all of the opinions you plan to testify to in this case contained and described in the report you prepared that is Exhibit 2 to this deposition?
A Yes.
Q And does Exhibit 2 completely describe the basis for each of the opinions expressed in that report?
A Yes.
Q When were you first contacted concerning this case?
A I think in February of 2006.
Q Who were you contacted by?
A That can be found in my correspondence report there. There was quite a bit of change in lawyers, and it could be that it was a Mrs. Schrak, who then left the case on maternity leave, and then it was a Mr. Hanson and then Mr. Wenzel. So I had hardly any contact with the law firm that handled the case.
Q From your answer, I take it that your first contact, as far as you can remember, in February 2006 was with Jennifer Schrak of the law firm representing Mr. O'Hanlon.
A I think so, yes.
Q And since February 2006, you've had contact with other attorneys, including Mr. Hanson and Mr. Wenzel, correct?
A Yes.
Q Have you had any contact with any other attorneys representing Mr. O'Hanlon, besides the three that you've named?
A Very briefly, Mr. Libovits.
Q Doctor, I'm going to caution you, to make a clear transcript, it's necessary that you wait until I finish my question before you start your answer. And I will try to do the same; that is, allow you to finish your answer before I start my next question. What were you asked to do when you were contacted in February 2006 on this case?
A To act as an expert witness in the case of O'Hanlon against Matrixx Initiatives, Incorporated.
Q And what issues were you asked to address as an expert witness?
A To look especially at the chemical aspects of the case.
Q When you say “especially the chemical aspects,” that implies to me there were other aspects to look at. Were there other aspects --
A Well, then cancel “especially.”
Q What you were asked to do was to look at the chemical aspects of the case, correct?
A I would prefer referring to the initial letters whether chemical aspects was actually mentioned. I think it was just mentioned expert witness.
Q Doctor, first of all, let me clarify. I'm not just talking about written correspondence. I'm talking about whatever contact you had with the plaintiffs' law firm and what you were asked to do at that time. Let me also point out to you, however, if at any time you want to refer to any portion of your file to answer my question, let me know and you're free to do so. Is there something you want to refer to in response to my question?
A We could look, please, at the original letter.
MR. WENZEL: Doctor, I have an extra copy of your file. I have two copies of your file. I'll use my marked-up one and you can look at that one. 252, I think, is when the correspondence is based. 252.
THE WITNESS: I think specifically chemistry was not mentioned in the correspondence. I was asked to give a fairly extensive report, and the deadline was June the 1st, 2006.
BY MR. LAZARUS:
Q Doctor, I'm going to ask the question again because I don't think I have an answer to it. What were you asked to do in this case? As an expert witness.
A To assist in the case.
Q To assist in what aspects of the case?
A It was not specified.
Q Okay. What did you understand the request that you assist in the case would entail?
A My opinions in order to find the truth on the case. Expert opinions.
Q On what subject matters?
A On the subject matter of O'Hanlon's loss of the sense of smell and the possible association with the use of Zicam cold remedy.
Q Was there anything more specific that defines your role in this case other than assisting with expert opinions regarding loss of smell and the possible association with Zicam?
A Not to my knowledge.
Q Before, you mentioned the chemical aspects of the case. What did you mean by that?
A Well, I am a chemist and therefore my emphasis will be on the chemical aspects rather than on medical aspects, which is not my field.
Q And what do you consider the chemical aspects of the case?
A The chemical aspects of the case are the questions whether zinc gluconate in the Matrixx no-drip nasal formula can induce anosmia in users of the product under certain conditions of use.
Q What do you consider the medical aspects of the case?
A The medical aspects are the diagnosis of the condition, the medical examination of the plaintiff, and the experience that only medical doctors dealing with anosmia cases have.
Q And what is the experience only medical doctors dealing with anosmia have?
MR. WENZEL: I'll object. It lacks foundation and calls for speculation because that's outside his field of expertise.
BY MR. LAZARUS:
Q Go ahead, Doctor. I'm just asking you to interpret what you told me.
A A medical doctor is licensed to examine patients with certain conditions, which include anosmia. And I have not examined the plaintiff, and, for instance, therefore I'm not qualified to make statements concerning his condition. I have to rely on the medical evidence provided to me through the materials given to me in this case.
Q Since your initial contact with the attorneys for Mr. O'Hanlon, has the -- has your role requested of you in this case changed at all?
A No.
Q Thank you. Tell me what your opinions are in this case you plan to testify to.
A My opinions in this case are that the anosmia or parasmia of Mr. O'Hanlon was causally related to the use of the Zicam nasal gel.
Q What else?
A And that Matrixx Initiatives, Incorporated bears the responsibility for this condition developing in Mr. O'Hanlon.
Q What other opinions do you have in this case that you're going to testify to at trial?
A My opinions in this case are the chemistry of zinc gluconate, which was in part misrepresented by Matrixx Initiatives, and findings related to the properties of zinc gluconate in solution and the question of the effects of zinc gluconate to the nasal mucosa and the olfactory center as well as -- and this is an important point -- the nature of the delivery device that comes with the product, the no-drip nasal gel. And it is my opinion that the delivery device was inappropriate, and proof of the inappropriateness of the delivery device follows from the fact that Matrixx, Incorporated has since changed significantly the delivery device by changing the nozzle from its original one-hole design to a five-hole design so that the spray of the product cannot reach deeply into the nasal cavity if it is used as prescribed in the instructions.
And that, in my opinion, constitutes already an admission by the manufacturer that their delivery device could potentially cause harm in some users.
Q Are there any other opinions you plan to testify to in this case?
A Another opinion pertains to the structure of the delivery device, which has a nozzle that is quite long, two-and-a-half centimeters, and therefore intuitively causes users to insert the nozzle deeply into the nose; whereas, at the instruction to the users, manufacturer wants that the nozzle should be inserted only one-eighth of an inch and at a certain angle. I maintain that this is an inappropriate way of advising users of the product, because intuitively if the pump has a large nozzle, the user will tend to reach deeper portions of the nose in order to fight a cold than if there was another design used.
Q Are there any other opinions you plan to testify to at trial in this case?
A Yes. More recently I have -- and this is given in my report -- I have found a paper by -- let's see. One moment here. Yes. There are several papers that I have now included. One is by Sunderman about the nasal toxicity. New mechanisms that are being used to account for the induction of anosmia by zinc gluconate and other zinc compounds. And then a paper by England and Cobertis published in 1999 on the measurement of the nasal pH in people with and without rhinitis. And this, I think, is a very important -- well, it is an important paper that strengthens all my previous conclusions.
Q The papers you just mentioned are cited in your report. Correct?
A They are cited in my report.
Q How did the England paper come to your attention?
A Internet. I checked on the nasal pH.
Q And when did that first come to your attention?
A Late in May 2006.
Q When were you first retained in a case alleging intranasal application of zinc gluconate causes anosmia?
A To my knowledge, sometimes in the autumn of 2005.
If I may add to this, I have a letter here from December 14, 2005 by Gayle Blatt, and that was a case involving Cold-Eeze, another nasal remedy.
Q What case that was?
A Cynthia Aaron versus the Quigley Corporation.
Q Was that the first case that you were contacted on concerning zinc gluconate causes anosmia?
A There may be another one by Loren Freestone that came earlier than that, but I never wrote -- I think so. That was it. Yes.
Q I'm sorry. You think what?
A I think there was a case before that from Loren Freestone. Orlansky, I think.
Q What's your best recollection as to when you were first contacted by Loren Freestone for the Orlansky case?
A It could have been in September of 2005, but I'm not sure.
Q All right. Now, how many Cold-Eeze cases have you worked on?
A Just one.
Q Just the Aaron case?
A Yes.
Q And how many Zicam cases have you worked on?
A As far as detailed reports are concerned, only the Gillespie case and the O'Hanlon case.
Q I didn't limit my question to detailed reports. What Zicam cases have you worked on to date?
A The question is how you define “worked on.” Like, Loren Freestone called me if I was available, because he wanted to take this case to court. And there were sometimes telephone conversations, but I never had to write a report on that case. And in the meantime I was informed the case has been settled.
Q Let me ask it this way, Doctor: How many Zicam cases have you issued invoices on for your time?
A The Gillespie case and then the Orlansky case. I think that's it.
Q Going back to my question about Cold-Eeze, with the definition in mind that I just gave you -- that is, a case on which you have billed someone for any time at all -- how many Cold-Eeze cases have you worked on?
A Just one. Just this one.
Q Have you billed for any time you spent on the Cash case?
A Which case?
Q Cash.
A That case is not known to me.
Q Are you working with Gary Lento on any Zicam cases?
A Gary Lento, yes. I was informed that this case has been delayed now until, I think, April 2007, and there has been no invoices from me sent to him.
Q At all?
A At all. But I did suggest to other lawyers that they may want to share some of the expenses with him.
Q Doctor, are there any cases for which you plan to issue an invoice and bill for the time you spent, but the invoice has not issued yet, that involves Zicam or Cold-Eeze?
A Well, I think there would be an invoice to the O'Hanlon case, and in the Cold-Eeze case, there still may be one, yes. And there's one outstanding invoice that has not been paid by --
Q Doctor, we're missing each other. I'm asking you for the cases which you spent time in that you either have billed or planned to bill that you haven't billed yet. You've mentioned the Aaron case involving Cold-Eeze, you've mentioned Gillespie, O'Hanlon, Orlansky, and Cash concerning Zicam. Are there any other cases --
A No.
Q -- On which you have billed time or have time on which you plan to bill?
A No.
Q Tell me what work you've done on this case to prepare to testify to your opinions.
A I have done what I consider important additional work compared to the previous cases, which strengthened the conclusions that I drew previously and which brought in some new information that is highly relevant in accounting for the symptoms and condition of Mr. O'Hanlon.
Q What work have you done specifically for this case?
A Literature work.
Q Sorry?
A Study of the literature.
Q Okay. What literature have you studied specifically for this case?
A Especially, I thought I studied the homeopathic literature, because the question that arose in my mind, whether a product can be truly classified as a homeopathic remedy at the concentration that it is offered. And secondly, the study of the nasal pH with and without colds I considered very important and relevant to this case. And the third thing was the correction of an error that was made by the scientists of Matrixx Initiatives, Incorporated concerning the actual concentrations of zinc ion in a 1 percent zinc sulfate solution. And the respective document is given in my file. Yes. This is document ZM123981.
Q Doctor, I see your file is page numbered. Can you tell us what page you're looking at.
A I didn't get a page.
MR. WENZEL: Right down here, Doctor.
BY MR. LAZARUS:
Q What page number is it?
A 44.
Q What's the error on Page 44?
A The error on Page 44 is that the scientists of Matrixx Initiatives, Incorporated assume that a 1 percent solution of zinc sulfate is made from the anhydrous form that is the water-free form of zinc sulfate. The true form that is used in a pharmacy is the heptahydrate, which means a salt of zinc sulfate contains 7 molecules of water of crystallization. That is the pharmacopeia-approved form of zinc sulfate. And if one uses that formula weight for the heptahydrate of zinc sulfate, the actual concentration of the free zinc ion drops substantially and becomes comparable or only insignificantly higher than that in Zicam no-drip nasal gel. And it becomes lower than in Cold-Eeze.
That is important because one of the defense strategies of Matrixx Initiatives, Incorporated was to argue that the level of zinc in the Zicam no-drip nasal gel was below the threshold at which it could cause anosmia. And that refers specifically to the 1938 Canadian study with school children using the 1 percent solution of zinc sulfate for nasal instillation in an attempt to combat an impending polio epidemic.
Q Doctor, what is your understanding of where Page 44 of your file came from and what it was intended to convey?
A Page 44 was sent to me without much comment from Loren Freestone some time ago.
Q So you don't know what context this document appeared in originally; correct?
A Yes, I don't know that.
Q Were you sent any associated papers to this document?
A I think there was just one page showing the composition of Zicam, the detailed composition. I may have it in here, but I may have lost that one. But that's an easy one that we can find. But there was no comment. That's why I did not act on it, because I didn't know what to do with it. I started to act on that document only when Gayle Blatt asked me to act on it in the Cold-Eeze case.
Q Gayle Blatt is an attorney representing --
A Gayle Blatt --
Q You need to wait. Gayle Blatt is an attorney representing the plaintiff against Cold-Eeze?
A Yes.
Q She is the attorney you were working with on the Aaron case?
A Yes.
Q And Gayle Blatt, as I understand your testimony, brought to your attention this document and asked you to comment on it?
A Yes.
Q Did she say what she wanted you to comment on?
A No.
Q What did you understand she wanted you to do with respect to this document?
A To analyze it correctly from a scientific point of view.
Q And where on this document does it say what form of zinc sulfate was being compared to Zicam?
A On the left column. The basic chemistry of zinc sulfate is listed as the composition ZnS04 is -- the formula weight is assumed to be ZnS04, and the formula weight is 161.676 calculated by the authors of this report.
Q Doctor -- I'm sorry?
A That is an error.
Q Okay. Doctor, is there a form of zinc sulfate that has that formula weight?
A Yes.
Q And what is the basis for your opinion that the wrong form of zinc sulfate is being compared on Page 44 to Zicam?
A The anhydrous form of zinc sulfate is not used. It's very difficult to buy even, even today, and the U.S. Pharmacopeia -- and I have a page in my report from the dispensatory of the United States of America, of the 25th edition, which specifically addresses this point of zinc sulfate being the heptahydrate.
Q What page is that in your file?
A That is Page 46.
Q And what date is the edition?
A The date of the edition is 1953, I think. Yes. The importance of this document is that on Page 47 of my report, they are actually addressing also -- on Page 48 -- pardon me -- they are specifically mentioning the Tisdall study from 1937 with the Canadian children. So I repeat, it was not the anhydrous form of zinc sulfate. It was the USP or pharmacopeia-approved form of zinc sulfate, which is the heptahydrate.
Q Doctor, read into the record, if you will, from Page 47 what statement you're referring to as proof that the zinc sulfate studies in Canada used the heptahydrate form of zinc sulfate rather than anhydrous.
A On Page 47 of my report it states, “The official” -- is that “official” -- “crystalline zinc sulfate contains 7 molecules of water of crystallization; the white vitriol of commerce contains but 3 molecules of water.”
MR. LAZARUS: “Vitriol” is v-i-t-r-i-o-l.
MR. WENZEL: Where are you? Can you point that out to me, Doctor? I don't know where you are on this page.
Thank you.
BY MR. LAZARUS:
Q Is that the statement that you were relying on for the --
A That is one of them. And the other one is --
MR. WENZEL: I'll mark a notation for you in case you need to interpret it.
THE WITNESS: And -- yes. That is what I'm relying to and also my attempt to obtain other forms of zinc sulfate have been unsuccessful.
BY MR. LAZARUS:
Q And when did you attempt to obtain zinc sulfate in other forms?
A Sometimes in May and also --
Q I'm sorry. May of 2006, Doctor?
A May of 2006. Here is another thing. Zinc sulfate USP. That means the US pharmacopeia. Or BP, which I think is the British pharmacopeia. And then they say here, zinc sulfate contains no less than 55.6 percent and no more than 61 percent of zinc sulfate corresponding to no less than 99 percent of the hydrated salt zinc sulfate times 7H20 USP. So that means if you want to prepare or use zinc sulfate and ask the pharmacist to make a 1 percent solution, he will reach for the USP form of zinc sulfate, which is the heptahydrate.
Q Doctor, do you have any evidence at all as to what the source was for the zinc sulfate that was used in the polio studies that took place in the 1930s and early 1940s in Canada?
MR. WENZEL: Could I have that question read back.
(Last question read.)
THE WITNESS: It must have been a USP or BP or Canadian pharmacopeia approved form of zinc sulfate, and that is the heptahydrate.
BY MR. LAZARUS:
Q Again, Doctor, the question is: What evidence do you have as to where the zinc sulfate was sourced for the polio studies in Canada?
A That is not listed in the paper by Tisdall. T-i-s-d-a-double 1.
Q So you don't have any evidence as to what the source was for the zinc sulfate used in the Canadian polio studies; correct?
A Correct.
Q Have you now described for me all the evidence that you rely on for your position that the zinc sulfate used in the Canadian polio studies was the heptahydrate form of zinc sulfate rather than the anhydrous form?
A As a chemist by training, I'm forced to this conclusion and I cannot see any exception to it.
Q Doctor, can you please answer my question. The question was whether you've described for me all the evidence that you are relying on for the position that zinc sulfate used in the Canadian polio studies was the heptahydrate form rather than the anhydrous form of zinc sulfate.
A I consider the fact that I'm a professional chemist part of the evidence.
MR. WENZEL: But let me -- he just wants to know is there any other documents or materials that you either reviewed or are aware of besides what you've already shown him as part of your position in that regard.
THE WITNESS: Well, there are catalogs of chemicals that one can look at, and there you always find the heptahydrate form.
BY MR. LAZARUS:
Q Are they in your file?
A No.
Q Have you gone back and looked at any such catalogs that were available in 1938 to 1943?
A Actually went down further than that, to the 19th century, and found no evidence that the other forms were used.
Q Used in any applications at all?
A Not for pharmacological applications.
Q All right. Doctor, we're talking about what work you've done for this case. And you said the additional work you did specifically for this case was studying of the literature concerning homeopathy, study of some literature concerning nasal pH, and correction of what you perceived to be an error by Matrixx concerning the concentration of zinc in the zinc sulfate solution used in the polio studies.
Is there any other work you've done specifically for this case?
A Yes. Examining the packing slips and reading the packing slips and what is written on the boxes, comparing what is now written on the new form of the Zicam nasal -- no-drip nasal sprays, which show that the company acknowledges that the previous delivery system could not protect users from having the product reach very deep regions in the nose. Obviously, the manufacturer of Zicam now do everything they can to avoid this, which, in my opinion, is an admission of the dangers of using the product in its previous form.
I also compared other delivery systems, and I have found that there are products available in which the user will not be able to insert the nozzle so deeply into the nose as when he uses Zicam. So the manufacturer could have used a different delivery system had they been more careful, in my opinion. Just one with a shorter nozzle, and such products are, in fact, being marketed at the present time. I think I even brought some, if you want to see them.
Q Are those in your file?
A I brought them today. Here they are. Hold on. Let's see what -- I have some boxes. See, this is a typical one-hole Zicam.
Q Doctor, if you could just identify for the record what the products that you brought with you here today are.
A This is a bottle, a .5 fluid ounce bottle of the Zicam no-drip liquid nasal gel one-hole nozzle product. This is the new version with the five-hole nozzle of Zicam no-drip liquid nasal gel, which I have purchased since. And here I have two products that could have been used by Zicam, manufacturer of Zicam. Here you see the nozzle is already substantially shorter. Right? And here I have --
Q Doctor, I've asked you to identify what it is so we have it on the record.
A Yes. This is a nasal spray manufactured by Target -- sold by Target. A nasal moisturizing spray for dry nasal passages. It doesn't have a specific name. It's sodium chloride with some preservative. And you see that the nozzle here --
Q Doctor, I just asked you to identify the products that you brought here today. Let's not make this deposition go longer than it has to.
A The next product that I want to introduce as evidence is NaSal saline moisturizer.
Q By what manufacturer?
A Sterling Health, division of Sterling Winthrop, Incorporated, New York, New York 10016, which is a saline moisturizer.
Q Okay. Doctor, thank you. Now, the saline nasal spray that you identified, according to the label; is distributed by Target Corporation, and the nasal moisturizer that you just identified is called NaSal, N-a, capital S-a-l. The NaSal comes in a I fluid ounce bottle. And the Target nasal spray comes in a 1.5 fluid ounce bottle.
And how did you go about findings these, Doctor? Were you just looking on the shelves of a pharmacy?
A Yes. They are OTC.
Q And have you done any analysis to determine whether or not either of these other delivery systems that you brought here today, how they would perform with Zicam nasal gel?
A I have tested the NaSal system, and especially with regards to the recommendation by Matrixx, Incorporated -- Matrixx Initiatives with a much shorter nozzle, it would have been much easier to prevent the deep instillations that obviously occurred in some unfortunate cases.
Q Doctor, is NaSal or the Target spray, either one of those, a metered spray? Do you know what I mean by that?
A Yes, I know what you mean. Not specifically.
Q Well, they're either metered or they're not. Are they metered-dose sprays?
A They're not metered.
Q Do you know what the viscosity is of the solutions that are contained in either the Target nasal spray or the NaSal moisturizer?
A It has a low viscosity because it's mainly sodium chloride.
Q And the directions for NaSal simply say, “Spray twice in each nostril as often as needed or as directed by a doctor.” Correct?
A Correct.
Q And the directions for use for the Target spray is “Squeeze twice in each nostril as needed.” Correct?
A Correct.
Q And can you conclude, based on the analysis that you've done thus far, that the NaSal delivery system or the Target nasal spray delivery system would have been adequate for purposes of a delivery system needed for Zicam?
A I have concluded that. Yes.
Q And on what basis?
A My basis is as follows: When I began to work on these cases, I used Zicam myself as a typical lay user, and I inserted the nozzle much too deeply. Only later I found out that one was not supposed to do this, and I interpreted this as the counterintuitive structure of the pumping device, which implies that one can and should, in fact, insert the nozzle deeply because the nozzle is so long.
MR. LAZARUS: Move to strike as nonresponsive.
BY MR. LAZARUS:
Q Doctor, can you answer my question, please. I asked you on what basis you've concluded that either of these other delivery systems would be adequate for the purposes needed for Zicam. And your answer?
A Personal experimentation.
Q And what have you done to document this experiment that you did?
A Nothing. Just tried it out.
Q As a general proposition, Doctor, should people read the directions on a product before they use it, a pharmaceutical product?
A Yes.
Q When you did your experiment, you said you later found out, after you had used the product, that you had inserted it much too deeply. Correct?
A Correct.
Q So I take it, then, Doctor, that you did not read the directions before you conducted this personal experiment with Zicam.
A That is correct. And --
MR. WENZEL: That's okay.
BY MR. LAZARUS:
Q That's the answer, Doctor.
MR. WENZEL: Honestly, it will go faster if --
THE WITNESS: I need to have a drink of water.
BY MR. LAZARUS:
Q Doctor, aside from your personal experiment, do you have any other evidence that either the NaSal applicator or the Target nasal spray applicator would be feasible and adequate for use in Zicam?
A Yes. The evidence arises from experiments using the pump in the Zicam product. And it turns out the pump can be extremely powerful and propel the product.
MR. WENZEL: I don't think that is what he is asking.
MR. LAZARUS: It's nonresponsive.
MR. WENZEL: Doctor, what he's trying to find out --
THE WITNESS: Maybe I need a little rest.
MR. WENZEL: All right. I think what he is asking -- if you need a rest, fine, but is given what Zicam is trying to do, i.e, reduce cold symptoms and/or shorten the duration of the cold, you want to know what evidence there is that either the NaSal product or the Target product pump-device system or delivery system would be adequate to -- for the Zicam product to perform its functions.
Is that close?
MR. LAZARUS: That's pretty close.
THE WITNESS: I thought I had answered this.
MR. WENZEL: In other words, would the Zicam product work if it had those delivery system?
THE WITNESS: Most likely it would be. It would not be as powerful.
BY MR. LAZARUS:
Q My question is what is your basis for saying that, Doctor?
A Experimentation with the delivery devices.
Q Doctor, did you want to take a break?
A Yeah.
MR. WENZEL: Thanks, Alan.
(Recess)
MR. LAZARUS: Ready?
THE WITNESS: Yes.
BY MR. LAZARUS:
Q Doctor, aside from the reports that we've marked as Exhibit 5, which are reports of Drs. Davidson and Jafek in this case, have you reviewed any other reports by any expert that you understood to be working with the plaintiff in any litigation involving intranasal zinc causing anosmia?
A “Plaintiff” being O'Hanlon?
MR. WENZEL: Any other plaintiff.
BY MR. LAZARUS:
Q Any other plaintiff.
A Forgive me. Repeat this so I can answer precisely.
Q I'm trying to find out if you reviewed the reports of any other experts while working with any plaintiff in a case against Zicam or Cold-Eeze?
A I did not.
Q Have you reviewed the deposition testimony of any individual that you understood to be an expert in any case solving Zicam or Cold-Eeze?
A No.
Q Aside from the documents contained in your file which we marked as Exhibit 4, are there any other documents that were produced by Matrixx in litigation that you've reviewed?
A No.
Q Are all of the documents that you reviewed from your Internet research or other research contained in your file?
A Yes.
Q Let me make sure the record is clear there are documents produced here today that I'm not marking. And I'll catalog them very briefly so we don't have to guess as to what I haven't marked.
Produced today by you or your attorney were notice of taking of deposition. We've marked a copy of that. Stipulated proposed protective order, subpoenas for various medical records from various medical providers that I'm not going to specifically identify on the record, unless Mr. Wenzel --
MR. WENZEL: No.
MR. LAZARUS: -- asks me to. And Mr. Wenzel has kindly said I don't need to do that.
The deposition transcript of Bonnie and Dennis O'Hanlon, and the transcripts of Dr. Schrauzer's depositions taken in the Gillespie case.
I will mark as next in order what appears to be a letter from Dr. Schrauzer to Moses Libovits dated August 18, 2006, which encloses additional material for inclusion in his deposition file, but which I do not believe was actually incorporated into what we've got marked as Exhibit 4.
Am I correct, sir?
THE WITNESS: You're correct.
MR. LAZARUS: Let's mark that as Exhibit 6, I think.
(Exhibit 6 was marked for identification.)
MR. LAZARUS: I'm going to mark as Exhibit 7 what look to be handwritten notes on both sides of the page. I'll show you that in a second.
(Exhibit 7 was marked for identification.)
BY MR. LAZARUS:
Q Doctor, showing you Exhibit 7. Can you tell me if that's your handwriting?
A Yes.
Q And what are those notes?
A These are just copies from the -- I think the packing slips of Zicam.
Q I'm sorry. Are these your notes from review of the product instructions and directions?
A Yes.
Q On the back of Exhibit 7, what's -- what are those comments?
A These are quotes from O'Hanlon's deposition.
Q And there are some quotes from or notes from O'Hanlon's deposition, meaning Mr. O'Hanlon's deposition, on the front page as well, are there?
A Probably, yes.
Q Yes or no?
A Yes. Yes.
Q Thank you. Let me ask you, so there's no question about what it says here, to read your notes on Exhibit 7 into the record.
A My note is a G down here.
Q It's a 7.
A On document 7 states as follows: Quote, “Temporary discomfort such as burning, stinging, sneezing or increased nasal discharge may result. Stop use and ask a doctor if symptoms persist,” end of quotation.
Second statement, “Ask a doctor if you have ear, nose, or throat sensitivity or if you are susceptible to nosebleeds. If swallowed, get medical help or contact a poison control center right away,” and then in quotes, “Satisfaction guaranteed.” And that is from the box of Zicam nasal spray.
Then the last statement on page -- on the front page document 7 is a quote from O'Hanlon. “Inserted 3/4 of an inch.” On probably February 14th, Valentine's -- Valentine's Day, St. Valentine's Day, or -- I can't read that, what it means. And then there's another brief entry, “1/8 of an inch” refers to the recommended depth of insertion by the manufacturer. So he inserted it more deeply.
On the back side of the page I take a quote out of the deposition of Mr. O'Hanlon and put it in quotes. “I snuffed” -- “I sniffed,” probably, “to make sure it got up.” And then again in quotes, “Extreme pain in his upper nose.” That's the end of this page.
Q Thank you, Doctor. Doctor, let me ask you, did Mr. O'Hanlon's manner of using the product in violation of the package directions contribute to the causation of his smell loss?
MR. WENZEL: I just want to object to the extent of this witness has not examined the patient and is not a medical doctor. It may be beyond his expertise.
BY MR. LAZARUS:
Q Go ahead, Doctor. Want me to repeat the question?
MR. WENZEL: So foundation.
BY MR. LAZARUS:
Q Here is the question, Doctor: Did Mr. O'Hanlon's manner of using the product in violation of the package directions contribute to the causation of his smell loss?
A Yes.
Q Specifically did Mr. O'Hanlon's act of inserting the Zicam bottle three-quarters of an inch into his nose rather than one-eighth of an inch into his nose make it more likely that he would experience smell loss?
MR. WENZEL: Same objection.
THE WITNESS: Yes.
BY MR. LAZARUS:
Q If Mr. O'Hanlon had inserted the product one-eighth of an inch into his nose rather than three-quarters of an inch into his nose, would he have experienced smell loss, in your opinion?
MR. WENZEL: Objection. Calls for speculation.
THE WITNESS: The correct question would be --
MR. WENZEL: Just answer the question.
THE WITNESS: Ask the question again.
BY MR. LAZARUS:
Q All right. If Mr. O'Hanlon had inserted the product one-eighth of an inch into his nose rather than three-quarters of an inch, would he have experienced smell loss, in your opinion?
A Yes.
Q If Mr. O'Hanlon had not sniffed up the gel, would he have experienced smell loss, in your opinion?
MR. WENZEL: Objection. Calls for speculation, based upon this witness's qualifications.
You can answer the question.
THE WITNESS: I would have to answer yes.
BY MR. LAZARUS:
Q So it's your opinion, then, Doctor, that even if Mr. O'Hanlon had inserted the bottle one-eighth of an inch into his nose and not sniffed the product -- I'm sorry. That's not allowable, Doctor. You can ask Mr. Wenzel a question after you're done answering my question. Okay?
MR. WENZEL: Or you can say you don't understand the question. Just answer the question. Let him ask the question.
MR. LAZARUS: Let me ask the question.
MR. WENZEL: It's got to be restated.
BY MR. LAZARUS:
Q So it's your opinion, Doctor, even if Mr. O'Hanlon had inserted the bottle one-eighth of an inch into his nose and not sniffed the product, he would still have sustained smell loss. Correct?
A Correct, with a qualification.
Q Now --
A May I now please speak to my attorney?
Q Let me finish this line of questioning.
MR. WENZEL: I'll remember your qualification, Doctor. Don't worry about it. I'll ask it on redirect.
BY MR. LAZARUS:
Q What was the orientation of the bottle as inserted into Mr. O'Hanlon's nose?
A We don't know this.
Q Do you have any evidence at all as to whether or not Mr. O'Hanlon angled the bottle towards the lateral nasal wall?
A No.
Q Do you know whether or not the -- there was a zero-degree angle to the bottle when Mr. O'Hanlon inserted it into his nose?
A I don't know.
Q Doctor, if the bottle is inserted at a 30-degree angle towards the lateral nasal wall and there's no sniffing by the user, will any of the gel get to the olfactory epithelium?
MR. WENZEL: Objection. Calls for speculation. Not his field of expertise.
THE WITNESS: Please rephrase the question, because gel is not equal to zinc. And zinc is the active ingredient.
BY MR. LAZARUS:
Q Doctor, how does zinc -- Doctor, how does zinc get to the olfactory epithelium if the gel does not?
A Theoretically, it could go there by diffusion processes.
Q Putting aside “theoretically,” does that happen?
A It may happen under certain circumstances.
Q Did it happen in this case?
A We don't know.
Q What circumstances would cause that to happen?
A If there are special inflammatory conditions making the nasal mucosa, that increase the permeability of the epithelial layers.
Q And how, then, does zinc get to the olfactory epithelium without any gel reaching the olfactory epithelium?
A Through diffusion transfer processes, in part using physiological transport substances such as carnosine. Carnosine is spelled c-a-r-n-o-s-i-n-e.
Q And you don't know whether or not any zinc was transported to the olfactory epithelium of Mr. O'Hanlon by this process, correct?
MR. WENZEL: By diffusion?
MR. LAZARUS: Yes.
THE WITNESS: I do not know.
BY MR. LAZARUS:
Q Now, back to my question. If the user orients the bottle at a 30-degree angle towards the lateral nasal wall, will any of the gel reach the olfactory epithelium?
MR. WENZEL: Just answer that question.
BY MR. LAZARUS:
Q Without sniffing.
MR. WENZEL: Don't trouble yourself as to whether or not -- what his question was is on the insert. Just answer his question.
THE WITNESS: Pardon me. I mean I have to be permitted to ask questions of clarification. You mentioned 30 degrees. What makes you say 30 degrees when --
BY MR. LAZARUS:
Q Doctor, I'm just posing a hypothetical question.
MR. WENZEL: He is just posing a hypothetical question.
BY MR. LAZARUS:
Q This will go a lot quicker --
A You have to say that --
MR. WENZEL: No. he doesn't. Here is what he does. He gets to ask the question, and if you don't understand the question, you can say I don't understand, would you please rephrase, and Mr. Lazarus may ask you what part didn't you understand. He is allowed to ask the questions, and you can ask for clarification.
THE WITNESS: Forgive me. Please rephrase your question.
BY MR. LAZARUS:
Q If the user orients the bottle at 30 degrees toward the lateral nasal wall and does not sniff, will any gel reach the olfactory epithelium?
A No.
Q And if the orientation of the bottle was 20 degrees rather than 30 degrees, would you have the same answer?
A No.
Q 20 degrees, you believe that gel won't reach the olfactory epithelium?
A The probability could increase that it reaches it.
Q When you say the probability would increase, are you saying it's more probable than not at a 20-degree angle without sniffing the gel will reach the olfactory epithelium?
A Yes.
Q At 10 degrees?
A Even more so.
Q At zero degrees?
A Even more so.
Q What about 25 degrees?
A That's between 20 and 30, so it's in between the two.
Q And do you have an opinion as to whether or not it would be more likely than not that the gel would reach the olfactory epithelium if the bottle was oriented at 25 degrees without sniffing?
A Yes.
Q Now, Doctor, I want you to assume that somebody has angled the bottle at 30 degrees and directed the gel into the lateral nasal wall and it has not reached the olfactory epithelium at that initial deposit. What effect on the transport of the gel will there be if the patient sniffs?
MR. WENZEL: Talking about the gel itself. The transport of the gel.
THE WITNESS: The gel would be transported into deeper portions of the nose.
BY MR. LAZARUS:
Q Would it reach the olfactory epithelium?
A It could very well in some cases.
Q Depending on what?
A The anatomy of the nose of the user. Whether there were swollen turbinates, whether there is heavy nasal discharge, and how powerful the pump was operated -- how powerfully the pumping device was operated.
Q What does how powerful the pumping device was operated have to do with whether a post-deposition sniff will move gel to the olfactory epithelium?
A Because initially a powerful pumping operation could have transported the gel more deeply to begin with, even at 30 degrees.
Q Do you know whether or not Dennis O'Hanlon had swollen turbinates at the time that he used the Zicam?
A He had no symptoms of the cold, but this is a medical question I refer to reports by the examining doctor.
Q So you don't know one way or the other?
A No.
Q Is that correct?
A That is correct.
Q Do you know one way or another whether Dennis O'Hanlon was experiencing any heavy nasal discharge at the time he used Zicam?
A From his deposition I know that he did not.
Q And did you know from any evidence that you've seen in this case how powerfully Dennis O'Hanlon operated the Zicam pump?
A I do not know.
Q Do you have any information about how he applied the pump for the nasal spray?
A Other than he inserted it at three-quarters of an inch, no.
Q What is a sniff?
A A sniff, by my definition, would be the often involuntary clear attempt to clear nasal passages by pulling in the air to remove obstructions of the nasal passages.
Q What kind of flow rate is produced when someone sniffs?
MR. WENZEL: Objection. Calls for speculation. If you know.
THE WITNESS: I do not want -- cannot estimate.
BY MR. LAZARUS:
Q Why not?
A Because it depends on the anatomy of the nose, the amount of obstruction, and individual properties of the user.
Q Do you have any information at all, Doctor, as to what kind of flow rate was produced by Mr. O'Hanlon's sniff after using Zicam in this case?
A No.
Q Will the flow rate of the sniff have any effect on whether or not gel administered to the lower portion of the nose can reach the olfactory epithelium?
A No.
Q So it doesn't matter how forceful the sniff is with respect to the likelihood of Zicam traveling to the olfactory epithelium?
MR. WENZEL: Objection. Misstates his testimony.
BY MR. LAZARUS:
Q Is that correct, Doctor?
A Yes. With a qualifier.
Q So there's no difference in distribution of the gel whether the user sniffs deeply and forcefully or sniffs shallowly and minimally in terms of force. Is that correct?
A With a qualification.
Q What is the qualification, Doctor?
A The qualification is a sniff is a sniff, and if I sniff shallowly, then I will have to sniff again until the obstruction is gone. So it is very difficult to only sniff halfway. That is like not sniffing at all.
Q Doctor, what scientific evidence do you rely on for your opinions concerning the effect of a sniff on flow rate and distribution of the gel?
A My personal tests.
Q What personal -- first of all, before you go any further than that, I'll ask you about those personal tests. Is there any other scientific evidence, besides your personal tests, that helps to inform you as to the effect of a sniff on air flow in the nose and distribution of the gel?
A There probably is, but it is not part of my testimony.
Q In other words, you haven't looked at any scientific literature for that purpose?
A No.
Q Is that correct?
A That is correct.
Q All right. So you're relying completely on the scientific tests that you've performed concerning the effect of sniffing, correct?
A Yes.
Q What scientific tests have you performed on the effect of sniffing on flow rate and distribution of the nasal gel?
A I would not call it a scientific test.
Q What would you call it?
A I would call it a simple test how my nose reacts to an obstruction and how I would respond to that obstruction. And that resulted in my sniffing in the gel.
Q And was this test, this simple test, not scientific test that you performed, done in the context of litigation?
A Yes.
Q In other words, it was done after you were retained as an expert witness to investigate the issue surrounding Zicam causing anosmia?
A Yes.
Q When did you do this test and were --
A I can't remember. Sometime in May.
Q Did you do it once, twice, three times? Tell me.
A Twice. But my qualifier here is I was already somewhat afraid that I could myself develop anosmia, and I may not have sniffed as much as a complete novice that put it in his nose. So that's why I'm not calling --
Q Doctor, if you could, very briefly, take us through how you performed this test.
A I instilled a small amount of the Zicam no-drip nasal gel and then actually I spontaneously sniffed it in. I did not want to sniff it in. It just so happened. And that taught me not to sniff in. It takes a conscious effort. Once your nose is obstructed, one wants to clear it by sniffing it in.
Q That's your interpretation of what happened; correct?
A Yes.
Q Did you know of any scientific literature that would allow you to translate the experience that you had during the course of this test to the overall experience in the general population of other users?
A I consider this evidence. For me this would be a self-evident point, but I did not study the scientific literature on the subject.
Q Did you do anything to document this test?
A No.
Q Did you film it, for example?
A No.
Q Did you take any notes concerning it?
A I may have, but I couldn't find them anymore.
Q So you may have taken notes but lost them? Is that it?
A Probably. Yes.
Q Do you have an independent observer watch this test performed?
A No.
Q Did you do this completely on your own?
A Yes.
Q And you're prepared to testify in court that this test that you performed on yourself is sufficient to allow you to reach conclusions about the effect of sniffing on distribution of the Zicam gel?
MR. WENZEL: Objection. Misstates his testimony.
THE WITNESS: In court I would probably not testify on this point because it is more a medical question.
BY MR. LAZARUS:
Q So you're not planning to testify to the effect of sniffing on the distribution of the Zicam nasal gel? Am I correct?
A You're correct.
Q Are you planning to testify on the question of the distribution of the Zicam nasal gel at all at trial in this matter?
A Yes.
Q And what is your testimony going to be as to the way Zicam is distributed in the nose?
A O'Hanlon's observation. Personal observation.
Q And what is that?
A What he described in his deposition. That he sniffed up -- he inserted the nozzle three-quarters of an inch and he sniffed it up. That is the evidence that I will rely on.
Q Doctor, are you going to be offering an opinion at trial in this matter that Zicam, in fact, reached Mr. O'Hanlon's olfactory epithelium?
A Yes.
Q And what's that going to be based on?
A I consider the evidence in itself to be evidence.
Q What scientific evidence are you going to use to support your opinion that when Zicam is used as Mr. O'Hanlon used it, according to his description, Zicam can, does, and did reach the olfactory epithelium?
A The symptoms that developed shortly afterward.
Q Any other scientific evidence that supports your opinion that under Mr. O'Hanlon's manner of use Zicam can and did reach the olfactory epithelium?
A The Gillespie case.
Q Did Julie Gillespie use the product in the same manner as Mr. O'Hanlon?
A Mrs. Gillespie used the Zicam gel, and anatomically it was found that her olfactory center was clearly visible. So that shows that in her case the gel could have reached the olfactory center, and, by analogy, I conclude the same thing could have happened to Mr. O'Hanlon.
Q Did Ms. Gillespie use the product in the same manner that Mr. O'Hanlon did?
A I'm not sure right now. We can check this.
Q Did Ms. Gillespie and Mr. O'Hanlon have the same nasal anatomy?
A No.
Q Did they have the same level of swelling of the turbinates, for example?
A We cannot tell that.
Q Is there anything else that you are going to rely on for your opinion that Mr. O'Hanlon's use of Zicam nasal spray caused the distribution of gel to his olfactory epithelium?
A Yes. I would state that the use of the terminology “gel” is inappropriate because the ionic zinc, the pharmacologically active zinc, can travel by diffusion without involving the gel.
Q Doctor, you have already told me, have you not, that you don't know one way or the other whether diffusion has any role in any Zicam or -- strike that -- any zinc reaching Mr. O'Hanlon's olfactory epithelium?
A I think you are overstating my responses, so I would like you to change it.
Q What evidence do you have that Mr. O'Hanlon had Zicam or zinc reach his olfactory epithelium through a diffusion process in this case?
A That is generally physiological properties of zinc. It will not just simply sit there. And once it hits the olfactory center, it can also reach it by diffusion. That's physiology.
Q So it's your testimony, Doctor, whenever any zinc compounds such as zinc gluconate gel such as in Zicam is administered into the nasal cavity, diffusion process will take zinc ions to the olfactory epithelium?
A That is correct.
Q And will produce some damage to the olfactory tissue?
A That is correct.
Q And will cause smell dysfunction?
A May cause smell dysfunction.
Q What is the variable that determines whether or not the zinc ions administered into the nasal cavity produce smell dysfunction?
A The local pH of the nasal mucosa is one of the most important ones.
Q What was the pH of Mr. O'Hanlon's nasal mucosa at the time he used Zicam?
A It was not measured.
Q Can you say one way or the other without speculating, sir, that diffusion played a role in zinc traveling to Mr. O'Hanlon's olfactory epithelium and causing his smell impairment?
A Mr. O'Hanlon at the time did not have a cold. We know from the work of England and Cobertis that people who do not have a cold have a more acidic pH of the nasal mucosa; therefore, the level of the pharmacologically active ionized zinc would have been higher and, yes, then the effect on the smell functions would have been more prominent.
Q I'll ask you again. What was Mr. O'Hanlon's nasal pH at the time he used Zicam?
A It was, according to my interpretation of the available scientific evidence from other cases, lower than in a person with manifest rhinitis.
MR. WENZEL: As in a cold.
THE WITNESS: As in a cold. And to further confirm that, I measured the pH in my own nose and found it to be not alkaline, weakly acidic, because I didn't have a cold.
BY MR. LAZARUS:
Q What do you mean when you say he did not, quote, “have a cold,” end quote?
A He stated so in his deposition.
Q And do you know what he meant by that?
A That he was afraid of developing a cold but did not have it yet.
Q Is Mr. O'Hanlon a medical doctor?
A No.
Q What does it mean clinically or scientifically to have a cold? When does one have a cold?
MR. WENZEL: Objection. Calls for speculation, outside of this witness's field of expertise.
BY MR. LAZARUS:
Q Do you agree it's outside of the scope of your expertise?
A I would say I agree with that.
Q So you don't know whether or not there's a cold virus present in advance of any particular number or severity of symptoms. Is that correct?
A Please rephrase the question. There's evidence that Zicam has no effect on cold viruses.
MR. WENZEL: That -- please, Doctor. That's not the question. Just state your question, again, Mr. Lazarus, please.
BY MR. LAZARUS:
Q Doctor, do you know what clinical manifestations determine whether or not there is a cold virus present in an individual?
A Individual? No.
Q Do you know what level of clinical manifestations are needed for a cold to be a potential cause of persistent smell loss?
A No. With a qualification.
Q Do you know at what point after introduction of the cold virus there is potential for destruction of smell function from the virus itself?
A No.
THE WITNESS: Can I speak to you for a moment?
MR. WENZEL: Okay. Go off the record for a moment.
(Discussion off the record)
MR. LAZARUS: Back on the record.
BY MR. LAZARUS:
Q Doctor, when you were talking about your test before, you said you instilled a small amount of Zicam into your nose. Did you instill the metered dose?
A I don't know.
Q What makes you doubt that you might have instilled the metered dose?
A Because it is very difficult to actually instill a metered dose. It depends how one prepares the pump.
Q Did you consciously try not to instill a metered dose?
A Probably.
Q Did you get any zinc to your olfactory epithelium during the course of this test?
A Yes. Probably.
Q How much?
A I don't know.
Q Through what process did you get zinc to your olfactory epithelium during your experiment?
A Through diffusion.
Q How much zinc needs to be transported through diffusion to the olfactory epithelium to cause smell dysfunction?
MR. WENZEL: Objection. Asked and answered.
THE WITNESS: Considering the great sensitivity of the olfactory tract and the mechanism of zinc diffusion, small amounts of zinc are sufficient.
BY MR. LAZARUS:
Q Well, how much?
A That is impossible to quantify.
Q Give me a range, Doctor.
A Microgram amounts.
Q As I said, give me a range, Doctor.
A I would say a hundred micrograms per dose.
Q And what is the basis for you saying a hundred micrograms of zinc through diffusion process will cause smell dysfunction?
A May cause. Because my own experience was I estimated roughly the amount of zinc, and I actually had temporary smell dysfunction. I did not have anosmia. I had dysfunction. And I can elaborate further upon request.
Q I want to get an answer to my question first, and then I'll come back to that. What is the basis for your opinion that a hundred microgram dose of zinc through diffusion process is sufficient to cause smell dysfunction?
A The effect of zinc ions on carbonic anhydrase especially.
Q And what about the effect of zinc ions on carbonic anhydrase supports the scientific opinion that a hundred micrograms of zinc through a diffusion process may cause smell dysfunction?
A Because the concentration -- the natural concentration of zinc in the nasal mucosa is comparatively low, and a hundred micrograms would be a much higher concentration, causing reactions to these very sensitive enzymes. And there's evidence that zinc inhibits carbonic anhydrase in experimental animals.
Carbonic anhydrase is an enzyme that catalyzes the decomposition of carbonic acid, H2C03, into carbon dioxide and water. Carbonic anhydrase is a zinc-dependent enzyme. We need carbonic anhydrase in the nose so that the balance between the air which is inhaled with the smelly substance in it is also expelled rapidly. If there is an inhibition of carbonic anhydrase activity, that process is impeded and that causes people then to experience a smell dysfunction. Characterized by sudden dislike for meat these people cannot or totally are revulsed by the smell of meat. And that happened to me after I used Zicam in this fashion. But it was not permanent. It was temporary.
Q Doctor, what scientific evidence are you aware of that quantifies the amount of zinc sufficient to cause smell dysfunction through interference with or inhibition of carbonic anhydrase?
A In my reports -- and I think even in the original here, is a paper written on the inhibition of carbonic anhydrase. Yes. By Masaya Kimoto and co-workers. Carbonic anhydrase in the mouse nasal gland, published in the journal “Histochemistry and Cytochemistry,” Volume 52, Issue No. 8, pages 1057 to 1062, published 2004.
Q And does that article quantify how much zinc instilled in the mouse nose is necessary to inhibit carbonic anhydrase to the point of causing smell dysfunction?
A Hold on. Off the record for a moment?
Q No. Not off the record, Doctor.
A Okay. Then let me look it up.
MR. WENZEL: Just take your time. Take your time.
MR. LAZARUS: Yeah.
THE WITNESS: I cannot quantify this information at the moment.
BY MR. LAZARUS:
Q So you're not aware of any scientific evidence that quantifies how much zinc instilled in a nasal cavity of a mouse is sufficient to cause smell impairment; correct?
A Inhibition of carbonic anhydrase activity.
Q That would cause smell dysfunction, correct?
A That is one cause.
Q I understand that, Doctor. Let me rephrase the question.
You're not aware of any scientific evidence that identifies the quantity of zinc instilled in a mouse nasal cavity which is sufficient to cause smell impairment through inhibition of carbonic anhydrase activity, correct?
A Correct.
Q And is the same true with respect to the quantity of zinc instilled in the nasal cavity in a human, that there's no -- let me rephrase the question. Bad question.
You're not aware of any scientific evidence that quantifies how much zinc instilled in the nasal cavity of a human and is sufficient to cause smell impairment through inhibition of carbonic anhydrase activity; correct?
A Correct.
Q Are you aware of any scientific evidence that demonstrates the instillation of zinc into the nasal cavity of a human is capable of causing smell dysfunction through inhibition of carbonic anhydrase activity?
A No.
Q Do you have an opinion, Doctor, as to how much zinc needs to be instilled into the human nasal cavity to produce permanent smell dysfunction through inhibition of carbonic anhydrase activity?
A No.
Q Are you aware of any evidence at all, Doctor, that indicates that diffusion of zinc causing an inhibition of carbonic anhydrase activity is capable of causing permanent smell dysfunction in a human?
A No. Just a minute. Let's leave it at no.
Q Are you aware of any scientific evidence that describes how smell impairment would manifest itself if someone was to achieve interference or inhibition of carbonic anhydrase activity through instillation of zinc into the nasal cavity?
A From my personal experience following the instillation of Zicam, I did not have permanent smell loss. I had just a dysfunction. In other words, things smelled in an odd way. So carbonic anhydrase is one mechanism, but it's not all of it. There's another one. At least another one. And then there's, of course, the actual destruction of the olfactory cells, which is the third one.
Q Tell me what the other mechanism -- let's try to get a shorthand going here, Doctor, because we're using a lot of words on this transcript.
You're basically testifying there are three mechanisms that you're aware of in which smell dysfunction can be caused by the introduction of zinc into the nasal cavity. Correct?
A Correct.
Q One of them is by direct action of the zinc on the olfactory epithelium through physical contact?
A Correct.
Q And that, of course, would require that the zinc in the gel be transported physically to the olfactory tissue, correct? We're putting aside diffusion now, Doctor.
A Okay.
Q Because, Doctor, diffusion is an indirect process. It goes into the tissue and then gets transferred.
A Both can have the same effect, but --
Q Would you agree there's one direct mechanism and that is delivery of the gel with the zinc in it to the olfactory epithelium?
A Directly, yes.
Q Now, you're also testifying that there are two indirect mechanisms. Do they both involve diffusion?
A Yes. One could say that.
Q All right. Now, you've identified one of them as a diffusion process which transports zinc ion to the olfactory epithelium through diffusion and then interferes or inhibits carbonic anhydrase activity. Correct?
A That is one mechanism, yes. Correct.
Q All right. Tell me briefly what the other mechanism is.
A Well, the other mechanism is the amount of diffusing zinc is sufficient. It can also have a destructive effect of the olfactory epithelium. That would be number two. And number three is a mechanism involving the substance called carnosine, c-a-r-n-o-s-i-n-e, which is -- and I will be slow -- beta haloneal histidine, which is a substance that can -- which is plentiful in the nose and actually can also transport zinc, and it can actually transport the zinc right into our olfactory center in the brain. So it's a very important transporting agent. And interference with the production of carnosine is also now believed to contribute to smell dysfunction.
Q Has that been scientifically proven to have happened, Doctor?
A Yes.
Q In a human?
A Probably not in a human.
Q In what species has this been proven to occur?
A I think in rats and mice.
Q In what doses?
A That is written in the literature. I do not know the numbers now.
Q Are you aware of any scientific evidence that demonstrates that zinc instilled in the nose can cause interference with carnosine biosynthesis sufficient to cause persistent smell dysfunction in a human?
A No.
Q You mentioned another mechanism that I hadn't appreciated before from your testimony. You said that zinc can be instilled in the nose in a sufficient amount so that, through diffusion, it can destroy the olfactory epithelium. Correct?
A Yes.
Q Are you aware of any scientific evidence which quantifies how much zinc would be necessary instilled into the nose to cause diffusion of a sufficient amount to cause persistent smell dysfunction through destruction of olfactory tissue?
A I could refer you to experiments -- could you please repeat that. I --
Q Yes. I will.
Are you aware of any scientific evidence which quantifies how much zinc would be necessary to instill into the nose to cause diffusion of a sufficient amount of zinc ion to produce persistent smell dysfunction through this mechanism of destruction of the olfactory tissue?
A Not direct evidence in humans.
Q What evidence in humans do you have?
A The case reports in the Zicam litigations.
Q Doctor, what about the case reports you've seen concerning Zicam which quantify how much zinc is necessary to cause destruction of the olfactory epithelium through diffusion process?
A The -- to answer this question, depends on the pH. And even the direct contact of Zicam in the olfactory center ultimately involves a diffusion process. The amount of zinc that will diffuse will depend on the pH of the contact surface. In people without a cold the England study shows the pH is lower; therefore, there will be more ionized zinc than with people with a cold where the pH is more alkaline. As a result, an exact quantification is not possible, in my opinion.
Q Doctor, back to my question. I don't think you responded to it.
MR. WENZEL: He said there was no exact quantification at the end of his answer. Your questions was what was the quantity. He said there is no exact quantity.
MR. LAZARUS: Let me repeat --
MR. WENZEL: Now you're getting argumentative.
MR. LAZARUS: Let me repeat the question.
BY MR. LAZARUS:
Q Let's try to keep on point. Let me offer a preface, Doctor. You've testified that the zinc does not need to physically be delivered directly to the olfactory epithelium in order to cause destruction of the smell tissue sufficient to cause an impairment. Correct?
A Yes.
Q This is, in the vernacular that we've adopted, you and I, an indirect mechanism of destruction of the smell tissue. Correct?
A Not quite.
Q Are we talking about a diffusion process or are we talking about direct mechanical delivery through applications of the pump?
A I would argue that even the mechanical delivery ultimately will involve diffusion processes.
Q Yes. But we're talking about -- are you separating -- strike that.
Doctor, you're theorizing a mechanism by which Zicam is delivered to smell tissue other than the olfactory tissue and then, through a transport and diffusion process, finds its way to the olfactory epithelium, and the zinc ions then cause destruction of the smell tissue. Correct?
A Yes.
Q In other words, they arrive at the olfactory epithelium through a diffusion process rather than a direct delivery. Correct?
A Correct.
Q All right. Now, my question is what about the case reports concerning Zicam scientifically establish that this diffusion process is capable of causing smell dysfunction in the absence of any direct delivery?
A In the absence of any direct --
Q Direct delivery of zinc ions.
A What about the scientific evidence --
MR. WENZEL: About the case reports that show that this can happen.
THE WITNESS: I would say these are the cases where the anosmia occurred at a rather long period following the instillation, the use of the pump.
BY MR. LAZARUS:
Q So it's your testimony, Doctor, that if there is a delay between the use of Zicam and the manifestation of smell loss, that indicates that the mechanism of loss is through a diffusion process rather than through a direct delivery of gel to the olfactory epithelium?
A One could hypothesize that. Yes.
Q Doctor, I understand that one could hypothesize that. But is there any scientific evidence proving?
A No.
MR. WENZEL: You can talk to me at the break.
MR. LAZARUS: We're getting close to the lunch period. What's your preference?
MR. WENZEL: We should eat, because my blood sugar is important for concentration, so my preference is we eat. But how we do that, it depends on --
THE WITNESS: Let's just now stop.
MR. LAZARUS: That's my question.
MR. WENZEL: Why don't we break now. We've been going two-and-a-half hours or so. So I don't know what's available here. Why don't we go off the record for a moment.
(Luncheon Recess)
MR. LAZARUS: Back on the record. Before I forget, let me get marked as the next exhibit in order, I think it's No. 8, a page of notes that I'll represent were stuck in the transcript of Volume I of Mr. O'Hanlon's deposition in the area of Exhibit 4 to the deposition of Mr. O'Hanlon.
(Exhibit 8 was marked for identification.)
BY MR. LAZARUS:
Q Doctor, I'll show you Exhibit 8, and I'll also show you a page in the exhibit where it was located, and ask if you can identify what Exhibit 8 is.
A Yes. Part of the Exhibit 8 is the entry here where they mention Nasarel as a prescription for Mr. O'Hanlon and --
Q Did you find the mention of Nasarel as something of a particular significance to your opinions in this case?
A The purpose of this was to satisfy my own curiosity whether or not the use of Nasarel or Prinivil could have caused anosmia in that patient.
Q What is Nasarel as you understand it?
A Nasarel is, in fact, sodium chloride. That's why I brought it.
Q You're referring to the NaSal solution you brought here today?
A Yes.
Q Is that what you're referring to when you say Nasarel?
A Right. I think so.
Q Am I correct that Exhibit 8 is some notes that you took from review of the transcript, Mr. O'Hanlon's deposition?
A Right.
Q Can you just read those notes into the record very quickly.
A “Nasarel and Flonase.” That's what he was prescribed or took. And I don't know what “CPAP” means anymore. And then I mention Prinivil and Atenolol. And I think --
Q Doctor, is it generally true that you were noting those medications so that you could further investigate whether there were other alternative causes of Mr. O'Hanlon's smell loss?
A Yes.
Q What's your understanding of the time period when Flonase was used by Mr. O'Hanlon in relation to his use of Zicam?
A There was no connection.
Q I'm sorry. What I meant was when was it in comparison to his use of Zicam?
A Sometime after that when he went to a doctor.
Q Okay. All right, Doctor. Thank you. Doctor, you've mentioned a couple times today some tests or experiments or personal tests that you've performed in connection with your investigation of the issues surrounding Zicam and smell loss. Tell me what tests in sum that you've performed in connection with your investigation of Zicam.
A I compared Zicam no-drip nasal gel with the pump, and I also tested the swabs.
Q I'm asking you what tests you performed.
A On my own to instill a small amount of it or to use it and to just check what symptoms I would get, if any.
Q All right. So one test you performed was to use Zicam cold remedy nasal gel in both the swab and the pump form on yourself to determine what happened to you after you used it. Correct?
A Yes.
Q Was this a scientific test or a personal test?
A Both.
Q What scientific method did you follow in performing this test?
A A subjective, feelings and symptoms.
Q And what did you do to document this test?
A Nothing much.
Q Did you do anything at all?
A I did jot down, but the purpose of this was for my personal education and also see if the product actually works.
Q Are you basing any scientific opinions or conclusions on the testing that you performed with Zicam cold remedy, administering it to yourself?
A I based on conclusions, subjective findings.
Q And what subjective findings are you using as a basis of conclusions arising from this test?
A Subjective symptoms.
Q And what were they?
A For example, after awhile, weakness in my muscles and pain on my left arm. And then also a smell disorder that I suddenly couldn't bear the odor of ham, fried ham, for example. This was actually you might say a kind of hyperosmia. I smelled too strongly. In other words, it was a distortion of the smell. It was not anosmia. It was hyperosmia.
Q And what conclusions do you draw from these symptoms that you experienced?
A These conclusions show that zinc -- after all, the olfactory system depends very much on zinc. In zinc-deficient animals, zinc-deficient animals are basically anosmic. So a lack of zinc causes anosmia. But we now know that an excess of zinc also causes anosmia. That is the paradoxical aspect of zinc in the olfactory system, and that's what interested me.
Q Doctor, what scientific evidence is there that use of Zicam in product-level doses causes weakness in muscles?
A My personal observation, and we have to generalize zinc; right? Zinc -- and zinc does that.
Q My question is what scientific evidence is there, sir, concerning whether Zicam used in product-level doses causes weakness in the muscles?
A My personal observation.
Q And that's it.
A Yes.
Q And what scientific evidence is there that use of Zicam at product-level doses can produce pain in one's arm?
A My personal observation.
Q And what scientific evidence is there that use of Zicam at product-level doses can cause someone to not be able to bear the odor of fried ham?
A My personal experience.
Q Okay. And, Doctor, is it your testimony that this type of experiment is the type of thing that scientists rely on in forming conclusions about toxic effects of chemical products?
A No.
Q What other tests have you done in connection with your investigation of Zicam?
A I put some on my skin on the arm, rubbed it in to see how quickly it is absorbed by the skin.
Q What conclusion did you draw from that?
A That it is quickly absorbed.
Q How quickly?
A Less than a few minutes.
Q Did you do anything to document or measure the results of this test? A No.
Q Is this the type of test or experiment that a scientist relies on to draw conclusions about the toxic effects of a chemical substance?
A It's an initial test to invite further studies or compare it with available evidence.
Q Did you do any follow-up testing to -- in terms of further study based on this test? A. Yes.
Q What did you do?
A I also took the oral spray mist, in other words, the zinc gluconate preparation of Zicam, and used it as recommended.
Q Again, both of these tests -- that is, putting some on your arm or skin to see what kind of absorption there is and your use of the oral spray mist -- those are basically just tests to elicit your own personal subjective observations; correct?
A Not quite, sir. If I may elaborate a little bit. For instance, if the zinc would just be sitting there, right, I can see with my eyes if it is, for instance, zinc oxide. Zinc oxide is used in bandages, for example. I could see with my eyes, and that would be an objective observation, that the zinc is sitting there, because zinc oxide is white and is visible. Same thing with zinc hydroxide. You can see it. In the case of Zicam, you could see that the entire thing disappeared. You couldn't see anything anymore. So that, in my opinion, is an objective observation of a rapid absorption.
Q Do you consider that a scientific test that an expert, a scientist, would rely on in forming conclusions about the toxic effects of chemical substances?
A Physiologic effects, not toxic.
Q And what evidence arose from these tests other than your own anecdotal accounts of your personal observations?
A I have not used this evidence in my report.
Q So you're not relying on these tests for any of your opinions in this case. Correct?
A To some extent I do rely on it. Yes.
Q What do you rely on it for?
A I rely on it that Zicam contains ionized zinc, which is sufficient evidence already proven, and that this ionized zinc has physiological effects and that this ionized zinc passes through biological membranes.
Q Was any of that open to question, Doctor?
A No.
Q So, really, it doesn't add anything to the data that's already out there in the existing scientific --
A For my own personal edification.
Q What other tests have you performed in connection with your work in Zicam litigation?
A I already mentioned the use of the oral spray. So that's about it. Yes.
Q What was the oral spray administered for? What was the purpose of that?
A To notice the astringent effect and possibly avert an oncoming cold.
Q You were trying to avert an oncoming cold with the oral mist?
A Yes.
Q Did it work?
A Just for the record, I am not attacking Zicam. It does shorten the symptoms of the common cold because of its astringent action. I'm not disputing that.
Q Just for my own edification, did the oral mist also act to prevent the cold?
A Yes, it did. But, unfortunately, following its use, I had again these weakness attacks that are documented in the literature.
Q Okay. Are there any other tests at all that you performed in connection with your work on Zicam litigation?
A We performed the analysis of Zicam products.
Q The chemical composition?
A Yes.
Q That was done by a laboratory, correct?
A Yes.
Q Anything else?
A We controlled the pH, but also had it measured independently.
Q Talking about the pH of the Zicam gel itself?
A Yeah.
Q You also did a test where you checked the nasal pH in your own nose after using Zicam?
A Yes. Yes. And before.
Q And what was your nasal pH before you used Zicam in that experiment?
A It is written in my report. I think it was 5.2.
Q And then how long did you wait before you tested the pH again after the use of Zicam?
A I cannot recall.
Q What was the nasal pH that you measured after the use of Zicam?
A 5.8.
Q So the pH went up?
A Yes.
Q And you don't recall how long a period of time passed between the time you used Zicam and your testing the pH in your nose?
A Maybe 30 minutes.
Q Is that documented anywhere in your file?
A No.
Q Do you have any other data points besides 30 minutes for the effect of Zicam on nasal pH?
A No.
Q Do you have any other data points besides your own for the influence of Zicam on nasal pH?
A Not that I used any --
Q What scientific evidence is there that your nasal pH is representative of what other people would experience after using Zicam?
A The England study, which shows that people without rhinitis have a fairly acidic nasal pH. And I've done that study before I was aware of the England study. So it complements, basically, these results.
Q Aside from reading the England study and testing your own pH on this one occasion, have you done any other research into the subject of nasal pH, either with or without the introduction of Zicam?
A No.
Q Is the question of what the nasal pH is after Zicam is introduced into the nose important at all to your opinions in this case?
A Yes.
Q What's the importance of it?
A The pH in the nasal mucosa determines the amount of the pharmacologically active zinc, zinc ion. May I interject? I did do another experiment.
Q Yes.
A I may even throw that in for future study. You see, many people, when they have the onset of a cold, they also take vitamin C in quantity. Now, vitamin C is an acid, ascorbic acid. So I did think that maybe in some people would develop anosmia had also been taking ascorbic acid before. So I did, in fact, do an experiment in taking vitamin C and then measuring my nasal pH, but the result was inconclusive. That's why I don't write it down or repeat it. So I didn't continue in that. But it just shows you that I looked from the broad perspectives in the general problem.
Q Have you done anything to determine whether or not Dennis O'Hanlon's nasal pH as a baseline or after introduction of Zicam would be similar to yours?
A I cannot do this study because I had never met Mr. O'Hanlon and nobody measured his nasal pH.
Q Doctor, any other tests that you performed in connection with your work on Zicam litigation?
A No.
Q By the way, with respect to the importance of pH, the higher the pH, the less pharmacologically active zinc ion there will be?
A Yes.
Q And I apologize if you've already told me this. But you talked about the effect of a cold on nasal pH. Generally speaking, does the presence of a cold virus increase the nasal pH or decrease it?
A According to the study of England and Cobertis, it increases the pH.
Q And in the England study did they determine at what point during the evolution of the cold process the pH begins to rise?
A I don't think they did that. They just measured people with colds and without colds without getting the time element in. We can check on that. The authors did not mention the degree of cold or the time, as -- measuring the time people were suffering with the cold. They just said you have a cold.
Q Doctor, going back to your experiment where you administered Zicam to yourself and you couldn't help but sniff up the gel, I understand from your testimony earlier that you did this before you read the directions on the bottom of the package. Correct?
A Yes.
Q So you -- I understand that you were not aware at the time that you did this experiment that there was a warning on the label against the sniffing up of the gel?
MR. WENZEL: Objection. Mischaracterizes the label. There's no warning on it. There's directions. There's no warning. No warning you're going to suffer any serious injury if you sniff it.
MR. LAZARUS: Mr. Wenzel, I object to the speaking objection.
MR. WENZEL: I object to your question. Mischaracterizes the statements on the package.
MR. LAZARUS: That's quite sufficient under federal rules.
MR. WENZEL: Okay.
BY MR. LAZARUS:
Q However you characterize the information on the label about not sniffing up the gel, am I correct that when you performed this experiment and sniffed up the gel, you were not aware of this information on the label?
A I think I was not aware. I may have been. The key point here is I was unable to control it.
Q Doctor, that's nonresponsive to my question. Please just focus on my question and we'll be done a lot sooner.
A I do not mind if it takes longer. I want to get the truth out.
Q I do mind if it takes longer. I'm paying for your time and I have other things to do.
MR. WENZEL: That's fair.
BY MR. LAZARUS:
Q Now, when you did this experiment where you used the Zicam, having not reviewed the label on the package or the bottle, you were also not aware of the manufacturer's recommendation regarding the angle of the orientation of the bottle. Correct?
A I may not have been, but the recommendation is at a slight angle, and I don't know what a slight angle means.
Q Doctor, again, you're going way beyond my question.
A I know.
Q It was a yes or no question. Were you aware or were you not aware of the recommendation?
A I'm not sure. I am not sure.
Q What angle did you use in your orientation of the bottle when you used it in this experiment?
A A slight angle.
Q In what direction?
A To the nasal wall.
Q When you say “a slight angle,” was that greater or lesser than 30 degrees?
A Lesser.
Q As I understand it, then, in this experiment you performed, you oriented the bottle at less than a 30-degree angle, you inserted the bottle at a depth greater than one-eighth of an inch, and you sniffed up the gel. Is that correct?
A It could have been one-eighth of an inch.
Q You're not sure whether or not it was more than one-eighth of an inch recommended on the bottle?
A I'm not sure.
Q And let me rephrase the question. When you used the Zicam in this experiment, you angled the bottle less than 30 degrees, you may or may not have inserted the bottle to a depth greater than one-eighth of an inch, and you sniffed up the gel. Correct?
A Correct.
Q From this particular use of Zicam, did you experience any persistent smell loss?
A No.
Q Okay. Moving to a more general question, Doctor, what scientific method did you employ in your investigation of the question surrounding whether Zicam causes smell dysfunction?
A Empirical method.
Q Can you describe the method you employed, please.
A I became aware of an increasing number of case reports and I checked the literature concerning anosmia following the use of zinc-containing cold remedies.
Q Is that the entirety of the method that you followed in your investigation?
A I checked the literature. I checked historical documents. I even went to the homeopathic literature in the 19th century, but that did not include nasal instillations of zinc. More like generally zinc physiology.
Q Did you review any more modern homeopathic literature?
A Yes.
Q None of the homeopathic literature that you found in your research discussed nasal instillation of homeopathic remedies?
A That is correct.
Q Prior to your involvement in the litigation concerning Zicam, have you ever -- had you ever done research of that type into homeopathy?
A Well, I can say that, yes.
Q Explain to me what you did.
A In a lot of my research, I was examining the effects of trace elements, including zinc, at what could be called homeopathic concentrations. And so I knew what elements do at the very low levels, and I was also aware that the pH is of absolutely pivotal importance in determining the absorption of a trace mineral such as zinc.
Q Had you ever, prior to your involvement in this litigation, researched the question of what concentrations are considered homeopathic and what concentrations are not?
A Yes.
Q In what context did you do that research?
A For my personal education as a chemist, and also being involved with homeopathic physicians as a consultant, it is an important question to know from a toxicological point of view.
Q What evidence do you rely on in support of your opinion that Zicam with the concentration of zinc gluconate it contains is not properly considered a homeopathic remedy?
A Because, as pointed out in my report and well-known homeopathic remedy containing zinc in Europe, in Germany, is available at -- without prescription only at the dilution of D4. All potencies below that are available only on prescription. Zicam, as D2, is a hundred time more concentrated.
Q So it's your testimony, sir, that a dilution of four times, 4x, is required to make a remedy homeopathic?
A No, sir.
Q Then what is the cutoff?
A A dilution 10,000 times corresponding to D4 would be homeopathic.
Q In homeopathic terms a 10000-fold dilution is called 4x. Correct?
A 4x.
Q As opposed to Zicam, which is what?
A 2x.
Q And what is the cutoff point for how many x's you need to make a remedy homeopathic?
A D4 or x4, according to German law.
Q Okay. We're not in Germany. Tell me what the rule is in the United States.
A I have pointed out in my report that in the United States the law is interpreted more liberally, and I pointed out in my review that as I checked the Internet, there is a cold remedy available where zinc gluconate is present at the concentration of D2; however, it's oral and not nasal.
Q Aside from the fact that Germany has chosen to require a 4D or 4x dilution for this one remedy in mind in order for it to be available over the counter, what else do you rely on to support your opinion that Zicam is not properly considered a homeopathic remedy?
A The very fact of the warning that if swallowed call a poison control center or medical doctor at once. If it was a true homeopathic remedy, such a warning would be completely unnecessary. Because that's an admission of Matrixx Initiatives that their product can do harm. Homeopathic products at homeopathic dilutions, by definition, do not do harm.
Q What scientific method are you employing to determine that the fact of a warning regarding swallowing the remedy makes it not properly considered homeopathic?
MR. WENZEL: Objection. Vague, ambiguous, unintelligible.
THE WITNESS: Empirical.
BY MR. LAZARUS:
Q What's the empirical --
A Because the empirical thing is I have a collection of homeopathic remedies, and on no one is there an indication like that.
Q Doctor, can you cite me to any statement in a treatise or a published peer review article which states that concentrations of the type that there is in Zicam are not properly considered homeopathic?
A For zinc, yes. In general, zinc valerate. It's just homeopathic usage that you don't declare something a D2 homeopathic.
Q But if I wanted to find an objective source which supported that statement of yours, where would I go to find it?
A Okay. Let me look at something. In a textbook of homeopathy.
Q What page?
A I don't know.
Q Is it in your file?
A Not at the moment, no.
Q You're saying generally you believe such a statement could be found in a textbook on homeopathy?
A Yes.
Q But you can't tell me, as you sit here today, which textbook?
A Because there are so many, no.
Q You can't tell me, as you sit here today, where I could find that statement in any given textbook?
A I could find it for you.
Q Have you done that research at the present time? In other words, to try to find an objective source that indicates at what level of dilution material such as zinc gluconate ceases to become or be considered to be a homeopathic remedy?
A In my report, I am pointing out the American regulations are not followed as stringently. The key issue is a homeopathic remedies are taken orally, and that is a difference compared to nasally. That is why I have refrained in giving this additional information.
Q What textbook, treatise, or published peer review article can you point me to which states that a homeopathic remedy cannot be taken nasally?
A I can only say I check the homeopathic literature and it is not mentioned that zinc salts should be taken or can be taken nasally. The correct application of homeopathy is to use globules with a glass of water. And even the D2 Highland cold remedy is a tablet which is supposed to be taken with water that dilutes it and orally. It's a completely different thing than when you instill a D2 zinc without any dilution into your nose. That's where toxicology comes in. And no scientific study is necessary for it.
Q So, Doctor, you conclude from the fact that you could not find any statement in the homeopathic literature that you reviewed that endorses nasal instillation as a homeopathic remedy, then it's not properly considered homeopathic?
A Correct.
MR. WENZEL: Find any references to rectal administration?
MR. LAZARUS: Excuse me, Mr. Wenzel. I don't appreciate you coaching the witness. You will have your opportunity to examine the witness to clear up anything you find to be muddied on the record.
MR. WENZEL: All right. I want to remind myself of this.
BY MR. LAZARUS:
Q Did you do anything -- strike that.
You said the scientific method you employed in investigating Zicam in its relationship to smell loss was empirical and consisted of your review of the literature regarding anosmia, historical documents, including the 19th century homeopathic literature; What else, if anything, have you done consistent with the scientific method to investigate Zicam's relationship to smell loss?
A Comparisons of the reported case reports or the number of cases compared to the 1938 zinc sulfate study with Canadian children.
Q So you looked at the overall number of cases that have been reported?
A Relatively small.
Q When you say “relatively small,” you're talking about the incidence of smell dysfunction from Zicam use appears to be relatively low?
A Yes.
Q How does it compare to the incidence of smell loss arising from the zinc sulfate polio studies?
A It is about the same, I would say. Also relatively low.
Q What is your basis for saying that they're essentially the same?
A Well, it was .5 percent in the -- let's see. It says, “From the observation made in the Toronto study, it would appear that not more than 25 percent of the children sprayed developed anosmia temporary. Inquiries have indicated that very few, if any, of the children who were sprayed in the special clinics reported subsequently persisting anosmia.”
And there they give the number. The number recorded of having anosmia with or without disturbing -- that's the smell, of taste also. Anyway, the number is fairly small.
Q What is the number, Doctor? By the way, you should identify for the record what you're reading from.
A Yes. I'm reading from the study by F.F. Tisdall, T-i-s-d-a-i-1, et al., and co-workers published in the Journal of Pediatrics, Volume 18, Pages 60 to 62, July 1938. And on table 1 -- on table 2. On table 1 they mention 15 cases have lost smell only, nine cases reported loss of taste only, 12 reported smell and taste, making a total of 35.
After six months there were seven cases of losing smell only, four losing taste only, 37 lost smell and taste, and a total of 53 reported smell dysfunction.
On table 2 of the same paper, the frequency of sprays administered is compared with the incidence of loss of smell or taste or both. After two months -- and I'm quoting here. After one -- if I may, with your permission, abbreviate that discussion and just say the result.
Q Please.
A The results would be that there is a relationship between the number of sprays and the cases of smell and taste loss. And after two sprays, the maximum cases occurred after two months. Interest of 22. After two sprays, however, after six months, the number increased to 30, which I find very interesting.
Q What's the significance of the number of sprays administered in that analysis, Doctor?
A It determines the dosage. Twice the spray is approximately twice the dosage.
Q In terms of incidence, though, how do you come up with an incidence number based on the data you just described?
A Well, I haven't calculated the incidence yet. I only need to say now to compare how many subjects there were involved and divided by. And we can do this.
Q Is that important?
MR. WENZEL: For what?
THE WITNESS: No.
MR. WENZEL: Objection. Vague.
THE WITNESS: No, it isn't.
BY MR. LAZARUS:
Q Well, if you have an opinion that the incidence of smell loss from Zicam is similar to the incidence of smell loss from zinc sulfate during the polio studies, do you need to know how many people have taken the zinc sulfate versus the zinc gluconate?
A No, I don't.
Q Does the background rate figure at all into your analysis of whether or not zinc sulfate compares to zinc gluconate in terms of its ability to produce smell loss?
A No.
Q Is the background rate an important fact at all in determining whether or not Zicam produces toxic effects in terms of smell loss?
A No.
Q Why not?
A Well, it is, if I may use an analogy, similar to saying certain cars like Ford Motor cars cause accidents at a certain percentage. And then come the BMW guy and says, yeah, but the BMW cars cause only a much lower incident of accidents. Accidents are accidents. The incidents don't matter. Cars are dangerous, give rise to accidents. Zinc is dangerous, gives rise to anosmia.
Q Is the zinc used in -- strike that.
Is Zicam used in the same manner that zinc sulfate was administered in the polio studies?
A I have here the picture of the pump used in the Canadian study.
Q What page of your file is that?
A That is Page No. 72 of my document collection, and the mode of administration was different.
Q And was the posture of the individuals administered the zinc sulfate different than the posture that you would ordinarily expect from a Zicam user?
A Yes.
Q You've seen references to the Shahinian position in the literature for zinc sulfate polio studies?
A No.
Q Do you know what the Shahinian position is?
A No.
Q Have you seen any references to children being turned inverted so that their head is below their center of gravity?
A No. But from the appearance of the pump, I would say certainly they did not have any precautions here.
Q Exactly what literature have you read concerning the zinc sulfate polio studies, Doctor?
A I mainly relied on the original paper here in the “Journal of Pediatrics.”
Q Is there any other literature concerning -- and I'm talking about original source literature -- that you've relied on concerning the -- strike that.
Is there any other source literature besides the Tisdall article that you have reviewed concerning the zinc sulfate polio studies?
A Not when I wrote my review.
Q Have you done any review reading since then regarding zinc sulfate polio studies?
A I may have and -- I may have.
Q What else have you reviewed concerning the zinc sulfate polio studies besides the Tisdall article that you've cited today?
A Other reports that I found on the Internet that quoted that work.
Q Okay. What Internet reports have you reviewed concerning zinc sulfate polio studies?
A Got some of them here in my collection.
Q While you're looking for that, Doctor, I take it part of your literature search in this Zicam litigation was some searching done on the Internet.
A No, not while I was writing the report. I don't trust the Internet enough to do it.
Q No. I'm not confining my question to when you were writing your report. I'm talking about your research that was conducted during your course of work on Zicam litigation in general. Has some of that research been done through searches on the Internet?
A Yes.
Q How much of it was done through searches on the Internet as opposed to actual review of texts from libraries or hard copies?
A Well, many of the hard copies can now be obtained through the Internet. And where necessary, I did that, getting the originals, yes.
Q Does your file contain any of the documentation concerning what search terms you used and what documents you found in connection with your Internet research?
A No.
Q Is that a no?
A In my opinion, yes.
Q It's not really an opinion. It's a fact question. Does your file contain any of the documentation concerning what words you used to search and what documents you found in connection with your Internet research regarding Zicam and anosmia?
A I have conducted my Internet and literature research primarily to reaffirm the personal conclusions that I derived from my own knowledge as a chemist and knowledge of zinc.
MR. WENZEL: He just wants to know if your file -- if your file, the physical file, contains, for example, the search terms you used to do that research.
THE WITNESS: Well, Google I used. Google.
MR. WENZEL: He is asking if you can see that by looking at the file, and it doesn't look like you can see that by physically looking at the file. Is that correct?
THE WITNESS: True.
BY MR. LAZARUS:
Q Doctor, when was it that you first formed an opinion and decided that Zicam was a cause for anosmia?
A As soon as I was contacted by the first lawyers.
Q When you say as soon as you were contacted, you mean during that first phone call?
A Yes.
Q And again, this is a phone call with Loren Freestone?
A Probably, yes.
Q And what information were you given by Loren Freestone that convinced you at that point in time that Zicam was the cause of anosmia?
A My knowledge about chemistry of zinc and my own experience with students that zinc is not as harmless as it is now being considered by many scientists. That is something I have been working on for a long time. So whenever I hear zinc, a red warning light has to go up.
Q But what information were you given by Loren Freestone that you used in reaching the conclusion right away that Zicam was causing anosmia?
A The case information.
Q What case information were you given?
A Whatever the case was. Orlansky.
Q You're really not answering my question, Doctor. What information were you given concerning the Orlansky case or otherwise that you used to form the conclusion at that time, along with your knowledge and experience, that Zicam was a cause of anosmia?
A None other.
Q I'm sorry. Say it again.
A None other.
MR. WENZEL: He just wants to know what information were you given. You can't say the case because the case is -- that's not the information you were provided. What did he tell you --
BY MR. LAZARUS:
Q What specific information were you given by Mr. Freestone that you considered in forming the conclusion at that point in time that Zicam was the cause of anosmia?
A That some people are using the cold remedies and develop anosmia.
Q Is that essentially it?
A Yes.
Q And then the subsequent research that you've done has reaffirmed your conclusion that you formed during that first phone call with Loren Freestone, correct?
A Correct.
Q And I'm going back to the question that I asked awhile ago, because I don't think you've given me a complete answer yet. What scientific method did you employ to investigate the issue that was posed by your conversation with Loren Freestone; that is, whether or not Zicam is, in fact, a cause of anosmia in its users?
MR. WENZEL: Objection. It's argumentative. You didn't ask that question before. When you prefaced your question by saying when I asked it before is argumentative.
MR. LAZARUS: I appreciate the objection. The record will speak for itself.
MR. WENZEL: Yes.
THE WITNESS: My suspicion that zinc gluconate is not a harmless substance was solidified by asking Dr. Robert Henkin from the Nose and Smell Clinic in Washington, D.C., in Georgetown. Robert Henkin is a friend of mine for 30 years. He is the absolute leader in anosmia science in the United States. And a member of the editorial board of my journal. And I asked him what he thought of zinc gluconate and he said he wrote -- or said to me it is a toxic substance. That's what he said.
BY MR. LAZARUS:
Q What else did you -- what other -- strike that. All right. So you're telling me that part of the scientific method that you used to investigate the issue was to call Dr. Robert Henkin and hear what he had to say; correct?
A That is one of the things. Yes.
Q What else?
A Well, then I would contact another friend of mine, Dr. Sunderman, who is also a member of my editorial board, and who wrote the article on nasal toxicity. And this is how, in order to shorten the time of information collection, I started. And then, of course, I looked at the literature myself.
Q What did you learn from -- is it Dr. Sunderman?
A Yes.
Q What did you learn from him that advanced your scientific inquiry as to whether Zicam causes anosmia?
A Dr. Sunderman wrote an article in, I think, my journal.
Q Doctor, we don't need to look for it. There's an article cited in your report by Sunderman on nasal toxicity. Is that what you're referring to?
A Yes.
Q What did he tell you that advanced your scientific inquiry?
A Well, that the question of zinc is a very crucial one and that zinc is harmful. And what really helped me a lot was the recognition that zinc can pass through the olfactory tract directly into the brain. That, I didn't know.
Q Until you spoke to Dr. Sunderman?
A Yes.
Q And what else did you do to use the scientific method to investigate whether Zicam causes smell loss in its users?
A Look at the chemistry of zinc gluconate.
Q Looked at it how?
A The idea was that if -- there are, of course, many zinc compounds available; for instance, in toothpaste we have zinc phosphate. Nobody will ever argue that zinc phosphate is a cold remedy. Why is that? Because zinc sulfate is an insoluble -- reasonably insoluble compound. Depends on the chemistry of zinc.
So you must know what zinc gluconate does. And reading the literature by the manufacturer about zinc gluconate, I got the impression that they assumed zinc gluconate to be harmless to the extent that it couldn't possibly be compared to zinc sulfate. And that is when I went back to the study of Guy Berthon -- Guy, as in French first name, G-u-y. The last name is Berthon, B-e-r-t-h-o-n -- who has done studies on the amount of ionized zinc as a function of pH in solutions of zinc gluconate.
From this I deduced that in Zicam approximately 60 percent or two-thirds of the total zinc is actually present in the same form as in zinc sulfate solutions. And this is where my warning lights turned on, that zinc gluconate is not a harmless substance.
Q So what did you do at that point in time to test whether or not Zicam, in fact, exhibits the same toxic effect when it's used that zinc sulfate is reported to have caused in the zinc sulfate polio studies?
A Determining the pH of the Zicam products.
Q Okay. What else did you do to test that question?
A None.
Q So you didn't -- you haven't done any tests to determine how Zicam biologically behaves in the nose?
A No.
Q Have you done any tests to determine how much Zicam is needed to cause any specific adverse effects on smell function?
A No.
Q Have you done any tests to determine where Zicam is distributed in the nose under various different usage variables?
A No.
Q Have you done any tests at all to directly analyze the question of whether Zicam causes anosmia?
A No; Well, I already mentioned that in my own case I developed a smell -- clear smell dysfunction, and on the basis of that, I would have considered it ethically impermissible to subject some people to tests like that. It's too dangerous.
Q Now, Doctor, there are scientific methods that have been used by other researchers to evaluate the extent of deposition and distribution of solutions in the nasal cavity. Correct?
A Of animals. You mean of animals? Are you --
Q Both.
A Of animals, yes.
Q You're not aware of any studies at all that evaluate where aqueous solutions travel in the nasal passages upon instillation?
A Sunderman quotes some of these.
Q Aside from derivative mention in the Sunderman article, are you aware of any studies that scientifically track where solutions go when they're administered into the nose?
A Solutions of what?
Q Solutions of any substance.
A Oh, yes. There are studies like that.
Q Including nasal drug deposition and distribution studies, correct?
A Yes.
Q Have you reviewed any of those in connection with your work in this case?
A Casually, yes.
Q Which ones have you reviewed?
A I cannot recall.
Q Are they in your file?
A No.
Q Why aren't they in your file?
A Because they're irrelevant to the case.
Q Why are they irrelevant to the case?
A Because the case reports speak for themselves, here.
Q Is that, however, a recognized scientific. method --
A Absolutely.
Q -- Of determining where specific materials will travel within the nasal passage through application of the material and tracking it, for example, through a dye tracer?
A Excuse me. Reformulate your question.
Q Okay. Is the method of instilling a solution into the nasal passage incorporating blue dye into the material or some other color dye into the material, and then analyzing its travel through tracking the dye deposition in the nasal passage?
A It's not applicable to Zicam.
Q Doctor, that's not what I asked you.
MR. WENZEL: He is asking is that an appropriate scientific method to look at or by deposition?
THE WITNESS: It is one method. Yes.
BY MR. LAZARUS:
Q It's a feasible method. It's a method that can be used in individuals to determine where things go in the nose under different instillation variables; correct?
THE WITNESS: May I speak to you?
BY MR. LAZARUS:
Q Not until you answer the question.
MR. WENZEL: Answer his question.
THE WITNESS: May I off the record say --
MR. LAZARUS: No. Not off the record.
MR. WENZEL: Maybe you don't know, Doctor. It's okay.
THE WITNESS: No, I do know, but I feel ill at ease, because I feel I'm being driven in a corner to say yes or no to a rather complicated question.
MR. WENZEL: Then you can say I can't give you a yes or no answer. Then he will ask you why probably.
THE WITNESS: I can't give you an answer.
BY MR. LAZARUS:
Q Doctor, maybe you misunderstood the question. I'll try it again.
Is the instillation of a substance with blue dye incorporated to track its travel within the nasal passage a recognized method of studying nasal distribution and deposition patterns?
A I'm sorry. I cannot answer this question.
Q Are you aware of studies that do that?
A Yes.
Q And do you criticize that as a methodology in general for investigating that subject?
A No. If I -- pardon me -- criticize the question, it stops at a certain point. It is true for solutions. Then I agree. Yes.
Q Okay. Where do you draw the line?
A Of the low viscosity, yes.
Q Why does it not apply to higher viscosity solutions?
A Because a high viscosity solution has completely different flow characteristics.
Q You're now talking about the principles of fluid dynamics?
A For instance, yes.
Q What are the differences in flow patterns when you increase the viscosity of the solutions?
A Less.
Q They travel less?
A Yes.
Q They tend to stay where they're put, where they're first deposited?
A Formally, yes.
Q They tend not to reach as far into the respiratory tract as lower viscosity solutions, correct?
A If administered under precisely the same conditions, yes.
Q In other words, all things being equal, the increase of viscosity will tend to limit the travel of the substance?
A Yes.
Q What is your cutoff point for when that's a feasible method of studying deposition and distribution and when it isn't?
A The chemistry of the substances that are being instilled.
Q In other words, the viscosity?
A No. Not just the viscosity.
Q What other variables make it a proper or improper method of tracking distribution and deposition of a substance?
A The composition -- the chemistry of the solution that is being administered.
Q How does that apply?
A Because we are going right back to the original questions, what is the pharmacologically active agent? Is it completely inert? Does it change on contact with the mucous membranes? So many factors come in.
Q I think we're missing each other, Doctor, so let me try to clarify it. I'm not talking about active ingredients or biological effects right now. All we're talking about is the specific question of where things travel upon distribution and deposition in the nose, not what happens after they get there and after they reach their resting place.
MR. WENZEL: Object.
BY MR. LAZARUS:
Q With that clarification, all we're talking about is whether or not dye tracer studies are a recognized method of trying to determine where things go in the nose in terms of deposition and distribution initially. We're not talking about diffusion or what happens through volatile compounds or anything of that nature.
With that clarification, is dye tracer studies a recognized method of trying to determine where things are deposited and distributed in the nose?
A It is a method.
Q Is it a recognized method?
A By whom?
Q By the scientific community.
A With qualifications, yes.
Q Is it a method that's been used by scientists and accepted as a contribution to scientific literature in understanding how things travel in the nose?
A Yes.
Q Have you performed any such studies?
A No.
Q Have you performed any studies at all to determine where something would travel when it's instilled in the nose?
A Yes.
Q Tell me what you've done.
A Again, on myself, in order to establish the sniff-up reflex action, I also instilled simply solutions of low viscosity. And I found I reacted the same way as I did to Zicam; that is, I spontaneously sniffed up the liquid.
Q Doctor, aside from your own experiment where you felt compelled to involuntarily sniff up the substance that you instilled in your nose, are you aware of any scientific evidence or literature which suggests that sniffing up the substance is an involuntary reflex action upon instillation of solution to the nose?
A The users of snuff will probably serve as examples.
Q Aside from that?
A I'm not aware.
Q Doctor, what else have you done to carry out the scientific method during your investigation of whether Zicam causes smell loss, besides what you've already described? I can go back over it if you want, what you've already told me.
MR. WENZEL: Don't go back over it.
THE WITNESS: Don't go. No. Nothing.
BY MR. LAZARUS:
Q Doctor, you have published research on toxic effects of metals, correct?
A On effects of metals, yes.
Q All right. You drew a distinction between toxic effects and effects. Are you more comfortable characterizing your research into pharmacologic effects than toxic effects?
A Nutritional effects, yes.
Q Is a nutritional effect a pharmacological effect?
A No.
Q What's the difference between toxicology and pharmacology?
A Well, pharmacology aims to find the limits at which a substance, a drug, can be administered without causing toxic effects. So there are no sharp divisions between pharmacology and toxicology. But in general the pharmacologists will avoid toxic dosages; whereas, the toxicologist may investigate pharmacological concentrations, and in this way side effects of potentially dangerous nature can be discovered.
Q Doctor, I understand that, you know, the core of your training and experience and professional expertise is in the field of chemistry.
A Yes.
Q Do you consider yourself a toxicologist?
A I was invited to become a member of the American College of Toxicology and have been a member for over 30 years.
Q Okay. Well, my question is do you consider yourself to be an expert -- do you consider yourself to be a toxicologist?
A Yes.
Q Do you have any board certifications in toxicology?
A Don't need to.
Q Doctor, my question is do you have?
A Well, I'm a member of the American College of Toxicology.
Q What are the requirements to become a member of the American College of Toxicology?
A To have published in the field.
Q In the field of what? Toxicology, pharmacology --
A Yes.
Q -- Chemistry?
A Yes.
Q All of these?
A Yes.
Q I just asked you a moment ago about whether you have ever published any research on toxicologic effects of metals and you said you published on nutritional effects. Have you published any research on the toxicological effects of metals?
A Let me think about that. No. However, I did observe toxic effects and -- you see, that is the interesting gray area between, you can say, nutritional pharmacology, when toxicity comes in, and that is my main field of interest.
Q Now, have you published on the toxic effects of compounds other than metals?
A Vitamin C, for example.
Q Anything else besides vitamin C?
A No.
Q Do you have any degrees in toxicology?
A No.
Q Have you taught any courses on toxicology?
A No.
Q Have you ever been consulted by a governmental agency on toxicological issues?
A Yes.
Q What issues?
A I have -- J have consulted with the -- I think it was then the assistant district attorney of Santa Ana about a murder case involving selenium. And I was asked by Gary Lento up in -- was it Fresno -- about a case of an accidental or a death of a lady, and I have defended a New York physician.
Q Sorry, Doctor. We're getting far afield from my question.
A I'm sorry. Way I have --
Q I'm talking about government agencies. You mentioned the DA in Santa Ana. Anything else?
A The New York court was a federal court.
Q I'm sorry. I'm not talking about courts. I'm talking about agencies.
A Let's say no.
Q All right. So the one publication that addresses toxic effects of a substance that you can recall writing is one on the toxic effects of vitamin C? Correct?
A No.
Q What else?
MR. WENZEL: You can review your publications if you need to.
THE WITNESS: Yes. Let me do that. That's a good idea.
I wrote a review of “Selenium yeast: Composition, Quality, Analysis, and Safety” in “Pure and Applied Chemistry 78,” Page 105 to 109, 2006. But --
BY MR. LAZARUS:
Q If you could just tell me what the substance is. You don't need to cite me the entire article or anything.
A Mainly on selenium.
Q Vitamin C and selenium?
A And cadmium.
Q Selenium and cadmium are both metals, right?
A Selenium is a nonmetal.
Q Cadmium is a metal?
A Yes.
Q Doctor, in publishing research on the toxic effects of vitamin C and selenium and cadmium, what scientific method did you employ to investigate the toxicology issues?
A In the case of vitamin C, we used normal healthy human subjects. They were given certain amounts of vitamin C for a certain period of time.
Q And what did you do?
A Well, we showed how elevated the pharmacological -- dosages of vitamin C affected the excretion of vitamin C in urine.
Q How did you show that?
A By measuring the levels of vitamin C in the urine and in the serum.
Q So you did that through testing?
A Excuse me?
Q You did that through testing?
A Yes.
Q What else did you do in terms of the scientific method in your investigation of the toxic effects of vitamin C to reach the conclusion that you ultimately published?
A We -- analysis of the data compared to control subjects, we found that the prolonged intake of vitamin C causes a conditioning effect that results in faster excretion of vitamin C than in normal subjects.
Q Was that the principal method of investigating, was giving the substance to individuals and testing the output as compared to testing of the output of a control group?
A Yes.
Q Was there anything else that you did in terms of scientific process --
A Yes.
Q -- To reach and ultimately publish your conclusions regarding vitamin c'S toxic effects?
A Yes. We did an additional study with human subjects, with pilots of the Marine air base up here in Miramar airport. We showed that elevated dosages of vitamin C caused a lowering of the high-altitude resistance of pilots.
Q How did you determine that?
A The pilots were given a certain amount of vitamin C and then subjected to a simulated high altitude in a high-altitude testing chamber which is available at the air base there, and it turned out that vitamin C reduced the high-altitude resistance.
Q How did you measure its effect on high-altitude resistance?
A This is measured how long a pilot can stay under these conditions before he demands to be let out.
Q So it was empirically tested?
A By and with medical controls, yes.
Q Anything else that you employed in terms of the scientific method for your investigation on the toxic effects of vitamin C?
A Statistical methods.
Q What statistical methods did you use?
A Pee test.
Q That was to compare the subjects in the human vitamin C to the control group?
A Yes.
Q You analyzed the results to determine statistically there was a significant difference?
A Yes.
Q Is that standard scientific methodology --
A Yes.
Q -- For evaluating the effects of a substance on humans?
A Yes.
Q With respect to selenium, what kind of scientific method did you employ in --
MR. WENZEL: I'm going to object.
BY MR. LAZARUS:
Q -- In investigating the toxic effects of selenium?
MR. WENZEL: I'm going to object. This is badgering at this point. The witness's resume, his education, his publications clearly establish that he is a known and authoritative scientist. To take him through every publication, ask him which scientific method he employed in each particular one is badgering. There's no sense to it.
MR. LAZARUS: I'd again ask you to confine yourself to objections without speaking objections.
MR. WENZEL: Well, I'm going to speak to them, because they may be appropriately done.
MR. LAZARUS: There's nothing improper about this line of questions, Mr. Wenzel.
MR. WENZEL: Yeah, there is. This is badgering. And I'm going to remember, when I'm taking your people's depositions, when you start objecting that this area has been gone over before and all these things, you've treaded over numerous areas of inquiry and gone over it ad nauseam. So you're just really opening the door to ad nauseam in depositions of your own experts.
BY MR. LAZARUS:
Q Shall I have the questions read back for you?
MR. WENZEL: Want to take a break, Doctor? If he is going to ask you about every scientific method, we'll be here for a couple of days.
MR. LAZARUS: First of all, there's a question pending, and second of all --
MR. WENZEL: Let's take a break, Doctor. It doesn't matter if there's a question pending.
MR. LAZARUS: Mr. Wenzel, it's inappropriate to take a break while there's a question pending. You know it and I know it.
MR. WENZEL: What's the rule?
MR. LAZARUS: What I just told you. It's inappropriate.
MR. WENZEL: What's the rule? Is there a federal evidence rule?
MR. LAZARUS: Mr. Wenzel --
MR. WENZEL: What? Do you want to answer the question or do you want to take a break?
THE WITNESS: Repeat the question. If I don't want to answer, I would like --
BY MR. LAZARUS:
Q Doctor, the question is what scientific method did you employ in your study of toxic effects of selenium?
A Standard scientific methods.
Q What were those tests?
A Tests of the organs of animals that were exposed to the substances to the selenium.
Q Okay. I have one more question on this area and then we can take a break. With respect to your research on cadmium that you published on the toxic effects of that substance, what scientific methods did you employ to study that?
A This was a collaborative studies where we analyzed organs of recently deceased subjects for cadmium and selenium in Germany, a total of 138 cases. We analyzed the kidney, the liver, and the prostates for selenium and cadmium as a function of age and smoking habits.
Q And in both the selenium and cadmium studies, did you employ control groups to evaluate the effects?
A The dead people were the controls.
Q But there were controls in both studies, correct?
A Dead people are dead people.
Q Were they used as control --
A These were autopsy cases which we analyzed.
Q Did you compare the levels that you found in the autopsies to any baseline?
A As a function of age and smoking habit.
Q Thank you.
MR. LAZARUS: Take a break.
(Recess)
MR. LAZARUS: Okay.
BY MR. LAZARUS:
Q Doctor, after you administered Zicam during your self-experiment, did you do any objective testing of your smell function?
A No.
Q What scientific evidence is there that Zicam reaches the olfactory epithelium directly through delivery from the applicator when the bottle is oriented at less than a 30 degree angle?
A In humans nobody has done that.
Q Has anybody done that in animals?
A Animal zinc gluconate was studied to cause anosmia, yes, but not because of using Zicam.
Q Not the distribution issue of whether it reaches the olfactory epithelium on orientation at a less-than-30-degree angle, correct?
A Correct.
Q So you're not aware of any scientific evidence that Zicam reaches the olfactory epithelium through delivery from the applicator when the bottle is oriented at a less-than-30-degree angle, correct?
A Yes.
Q Now, in reaching the opinion that you testified to earlier, that orienting the applicator at less than a 30 degree angle may deliver Zicam to the olfactory epithelium, what scientific method have you employed to reach that conclusion?
A I have not done the scientific study to reach this conclusion because nowhere could I find the angle of 30 degrees.
Q What scientific evidence is there that the act of sniffing tends to draw material beyond the middle turbinate up to the olfactory area?
MR. WENZEL: If you know. Object. Lack of foundation. Outside of this witness's expertise.
THE WITNESS: Oh, you are waiting for the answer?
MR. WENZEL: Yeah. Yeah. I'm sorry. My objections are for the record.
THE WITNESS: I drew my conclusions from the warnings on the product.
MR. WENZEL: No. No. Move to strike. Not --
THE WITNESS: I don't know.
BY MR. LAZARUS:
Q You're not aware of any scientific evidence that sniffing tends to draw material beyond the middle turbinate to the olfactory area? Is that correct?
A Yes.
Q What scientific method have you used to determine that sniffing does draw the nasal gel up to the olfactory epithelium?
A None.
Q What is the direction of flow when an individual sniffs?
MR. WENZEL: If you know.
THE WITNESS: I don't know. It goes upward. Yes.
BY MR. LAZARUS:
Q How far upward?
A Depends on the anatomy of the nose, the size of the nose, and the amount of stuff snuffed.
Q Is material being pulled down the respiratory track towards the lungs when you sniff?
A In some cases it can be.
Q Doctor, I don't want to prolong this if I don't have to, so I'm just going to ask you if you agree with Mr. Wenzel's objection before, that this is outside your area of expertise to talk about the effects of sniffing?
A Yes.
MR. WENZEL: We have an expert in that area.
BY MR. LAZARUS:
Q Is zinc a volatile element?
A Yes.
Q What is a volatile element?
A A volatile element is it can be vaporized at a boiling point. And that's true for zinc.
Q Is it true for zinc under conditions of use within the human nasal passage?
A No. Excuse me. Is it -- repeat that question.
Q I'm sorry if I botched that. I'm asking whether or not zinc is volatile when it's instilled, as in Zicam, into the human nasal passage?
A No. Not volatile.
Q Have you reached the conclusion as to what dose of Zicam is needed to reach the olfactory epithelium to cause permanent smell dysfunction?
A No.
Q Do you know anybody who has?
A Possibly Mr. Davidson. Dr. Davidson.
Q And do you know what his opinion is in that area?
A A fairly low amount is sufficient.
Q But is there any quantification of the dose needed?
A Based on the case reports, an approximate one probably.
Q Well, I need this to be a little more definite on the record. Are you aware of any scientific evidence that quantifies the dose of Zicam needed to be delivered to the olfactory epithelium to cause permanent anosmia?
A The minimum dose corresponds to the amounts recommended on the package.
Q What's your scientific evidence that supports that conclusion?
A The case reports.
Q Same question as to permanent parasmia. What dose of Zicam is needed to be delivered to the olfactory epithelium to cause permanent parasmia?
MR. WENZEL: In anybody? Object. That's vague and ambiguous and unintelligible and whatever. Lacks foundation.
Go ahead, Doctor.
THE WITNESS: From the case reports, the amount is sufficient if the substance Zicam is used as recommended.
BY MR. LAZARUS:
Q Doctor, are you experienced in calculating dose-response curves for chemical substances?
A Yes.
Q Have you done that with respect to Zicam?
A No.
Q How would you go about doing that for Zicam if you were so inclined?
A I would not do it.
Q Do you know what the background rate of persistent smell loss from virus processes is in the general population?
A I have read it sometimes. Yes.
Q What is it?
A I forgot the percentage.
MR. WENZEL: Do you have an estimate?
THE WITNESS: I don't want to estimate. It can be found in the literature.
BY MR. LAZARUS:
Q Have you considered the background rate of persistent smell loss from viral processes in analyzing whether Zicam causes anosmia?
A Yes, I have.
Q What information have you considered in forming your opinion?
A Irrelevant to the question of Zicam's effects.
Q So you haven't considered it? Is that correct?
A I have considered it.
Q Why did you consider something that was irrelevant?
A I found out after I considered it. Beforehand.
Q What about the information concerning background rate of persistent smell loss from viral processes indicated to you that this was not a relevant inquiry in evaluating Zicam's relationship with anosmia?
A The case reports are sufficiently clear that lead me to conclude that it was Zicam and nothing else.
Q And under what circumstances are case reports sufficiently clear to, in and of themselves, justify a scientific conclusion of causation rather than association?
A When we are dealing with a study that would be difficult to do for ethical reasons. And, for instance, the instillation of Zicam in an attempt to reproduce a percentage of cases of permanent anosmia would not be approved by an ethical committee.
Q Would there be any ethical bar in conducting a retrospective epidemiological study to determine whether there is an increased risk of smell loss from Zicam among users of that product?
MR. WENZEL: Just whether there would be an ethical bar to doing such?
THE WITNESS: Yes.
BY MR. LAZARUS:
Q What would be the ethical bar in examining retrospective data concerning whether or not there was an increased risk of Zicam among the user population -- increased risk of anosmia among the user population of Zicam?
A In such a study there would be no ethical limitations.
Q All right. An epidemiological analysis utilizes a control group to determine whether there is an increased incidence of a health effect in the exposed population, correct?
A Yes.
Q There is no control group utilized in case reports, is there?
MR. WENZEL: I'm sorry. Say that again. There's no control group?
MR. LAZARUS: Right.
THE WITNESS: There can be. By examining the patient's records, a control group may emerge. For example, if you have like Dr. Davidson, 30 or 40 cases, you may, for instance, find out that only smokers reacted to Zicam. So, in other words, a case report can eventually even produce data on the control. For instance, you could say yes, people who had severe anosmia used Zicam preventively. People who had nonpersistent anosmia were those people who used it when they already had a cold. So, in other words, a case report is a source of controlled data.
BY MR. LAZARUS:
Q Is it your testimony, Doctor, that case reports typically are -- typically involve the use of controls?
MR. WENZEL: Objection. Incomplete hypothetical.
THE WITNESS: No.
BY MR. LAZARUS:
Q Now, did Dr. Davidson's case series use a control group for comparison?
A No.
Q Are you familiar with Dr. Jafek's case series?
A I think I am. Yes.
Q Do you recall whether or not he used any control group for comparison in his case series?
A I don't think he used one.
Q Now, in your report you've made certain statements and offered certain opinions concerning the effect of statements on the Zicam labeling and how they affect user impressions and behavior. Correct?
A Yes.
Q Have you done any scientific research to investigate the effects of statements made on product labels on user impressions and behavior?
A No.
Q Have you done that with respect to the Zicam label and the statements made on its label?
A No.
Q Do you have any opinions that you plan to offer in this case concerning the effect of information on the Zicam label on the impressions and behavior of Dennis O'Hanlon?
A Yes.
Q What are the opinions you plan to offer in this case concerning the effect of the Zicam label on O'Hanlon's impression and behavior?
A All I would probably say is O'Hanlon represents a typical lay user who wants to use the product to treat or prevent a cold and uses it. That's all that needs to be done there.
Q You're going to offer the opinion that Mr. O'Hanlon represents a typical user of Zicam?
A Yes.
Q And what is the basis for that opinion?
A Well, my own experience. I consider myself a typical user, and I know for a fact that few people read the small print.
MR. WENZEL: Well, you know, this might be an area outside of expert testimony truly, but --
MR. LAZARUS: Are you withdrawing him on that area?
MR. WENZEL: Well, can you ask him questions because it's -- foundationally I'm a little concerned how he would know he is a typical user. If you want to inquire further to determine there's any foundation to allow him to testify about that, fine.
MR. LAZARUS: I think the record is pretty clear.
MR. WENZEL: Yeah. That's fine.
BY MR. LAZARUS:
Q Putting aside any research that you personally conducted, have you utilized any scientific research in evaluating the effects of label information on user impressions and behavior?
MR. WENZEL: In his career or in connection with his work on this case?
MR. LAZARUS: Thank you.
BY MR. LAZARUS:
Q I'm talking about in your report, in your opinions in this case.
A I have used only my personal impression.
Q What is it in your professional background and training and experience that qualifies you to offer scientific opinions concerning how specific label information will or will not induce specific consumer impressions and behavior?
A I have been a consultant for probably 10 companies and have been involved in product development in which labeling was necessary. And I was frequently asked to review the design labels or check labels for accuracy and the information given therein.
Q Anything else?
A And I've developed my own cosmetic product where I have to think about labeling very carefully in terms of the existing regulations.
Q What product is that?
A That is a skin-care product called Panoderm.
MR. WENZEL: Say it again.
THE WITNESS: It's called Panoderm. P-a-n-o-d-e-r-m.
MR. WENZEL: Okay.
BY MR. LAZARUS:
Q Is that sold over the counter?
A Yes. It's sold to doctors, I think.
Q I can walk into any drugstore and find that?
A Probably not. It's sold by American Biologics.
Q What's that used for?
A As a general skin-care product.
Q And you developed that yourself?
A Yes. I patented it.
Q And did you design the product label?
A I helped designing it. Yes.
Q What portions of the product label did you design?
A Initially all of it.
Q And ultimately?
A I have no idea what happened since.
Q Is that an FDA-regulated product?
A I think so. Yes. It's been on the market now for 15 years probably.
Q Prior to your involvement in Zicam litigation, have you ever performed research into what is and what is not required of homeopathic products by federal regulations?
A Yes.
Q Under what circumstances?
A Well, because in the development of nutritional supplements, we are dealing at levels that are homeopathic, and therefore the question of dosage is very similar to homeopathic dosages. And on the basis of that, I have a pretty good knowledge of when the cutoff point for a given substance is and becomes pharmacological or even toxic.
Q With respect to the nutritional supplements you're working on the development of, was there somebody else who was providing the expertise on regulatory requirements in the regulatory process?
A No. I looked it up myself.
Q What qualifies you to offer scientific or medical opinions concerning actual cause of Dennis O'Hanlon's smell dysfunction?
A My general knowledge on the subject of trace minerals. And zinc, especially.
Q What scientific method have you employed to form your opinion that the actual cause of Dennis O'Hanlon's smell dysfunction was Zicam rather than a viral process or anything else?
A I have compared some of the other substances he was exposed to and eliminated those as possible causes of agents. Like he used a leather spray, Armor leather spray. I checked the Internet, for example, if there is any ever case of anosmia caused by Armor leather spray, which is a very popular spray. And I haven't found not one single evidence that ever anybody -- and this is an older product -- has ever reported loss of smell after using Armor leather spray. And when I looked up the Internet for Zicam, I got hundreds of cases. So that is how I based my evidence.
Q What other possible causes did you consider and rule out based on Internet research with respect to Dennis O'Hanlon's smell dysfunction?
A I was for a while thinking -- well, no. None other. No.
Q Putting aside the question of Internet research, what other possible causes did you consider and rule out as causes of Dennis O'Hanlon's smell dysfunction?
A I looked at his medical records. I was interested if he possibly suffered brain trauma at one time or had some other condition that -- or was on certain drugs that could cause changes in smell acuity, and I couldn't see any reason.
Q Prior to your involvement in this litigation, had you ever done any formal research into the causes of anosmia?
A Formal research, no.
Q Prior to your involvement in this litigation, had you ever done any research into the determination of whether intranasal zinc application can cause anosmia?
A No.
Q Prior to your involvement in this litigation, had you ever attempted to determine the cause of a specific individual's smell dysfunction?
A Yes.
Q Tell me what you did --
A Well, as a chemist, you see, there are certain substances that will result in temporary paralysis of the olfactory functions. Hydrogen sulfide is a good example. Hydrogen selenide is a good example. I worked close with hydrogen sulfide. S-u-i-f-i-d-e. And, you see, we chemists are exposed to such substances. We have students that may be exposed to such substances. So a knowledge of toxicology is very important. So we know that certain substances causes disturbances of smell function and taste function.
MR. LAZARUS: Move to strike as nonresponsive.
BY MR. LAZARUS:
Q Doctor, my question is whether you've ever, before your involvement in Zicam litigation, undertaken to determine whether an individual who has suffered smell dysfunction developed that condition as a result of any specific cause?
MR. WENZEL: As to his work on Zicam cases?
MR. LAZARUS: Prior to his involvement.
MR. WENZEL: Oh, prior to his -- sorry.
MR. LAZARUS: That's all right.
THE WITNESS: I'm not a medical doctor.
BY MR. LAZARUS:
Q I understand that and that's why I'm asking the question. Have you ever attempted to determine the specific cause of an individual's smell dysfunction prior to your involvement in this litigation?
A Right. And I have had one case of a person that lost his taste and smell following a viral infection. Yes.
Q Did you make a determination as to whether his smell and taste dysfunction was caused by a viral infection or some other potential cause?
A Based on his testimonial it was a viral infection.
Q Did you rule out other potential causes to determine that it was a viral infection in that instance?
A No.
Q Did you leave that to a medical doctor?
A Not even that. This was a person who had suffered permanent smell and taste function loss after a severe viral infection, and 30 years later he was still trying to sniff his food in order to get some taste sensation out of it. And he told me it was a viral infection, so -- that was one example.
Q Based on that, you concluded as a matter of scientific process that his smell dysfunction was caused by a viral infection?
A I concluded nothing. I just took the information.
Q Doctor, what is it in your professional background, training, and experience that qualifies you to offer opinions concerning what does and does not qualify under homeopathic medicine as a homeopathic remedy?
MR. WENZEL: Objection. Asked and answered and previously testified to.
MR. LAZARUS: I don't think so.
MR. WENZEL: He said he developed homeopathic products himself.
BY MR. LAZARUS:
Q Is that it?
A Yes.
Q And what homeopathic product did you develop?
A The selenium, for example, is a homeopathic product.
Q Did you develop selenium as a homeopathic product?
A I developed supplements, yes. And if you want to know, as an aside, I was even accused by our medical faculty that I was doing the big no-no in studying homeopathy at the University of California San Diego. Seriously, the levels -- and that is, of course, what separated me from the pharmacologists that -- and that is the real fundamental issue here also bordering on the Zicam case. My research has shown that levels very, very low can have profound effects, and that is basically what homeopathic practitioners have been preaching all along. But I've done that scientifically without using the terminology of homeopathy, eventually being damaging to my career.
Q When you say your research has shown that levels very, very low can have profound effects, are you talking about selenium?
A Not only selenium but also other metals. Cobalt, zinc, copper.
Q Is it fair to say that all the work that you've done to investigate whether intranasal application of zinc compounds can cause smell dysfunction has come since you began working with attorneys in cases against Matrixx and Quigley?
A Yes.
Q Were you aware that Robert Henkin is a member of the scientific advisory board of the Quigley Company, which is a maker of Cold-Eeze?
A I didn't know that.
Q Have you published in any scientific journal any of the opinions that are stated in or on the report in this case?
A No.
Q Have you made any effort to do so?
A Absolutely not.
Q Have you submitted any of the opinions stated in your report for any form of formal peer review?
A No.
Q Did you consider yourself an expert on the olfactory effects of intranasal zinc prior to being retained in the Zicam litigation?
A No. I was retained as a chemist.
Q Aside from the case reports by Drs. Jafek, Davidson and Hirsch, are you aware of any peer review publication of opinions that Zicam is the cause of anosmia?
A No.
Q Are you aware of any peer review publication of the opinion that Zicam can reach the olfactory epithelium in the absence of sniffing?
A Could you kindly repeat this.
Q Are you aware of any peer review publication which states the conclusion that Zicam can reach the olfactory epithelium in the absence of any sniffing?
A The only published paper I would consider is the paper by Davidson and Alexander.
Q And Davidson and Alexander concluded that ordinarily a sniff will be required to cause Zicam to reach the olfactory epithelium. Correct?
A I think so. Yes.
Q Are you aware of any peer review publication, besides Davidson's, which indicates that Zicam can reach the olfactory epithelium?
A No.
Q Do you now consider yourself an expert on the olfactory effects of intranasal zinc?
A No.
Q Do you now consider yourself an expert on nasal drug distribution?
A No.
Q Do you now consider yourself an expert on anosmia?
A No.
Q Do you now consider yourself an expert on nasal anatomy?
A Huh?
Q Nasal anatomy.
A Don't have to, no.
Q Do you consider yourself an epidemiologist?
A I have done epidemiological studies. I use it. But fortunately I am not an epidemiologist by training.
Q Did you say fortunately you were not?
A Fortunately.
Q Why do you say that?
A Because epidemiology is a very boring science.
Q Doctor, did I understand you properly or accurately before to say that you're not going to offer any opinions attacking the efficacy of Zicam as a cold remedy?
A No.
Q Poor question. Am I correct?
A You are correct.
Q What scientific disciplines are dedicated to studying cause and effect relationships between exposures to allegedly toxic substances and adverse health effects?
A A great many of them. Nutrition, pharmacology, toxicology.
MR. WENZEL: Epidemiology?
MR. LAZARUS: Mr. Wenzel, please don't coach the witness.
THE WITNESS: Epidemiology comes second to -- you already have to have evidence of epidemiology, are like the bookkeepers that analyze the data. But they have to rely on information of people such as myself, the chemists and biochemists, to give them data background.
BY MR. LAZARUS:
Q Why is testing important to the scientific method?
MR. WENZEL: Objection. Vague, ambiguous. Irrelevant in the manner phrased. Overbroad.
THE WITNESS: Could you please reframe?
BY MR. LAZARUS:
Q Yeah. My question is -- let me ask you this first: Is testing important to the scientific method?
A No.
Q Why not?
A Because in some very important cases you cannot test.
Q Ordinarily is testing important to the scientific method?
A When it can be accurately defended, it is used.
Q In other words, when there is a test that can be performed to evaluate the truth or falsity of a hypothesis, the scientific method would require that you try to perform such a test?
A Not necessarily.
Q Under what circumstances is it appropriate for a scientist investigating a hypothesis, such as a cause-and-effect relationship, to not perform a test that can reasonably be performed?
A Because there are some facts that are self-evident, and I think, applying logic, a good scientist recognizes a self-evident fact.
Q In other words, not all propositions need to be established through testing: Some of them are self-evident?
A Exactly.
Q Are any of the propositions that you rely on in your opinions in this case self-evident?
A I consider all of them self-evident.
Q Now, if all those propositions that you rely on in your report are self-evident, I take it that no good-faith, reasonable scientist would disagree with your opinions.
A That is correct.
Q Is it your view, then, that anybody who disagrees with your opinions about the causal relationship between Zicam and anosmia is not a reasonable scientist?
A Yes.
Q And is it your view that anybody who disagrees with your opinions about the causal relationship between Zicam and anosmia is not practicing science in good faith?
A Yes.
Q Is it generally accepted in the scientific community that Zicam causes anosmia when used according to the package directions?
A It will be.
Q But it's not right now?
A It cannot be right now.
Q Why not?
A It's too early in the case. The caseload has started.
Q Is it generally accepted in the scientific community that Zicam can cause anosmia when used in violation of the package directions?
A The answer would be no, but for reasons which I can go into.
Q Doctor, when you review the conclusions of scientists on topics that are outside your own specific areas of expertise, what do you look for in trying to determine whether their conclusions are probably correct?
A Following through the experimental design, the logic of the conclusions.
Q Do you look for whether they have rigorously tested the hypothesis?
A Of course, yes.
Q And if they haven't rigorously tested the hypothesis, does that tend to cast doubt on the accuracy of their conclusions?
A Not necessarily.
Q Under what circumstances do you think it's appropriate for a scientist to conduct less than a rigorous test of the hypothesis before reaching a conclusion?
A When the evidence is already self-evident.
Q And who determines whether or not the evidence is sufficiently self-evident to justify departing from the usual scientific method of intellectually rigorous testing?
A Common sense.
Q What is the post hoc ergo proctor hoc fallacy?
A To draw conclusions from a fact to the cause, I would say. Yeah.
Q Why is that a fallacy?
A Well, it can be a fallacy, yes, because you can be influenced at the beginning with your conclusions and falsely -- for example, if I may say so, if -- well, anyway, I don't want to give an example. It's quite obvious.
Q How does publication of a case report make it more likely that the observation in the case report reflects a true causal relationship?
A Because it goes through several stages. As a medical doctor, if a case come in -- take, for example, the first cases of AIDS. It had to be reported that there was some very unusual infections appearing in a certain group of people, right? So this has to be reported. But in order to get this report in, it goes through rigorous checks, peer review, editors. And so this is already a filter, a substantial filter of the facts. And therefore a case report in a peer review journal has a high level of credence and is very, very important, as the case of thalidomide -- t-h -- and HIV has proven.
And it is very crucial that editors -- and being an editor myself, it is very important that such cases are reported, because you cannot wait until an epidemic breaks out and only then have epidemiological evidence. You have to stop it as soon as possible, and --
Q In the case report that was initially published concerning observations of the AIDS virus, did the scientific community respond to that by concluding there was a causal relationship or by looking to further study whether or not there was a causal relationship?
A Looking to -- well, at that time, of course, the virus was not known. And then, of course, the whole barrage of research started in this case. So it is a starting point for further exploration.
Q Ordinarily initial case reports are hypothesis generating and suggestive of studies that need to be done to evaluate whether or not a relationship is causal; correct?
A That is correct, unless the evidence is self-evident.
Q Right. Okay. Now, what is the difference between an association and causation?
A An association doesn't prove causation. But an association firmly disproves something else. This is often what epidemiologists use in defense. A direct association rules out the opposite hypothesis.
Q Now, an association can be false, it can be true, or it can be causal, correct?
A I would not say that an association should be called false. An association is an association.
Q Okay. It can be proved true or it can be proved causal if it is an association?
A Like, for instance, the number of stork nests correlate with the birth rates in the village. That is used as an argument against falsely using statistics. But I could argue -- well, anyway, I won't go into that stuff. We agree on that point.
Q Are there studies published whose primary purpose is to generate or present hypotheses for further studies?
A Yes.
Q How does the case report ordinarily differ from an epidemiological study?
A Well, a case report is not subject to the stringent methodology required for epidemiology.
Q And is it true that peer review of an epidemiology study is important to help expose any flaws in the design of the study?
A Yes.
Q What does the term pathomneumonic mean?
A Pathomneumonic means that there are certain signs or symptoms suggestive of a disease-causing effect or a disease pathology.
Q Is it essentially the existence of a signature for a particular disease or relationship?
A A signature.
Q Is irritation or burning in the nasal passage pathomneumonic for destruction for small tissue?
A No.
Q Is it pathomneumonic for the destruction of any tissue?
A Yes.
Q Is it pathomneumonic for the permanent destruction of any tissue?
A No.
Q Does -- do olfactory -- strike that. Does olfactory tissue regenerate?
A No. Sorry. You have to be more specific.
Q Does olfactory epithelium regenerate?
A You still have to be more specific. The epithelium is one thing. The actual cell, the neuron that --
Q Let me try it one more time. Does olfactory neuroepithelium regenerate?
A No.
Q What do you base your opinion that olfactory neuroepithelium does not regenerate on?
A Here the evidence is from the fact -- in fact, in my -- on page so and so is a graph.
Q Page what?
A Page 117. Page 117 shows the decline of smell acuity with age, and you can see that generally with age people lose the ability to smell, the sense of smell. If there was regeneration, we would have a straight line. So this in itself shows that it does not regenerate.
Q All right. So you view --
A But that's for humans.
Q So you view the evidence that smell acuity declines with age as demonstrating the proposition that olfactory neuroepithelium does not regenerate?
A Yes. One of the things.
Q Now, this graph on Page 117, what is that drawn from?
A That is drawn from -- I think from the same -- from the same source I got 116 from. Could be that. I don't know how I got that anymore.
Q Doctor, is irritation or burning in the nasal passage pathomneumonic of deterioration of the sense of smell?
A No.
Q Do substances other than zinc cause irritation or burning of the nasal passage?
A Yes.
Q Can one experience smell loss without experiencing any burning sensation?
A Yes.
Q Can one experience smell loss from destruction of olfactory epithelium by zinc ions without experiencing any burning sensation?
A Probably, yes.
Q Why do you say that?
A Well, it depends when one applies, if one would apply the zinc specifically into the olfactory center, one may not experience any effect on the nasal passages and therefore no burning sensation.
Q Are you suggesting that there are no pain receptors in the olfactory epithelium?
A There may not be necessarily.
Q Do you know one way or the other?
A Medical question. I pass.
Q So the answer is no, correct?
A I don't know.
Q Can one experience burning without experiencing subsequent smell loss?
A Oh, yes.
Q So is it true, then, that smell loss and burning sensation after introduction of zinc, for example, into the nasal passage can exist independently?
A Yes.
Q And they can exist together?
A And they can exist together, yes.
Q And smell loss can take -- strike that. So burning can be experienced with or without the introduction of zinc, correct?
A Yes.
Q So, for example, if we took the zinc out of Zicam and administered that to the nasal passage, there could still be burning, correct?
A If you took the zinc out of Zicam, not necessarily, no. No, you can't say that.
Q You don't believe that zinc-less Zicam would cause any burning in the nasal passage?
A Zinc-less Zicam will not cause burning in the nasal passages.
Q What do you base that opinion on?
A Because the pharmacological effect of Zicam is based on the astringent action of zinc ion. And the zinc and the astringent action causes the sensation of burning and so forth. If you take the zinc out, it becomes like your Nasarel. You inject it and you feel nothing.
Q Now, when one introduces zinc into the nasal passage and experiences a burning or irritation, can that burning or irritation be taking place in areas of the nose other than the olfactory epithelium?
A Yes.
Q For example, the turbinates in the lower portion of the nose?
A Yes.
Q And is there a way for an individual who is experiencing burning or irritation after introduction of zinc into the nasal passage to pinpoint where within the nose that burning sensation is emanating from?
MR. WENZEL: Objection. Calls for speculation. Outside the scope of this witness's expertise.
THE WITNESS: Well, I will answer anyway. Sure people know whether it burns down here or further up. Yes.
BY MR. LAZARUS:
Q What do you base your conclusion on?
A Common sense.
Q And do you know of any scientific evidence that indicates how diffuse the burning sensation will be in terms of the ability to recognize and pinpoint its location? Is that enough?
A Yes.
MR. LAZARUS: The question was “Is that a no?”
BY MR. LAZARUS:
Q Do you have any expertise in how colds occur? A. Just general ideas that everybody has.
Q Have you ever done any research prior to involvement in Zicam litigation concerning the cause -- the mechanism and incidence of post-viral anosmia?
A No.
Q Have you done any since you've been retained in Zicam litigation?
A No.
Q Do you know whether post-viral anosmia is a sudden or gradual process or both?
A It can be both, I would think.
Q What do you base that opinion on?
A Common sense.
Q You base it on the scientific evidence?
A No.
Q Before, when we were talking about questions of where solutions travel in the nose upon instillation, you mentioned the topic or discipline of fluid dynamics. Is that the appropriate discipline to investigate how things are distributed in the nose upon instillation?
A It's one aspect of it. One has to be more general than that.
Q What disciplines come to mind as ones that might appropriately be called upon to investigate the nature and extent of nasal drug distribution and deposition within the nasal cavity?
A Well, one needs to have the mechanism how the substance is transported through the nasal epithelium, and that depends on the chemistry of the substance. Like right now they are investigating nasal instillation of insulin, for example. Now, that requires completely different studies than you would use for Zicam, for example. So it has to be very specific for each substance.
Q What types of expertise are needed to make those evaluations?
A Well, I think a Ph.D. in chemistry, pharmacology, biochemistry would be sufficient.
Q You know, I may have asked you this before, and if I did, I apologize, but are you aware of any scientific evidence that looks at the question of whether sniffing is a reflex action in response to instillation of solution in the nasal passage?
MR. WENZEL: You did ask it. He said no.
THE WITNESS: No.
BY MR. LAZARUS:
Q Is it, in your view, generally accepted in the scientific community that an individual who instills solution into the nasal passage will involuntarily and as a reflex action sniff?
A Yes.
Q Can you point me to any statement in any published treatise, textbook, or peer review article which scientifically demonstrates that?
A No.
Q Can you point me to any statement in any published treatise, textbook, or peer review article which even says that?
A No.
Q What variables, if you know, will determine whether or not someone will experience this involuntary reflex action in the form of sniffing?
A That is general reflexes are all right. If he has a form of paralysis, he will not be able to do it. But if he is -- his reflexes are okay, he will do it. It's very much you put your hand on a hot plate, if your nerves function, you will remove your hand. There's no scientific study necessary. But if you have damaged nerves, some people don't have a sense of the danger of the heat and they will actually burn their hand. So prediction is you need to be normal with respect to your neurological makeup. Then you will reflex.
Q So your opinion is that anyone with normal reflexes will experience an involuntary reflex action of sniffing when a solution is introduced into their nasal cavity. Is that correct?
A Yes.
Q Do you know of any scientific literature that supports that?
MR. WENZEL: You've asked this three times now, Alan.
THE WITNESS: I did not check the literature, but I'm sure it exists.
BY MR. LAZARUS:
Q Did Dennis O'Hanlon read the directions on the product before he used it, to your knowledge?
MR. WENZEL: Objection. Calls for speculation.
THE WITNESS: I don't know.
BY MR. LAZARUS:
Q Do you know if he understood the directions, if he did read them?
A I don't know.
Q What is your understanding, very briefly, of how Dennis O'Hanlon used the product?
MR. WENZEL: Asked and answered so long ago. This is really ridiculous at this point. It's badgering everybody.
THE WITNESS: I considered Dennis O'Hanlon an example of a typical user who goes to the store --
MR. WENZEL: No. No. No. Just -- you know. Help yourself here, Doctor. Tell him how you understood he used it.
BY MR. LAZARUS:
Q Let me repeat the question.
What is your understanding, very briefly, how Dennis O'Hanlon used the product? Just what he did.
A He inserted it deeply to reach -- probably he felt an irritation in the higher portions of his nose and tried to reach it, which is normal for someone who has a feeling up here. And I only found out his weight is 270 pounds. So he must be a fairly tall, heavy-set fellow. So if he has something up there in the nose and just squirt it in, what the hell? He doesn't care one way or the other. Like I did. He is not going to measure .8 of an inch. He says I'm a big man. I can take it. Squirt it in. That's how he used it.
Q This understanding of how Dennis O'Hanlon used the product is based on your review of his deposition?
A In part, yes.
Q And what else?
A My own use of the product.
MR. WENZEL: Just stay with Mr. O'Hanlon, please.
THE WITNESS: Well, I was asked what else.
BY MR. LAZARUS:
Q Do you have any -- tell me what your understanding is about the characteristics of Mr. O'Hanlon's nasal anatomy.
A He had no abnormality, in my opinion. In my recollection.
Q And you're basing that on your review of the medical records?
A Yes.
Q Anything else?
A No.
Q Do you have an opinion, Doctor, as to whether or not the typical individual has a straight pathway between their nasal opening and olfactory epithelium?
A Some people do, some people don't.
Q What is that understanding based on?
A On differences in anatomy and the very fact that, in other cases, examining physicians are pointing out, yes, your olfactory center is visible when we look into your nose.
Q What examining physicians are you referring to?
A Possibly the gentleman who examined Julie Gillespie.
Q What about the gentleman who examined Mr. O'Hanlon?
A I don't know.
Q Is there anything else that you're aware of that indicates whether or not most individuals have a straight and unobstructed path to the olfactory epithelium from the nasal opening?
A Well, temporary obstructions. Mucous.
Q Let me ask you this: Have you ever seen a statement in a published treatise, textbook, or peer review article that suggests that the pathway between the nasal opening and the olfactory epithelium is straight and unobstructed in most people?
A No.
Q Do you believe it's generally accepted in the scientific community that there is a straight and unobstructed path between the nasal opening and olfactory epithelium in most people?
A I don't think so.
Q In terms of review -- looking into the nose to determine whether you can visualize the olfactory epithelium, is it your understanding that endoscopic instruments are ordinarily used to visualize this tissue?
A Yes. But this is a medical question, so --
Q So it's beyond your expertise?
A Yes. You could use other methods.
Q Have you ever conducted a distribution study of an aqueous solution in a cadaver?
A In what?
Q A cadaver.
A No. No.
Q Is that a generally accepted method of evaluating the distribution pattern of an aqueous solution?
A I would not accept it.
Q Do you have an opinion as to how specifically Dennis O'Hanlon's smell loss was caused by Zicam?
A Well, this is in the record, how quickly it appeared after the instillation.
Q Doctor, really what I'm referring to is you testified to several potential different mechanisms for zinc ions to interfere with smell function. And I'm trying to find out whether you have an opinion as to how Zicam caused smell dysfunction in Dennis O'Hanlon.
A By all three mechanisms together.
Q What's your basis for that?
A From the general idea that housing functions and how carelessly it has been introduced in one of the most sensitive organs that we have. And that is the olfactory organ. If you look at the chemistry of it, what the nose nerves have to do in order to recognize the smallest differences between smells, right, it shows you we're dealing with an immensely sensitive part of the nose. And therefore the answer is it's extremely sensitive and the cause situation is there.
Q I'm not sure what question that's an answer to.
A Neither am I.
MR. WENZEL: He did answer your question. He said all three mechanisms.
MR. LAZARUS: And I asked what the basis was for that.
BY MR. LAZARUS:
Q What is the scientific basis for your belief that all three of the mechanisms that you've cited occurred together to cause dysfunction in Dennis O'Hanlon?
A You see, my brain is like Google. It does not come up immediately. But I can now give you, I think, a satisfactory answer to this, which even pleases me. And that is if you look at the Tisdall study that we reviewed before -- and there is something absolutely fascinating, which I think proves my point beyond any doubt and that is very interesting, and I have to admit I only recognize the significance now.
After two months they had 35 cases. All right. But after six months it almost doubled. It went to 53. This means that the zinc remained in the nose and active for such a long time. And that is a most significant observation, which rules out the fact that the zinc just come in there and then somehow disappears. It stays there and does all kinds of jobs on your nasal epithelia. I need to go to the restroom.
Q Can I follow up with one question on that before we lose the train of thought? It will be real quick. That is, can you think of any other explanation why there would be 53 cases after six months when there were only 35 cases after two months?
A Let me see. Not at the moment.
Q Okay. Thank you. Take a break.
(Recess)
MR. LAZARUS: Ready to resume?
THE WITNESS: Ready to resume.
MR. WENZEL: I'm ready. Go ahead.
BY MR. LAZARUS:
Q Okay. Doctor, once the Zicam nasal gel enters the lower portion of the nasal cavity, how is the gel transformed?
A The gel is absorbed very rapidly, and in that process there are chemical changes. And the zinc is gradually going to be transported somewhere else deep in the nose.
Q Well, what chemical changes occur during that process?
A Well, we have the astringent effects, which can result in superficial destruction of mucous membranes, in changes of the confirmation of proteins on the surface, which then will result in diminished excretion of mucus. And that is related to, you could say, the claim that Zicam shortens the duration of a cold. But the zinc will remain there and slowly diffuse further in the nasal passages. And I consider that the problem. Yes.
Q Now, in terms of the causation of smell dysfunction, is there any other material transformative process besides positively charged zinc ions dissociating and traveling deeper into the nose?
A Yes. And one of the mechanisms is involving carnosine, because carnosine has histidine attached to it, and histidine is an amino acid that has a prosthetic group, which is the imidazol, i-m-i-d-a-z-o-l, group of histidines, which is known to form a stable chelate with zinc. And therefore carnosine is considered also a zinc transporter. So it is not just simply diffusion. It is more complicated than that. There may be other transporting substances also for zinc.
Q Doctor, I think you said your work in the last four years -- strike that.
In the last four years, have you testified at deposition or trial or in the form of an expert report in any litigation other than litigation involving intranasal application of zinc?
A Correct.
Q Well, my question was have you. Is it correct you haven't?
A I have not.
Q Now, is there any way to scientifically test which of the mechanisms you've identified as causing smell loss from intranasal application of zinc was the actual cause of any specific individual's smell dysfunction?
A Probably not as I would see right now. Be nice if there was one. But it's too complicated.
Q Is there any way you can test scientifically to determine whether an individual's smell impairment was caused by a reaction to Zicam as opposed to another cause?
A I think one can distinguish, for example, if, first of all, an analysis of the patient's history reveals that it was an opium user, then of course I would have to consider that certain drugs are known to impair smell acuity or having a sense of smell. Or if I discover through nuclear magnetic resonance there is a brain tumor. Yes, there is methods to distinguish -- to eliminate such alternative causes of anosmia.
Q Are there any objective testing methods to do that?
A Yes. I just mentioned them.
Q I'm not sure I followed you. Are you talking about objective testing to determine -- well, whether there's a brain tumor. I understand that one. But in the absence of something like a brain tumor, is there any objective way to test whether or not Zicam as opposed to other things, like a viral process, was the cause of anybody's smell dysfunction?
A I think so, yes. For instance, in Parkinson's disease, the first thing that goes, I understand, is the olfactory function. And so if an older person comes in the medical office and says I lost my sense of smell, he could have the beginning of Parkinson's disease, for instance. So there are other causes, yes.
Q But is there any way to determine that scientifically?
A Retrospectively, yes.
Q Let me put it this way: Is there any objective testing that you're aware of to scientifically and definitively determine whether someone's smell dysfunction was caused by a cold virus or by toxic exposure?
A Yes.
MR. WENZEL: That you know of.
THE WITNESS: Yes.
BY MR. LAZARUS:
Q What is it?
A Well, you can check for antibodies against a virus and you can check for residual drug remnants in the nasal area, for instance.
Q Okay. I want to switch gears, and I want to focus you so that we understand each other on the “permanent” aspect of my question. What scientific data or scientific literature are you aware of that demonstrates that intranasal application of zinc sulfate causes permanent smell loss?
A The end of the Tisdall paper actually states, “A study of the changes” -- let me see. That's discussion. Get to the summary. “Human beings should be carefully studied to determine if the persisting disturbance of smell and taste may be due to injury of the olfactory area.”
So he is recommending such a study. So one should look at these people and see if their olfactory center is injured -- has been injured.
Q That's not a conclusion that permanent smell loss was caused by the zinc sulfate experiments, is it?
A That is from the paper of the zinc sulfate experiment.
Q My question is whether or not that statement is a conclusion that the zinc sulfate experiments resulted in permanent smell loss.
A Well, they compare it to the effect of zinc sulfate in rats on the destructive effect on the olfactory epithelium, and therefore they draw an analogy, the way I at least see it.
Q Is that what you rely on in support of your opinion that Zicam -- strike that -- that zinc sulfate causes permanent smell loss in humans?
A I was just reading an opinion here. The people have not used zinc sulfate in humans since.
Q Is there any scientific data that you're aware of that demonstrates that zinc sulfate as used in the polio experiments caused permanent smell loss?
A “Permanent” is a very strong term.
MR. WENZEL: That's what he is asking you. So just stay with the question.
THE WITNESS: The answer is no.
MR. WENZEL: Beautiful.
BY MR. LAZARUS:
Q Are you aware of any scientific data which demonstrates that the application of Zicam at product-level doses causes permanent smell loss?
MR. WENZEL: In humans?
MR. LAZARUS: In humans.
THE WITNESS: I think the time is too short to draw that conclusion.
BY MR. LAZARUS:
Q And are you aware of any scientific data which demonstrates that the application of Zicam at product-level doses causes permanent smell loss in animals?
A I have referred to one study performed and I have mentioned it here. It says here, “In sufficiently large volumes or probably higher concentrations than that used in the Zicam product, zinc gluconate may disrupt olfactory epithelium in the mouse.” That's what it says here.
Q Page?
A Page 56 of mine.
Q Page 56 of your file, correct?
A Yes.
Q Go on.
A And then it says -- well, I don't need to go on. I think that answers your question.
Q And you believe that that statement demonstrates scientifically that the application of Zicam in product-level doses causes permanent smell loss in animals?
A It just says that it causes -- it disrupts the epithelium in the mouse. That is most likely not permanent, but I have testified before that the animal olfactory epithelium cannot be compared to the human olfactory epithelium because the humans --
MR. WENZEL: Come on, Doctor, please. Just respond to the question.
THE WITNESS: I'm getting tired, too.
MR. WENZEL: I understand that. That's why I'm suggesting it. He just asked research indicating permanent loss of smell in animals at product-level doses. Period. Not concerned about any other --
THE WITNESS: So whether it's permanent.
BY MR. LAZARUS:
Q Right.
MR. WENZEL: At product-level doses.
THE WITNESS: I would say from the evidence either we don't know or it is not permanent.
BY MR. LAZARUS:
Q Now, what you were just referring to, that was some information concerning a mouse study performed by a member of Matrixx's Scientific Advisory Board?
A Yes.
Q Yes?
A Yes, please.
Q Have you reviewed that study?
A From what I have, I've read it, yes.
Q What have you reviewed concerning that study?
A Well, whatever I received in this document.
Q What is it?
A Here it is. The effects of large volumes -- I gave you the ZM numbers.
Q Give me the page in your file.
A 53 to 57.
Q Okay. This appears to be a PowerPoint presentation?
A Yes.
Q Is this the only data you've reviewed concerning the mouse study performed by the Matrixx Scientific Advisory Board on behalf of that board?
A Let's see. Yes.
Q Now, this is the mouse study, as you understand it, that's referred to in the Scientific Advisory Board statement summarized in the filings with the Securities & Exchange Commission?
A That, I don't know.
Q Have you reviewed any of the dye-tracer distribution studies that were performed with the Zicam gel?
A No.
Q Have you reviewed any of the epidemiological analysis done by Judith Jones, a member of the Scientific Advisory Board of Matrixx?
A I think I did, yes.
Q What did you review in that regard?
A Irrelevant.
MR. WENZEL: No. What did you review?
BY MR. LAZARUS:
Q My question is not irrelevant, sir.
A Well, certain statements of this study, and I didn't think --
MR. WENZEL: No, no, no. He is just asking what you reviewed.
BY MR. LAZARUS:
Q I asked if you reviewed any of the epidemiological -- listen to my question, sir.
A Yeah.
Q Have you reviewed any of the epidemiological analysis done by Judith Jones, a member of the Scientific Advisory Board of Matrixx? You said you thought you did, and I'm trying to find out what you reviewed.
A Here it says, “The epidemiologic study demonstrates that three of the most common conditions associated with anosmia are the common cold, sinusitis and nasal injury.”
Q Doctor, in the interest of time, I going to interrupt you. I apologize.
A That's all I studied.
Q You haven't seen any of the source documents for that statement?
A No.
Q All right. Doctor, you've worked on some Cold-Eeze litigation. How does Cold-Eeze differ in composition than Zicam?
A Higher concentration of zinc.
Q How much higher?
A A little more than twice as much zinc as in the Zicam nasal gel.
Q And what is a product -- a single application dose of Cold-Eeze in terms of volume?
A I didn't measure it.
Q So you don't know what the volume is of a single dose of Cold-Eeze compared to Zicam, correct?
A Correct.
Q Do you know if Cold-Eeze is delivered in a metered-dose application?
A It is in a rather similar application. I think I measured it as .2 grams.
Q .2 grams in a dose?
A I think so. Yes.
Q And how did you define “a dose”?
A Just by using a certain amounts of sprays under controlled conditions and detect the weight.
Q Did you make any effort to try to approximate how much would be used by a user in a single application?
A I think I've written that somewhere down someplace. I don't know now. But I used to know it, yes.
Q Is Cold-Eeze delivered in a similar application applicator as Zicam?
A Yes.
Q Are there any differences between the applicator used with Cold-Eeze and the applicator used with Zicam?
A I would say, apart from the difference in the zinc level, not significant differences.
Q Does the fact that Cold-Eeze has more than twice the amount of zinc concentration as Zicam, in your view, make Cold-Eeze twice as toxic as Zicam to the olfactory epithelium?
A I would say more than twice, because the pH is lower. PH of Cold-Eeze was 5.4 and the Zicam nasal gel was buffered to 7.4. So anyone who used Cold-Eeze got more zinc and therefore had a lower pH experience.
Q How does the viscosity of Cold-Eeze compare with the viscosity of Zicam?
A Not significantly different.
Q Do you have specifications in your file that answer that question?
A No.
Q An experiment you performed, I don't think you mentioned it earlier, was you activated the Zicam applicator and measured the travel in the open air of over eight inches, correct?
A Yeah. But not quite in the open air. There was some resistance approximating something in the nose. There was some resistance, because measuring without any resistance, I notice it flies so far under some conditions, several feet. So that's why I didn't measure.
Q Just shooting it into the open air, that doesn't constitute a real-world comparison of how it behaves in the nose; correct?
A Exactly.
Q Well, what did you do to try to make it more realistic in comparison of how far Zicam will travel in the nasal cavity?
A I put a piece of paper parallel to it and watched how far it would squirt. And I have some graphic examples of this.
Q There's a graph that's included in your file that's a one-page. Am I correct?
A Yeah.
Q Aside from that one-page draft, which basically shows where the drops fell, is there any other documentation concerning this experiment?
A No.
Q To determine -- what was the purpose of that experiment?
A Well, there was a statement that it would not -- could not possibly reach the olfactory center. But then with the pump, it shows that eight inches is far more than needed for any nose to be reached. So that was the -- for any size of nose, the pump can transport the product to the -- theoretically to the olfactory center.
Q Now, you're aware, sir, are you not, that there are structures made up of tissue and bone and cartilage within the human nose that potentially get in the way of the Zicam stream and prevent it from traveling all the way into the inner nose?
A Absolutely.
Q Did you do anything in your experiment to approximate that characteristic of the human nasal anatomy?
A No.
Q Aside from the case reports published by Drs. Jafek, Davidson, and Hirsch, have you reviewed any other reports of adverse events concerning Zicam?
MR. WENZEL: What was the question again? I'm sorry.
BY MR. LAZARUS:
Q Aside from the case reports, have you reviewed any other reports of adverse events concerning Zicam?
MR. WENZEL: Any other reports. Okay.
THE WITNESS: Yes, I did.
BY MR. LAZARUS:
Q What did you review?
A Well, in the Internet you find all kind of things, and some of these are from that. But I rely mainly on the peer review information.
Q Would you agree with me that any reports on the Internet of individuals stating that they used Zicam and noticed smell dysfunction after that are properly considered by a scientist to be anecdotal in nature?
A Yes.
Q Do you put any scientific value on such reports in evaluating the cause-and-effect relationship between Zicam and anosmia?
A No.
Q Why is that?
A Because I didn't have to. I had the Alexander and Davidson report, which was in a peer review journal and which looked, to me, pretty good, so --
Q Is there any other reasons why you didn't put any scientific weight on anecdotal accounts that appear on the Internet that considered people's experience?
A They are already open to all kinds of criticism and all kinds of argument, which I agree.
Q As a scientist you wouldn't rely on such data?
A I would take note of them but not rely on them.
Q Doctor, if you take a look at Exhibit 2, which is your report. Do you have it in front of you?
A Yes.
Q I know there's another copy of it in Exhibit 4, which is your file, your report in this case. That's it. Look at Page 2 of the report. I'm sorry. Page 3. Turn the page.
A Do you mean part 4 or page -- right in the front?
Q Right there.
A Ah. Okay. That's Page 3. All right.
Q What's the heading on that page?
A “Summary of Argument.”
Q Why is this titled “Summary of Argument”?
A I just considered it a Summary of Argument.
Q And does that title accurately reflect what you were intending to convey on Page 3 of your report?
A I think so.
Q Does the Summary of Argument accurately reflect the tone and contents of the report it summarizes?
A I think so.
Q Does this summary reflect your understanding of your role as an expert witness in litigation?
A Yes.
Q Would you characterize the tone of the Summary of Argument as argumentative?
A No.
Q Evocative?
A No.
Q How would you characterize it?
A Objective.
Q Would you characterize it as a dispassionate report of scientific findings?
A Yes.
Q Why did you title it Summary of Argument?
A Well, because the scientific argument -- the term “argument” is not used, at least in my usage of the language, as argumentative, but just simply as a summary of the points of interest. Not to be argumentative.
Q About halfway down the page there's a statement that says, “In mildly acidic solutions with pH values similar to those measured in the nose of some people, close to 2/3 of the zinc would be present in the same aggressive ionic form as in solutions of the sulfate.” What's the basis for that statement?
A The -- “In mildly acidic solutions with pH values similar to those measured in the nose of some people,” I'm referring, for instance, the England study that we have mentioned already. From that pH and the graph given by Berthon, you can estimate that close to two-thirds of the zinc are in the ionic form.
Q So when you say “measured in the nose of some people,” you're referring exclusively to the data contained in the England study?
A Not necessarily. My own, for example.
Q Your nose?
A Nose pH.
Q Your nose plus the data in the England study, correct?
A Some people, yes.
Q You say in the next sentence, “The manufacturer apparently knew that the product could potentially cause harm.” What's your basis for offering an opinion as a scientist on what the manufacturer knew about the characteristics of this product?
A Well, the very fact that they warned if swallowed, one should call the poison control center and a medical doctor at once. That, in my opinion, shows that the manufacturer of what he considers a homeopathic remedy knew something about the compound may be potentially harmful.
Q You're not talking about knowledge that the product could potentially cause harm to the olfactory sense, are you?
A In general terms, it can cause harm.
MR. WENZEL: No. He is asking if that is what you meant by that. I think his answer was that what he is saying there in general terms is it could be harmful, not in the olfactory sense.
THE WITNESS: Then comes the continuing sentence.
BY MR. LAZARUS:
Q That's why I'm asking the question, Doctor. What basis do you have as a scientist to conclude that the manufacturer apparently knew the product could cause harm? You mentioned the swallow warning. What else?
MR. WENZEL: Anything else?
THE WITNESS: Well, there was the evidence from the Canadian study. That Berthon paper was well before the appearance of Zicam on the market, so they must have known about the existing literature, and that is why I wrote it.
BY MR. LAZARUS:
Q And you believe as a scientist you can draw that inference based on the fact that the manufacturer knew of the potential harm from the evidence you just cited?
A Yes. The second part of the sentence is of importance here.
Q Now, you say, “In order to prevent this from happening, users were advised to hold the nozzle of the bottle ‘at a slight angle.’ ” What basis do you have to draw inferences about what the manufacturer intended by the phrase “at a slight angle” on the label?
A To prevent the gel going too deeply to the olfactory center of the nose.
Q And what is the basis for you to draw that inference? What evidence do you have?
A The statement that it should be used at a slight angle and that you shouldn't sniff it up.
Q Is there any other evidence that you are relying on to opine that the phrase -- that the direction “to hold the nozzle of the bottle ‘at a slight angle’ ” was made in order to prevent smell loss?
A The very fact that more recently the nozzle was changed.
Q As a scientist, you believe the fact that the nozzle was changed is evidence that the prior design was known to be unsafe by the manufacturer?
A It is an admission, yes. I consider that an admission.
Q Is that your personal opinion or is that a scientific opinion?
A It is a scientific opinion.
Q What scientific method did you employ to reach that opinion based on that data?
A A forensic -- my opinion as a forensic scientist looking for a guilty party. I would say yes, you knew it. I caught you.
Q Is that your role as an expert witness, to try to look for the guilty party?
A I am also a forensic examiner.
Q Is there a way for us to determine which hat you were wearing at any given point in your report, whether it be a forensic examiner or a scientist with a background in chemistry?
A I would say 99 percent chemistry, 1 percent forensic.
Q You go on to say in this report, “Some users may have intuitively assumed that the gel was to be pumped into the nose as deeply as possible.” What is the basis for that statement?
A Common considerations, how I would behave if I saw a disposal unit with a one-inch long nozzle, and if I had a feeling that a cold starts on the top of my nose, by golly, I would try to reach that gel right up there.
Q Do you consider that a scientific opinion or a personal opinion?
A Both. It's a human --
MR. WENZEL: Is it a -- I think that Mr. Lazarus's question is very fair. I mean is it a common-sense thing to you or as an expert?
THE WITNESS: Well, I would say both, really. Both.
BY MR. LAZARUS:
Q So you're basing it both on scientific evidence and the application of scientific principles on the one hand and your view of common sense on the other?
A Yes.
Q What scientific evidence and what scientific principles are used to determine that some users may have intuitively assumed that the gel is to be pumped into the nose as deeply as possible?
A As I mentioned, if you have a phenomenon -- let's go away from the nose for a moment. If my finger hurts, I'm going to put the agent on my finger, I'm not going to put it on my arm. And that is, in my opinion, sufficiently scientific, isn't it? You put it where you have the symptom. And where you have the symptom, the common user, scientific or not, will say that's where I want to put it. You cannot say, oh, I'm going to put it way away from where it hurts, because they say on the instruction you shouldn't. That is the key issue here. I agree with you.
Q Doctor, is that opinion based on your intuitive sense of things or is it based on some scientific data and process?
A The use of the term “scientific data” cannot be used here, because who would study things like that? That's common sense.
MR. WENZEL: Okay. That's fine. That's a fair answer.
BY MR. LAZARUS:
Q Without going through each statement in this report, when you attribute a state of mind to the manufacturer and a purpose to the manufacturer of reasons why they said things on the label or made design decisions, are you basing that on any scientific data and process, or are you basing that on your interpretation of the historical events?
A I would say both.
Q When you say, then, “To avoid this from happening,” meaning reaching the olfactory cleft, “the nozzle of the spray bottle has since been modified so as to direct the gel to the sides of the nostrils rather than straight up,” are you aware of any document which indicates that that was the thought process of the manufacturer?
A Yes. And it's the box of the product, where it states, it now reaches the part where we want the product to go, and I think they say something not straight up or something like that.
Q Is that your understanding of what the new box said?
A Uh-huh.
Q You believe the statement on the new box is an admission that the prior design reached the olfactory epithelium?
A As a forensic scientist I draw that extrapolation, yes.
Q Is there any scientific data to support that extrapolation?
A The case reports.
MR. WENZEL: I don't know whether it falls within the range of scientist. You're getting kind of argumentative.
MR. LAZARUS: Neither do I. It's in his report.
MR. WENZEL: You're asking questions that kind of beg an argumentative response. But anyway --
BY MR. LAZARUS:
Q These inferences that you've drawn about the manufacturer's state of mind and the purpose and the labeling and design decisions, do you believe it consistent with the scientific method to draw these inferences?
A Yes.
Q Can you point to any published treatise, textbook, or peer review publication which suggests that determinations like these are within the realm of the scientific method?
A No. Can you?
MR. WENZEL: This is your opinion, Doctor. These are not his opinions, so you don't get to ask the questions.
BY MR. LAZARUS:
Q Your ultimate opinion in this report --
A Actually, I would like to know if such reports are available, to be quite frank --
MR. WENZEL: He is not going to answer.
THE WITNESS: -- of any disrespect. I really would like to know. I couldn't find any. So it's not for not trying to find it.
BY MR. LAZARUS:
Q Trying to find what?
A Well, I would like to find such papers that would say I've analyzed these and these labels and I found that within the accepted scientific method what he or she says about that label is either this or that. I have not ever found a paper. I don't even know in what journal these things would be published.
Q Doctor, your ultimate conclusion, I believe, in this report is that Matrixx should bear responsibility for Dennis O'Hanlon's smell loss?
A Yes.
Q And is it your view that that's the appropriate role for an expert witness, to decide who should bear responsibility for the occurrence of some injury?
A Yes.
Q This bio- --
A Pardon me. In the opposite sense, I would not have hesitated one second to completely put Zicam into the safe category; in other words, I would not have hesitated.
MR. LAZARUS: Move to strike as nonresponsive.
BY MR. LAZARUS:
Q Doctor, the Biological Trace Element Research Institute, is that your consulting company?
A Not quite. It's my -- the consulting is separate.
Q What is the Biological Trace Element Research Institute?
A The Biological Trace Element Research Institute --
Q Doctor, number one, your back is turned to the court reporter making it very difficult to hear you. Second of all, I don't need an elaborate discussion of this. I'm just asking a question.
A The major operation is we publish this journal and we're doing independent research on many subjects.
Q Is this a for-profit organization?
A Nonprofit.
Q Nonprofit. One of the things that you say in your report is that your research activities concern the chemistry of coordination compounds. Briefly, what is a coordination compound?
A A coordination compound is a compound usually of a metal with another molecule, which we call a ligand, which, for instance, could be gluconate, and zinc gluconate would be a coordination compound or coordination complex.
Q You say you're a founder of a new discipline called bioinorganic chemistry?
A Yes, sir.
Q When was that discipline founded?
A I think around 1970 or so.
Q And your journal and this discipline of bioinorganic chemistry, they're tied together, correct?
A Yes. But not necessarily so.
Q I mean is there a society?
A There is a nonprofit society, yes.
Q What's it called?
A The International Association of Bioinorganic Scientists.
Q And do they hold conferences?
A Yes, they do.
Q And at the conferences are papers presented?
A Yes. We have had conferences and --
Q How many years has that been true?
A Well, it was founded in 1975, and we had quite a few conferences.
Q Has the -- has that society ever -- first of all, are you a member of that society?
A I'm the president.
Q And has that society ever held a conference in Greece?
A No.
Q Anywhere outside the United States?
A Let me think. I don't think so right now. No.
Q Has that society ever published any research or presented any research on the effects of intranasal zinc?
A No.
Q You say in your report on Page 4 that, “So far as the medical aspects of taste and smell disorders are concerned, I have studied the available literature and case reports.”
A Yes.
Q Have you done a thorough and extensive study of the available literature and case reports concerning the medical aspects of taste and smell disorders?
A No.
Q Have you done a superficial study of the available literature and case reports on that subject?
A One could say that.
Q Have your discussions regarding general issues of anosmia as referenced on Pages 4 and 5 of your report with Dr. Henkin been the part of the basis for any of your opinions in this case?
A No.
Q Same question as to your consultations with Mr. William Sunderman that are identified on Page 5 of your report.
A No.
Q You described earlier that your conversations with these gentlemen came very early on in your involvement in the Zicam and Cold-Eeze litigation and essentially identified for you some literature that you might profitably pursue reviewing to better understand the topic. Correct?
A Yes. May I interject; however, I would like to make the point that I tried -- or I actually did not use these opinions. I tried to deduce all opinions myself, but was pleased to see that there's good correlation with whatever Henkin or even now what the Zicam people say. There's actually no disagreement.
Q Now, correct me if I'm wrong, as I understand your testimony, you had actually already formed an opinion that Zicam caused anosmia before you called up Dr. Henkin and Dr. Sunderman?
A Absolutely. Yes.
Q Do you have any notes from your conversations with Drs. Henkin and Sunderman?
A Unfortunately not. No.
Q Just so I'm clear and we have the record clear, you're not relying on anything said to you by Dr. Henkin and Dr. Sunderman to support your opinions in this case, correct?
A I think that would go too far. I would say in the initial cases I didn't. Now I'm using some of the findings. For example, I did not know about the carnosine nor the carbonic anhydrase. These were items that were coming to my attention through Dr. Henkin and his work. Yes.
Q These items came to your attention during the course of your work on the litigation; correct?
A On -- yes.
Q Had you ever done any research, prior to your involvement in this litigation, on the toxic effects of zinc gluconate specifically?
A No.
Q In the world of chemistry and toxicology, is the elements that a specific compound is attached to and the other substances that are present in the environment where the substance is used, are those significant to the substances' properties?
A Yes.
Q And are they significant to the substances' biological effects?
A Absolutely, yes.
Q You say on Page 5 of your report that in 1991 you reported the synthesis of novel complexes of zinc with unusual coordination numbers.
A Yes.
Q What's an unusual coordination number?
A Normally metal ions have a positive charge and they will surround themselves, for example, with water molecules. And the coordination number is 6Y. Because the water molecules will arrange themselves in the shape of an octahedron, which has six corners. And our work at this time showed that one can have complexes with coordination numbers, let's say, 5. And, for instance, in carbonic anhydrase, as I recall, the coordination number of zinc is 5. So these would be unusual coordination numbers.
Q Okay. Doctor, you told me before that to become a member of the American College of Toxicology you need to publish in the field of toxicology, pharmacology, or chemistry, correct?
A Yes.
Q Is there anything else that you need to do in order to be accepted for membership in the American College of --
A I think you have to have a university degree.
Q In what?
A In these disciplines. Yes.
Q Is there anything else that you can think of that's a requirement for admission to the American College of Toxicology?
A No.
Q I imagine you have to pay some dues.
A You have to pay some dues.
Q Do you know how you came to the attention of Mr. Libovits or his law firm?
A How did I come to their attention? I frankly don't know. No. Through word of mouth. I don't advertise or anything.
Q All right. I know we touched on this, but I don't think we completed the subject. Do you have data on what the rate of anosmia is among Zicam users?
A It's very small.
Q But do you have any data on what the incidence is besides “very small”?
A At the moment, no. Definitely less than half a percent.
Q Have your opinions changed at all since you issued your report in the Gillespie case?
A Yes. Strengthens it. My opinions are now strengthened.
Q Have they changed in kind, however?
A No.
Q Were there any opinions that you've developed since you prepared your report in the Gillespie case?
A Yes. The importance of pH.
Q Anything else?
A And the question of the concentrations, homeopathic, and the labeling, the detailed analysis of the labeling and the warning. Yes. All these things.
Q And all of that is based on work that you've done since you prepared the report in the Gillespie case, correct?
A Exactly.
Q And by “work,” 1 mean review of literature.
A Mainly, yes.
Q Well, is there anything else you've done besides literature reviews on those topics?
MR. WENZEL: He already testified.
THE WITNESS: I think I already testified I did experiments after that, yes.
BY MR. LAZARUS:
Q I believe the experiments you testified to here today were predating the Gillespie -- maybe -- well --
MR. WENZEL: You asked him to define the pH in his notes. Remember?
MR. LAZARUS: Let me put it this way. I think I may detect the distinction now.
BY MR. LAZARUS:
Q Since the time of your deposition in the Gillespie case, have you done any work besides the literature research?
A Yes. I've done some of the experiments with zinc. These are not mentioned in the Gillespie case, so I had to do them afterwards.
Q You testified in the Gillespie case about putting the zinc on your arm.
A I did. Okay. But I didn't mention it in the report. So there was some overlap report writing, deposition. And these things happen without my control.
Q Let me ask this way to try to make it clear. The second section of your deposition in the Gillespie case took place in mid May. Have you done anything besides review literature since then?
A Yes. I think in mid May -- besides -- well, probably not.
Q Did you take anything of significance for your opinions in this case from the deposition of Bonnie O'Hanlon?
A Well, yes. The use of the product and the symptomatology that he reports. And also his general status of health.
Q Since the preparation of your Gillespie report, have you reviewed any documents, any additional documents, concerning the studies by the Matrixx Scientific Advisory Board?
A Well, that was the -- the one we've already discussed.
Q Yes.
A Yes. On Page 43.
Q I don't want to quibble with you, but I don't see anything on Page 43 which indicates that was a document issued by the Scientific Advisory Board of Matrixx.
A Well, it has the ZM number, and I assumed it was Matrixx.
Q All right. Let's move on. Doctor, referring to Page 8 of your report where you set forth a description of the product, do you have any opinion in this matter that the Zicam used by Dennis O'Hanlon was outside the intended specifications?
A I have no -- other than I believe the quality of the Zicam product is uniform based on my analysis of several sentences.
Q So your opinions regarding the flaws in Zicam were based on its design, not it's manufacturing process, correct?
A Yes.
Q The zinc sulfate solution that was used in the Canadian polio studies, was that diluted?
A It was 1 percent and it contained Pontocaine.
Q I appreciate that. I guess what I was referring to is dilution in the sense of the way homeopathic remedies are diluted. Do you understand how that process works?
A Yes. And this would correspond to roughly D2. 1 percent is I in 100. 2 -- 1 in 10 is D1. 1 in nothing is DO.
Q Is it your testimony that the zinc sulfate used in the polio studies went through a dilution process similar to that which homeopathic remedies undergo?
A The dilution process of homeopathic remedies is somewhat different. They use special methods of distributing their product, so it is different. But one could say those things that are used in solution, then it would be D2.
Q You talked before about the German regulations that require that a remedy you're aware of in -- sold in Germany be offered over the counter at one dilution but not at another. Right?
A Yes.
Q That example, do you have any documentation concerning that?
A Yes. I think I included it.
Q You've cited to something called Zimmermann Homoopathische -- I'm not even going to try that, but it seems to be a German publication.
A Right.
Q For the benefit of those of us who don't have that readily available in our libraries and don't speak the language anyway, what's contained at Page 318?
A I will translate it for you. Thank you.
Q I don't need you to read the whole thing. What page of your file are you looking at?
A 132. And it mentions Zincum Valerianicum and that's a -- Valerianicum. And it says here one-hundredths dilution is D2, which we would agree to. And then it says “Available only on prescription until D3 inclusive.” In other words, even D3 requires a prescription.
Q All right. Now, do you know what policy factors went through the determination that Zincum Valerianicum should be obtainable only on prescription when it's diluted less than four times?
A The German Homeopathic Union and the German health authorities check on that. And this is -- I checked that book. This is true for many homeopathic remedies. They are available in prescription only at a certain dilution.
Q But it's your understanding that whatever determination was made as to when things would be available only by prescription and when they will be available over the counter, whether it be a homeopathic remedy or not, that that's the result of a policy decision by a governing body in Germany?
A Yes.
Q And policy decisions such as those are influenced not only by scientific data, but also by precautionary public health standards that government agencies routinely apply in making regulatory decisions; correct?
MR. WENZEL: I'll object. That calls for speculation. In the ideal world maybe. Don't guess, Doctor.
THE WITNESS: I would say yes.
BY MR. LAZARUS:
Q Have you reviewed the regulations for or practices in any other country besides Germany to evaluate your -- to evaluate the propriety of Zicam being marketed as a homeopathic remedy?
A Yes. I looked in the United States. And as I mentioned in my report, Americans are more liberal and leave this door somewhat more open with the proviso that this applies only to oral administration.
Q When you say they're more liberal, you're referring to them making a different policy determination than the German government?
A Or more specifically that they allow lower potencies.
Q On Page 10 you talk about the pharmacological and toxicological aspects of zinc salts. You say, “At higher levels, zinc can have beneficial as well as adverse effects, depending on chemical form, dosage and manner of application.”
A Yes.
Q I take it it's your opinion, Doctor, that the nature and extent of the effects of zinc compounds depend on the chemical form, the dosage, and the manner in which it's applied.
A Yes.
Q And that would include the amount of zinc contained in the compound?
A Yes.
Q And that would include the amount of zinc delivered to the target organ by the manner of application?
A Yes.
Q And you would agree that the amount of zinc delivered to the target organ will vary depending on the concentration and amount of zinc, the volume of the substance, and the manner of its application?
A Yes.
Q You say on Page 10 also that “The nasal mucosal membranes are more sensitive to the destructive effects of zinc salts than oral tissues.”
A Yes.
Q What do you base that on?
A Well, because oral tissues are generally far more resistant or else we couldn't eat. But we are not eating with our noses. If we were to eat through our noses, our noses would collapse. So it's, I think, quite logical that the nasal mucosa are, in fact, very sensitive because they have a completely different job than the oral mucosa.
Q When you say “nasal mucosal membranes,” you're talking about all of the membranes of the nose; correct?
A Inclusive.
Q It's more that just the olfactory epithelium?
A Yes.
Q When people use the term nasal membrane or nasal epithelium, they're not necessarily talking about the olfactory epithelium?
A This is correct.
Q In fact, most of the tissue within the nose is not olfactory epithelium --
A Correct.
Q The olfactory epithelium is a small patch of tissue that's located near the roof of the nose.
A Yes.
Q Do you agree it's located in a fairly sheltered area in the nasal cavity?
A Yes.
Q Is zinc oxide soluble in water?
A To a very small extent.
Q In your report you've cited to some materials prepared by someone named G.A. Eby. Do you know who that is?
A Yes. He is an inventor of the zinc lozenges.
Q Do you understand as the inventor of the zinc lozenge, he's something of a competitor in the cough and cold market of Zicam?
A That, I didn't realize, but it could be true.
Q Have you ever spoken to him?
A No.
Q Do you know anything about his scientific qualifications?
A No.
Q Is gluconate a naturally occurring endogenous substance?
A Not to my knowledge.
Q Gluconic acid?
A Not to my knowledge.
Q Have you done any research on it?
A Well, gluconic acid is made industrially by the oxidation of glucose. But in the human body, very little, if any, of the glucose is oxidized to gluconic acid. It's a different pathway of metabolism.
Q You say on Page 12 of your report that in zinc gluconate complex, the zinc is less reactive and less aggressive than the zinc in zinc sulfate.
A Yes.
Q Is that your opinion?
A Yes.
Q And when you say “less reactive,” are you talking about its slower dissociation?
A Well, you know, reactivity, there are two aspects: The thermodynamic, which is very general, and the kinetic, the kinetic rates. Now, gluconate forms a relatively labile complex. And so some of -- about 30 percent of the zinc is then captured partly by gluconic acid. But that doesn't mean that it cannot reassociate and free the free zinc ion. So we're dealing with a dynamic situation, an equilibrium situation.
Q It also depends on the pH of the environment?
A Strongly dependent on pH, yes.
Q Generally speaking, is zinc sulfate a stronger acid than zinc gluconate?
A You have to rephrase this question.
Q Is it more acidic than zinc gluconate?
A Zinc sulfate solutions are somewhat more acidic. Yes.
Q How much percentagewise?
A In terms of pH, I would say I unit of pH.
Q On a scale of what?
A 14.
Q So --
A So I would say if zinc sulfate has a pH of 4.5, then zinc gluconate would be around 5.5 at the same concentration.
Q Doctor, looking at Page 14 of your report, which is the part where you're critiquing some of the statements made in the SEC filing concerning findings of the Scientific Advisory Board of Matrixx.
A Yes.
Q Concerning animal studies, you say, “The olfactory system of humans differs substantially from that of animals. The negative results in animal studies observed cannot be used to declare the drug as safe for humans.”
We talked about this before, and I don't want to go into any detail, but is it fair to say in your analysis you accept the positive results of toxic effects in animal studies but not the negative results, for purposes of forming your opinions in this litigation?
A Yes.
Q And as you described it earlier, my understanding is the reason for that is because you need to be careful when you're talking about safety and that has to color your review and interpretation of the scientific data arising from animal studies?
A Yes.
Q And you believe it's important to take that approach when toxicity is at issue?
A Yes.
Q On Page 14 you also say, “The results of cadaver studies are inconclusive, as these can never completely reproduce the behavior of the living body.” Is that the reason why you don't think the cadaver studies are of scientific importance in determining the distribution of Zicam and any other solution?
A Yes. Because of the peristaltic effects which only the living organism has.
Q You say on Page 14 that one of the reasons for your views on distribution are inspection of the anatomy of the human nose. Was that research that was done in connection with your work on the Zicam litigation?
A Yes.
Q We're very close to being finished, Doctor, for your information.
You say on Page 15 that epidemiology studies can be expected to produce reliable results only if the database is reasonably complete. When you say “reasonably complete,” are you just talking about the size of the sample?
A No. Also the timing.
Q What size of a database do you think is needed for reliable study of the causes of anosmia?
A That depends on the incidence. The smaller the incidence, the larger the number of cases required.
Q For -- if you assume that post-viral anosmia occurs in .25 percent of the population, generally speaking, how large a database would you need to accurately assess the incidence?
A I would estimate about 10,000.
Q On Page 15 you criticize the statement that a lack of benign characteristics to Zicam in the mouse at large doses is hardly surprising since an overdose of virtually all over-the-counter or prescribed medications would generally have adverse effects on health. Do you see that?
A Yes.
Q Okay. Now, your criticism is that this argument is not admissible since the Zicam no-drip nasal gel is marketed as a homeopathic remedy. The absence of adverse effects is a generally known hallmark of homeopathic remedies. Do toxicological principles of dose response and the need to consider dose in determining whether a substance is a poison, a benefit, or neutral, apply differently to homeopathic remedies than to other substances?
A No.
Q Let me ask you again. Is that a scientific opinion or is that a personal opinion that the concept of dose makes the poison does not apply to homeopathic remedies?
A Excuse me. I didn't think that would follow. The dosage does not apply to homeopathic. What do you mean by that?
Q Let me put it to you this way. I'll try to make it quick. You're criticizing a statement made by a member of the scientific advisory board, apparently, that the fact that there was some harm at very high doses to the mouse was hardly surprising since an overdose of virtually all over-the-counter or prescribed medications will generally have adverse effects on health.
Isn't that simply a statement of the fundamental toxicological principle that whether a substance has adverse effects will depend on the dose?
A Yes.
Q And you've heard of examples that people use to illustrate that, such as water is harmful if you have too much of it but it's beneficial and necessary at some level, correct?
A Yes.
Q All right. Now, do you understand that statement there as a statement of that principle of the dose makes the poison?
A That statement is based specifically what is associated as a homeopathic remedy. I can take these globules, the whole bottle, and nothing will happen to me. There are, in fact, some homeopathic remedies which, by law, contain nothing. So you take a placebo and eat kilograms of it. So the answer would be the rarest and they correctly say over-the-counter or prescribed medications. Now, Zicam is not a prescribed medication. It is marketed as a homeopathic remedy. And for a homeopathic remedy, the demand is I don't have to put any warning in it. I can take it.
Q Is it your understanding that Dennis O'Hanlon inadvertently sniffed up the gel or did he intentionally sniff?
A He may have intentionally sniffed it.
Q You don't know one way or the other?
A I don't know one way or the other, because the distinction is very difficult to make by any standard.
Q On Page 17 you set forth the statement on the newer container package, which says, “The Control Tip Sprayer on this Zicam Cold Remedy puts the medicine where you need it, just inside your nose, not far up the nasal cavity.” I take it by your interpretation of this, you're interpreting “far up the nasal cavity” to mean the olfactory area?
A Yes.
Q What's the basis for that?
A It follows from the statement.
Q Aren't there other portions of the nasal anatomy that are higher than the very lowest portion of the nose that can be referred to there? For example, the middle turbinate, the upper middle turbinate?
A They didn't mention that. They just speak of the nasal cavity, which includes the turbinate region.
Q Doctor, that's all the questions that I have. Thank you very much for your testimony.
A Thank you, sir.
Q Before you do, I will make arrangements with Mr. Wenzel in terms of submitting an invoice and getting you paid.
A Thank you.
MR. WENZEL: Is that okay with you, Doctor?
THE WITNESS: Yes.
MR. WENZEL: Are you sure? I don't have any questions.
MR. LAZARUS: Thank you very much, Doctor. Good to see you. (Discussion off the record.)
MR. WENZEL: Handling signatures. Send it to me. I'll send it to the witness. I'll notify counsel of any changes to the deposition and have the deposition signed within 30 days of my receipt. If not so notified, a certified unsigned copy may be used as if signed.
MR. LAZARUS: Agreed.
(TIME NOTED: 4:53 p.m.)
INDEX
THURSDAY, AUGUST 24, 2006
WITNESS EXAMINATION
GERHARD SCHRAUZER, Ph.D.
(BY MR. LAZARUS) 4
