Ronald Kennedy

Ronald Kennedy

The final issue is that certain vaccines are just not appropriate and have not been tested well enough to mandate mass vaccination of infants, and this deals with informed consent and the parents' right to personal choice. Regarding the lack of a mechanism to study the basis for adverse reactions to vaccines, I along with several colleagues have submitted grant applications to the National Institutes of Health to study the basis and mechanism of adverse reactions seen as a result of the hepatitis B vaccine. We made three attempts.
In each attempt the grant application was not considered for funding.-----Ronald Kennedy

Transcripts
http://commdocs.house.gov/committees/gro/hgo62560.000/hgo62560_0.HTM#107 I would like to take this opportunity to thank you for the invitation to speak to this committee regarding issues related to vaccines, public safety, and personal choice. My name is Ronald Kennedy, and I am a professor of microbiology and immunology and obstetrics and gynecology at the University of Oklahoma Health Sciences Center. I am a research scientist and teach medical and graduate students.
    My education has taken me from Connecticut, where I was born, to New Jersey, to Hawaii, where I received my master's and doctoral degrees, Houston and San Antonio, TX, and finally Oklahoma City.
    My training is in microbiology and immunology and I have been working in the area of vaccinology since 1981, when I first started working on the immune response to hepatitis B surface antigen, the component of the hepatitis B vaccine.
    Since that time I have performed basic and applied research as it relates to a variety of viral, bacterial and cancer vaccination strategies. Included in these efforts were studies to develop and/or improved vaccines to hepatitis B virus, the human immunodeficiency virus, HIV, hepatitis C virus, and simian virus 40, among others a virus that been recently associated with cancer in humans.

Because of my expertise in animal models for infectious diseases, particularly non-human primate models, I've also performed a number of collaborative studies with investigators on vaccines for haemophilus influenza type B, group A and group B streptococcus and meningococcus, among others.
    As a number of these infectious diseases cause diseases in newborns and infants, I have become aware of the difference between how newborns respond to vaccination when compared to an adult.
    I consider myself pro-vaccine. However, growing up in the field of vaccinology as I have, I am aware of a number of issues and considerations that should be brought forth when it comes to vaccines, public safety, and personal choice.
    I would like to briefly mention three issues as it relates to the subject of this hearing.
    The first is a lack of a mechanism to study the basis for adverse reactions to vaccines.
    The second is, how can we improve vaccine safety, particularly when immunizing infants?
    The final issue is that certain vaccines are just not appropriate and have not been tested well enough to mandate mass vaccination of infants, and this deals with informed consent and the parents' right to personal choice.
    Regarding the lack of a mechanism to study the basis for adverse reactions to vaccines, I along with several colleagues have submitted grant applications to the National Institutes of Health to study the basis and mechanism of adverse reactions seen as a result of the hepatitis B vaccine. We made three attempts.
    In each attempt the grant application was not considered for funding. The reasons of the peer review panel were the application was descriptive and a fishing expedition. We had compelling evidence but no direct cause and effect, and limited preliminary data.

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    As someone who has been funded continuously from the National Institutes of Health since 1984 and who has served on grant review panels for the National Institutes of Health since 1987, I was aware that such comments were a kiss of death. More importantly, I did not disagree with the panel's perception of the grant application. However, it was the nature of the subject matter. Since everyone has a perception that vaccines are completely safe, why would they want to study adverse reactions?
    If the National Institutes for Health or Centers for Disease Control and Prevention will not support research by investigators outside their institutions into the basic mechanisms of adverse reactions of vaccines that are presently being used to immunize infants, perhaps the pharmaceutical companies who make the vaccines would fund such work by outside investigators. Honestly, I do not think that the vaccine manufacturers would be interested in supporting efforts that might show that their product is harmful.
    I would urge you to provide research funds that are currently unavailable to study serious adverse reactions to vaccination such as those seen with hepatitis B.
    My second issue is how can we make vaccines safer, particularly in infants? In my opinion, this requires more substantial testing, a requirement that each lot of vaccine be tested in non-human primate models for safety and comparative potency. Many of the present vaccine products have bypassed non-human primate studies and gone directly from rodent studies into human clinical trials. This was based on cost and comparability issues.
    Additionally, other vaccines have shown problems in non-human primate models, and these were ignored and the product went into human clinical trials anyway.
    It is important to test vaccines in immunologically similar animals and in an outbred population like us, particularly when addressing issues like long-term safety and comparable potency of a given vaccine lot.
    My final issue relates to whether certain vaccines are appropriate for infant immunization and whether parents should be informed about the risk versus benefit of vaccination. More importantly, the physician who administers that vaccine is probably not aware there are any risks.

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    Two specific vaccines come to mind, hepatitis A and hepatitis B. I will not go into a long-winded scientific process and simply state that the chance of an infant or child getting either hepatitis A or hepatitis B is close to none or nonexistent. When the potential for exposure does exist, those risk factors are easily identified. Even more disturbing is that hepatitis A causes a self-limiting infection and does not cause chronic disease. It is my opinion that parents should be made aware of the risks and benefits of each vaccine where the chance for infection during infancy is minimal to nonexistent.
    Certain vaccines, such as the enhanced and inactivated polio, diphtheria, tetanus, acellular pertussis, and the haemophilus influenza type B conjugate vaccines have significantly reduced infant mortality and morbidity and should be considered for infant immunization. However, other vaccines such as hepatitis B may be more effective when given at a later age rather than at birth. Informed consent for vaccines such as hepatitis A and hepatitis B should be considered and parents allowed to choose based on their perceived risk to benefit from vaccinating their infant.
    To further illustrate my points, I would like to discuss adverse reactions and the need to support funding activities. The example I am going to pick is the whole cell pertussis vaccine.
    This vaccine started for universal immunization of infants in developing nations in the 1940's. The whole cell pertussis vaccine causes frequent systemic symptoms such as irritability, lethargy, loss of appetite, and fever in 72 hours following immunization in up to 50 percent of subjects. More severe reactions include prolonged inconsolable crying, high pitched fever, screaming, fever above 104.9 degrees Fahrenheit, febrile and afebrile seizures, and shock-like states that can last up to 36 hours. In comparable trials, these adverse effects were more common in DTP recipients than in DT vaccinees. This suggested that the pertussis vaccine caused these reactions.

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    The public believes that the whole cell pertussis vaccine causes brain swelling and permanent neurologic damage and is widespread. However, scientific epidemiologic data to support a casual relationship are said to be inadequate, and this is simply not true.
    Why is this the perception? First, there is no support for basic research into adverse reactions. The data on the casual relationship and inadequate nature to show a cause and effect, a lot of the data comes from the vaccine manufacturers. New and improved vaccines should decrease the adverse reactions, and the acellular vaccine is certainly associated with the lower incidence of these reactions.
    Will we ever understand the mechanism of how the whole cell vaccine produced these side effects, and is there any association with neurologic problems? This is unlikely, because this has been going on for 50 years, and what research really has been done? My question is, why then is the whole cell vaccine still being used?
    Regarding the area of informed consent, I would like to quote from Chapter 17 in a textbook entitled Pediatric Infectious Disease, Principle and Practices. The editors are two pediatric infectious disease specialists. The textbook was published in 1995 and it is one that I use to teach medical students. In the area of informed consent, I am quoting directly from the book.

    Vaccines should be administered only after consent has been obtained from the parent, guardian, or in some cases the vaccine recipient. In the United States informed consent should be in writing and include an explanation of the disease to be prevented, the benefits and risks of immunization and the side effects that parents should look for following immunization.

    Relative to requirements, again I am quoting from this chapter.

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    Every time a public or private health care provider in the United States administers a particular vaccine, it is required to provide a legal representative of a child or any other adult or individual receiving a vaccine a copy of the vaccine informed statement prepared by the CDC. In addition, the names of the patient and parent, the date, site of immunization, dose, manufacturing vaccine lot number, name of person who administers the vaccine, and the place where the vaccine is administered should be recorded. This information is absolutely important if an adverse reaction occurs following immunization.

    I think this is part of the problem with the adverse vaccine effects reporting system. Health care providers are not required to obtain the signature of the patient, parent or child's legal representative to acknowledge receipt of the vaccine information statement. This is an absolute must.
    I want to thank you for the opportunity to appear before this distinguished committee. I would be happy to answer your questions at the end of the testimony.

Dr. Kennedy, you said you submitted an application to NIH for a research grant on the hepatitis B vaccine; is that correct?
    Dr. KENNEDY. Yes. Myself and a number of other colleagues.
    Mr. BURTON. You have had grants before? You have done research before?
    Dr. KENNEDY. Yes, since 1984. In fact I had the early grants on looking at the immune response to the plasma-derived hepatitis B surface antigen.
    Mr. BURTON. Did they give any reason why they turned your grant request down?
    Dr. KENNEDY. Yes. Essentially that it was—the term ''fishing expedition'' means that you have a big juicy worm and you are throwing it out there and hoping that someone will bite on it.
    Mr. BURTON. Do you still have a copy of that grant application?
    Dr. KENNEDY. Yes. I can provide that.

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    Mr. BURTON. Can you give me a copy of it?
    Dr. KENNEDY. Certainly can.
    Mr. BURTON. I would like to have a copy as soon as possible.
    Dr. KENNEDY. We did two additional revisions on the grant through the process.
    Mr. BURTON. I want to take a close look at it, if I could.
    Dr. KENNEDY. OK.
    Mr. BURTON. Maybe we will have a hearing on that grant application itself and haul the people in here.
    Dr. KENNEDY. I would rather you not. The process of NIH does work, but I think the problem is the understanding of——
    Mr. BURTON. Wait just a minute. You say the process does work. How long ago did you submit this grant application?
    Dr. KENNEDY. 1997. And how we are supporting our present efforts to address these issues relative to adverse reactions are kind of through private funds.
    Mr. BURTON. I don't mean to interrupt you, but my granddaughter almost died. While your grant application sits there, how many other adverse reactions have occurred like that and how many other parents may have lost their child like the lady that was sitting over there? I think something as important as that should get timely review. So I would like to see your application. You let me worry about what to do with it, OK?
    Dr. KENNEDY. OK.

Mr. BURTON. Let me ask Dr. Kennedy a question. What did you say was the percentage of reactions to the pertussis vaccine within the first 48 hours?
Dr. KENNEDY. It was within the first 72 hours. Approaching 50 percent.

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    Mr. BURTON. Fifty percent. Just a second. Fifty percent would have an adverse reaction within the first 72 hours?
    Dr. KENNEDY. I will provide you with the documentation that quotes that.
    Mr. BURTON. In many cases that is not of long duration.
    Dr. KENNEDY. Right. Correct.
    Mr. BURTON. It is something that comes and goes.
    Do you have any percentages that show the adverse reaction that is of long duration?
    Dr. KENNEDY. No, I don't.
    Mr. BURTON. So we really don't know. You know that there is an adverse reaction that is pretty substantial within the first 72 hours in half of the cases where they give those shots.

Mr. BURTON. I think that is a very good point, doctor.
    Who manufactures the DTP vaccine?
    Dr. KINSBOURNE. Lederle.
    Dr. KENNEDY. Wyeth Lederle Pediatric Vaccines it is now called.
    Mr. BURTON. Is that the only one that manufactures that?
    Dr. KENNEDY. No. There are a couple others that make the whole cell pertussis. I don't know it off the top of my head.
    Dr. KINSBOURNE. Connaught is another company.
    Mr. BURTON. Those are both domestic companies here in the United States?
    Dr. KINSBOURNE. I think Connaught is largely Canadian.
    Dr. KENNEDY. It's Pasteur Merieux Connaught, but they have a manufacturing facility in the United States, in Pennsylvania.
    Mr. BURTON. You may not know this. I may have to check into this in a later hearing or something. Do you know if they give any funds or grants or honorariums to anybody over at NIH or CDC?

Mr. BURTON. Thank you. I would like to have that information if I could.
    I just can't for the life of me fathom why that one vaccine is still on the market and being manufactured and sold here and used in the United States. I just don't understand that.
    Can you explain that, Dr. Kennedy?
    Dr. KENNEDY. I can maybe address the situation relative to the issue of combination vaccines and why it may still be there. There were studies done where they were combining the DTaP vaccine with the haemophilus influenza type B glyco-conjugate vaccine, and a number of studies, both in non-human primate models and in children, suggested that by combining and then giving it at a single site that you would interfere with the ability to respond to the haemophilus influenza type B [HIB] component, and the interference appeared to be as a result of the acellular components.

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Dr. KATZ. This vaccine has been used for 40 years in this country and its record of achievement has been a very successful one. What he is describing as 50 percent is sore arms, sore legs, redness, fever. It's not life-threatening reactions. It is more reactive than the acellular vaccine, which is why most people have switched to the acellular vaccine, but these are not life-threatening reactions that have been shown with the whole cell pertussis to be any more than with any other acellular pertussis.
Mr. BURTON. These are FDA serious events in 1999. How many are in here, 1,500 or more?

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    Dr. Kennedy, of these 50 percent of the reactions were any of them pretty severe?
    Dr. KENNEDY. Yes. Quite a few were more severe, such as the high pitched screaming, the crying, the fever, the shock-like syndrome.
    Mr. BURTON. Running around and waving their arms and that sort of thing?
    Dr. KENNEDY. Yes, but the percentage I could not find.
    Mr. BURTON. I will tell you that is exactly what happened to my grandson. Exactly. He ran around waving his arms, a high pitched scream, waving his arms up and down, and everything else, and he's autistic now.
    I'm getting a little emotional about this. I think we will conclude this hearing. But I want to tell you, this isn't the end of it.
    We stand adjourned.
    [Whereupon at 7:30 p.m., the committee was adjourned.]
    [Additional information submitted for the hearing record follows:]
    INSERT OFFSET FOLIOS 214 TO 228 HERE

    [The official committee record contains additional material here.]

http://commdocs.house.gov/committees/gro/hgo62560.000/hgo62560_0.HTM#120

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Dr. KATZ. We haven't used that vaccine for several years, Mr. Burton. I think one of the things that I would love to point out to you is that we do improve. We use the acellular vaccine in this country. The British continue to use the vaccine that Dr. Kennedy has described. We haven't used it for several years in this country.
    Mr. BURTON. Is the DTP vaccine rather than the DTaP vaccine still being used?
    Dr. KATZ. The DTaP vaccine is being used, which has an infinitesimal degree of reactivity compared to the DTP.
    Mr. BURTON. The Department is behind you. Is the DTP vaccine still being used in this country?
    Mr. EGAN. Yes.
    Mr. BURTON. It's still being used in this country. So, Dr. Katz, you are incorrect. It is being used in this country.

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    Dr. KATZ. If it is, it's in a very small percentage.
    Mr. BURTON. It doesn't matter if it's your kid or your grandchild. If they get a DTP vaccine and there is this adverse reaction that Dr. Kennedy is talking about, it's of great concern to people, and we don't know whether it leads to autism or not, but I have an autistic grandchild, and we've had a number of other people that have seen tremendous problems with autism, and they are still using that vaccine. You said you didn't think they were.
    Dr. KATZ. I said they are still using it in the United Kingdom. They don't use acellular pertussis vaccine.
    Mr. BURTON. That's the United Kingdom. It's not the United States of America.
    Dr. KATZ. The World Health Organization is using it throughout the world. We are the only country with the exception of Japan that made the switch.
    Mr. BURTON. I know, but if it's causing adverse reactions that are so severe that they affect people in the first 72 hours, 50 percent of them, it should be something that is clearly looked into, and if there is any indication it may cause autism, it should be really scrutinized.
    Let me yield to the doctor here, and I will come back for some more questions in a moment.
    Mr. WELDON. Maybe our friends in the back can answer. I thought we withdrew all the DPT, the cellular pertussis in the United States. It is still licensed and it is still sold in the United States; is that correct?
    Mr. EGAN. Yes.
    Mr. WELDON. The FDA has never ordered that to be withdrawn? Why was it not ordered to be withdrawn considering the higher incidence of side effects? They felt that the side effects were not sufficiently life-threatening to warrant it's withdrawal? Is that the rationale?

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    For the record, Mr. Chairman, this pertussis issue is something that I followed through the years, and I thought it was completely off the market. That may be something that we may need to address.
    If I may just go a little bit further. Dr. Kinsbourne, I really enjoyed your testimony. You seem to get at a lot of the problems. Some of the issues that you brought up I've had conversations with other scientists and some of the folks that have already testified. The real bottom line issue is that there would have to be very significant funding to get at these issues, because it would require some very large studies that would have to be extended over many, many years, correct?
    Dr. KINSBOURNE. Yes, sir.
    Mr. WELDON. Unless those studies are done, the questions that you were posing are very difficult for us to answer, correct?
    Dr. KINSBOURNE. Could not be answered until they are done. So the sooner they are started the sooner they will be answered.
    Mr. WELDON. The only other point I would like to make, Mr. Chairman, is that if these studies are done, they may show that the vaccines are much safer than is being alleged by some of the people who have provided testimony. Until they are done, the public discontent that exists among some element in our country is not going to go away, and it would be a mistake for us to just take the face value of some who have testified alluding to the fact that all is well. All may not be well, and the responsibility ultimately is going to fall to political leaders in this country to make sure that the proper research is done.
    I again want to thank you, Mr. Chairman, for holding these hearings.
    Mr. BURTON. Thank you, doctor.
    Mr. WELDON. Did you want to respond to my comments at all?
    Dr. KINSBOURNE. Only to agree wholeheartedly. I think even if the public were to see that the work was being done they would comply more willingly with the mandates.

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    Mr. WELDON. I will share this with you, Dr. Katz. In politics they say perception is reality. If your opponent buys $500,000 worth of TV ads and says that you cheated on your wife even though you have never cheated on your wife, if the end result is that three out of four voters conclude that you cheated on your wife and therefore they should vote against you and you lose your reelection, that is reality. Even if our vaccines are extremely safe, if the perception is growing out there that the vaccines are not safe and people are starting to refuse their vaccinations, then we've got a problem. The way to address this, though, is we need to better fund the agencies that need to do the research.
    Mr. BURTON. I think that is a very good point, doctor.
    Who manufactures the DTP vaccine?
    Dr. KINSBOURNE. Lederle.
    Dr. KENNEDY. Wyeth Lederle Pediatric Vaccines it is now called.
    Mr. BURTON. Is that the only one that manufactures that?
    Dr. KENNEDY. No. There are a couple others that make the whole cell pertussis. I don't know it off the top of my head.
    Dr. KINSBOURNE. Connaught is another company.
    Mr. BURTON. Those are both domestic companies here in the United States?
    Dr. KINSBOURNE. I think Connaught is largely Canadian.
    Dr. KENNEDY. It's Pasteur Merieux Connaught, but they have a manufacturing facility in the United States, in Pennsylvania.
    Mr. BURTON. You may not know this. I may have to check into this in a later hearing or something. Do you know if they give any funds or grants or honorariums to anybody over at NIH or CDC?
    Dr. KATZ. No.

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    Mr. BURTON. They do not?
    Dr. KATZ. No.
    Mr. BURTON. You're sure about that?
    Dr. KATZ. I am sure that people at NIH are not allowed to take funds even from universities. If I invite an NIH investigator to give a lecture at Duke, I can't even pay him an honorarium.
    Mr. BURTON. According to my assistant here, that isn't the case.
    Dr. KATZ. Maybe you could ask Dr. Rabinovich. She works at NIH.
    Mr. BURTON. They can accept honorariums, I believe. Can't you?
    Dr. KATZ. Regina, do you want to respond?
    Mr. BURTON. Aren't you the general counsel?
    Dr. RABINOVICH. No. I'm here from the National Institutes of Health. We do receive ethics training, and I've never accepted an honorarium. There may be other situations in which intramural investigators can. We can provide that information for you.
    Mr. BURTON. I'd like to have that.
    Dr. RABINOVICH. But I do not.
    Mr. BURTON. Thank you. I would like to have that information if I could.
    I just can't for the life of me fathom why that one vaccine is still on the market and being manufactured and sold here and used in the United States. I just don't understand that.
    Can you explain that, Dr. Kennedy?
    Dr. KENNEDY. I can maybe address the situation relative to the issue of combination vaccines and why it may still be there. There were studies done where they were combining the DTaP vaccine with the haemophilus influenza type B glyco-conjugate vaccine, and a number of studies, both in non-human primate models and in children, suggested that by combining and then giving it at a single site that you would interfere with the ability to respond to the haemophilus influenza type B [HIB] component, and the interference appeared to be as a result of the acellular components.

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    They do not know the mechanism. They knew if they took out the acellular component and did a DT/HIB combination, it went fine. If they did the DTaP at one site and then the HIB at the other site, the response was fine. If they did the DTP/HIB, it appeared to be fine from a standpoint of responding to all four of the components.
    That could be one of the potential reasons, because some of the first licensed combination vaccines are DTP/HIB, et cetera. It doesn't make sense, but that's——
    Mr. BURTON. I'm not sure I comprehend if there is that kind of a reaction in 50 percent of the cases in the first 72 hours why it's on the market. I just do not understand that.
    Do you have any reason why that would be the case, why they would keep that on the market and continue to use it?
    Dr. KENNEDY. Yes. If people are not complaining, you can make quite a bit of money. What it comes down to the vaccine manufacturers, it's money if the vaccine has already been produced; its already licensed.
    Mr. BURTON. I know, but the people sitting behind you are not influenced by these pharmaceutical companies. I'm sure of that. So why would they not insist that it be taken off the market?
    Dr. KATZ. This vaccine has been used for 40 years in this country and its record of achievement has been a very successful one. What he is describing as 50 percent is sore arms, sore legs, redness, fever. It's not life-threatening reactions. It is more reactive than the acellular vaccine, which is why most people have switched to the acellular vaccine, but these are not life-threatening reactions that have been shown with the whole cell pertussis to be any more than with any other acellular pertussis.
    Mr. BURTON. These are FDA serious events in 1999. How many are in here, 1,500 or more?

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