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Graduate School and School of Medicine, Philadelphia, PA, June 1, 1990. 1990 Science Citation Index ranked Dr. Fauci as the eighth most-cited scientist among 1.3 million scientists publishing in the time period 1981-1988. 1990 Humanitarian Award of the Human Rights Campaign Fund Federal Club of Houston. The First International Chiron Prize for Biomedical Research awarded by the Scuola Superiore di Oncologia e Scienze B Biomediche (Genoa) and the Scuola Internationale di Oncologia e Medicine Sperimentale (Rome), 1990. Doctor of Medicine and Surgery, Honoris Causa, Universita di Roma, "La Sapienza," Rome, Italy, 1990. The Fifth Annual Gene Frey Memorial Award for Medicine, The Whitman-Walker Clinic, Washington, DC, November 17, 1990. The 1990 Presidential Award of the New York Academy of Sciences. Visiting Professor of Medicine at a large number of major medical schools throughout the country.

Publications :

Dr. Fauci has authored over 700 scientific publications in the field of basic and clinical immunology and infectious diseases.


Senator HARKIN. Thank you very much, Dr. Fauci.

Let me just ask you a couple of questions about the vaccines. One has to do with the licensed vaccine to protect infants against meningitis.

Dr. Fauci. Right.

Senator HARKIN. This is a long-term interest area of mine. Is this the same kind of meningitis that causes hearing loss?

Dr. Fauci. Yes; both hearing loss and mental retardation may result from Haemophilus influenzae type b.

Senator HARKIN. And is this vaccine now available?
Dr. Fauci. Yes.

Senator HARKIN. What is the earliest age that a child can take that vaccine, and who should take it?

Dr. Fauci. Well, this is the first time since the 1960's that we have a new vaccine against an important childhood disease. The reason this is so important is that children, by the nature of the development of their immune system, cannot seem to make immune responses against what we call polysaccharide components of bacteria until they are 1, 2, or 3 years old and sometimes even older. However, this particular type of meningitis usually affects children who are much younger, within months of birth.

The advances here and this was a very important contribution of one of the intramural scientists in the National Institute of Child Health and Human Development—was to develop a combination of a protein conjugate with the polysaccharide to allow the infant's immune system to recognize and respond to this. So, now we have a vaccine available that may be used when the infant is most vulnerable. So, this is a very, very important advance. Prior to this, we could not vaccinate children then because their immune systems would not recognize the particular bacteria.

Senator HARKIN. So, you can vaccinate them at
Dr. Fauci. A few months.
Senator HARKIN (continuing). A few months of age.
Dr. Fauci. Yes.

Senator HARKIN. And does this protect them for—is it like a smallpox vaccination? I don't know what the right phrase is, but they do not have to be revaccinated later on or anything like that?

Dr. Fauci. No; actually the important thing is that children are very vulnerable to this. When they become adults, they are much, much less vulnerable to this. So, that period is the critical period.

Senator HARKIN. I understand.

We have provided funding-staying on vaccines here and encouragement for development of a children's vaccine. I know Senator Bumpers has been very active in that area. This would be one vaccine which would cover seven or eight of the more common childhood vaccines all in one dose.

How optimistic are you that such a vaccine can be developed in the relatively near future?

Dr. Fauci. Well, we are optimistic about this, Senator, because we feel that we have already in place the basic research knowledge that can at least get a very good start on this. What we need to do now is to apply some of that technology to the development of this, as well as to continue our effort in basic research in that area. And I could just very briefly give you some of the objectives as you mentioned.

The first thing is to have a vaccine which is stable at ambient temperature, that is administered orally, and that can produce lifelong immunity when administered as a single dose in childhood.

What have we been doing over the past year with the money that you have given us to try and implement the basic science to get such a vaccine?

Well, first what we have done is that we have established a vaccine production facility. We have accelerated our research on mucosal immunity, and we have evaluated vaccine prophylaxis against infectious diseases in children that we have not had as much effort on. Right now we are studying the concept of maternal immunization, both in an animal model and in the human system. So, already this year we have had activity heading toward the goal of a children's vaccine and I think it is a feasible goal within this decade.

Senator HARKIN. I was contacted recently about the AIDS vaccine which has been developed by MicroGeneSys. Are you familiar with that?

Dr. Fauci. I am very familiar with it, yes, sir.

Senator HARKIN. I understand that the drug is ready to move into phase II clinical trials to determine whether or not the drug is effective.

What is the status of the clinical trials for the AIDS vaccine developed by MicroGeneSys?

Dr. Fauci. Yes, Mr. Chairman. The MicroGeneSys vaccine is a recombinant vaccine of the GP-160 protein of the envelope of HIV.

In 1987, we initiated a phase I Clinical trial in the intramural program using accelerated doses of the GP-160. We have just recently initiated the GP-160 in individuals who are already infected with HIV using it namely as an immunoadjuvant.

In addition, in our vaccine evaluation units extramurally, we are testing the GP-160, and it has been used as a boost in association with a Bristol Myers product, which is a high vaccinia initial dose and then boosted secondarily with the MicroGeneSys vaccine.

With regard to your specific question, we have called together a group of experts on an ad hoc basis to advise us on whether we

should go forth with any vaccines in an efficacy trial at this particular time, in this country or worldwide. The overwhelming recommendation of the group was to establish efficacy after a challenge in an animal model and before we went ahead and conducted a large scale efficacy trial on humans, and that is in fact what we are doing

Certainly the MicroGeneSys product is one that is well on its way. It is proven to be safe, and it is proven to be immunogenic in that it induces both humoral and cellular immunity. That certainly would be one of the candidates that we would look very favorably upon when we get to the stage of looking at an efficacy trial in humans.

Senator HARKIN. My follow-up question on that was you are going to test this in animals first.

Dr. Fauci. Before we go, in this country, into an efficacy trial

Senator HARKIN. But I understand, if I'm not mistaken, that the AIDS vaccine has already been proven safe for humans. Is that right? Dr. Fauci. It has been proven safe, yes, sir.

Senator HARKIN. Then why would you not go ahead and test this on humans rather than going

Dr. FAUCI. The reason for that is that it was the overwhelming recommendation of our committee that, given the limited target populations that you have in this country that you could use for a vaccine trial, it was important to determine efficacy in animals first. Although we know it is safe, there is no indication, given the complexity of the immune response to HIV, that it would be effective in humans.

The animal studies are not for safety. They are for giving the animal a vaccine and then challenging the animal with a live virus to prove that the particular candidate is effective. It has more to do with efficacy than it does with safety.

Senator HARKIN. I just have a hard time understanding. If it's safe, why not try the efficacy on humans? You are talking about people that have AIDS.

Dr. Fauci. Right.

Senator HARKIN. I went through this a year or two ago with a friend of mine who was dying of AIDS who is since deceased. He was willing to try anything. He didn't care. He knew he was dying. So, why not go ahead and try

Dr. FAUCI. It is a different story when you are talking about prevention versus treatment. If you have someone who is already ill and is deteriorating, then the philosophical approach of trying something that might necessarily be a high risk is a different situation than consuming a population for immunization that you would want to save for something that has been shown experimentally to be effective. The overwhelming recommendation by our advisors is that you should not utilize populations in this country that could be candidates for a vaccine until you have an indication that the vaccine would be effective.

Now, the situation would likely be different because I know that MicroGeneSys is now negotiating with doing an efficacy trial in foreign countries in which the rate of new infection is extraordinary because those individuals would have such a high rate of infection, they could tell right away and very quickly whether it would be effective or not.

Senator HARKIN. Well, I don't know that I understand that completely.

I am told—and again, this is not of my own knowledge that almost all of the vaccines currently in use were not developed using animal models and that some vaccines which looked extremely promising in animals did not achieve significant results in humans.

Now you are saying that the animal tests should come before human efficacy tests even when the vaccine is proved to be safe.

Dr. Fauci. Mr. Chairman, there have been no vaccines to date that have been tested for efficacy. The information you are getting are situations in which a product was tested in an animal and shown to be safe and then gone on and done a phase I trial in hu

а mans to show if it is safe in humans. The recommendation of the groups that I am talking about has less to do with safety than it has to do with proving that it can work. There have been no

Senator HARKIN. I guess I just don't understand, if it is safe and you can get a control group who volunteer for efficacy tests, to see that it works, why you couldn't go ahead and do that rather than going through animals first. I can understand that in some cases, but in the AIDS situation, I have a hard time understanding.

Dr. Fauci. In order to prove efficacy in a population, you would have to have a population that has a reasonably high risk of getting infected because you will have to test the vaccine on individuals who are not yet infected. There should be no imminent danger to them of dying because they are not infected yet.

However, there are some populations in which there is a high rate of infection, and the recommendation is that you should use a vaccine in those populations only after you have shown that that vaccine can be effective in preventing an infection in an animal that has been challenged because otherwise you might vaccinate a high-risk population, and then you look around and you do not have any more populations to vaccinate because you have used up the high-risk populations in this country.

Senator HARKIN. I may have to get some more information on this.

Dr. Fauci. I would be happy to discuss that with you in more detail.

Senator HARKIN. I think I understand it. It's just my limited scientific knowledge is what is preventing me from fully comprehending it.

I recognize Senator Reid for any questions you may have.
Senator REID. Thank you very much, Mr. Chairman.

Dr. Fauci, what type of research is being done to pursue the chronic fatigue syndrome?

Dr. FAUCI. The research associated with the chronic fatigue syndrome is several-fold. One is looking at the epidemiology and natural history. As you are probably aware, this has been a very elusive disease in trying to determine what the criteria for diagnosis is. As we are learning more and more about that, there is research now into looking at the pathogenesis and at what are in fact the defects in individuals who have chronic fatigue syndrome. And that is moving along right now. In fact, we have issued a request for applications for cooperative groups to study chronic fatigue syndrome. It is really a question of getting the natural history down and then looking at the pathogenesis. And we have actually done some more surveillancing in association with the CDC and epidemiological studies.

Senator REID. Is the National Institute of Allergy and Infectious Diseases cooperating with CDC in this endeavor?

Dr. Fauci. Yes, sir, we are.

Senator REID. How many staff members at NIH, full or parttime, are working on this chronic fatigue syndrome?

Dr. Fauci. Well, we do not have individuals who specifically are involved in chronic fatigue syndrome. We have a Division of Microbiology and Infectious Disease with a large number of individuals. One of the areas that we are concerned with is chronic fatigue syndrome. We do not specifically assign an individual to chronic fa tigue syndrome. We do in our intramural research program have one of the leading scientists in the world in chronic fatigue syndrome, Dr. Steven Strauss, who has been responsible for a number of very important studies over the last several years.

Senator REID. So, do you feel that enough attention is being focused on this disease? Within the limits of your budget I assume is what you are going to say.

Dr. Fauci. It is a frustrating situation, Senator, because since there is such a poor handle on just what this disease is. We would like to be able to do more, but before we can do that, we have to have something to grasp onto. And that is the reason why it is important to delineate, as best as possible, what the natural history is, what the criteria for making a diagnosis of this disease is, and then to determine alternative therapies to treat it. So, in a broad sense, I am not satisfied with the amount that we are doing because we have not yet reached that stage in understanding the disease to be able to apply specifically more effort into it.

Senator REID. As you are aware, in Douglas and Lyon Counties in Nevada there are large numbers of these cases that have been identified. And the University of Nevada Medical School has been doing research in this area for a number of years. Has the NIH used the benefit of the University of Nevada at Reno Medical School for the work that has been done?

Dr. Fauci. We recently issued a request for applications to establish chronic fatigue syndrome cooperative groups. Hopefully, the University of Nevada will submit a competitive application. Regarding the broader question of prevalence in Douglas and Lyon Counties, that is one of the areas that is being very closely looked at in the collaborative effort between the Centers for Disease Control and the NIH.

Senator REID. One reason I mention this is that there are hundreds and hundreds of samples of chronic fatigue syndrome patients whose blood has been stored at the University of Nevada at Reno. Are you aware of this?

Fauci. Yes, sir; in fact, we did a significant large study at the NIH on those individuals looking at every available parameter that we have immunologically and otherwise, and we did not come up with any pattern at all that we could pursue. But that does not mean that we are not continuing to try and find inroads into the

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