Animal studies and HIV research

Editor – Mr Johnson replied:

SJ. Mr. Carey tries to fabricate the truth about clinical trials.
Phase one can use as few as half a dozen people. It is typical of those
who defend vivisection to throw a broad scope over clinical trials, it is
true to say that thousands may be involved but this is overall not in
phase one trials.

I am now being castigated for telling the truth. The point that Mr
Johnson does omits is that drugs have to go through Phase 1, 2 and 3
trials before they are given approval. Therefore drugs have been tested
(with some exceptions) in thousands of people before they are marketed. In
other words, no drug is given approval just on the results of Phase 1
studies.

WC.I could have made the following claims: 1. Only animal studies can
provide and relevant data to help us understand disease in humans and to
develop drugs for humans.
SJ. False: Animal studies can never predict fully what will happen when
drugs are metabolised by humans.

This is true, which is why I did not make that claim.

WC. Only animal studies can provide us with the information we need,
in addition to any other methodologies, to progress from the stage of
synthesizing a new chemical entity to giving that entity to human beings
for the first time with an acceptable risk to their health.
False: Again if this is so then why do clinical trials. This is where the
side effects are picked up not in animals.

Clinical trials are done to give us sufficient information to give
approval for marketing drugs in humans, including metabolism,
pharmacological action and side effects.

WC. Mr Johnson wrote: If we do more clinical trials with a greater
number of people then side effects would be picked up much earlier [WC:]
Typically several thousand people are studied in Phase 1, 2 and 3 studies
before drugs are marketed. Of course more side effects would be picked up
if more people were studies, but how many more? 100,000? A million?
SJ. Mr. Carey goes from the sublime to the ridiculous. I would ask him how
would 100,000 animals prove anything. Teropteren was tested on 18,000 mice
and seemed to work but it failed in the children to whom it was
administered.

It was Mr Johnson who was suggesting that we do more trials with more
people.

I am sorry that Dr Mitchell has suffered ill health. It is not
appropriate of me to comment on that ill health since I do not know the
details of what happened.

Mr Mitchell has no evidence that I blatantly disregard adverse
reactions, and therefore it is ill advised of him to make such
accusations, which does his cause no good. As medical students and
doctors, we are constantly alerted to adverse reactions, and are trained
to act upon them. If you condemn me for that, you are condemning the whole
medical profession.

Surely the irony of Dr Mitchell’s contribution cannot be lost on
anyone. He is angry that he was converted to human from animal insulin. It
was a logical decision to convert to human insulin (how can the AV object
to that?). Any problems that have subsequently arisen need to be
investigated so that they can be prevented.

If animal tested drugs are safe then why are so many withdrawn in the
post-animal testing clinical stages - I have counted six of these being
reported since March.

As I have previously stated, animal studies are not done to prove a
drug is safe and effective for humans. Many are found during Phase 1, 2
and 3 studies not to work well enough or are not sufficiently safe to be
approved or developed further, and are therefore dropped. To test whether
they are suitable for humans, they are tested in humans.

Why are some not accepted by the FDA even though they have passed the
clinical trials?

Generally, if drugs are not accepted by the FDA, they cannot have
passed the clinical trials in that the FDA have identified a problem.
There might be other specific reasons for a particular drug.

And why do we see the FDA and CSM websites continually listing drugs
being withdrawn or having their warnings drastically amended because of
adverse reactions with human patients if the earlier animal testing
accurately predicts the effects on humans?

Please see my previous responses. Animal testing does not accurately
predict the effects on humans. Animal studies are not done to do that. I
have discussed some of the reasons why animal studies are done in my
previous contributions. Although generally drugs are tested on several
thousands of people, some side effects, which can be severe, are
relatively rare, and therefore tens or hundreds of thousands of people
need to be exposed to that drug before they come to light. Other problems
might come to light, eg interactions with other drugs. To allow for this,
drugs are monitored after market approval (pharmacovigilance and Phase 4
studies), and if such problems are detected, that drug is withdrawn, or
has its approval status changed, eg it can only be prescribed on a named
patient basis, or warnings of potential drug interactions are given, etc.

Dr Bross wrote:
In fact in standard statistical practice, error rates are usually set at
less than 5% . What Dr. Carey is trying to justify here is an error rate
of 75% in a context where human lives are at stake. Although this cannot
be done, he brands anyone who disagrees with him as "scientifically and
statistically illiterate".

In the world of drug development, Dr Bross is confusing 2 issues. The
analogy that AV put forward is clearly ludicrous. Let me risk another
analogy. If I design and build an aeroplane, is it valid to say that I
could toss a coin to decide whether it would fly? 50% it will, 50% it
won’t?

For the Undecided, let me explain the 2 issues involved.

If an animal model for epilepsy is right 25% of the time, on average,
if we test 10 drugs that worked in animals, 2.5 will work in humans.
Although not as good as we would like, it does offer a feasible model for
developing an anti-epileptic drug, ie better than having to test a million
to get 2.5 possible ones. In other words, 25% is a measure of the success
rate of a model.

Dr Bross is quite right to say that the statistical error rate is set
at (usually) 5%. In biomedical research, many of the parameters we measure
vary from moment to moment. We therefore have the problem in determining
whether, for example, a drug really did have an effect, or was any change
observed one that might have happened anyway. To get round this problem,
statistics are used to determine whether that change could have occurred
by chance. (see a previous contribution of mine re a point raised by Mr
Nobis). For example, blood pressure can vary quite considerably. Systolic
BP might be 180 before a dose of a drug, then afterwards it might be 170.
However, we cannot say for certain whether the drug caused the decrease,
as by chance it might have gone down anyway. We therefore do the trial in
lots of people, and do a statistical analysis in which the statistical
error is the measure of the likelihood that any decrease was a chance
finding. Set at 5%, this means that there was a 1 in 20 chance that any
decrease occurred was because of a chance finding. This is small, and it
is taken that the drug can be considered to have caused the decrease if
the 5% criterion was achieved. To be even more certain, a smaller error
rate can be selected, eg 1%, but this would mean more people would have to
be tested.

The statistical error rate of a study, and the success rate of a
model are completely separate things, and must not be confused.

Ms Edwards wrote:

According to Dr. Carey AVs are apparently ‘prepared to fool the
unwary in pursuit of their cause’, guilty of ‘repeating erroneous or
irrelevant statements’ and suffer from selective amnesia for failing to
refer to or answer his question re drugs A,B,C&D.

The Undecided will note that Ms Edwards does not answer my question.

Which is why scientific AVs such as Dr. Greek, Dr. Croce, et al have
credibility with AVs not grounded in science, since they have experience
of vivisection and medical issues, have been courageous enough to defy the
status quo, taken the trouble to write books and have no vested or
conflicting interests.

I invite Dr Greek and Dr Croce to answer my questions. If they can, I
concede that I am wrong. If they don’t, will you concede that you are
wrong?

Vaccination is a highly controversial and contentious issue.

There is nothing controversial about whether vaccines, in general,
work, but there is sometimes disagreement when and how they should be
given.

In other countries, simple measures such as swamp drainage and strict
laws pertaining to stagnant water sources ensure malaria is kept in
check.In developing countries vaccination programmes,extremely lucrative
for the pharmaceutical companies,are tantamount to putting the cart before
the horse. With diseases of poverty the focus should be on nutrition,
hygiene and health education.

Every decent person supports the implementation of those other
measures, but they will not completely eliminate all microbiological
disease. We wish to ensure no one dies of measles etc.

Artificially induced disease in animals is never identical to the
naturally arising disorder in patients, man or animal, making animal
research a logically flawed process.

One must be careful in the use of logic. We all know that joke that
runs as follows:

1. People die climbing mountains.
2. More people die in bed than on mountains.
3. Therefore beds are more dangerous than mountains.

The first 2 statements are true, and the logic applied has been
impeccable. However, the conclusion reached is patently absurd. How has
this happened? The answer is that the facts considered have been
selective, and that certain other relevant facts have been ignored, eg
people when seriously ill go to bed, and do not climb mountains etc. The
arguments posited by the AV follow the same pattern, eg:

1. Drugs and vaccines have side effects and do not always work in
humans.
2. Drugs and vaccines are tested in animals.
3. Therefore animal testing does not prove that drugs are safe and
effective in humans.

Again, the first 2 statements are true and there is a logic leading
to statement 3.

1. Thalidomide caused birth defects.
2. Thalidomide was tested in animals.
3. Therefore animal testing is of no value in drug testing.

Again, the first 2 statements are true and there is a logic leading
to statement 3.

Dr Mitchell referred to the web site: http://vivisection-
absurd.org.uk/diabetes.html. In essence, the arguments boil down to this
pattern. Insulin might have been discovered in humans, but to understand
in depth how it works and to develop it into a drug requires animal work.

The Undecided must understand that many of the statements that AV
make are true, but by being selective with their facts, and ignoring other
relevant ones, they come to the wrong conclusions about the value of
animal studies.

Of course, it is a valid to argue that doing animal studies is
barbaric and should be stopped. But the majority of people - lay people,
medical scientists and doctors - agree that it is something that we are
prepared to accept as long as the suffering is minimized, and benefit to
humans is gained which we could not obtain from other methods. The AV
should just state that all animal work should stop, irrespective of the
effect on research, including the severe curtailing of the development of
new drugs and the understanding of disease processes.

Yours faithfully

William D H Carey

WC. The question of how much profit is made by pharmaceutical
companies (just as in any other company) is a political one (in the UK the
profits are regulated by the government). Clearly those companies have to
make profits so they won’t go bust and so that they can pay for pension
schemes (I would be interested to know if Mr Johnson has such a pension.)
But that is for political debate, not a scientific one.

SJ. Animal studies are all about profit not health. I can’t see what
Mr. Carey is getting at about pensions; this definitely is off topic so I
will leave it at that.

WC. Mr Johnson wrote: If we do more clinical trials with a greater
number of people then side effects would be picked up much earlier
Typically several thousand people are studied in Phase 1, 2 and 3 studies
before drugs are marketed. Of course more side effects would be picked up
if more people were studies, but how many more? 100,000? A million? The
costs would be prohibitive. Therefore a compromise has to be reached, and
from experience that is about a few thousand, depending on various
factors. TB is a natural phenomenon. Does Mr Johnson suggest that we do
not treat it?

SJ. Mr. Carey tries to fabricate the truth about clinical trials.
Phase one can use as few as half a dozen people. It is typical of those
who defend vivisection to throw a broad scope over clinical trials, it is
true to say that thousands may be involved but this is overall not in
phase one trials.

WC.I could have made the following claims:
1. Only animal studies can provide and relevant data to help us understand
disease in humans and to develop drugs for humans.

SJ. False: Animal studies can never predict fully what will happen
when drugs are metabolised by humans.

WC. Only animal studies can provide us with the information we need,
in addition to any other methodologies, to progress from the stage of
synthesising a new chemical entity to giving that entity to human beings
for the first time with an acceptable risk to their health.

False: Again if this is so then why do clinical trials. This is where
the side effects are picked up not in animals.

WC. I quoted 97% as a general point. A recent report highlighted the
differences in cancer rates between chimpanzees and humans even though
they have 99% homology. This, of course, would be another reason why we
should study animals; why is there a difference, and does that help us
understand cancer and open up treatment possibilities?

False: Mr. Carey seems to be confused as to whether animals are
physiologically the same as humans, which of course they are not. We
should be studying people not an animal whose similarities only give us
the wrong answers. In any case rodents are the animals favoured in cancer
research and there have been many trumpeted breakthroughs which have never
materialised.

WC. “No. My objection to this metaphor is that it is wholly
misleading and an example of the extent to which AV are prepared to fool
the unwary in pursuit of their cause”.

SJ. A case of the kettle calling the frying pan black I would say.
The pro vivisection brigade has yet to prove that animal studies work. Who
is fooling whom, such an easy statement to make Mr. Carey?

WC. Mr Johnson wrote: If we do more clinical trials with a greater
number of people then side effects would be picked up much earlier
Typically several thousand people are studied in Phase 1, 2 and 3 studies
before drugs are marketed. Of course more side effects would be picked up
if more people were studies, but how many more? 100,000? A million?

SJ. Mr. Carey goes from the sublime to the ridiculous. I would ask
him how would 100,000 animals prove anything. Teropteren was tested on
18,000 mice and seemed to work but it failed in the children to whom it
was administered.

WC. The costs would be prohibitive. Therefore a compromise has to be
reached, and from experience that is about a few thousand, depending on
various factors.
TB is a natural phenomenon. Does Mr Johnson suggest that we do not treat
it?

SJ. That is exactly my point Mr. Carey, it is all about money, now
you have admitted it, money comes before safety.
TB seems to prove that animal studies are irrelevant a recent news item
shows concern for cattle not humans,
Farmers whose cattle have TB. don't seem to be concerned about
transmission to themselves, not a mention of transmission to humans or
thought fatalities amongst humans. It seems as if animal studies again do
not apply to humans but profit seems paramount.

WC. Mr Johnson wrote:
Mr. Carey does a magnificent job of destroying his own argument. His first
statement: "How is it that smallpox, known for at least 3,000 years,
responsible for the deaths of millions of people, with 50m cases annually
in the early 1950s, disappeared in 1979"?
The undecided will notice that Mr Johnson does not answer my question.

I think you will find if you read my posts thoroughly, that I have
answered them. I merely have not answered them the way you wish me to.
He again overlooks the evidence presented here in an earlier posting by
myself, which proves that the smallpox vaccine not only did not eradicate
the disease, but actually caused epidemics. I would ask him to read my
postings more thoroughly. And again he uses the old chestnut that we
(laymen) do not understand the diseases. What is there to understand about
death Mr. Carey? If I see a dead man I don’t have to understand the
disease he died from I just know he is dead, I don’t have to take a degree
to be qualified to understand this.

The plague (one form being bubonic) still exists (smallpox), the
major source of the bacterium responsible being woodland rodents. We do
not yet have an effective vaccine, though work is continuing.

I’m afraid you are not up with research MR. Carey. Recent research
seems to show that rats did not transmit the plague. It concludes that
humans transmitted it after all. He ends this part of his comment with:

What is? your point, Mr Johnson?

My point is as before there is no proof that vaccines eradicated
disease! I can see his point clearly. His statement that "works continues"
is of course to keep the status quo.

What is your point Mr. Carey in repeating the admission that: ANIMAL
STUDIES DO NOT PROVE THAT DRUGS ARE SAFE AND EFFECTIVE IN HUMANS; NOR ARE
THEY DESIGNED TO DO THAT SINCE CLEARLY THEY CANNOT. I can’t see what
you’re getting at, apart from hanging yourself. I would say that’s
straight from the horse’s mouth.
The headline read:

Scientists took male Sprague-Dawley rats and hurt
them by injecting them with a chemical substance
called Freund's Adjuvant.

The United States Department of Agriculture (USDA)
calls the use of Freund's Complete Adjuvant (FCA)
a "painful procedure."

USDA defines "painful procedure" as:

"...any procedure that would reasonably be

expected to cause more than slight or momentary

pain and/or distress in a human being to which

the procedure is being applied."

USDA allows the use of FCA to:

"To insure the most humane treatment of the lab

animals while obtaining necessary scientific data."

Jill Tall, the senior author, and colleagues induced
pain in laboratory rats, and then (incorrectly)
concluded that soy helped to reduce pain.

Robert Cohen called Jill Tall, He found her study to be extremely
flawed, and told her why.
Early on in there conversation, I asked Jill how she could
perform a digestive study on rats, and apply her data to
humans, when rats have completely different enzymes, and
do not even have gall bladders. When I told her
that rats lack this hepatic organ, her response was:

"I did not know that."

Jill compared rats eating soy protein to rats eating
milk protein (casein), and concluded that soy helped
to reduce pain. What she did not consider was that
milk protein helps to induce pain. He explained to her
that casein is extremely allergenic, and that after
humans eat casein they produce histamines, then
mucous. Swelling and pain results. Her response:

"I did not know that."

Jill will one day have her paper published in the
prestigious Journal of Pain.

Had the Marquis de Sade been a scientist, his
publication of choice would have been the
Journal of Pain. Dr. Mengele (of Nazi fame)
and Jeffrey Hahmer most certainly would have
been subscribers.

While Dr. Carey sets out to defend animal research in BMJ, he ends up
unable to provide any valid scientific justification for it.

As I noted in my previous response, "he speaks with the usual
arrogance of a medical specialist whose authority is not to be questioned
by a non-specialist." Here is a good example of his "debating style":

Dr. Careu paraphrases an AV argument as follows: "Animal models can
only predict the results in eg 25% of the time. If we were to toss a coin,
we would be right 50% of the time. Therefore it is better to toss a coin."
He goes on to say:

"It sounds good, and to the scientifically and statistically
illiterate it seems compelling."

In fact in standard statistical practice, error rates are usually set
at less than 5% . What Dr. Carey is trying to justify here is an error
rate of 75% in a context where human lives are at stake. Although this
cannot be done, he brands anyone who disagrees with him as "scientifically
and statistically illiterate".

As a professional biostatistician with experience in public health
research for more than half century, I am not impressed with this kind of
"debate". Carey's confused arguments and false analogies suggest to me
that he is a statistically illiterate doctor who it trying sound like an
biostatistician. Apparently, when Dr. Carey thinks he is dealing with a
"non-specialist", he simply fakes it.

I do not regard such tactics as acceptable in a scientific debate in
a medical journal. Indeed, if his claims were made in a peer-reviewed
publication, he could be in some trouble. As I said previously: "Carey
does not seem to realize that he is in an extreme conflict of interest
situation here,this issue directly affects his own livelihood. Courts
discount testimony given in conflict of interest situations and the public
should do this too."

Carey's response is: "I am sorry Dr Bross thinks I am so stupid not
to understand that first statement. I should point out that on my first
posting I stated: Competing interests: I work in a CRO doing Phase 1 and 2
studies." He adds this PS: "My livelihood does not depend on animal
studies in that if and when animal studies are no longer required, I would
still have a job." Yet his current livelihood depends on animal studies
whether or not his future livelihood will.
This peculiar denial suggests that he is unclear on the whole concept of
conflict-of-interest.

Irwin D. Bross, Ph.D. President Biomedical Metatechnology Inc.
109 Maynard Drive Amherst NY 14226 USA (716) 832-4200

Editor – Let us review where we are in the current debate.

Before accusing me of making false claims, I suggest that Mr Bogle
makes the effort to understand what I said. This will help improve his
credibility in the eyes of the undecided. In case I did not explain
clearly enough, I will do so again. As in the examples he has quoted, PET
scanning can answer many useful and interesting questions about brain
physiology and pharmacology. I did not state otherwise. Mr Bogle needs to
understand what a PET scanner etc can and cannot do. A PET scanner etc
cannot measure blood pressure, which is what a sphygmomanometer does. A
sphygmomanometer tells us nothing about brain physiology and pharmacology.
We use different technologies for answering different questions.

I could have made the following claims:

1. Only animal studies can provide and relevant data to help us
understand disease in humans and to develop drugs for humans.

2. Only animal studies can provide us with the information we need, in
addition to any other methodologies, to progress from the stage of
synthesizing a new chemical entity to giving that entity to human beings
for the first time with an acceptable risk to their health.

I did not claim that PET scans etc cannot help us develop medicines.
Had I made claim 1 above, Mr Bogle would have a valid point. The claim I
made was the second one, which does not exclude those other methods. We
use such techniques as PET scans in the studies we conduct. Once the
safety of the new chemical has been assessed, it THEN can be given to
humans and the PET scans etc performed. If a drug reduces the blood
pressure dramatically, we will kill the person long before we can get them
into a PET scanner.

I quoted 97% as a general point. A recent report highlighted the
differences in cancer rates between chimpanzees and humans even though
they have 99% homology. This, of course, would be another reason why we
should study animals; why is there a difference, and does that help us
understand cancer and open up treatment possibilities?

Ms Robinson wrote:
Dosage can be critical, but drugs are administered in standardized doses.

Many drugs are given at different dosages depending on the patient. A
few drugs are given under tightly controlled conditions such as according
to the patient’s weight if accurate dosing is required.

It is unfortunate that drug development over all is motivated as much
by prospective profit as by a desire to help those who suffer.

The question of how much profit is made by pharmaceutical companies
(just as in any other company) is a political one (in the UK the profits
are regulated by the government). Clearly those companies have to make
profits so they won’t go bust and so that they can pay for pension schemes
(I would be interested to know if Mr Johnson has such a pension.) But
that is for political debate, not a scientific one.

For these and other reasons this group labels many new drugs: "Do Not
Use until Five Years After Release."

This advice, in one sense, is sound. The problems are:
1. If everyone followed this advice no new drugs would be taken after
registration and so no new ones would be developed.
2. It might be a new drug is a very good one for that patient, even to the
point of saving his or her life.

To allow for those factors, patients can discuss the treatment
options with their doctors, and then make the decision on what to take
based on their view of risk etc.

The perhaps over-used "tossing a coin" metaphor Dr. Carey objected to
is derived from the fact that animal responses as a whole correlate with
those of humans less than 50% of the time.

No. My objection to this metaphor is that it is wholly misleading and
an example of the extent to which AV are prepared to fool the unwary in
pursuit of their cause. Most probably to majority of AV do not understand
the fallacy of the analogy. But there are those who do, and urge their
acolytes to repeat this argument, which typically goes something like
this:

‘Animal models can only predict the results in eg 25% of the time. If
we were to toss a coin, we would be right 50% of the time. Therefore it is
better to toss a coin.”

It sounds good, and to the scientifically and statistically
illiterate it seems compelling, which is why such an argument is presented
on many street stands. But suppose I were to change the analogy, and
instead of using a coin, were to throw a die. Then it would be right 1 in
6 times, or roughly 17% of the time. So, which is it? A coin or die? The
answer, is of course, neither. The true analogy would be a theoretical die
with, say, a million ‘sides’. The chances of getting the right throw would
be 1 in a million, or 0.0001%. A model, therefore, which is right 25% of
the time, or 5%, or even 1% would be better as they are all greater than
0.0001%. 1% is not brilliant, but it is 10,000 times better than 0.0001%.

Mr Johnson wrote:
If we do more clinical trials with a greater number of people then side
effects would be picked up much earlier

Typically several thousand people are studied in Phase 1, 2 and 3
studies before drugs are marketed. Of course more side effects would be
picked up if more people were studies, but how many more? 100,000? A
million? The costs would be prohibitive. Therefore a compromise has to be
reached, and from experience that is about a few thousand, depending on
various factors.

TB is a natural phenomenon. Does Mr Johnson suggest that we do not
treat it?

Dr Bross wrote:
William DH Carey identifies himself as a Clinical Pharmacologist and
enters the animal research argument with the usual arrogance of a medical
specialist whose authority is not to be questioned by a non-specialist.

I have never suggested that non-specialists should not enter the
debate and question what we do. What I do ask of them is to try and
understand what we do and why we do it. If that were my opinion, I would
not bother to enter this discussion. Let me make another analogy –
Titanic. After it sunk, many criticized the designers for not having
enough lifeboats. It is an obvious point and any layperson could, and did,
make it. However, one could not expect a non-engineer to give a detailed
analysis on how to build a boat that won’t sink. I would not presume to
tell a ship designer how to build a ship. I am not arrogant enough to do
so.

But where should one go to get the training that would enable one to
"understand fully the issues involved"? Must one be a Clinical
Pharmacologist doing animal testing to get this training? This happens to
be a very narrow specialty; it cannot encompass the very wide range of
expertise needed to "fully understand these issues". The relevant
specialties span the range from those at the molecular level (e.g.,
biochemistry and genetics) to those that study diseases in large human
populations (.e.g, epidemiology and biostatistics)–with a large number of
specialties in between! Carey might not like admit it, but there simply is
no specialist who FULLY understands these issues. To pretend otherwise, is
really scientific fraud.
Consider Carey’s own example:
"Ms Robinson wrote: the late German surgeon Werner Hartinger declared:
"There is no sound basis for animal testing...It has no scientific basis
because the results of vivisection have no value whatsoever until they are
reproduced in man. The metabolic breakdown is completely different between
man and other species. Man is the only effective yardstick."

Of course no-one understands fully all those issues, but that does
not mean that none of us can give an opinion, or we, as a human race,
would never do anything. No doctor understands all of medicine – does that
mean no doctors should practise? What it does mean is that someone who has
trained as a doctor and in drug development has a better understanding of
the issues involved, and is in a better position to help those not in the
relevant fields to understand the issues. When you get on an aeroplane, do
you go to the pilot and say that your knowledge of piloting a jumbo jet is
as valid as mine, so I’m going to fly the plane? Is a lawyer’s opinion on
how to treat a heart attack as valid as a doctor’s? I do not tell
surgeons how to operate as I am not a surgeon. That would be arrogance.
And in any case, his statement that ‘The metabolic breakdown is completely
different between man and other species’ is not true, if he did make that
statement, and if what he meant was that the metabolic breakdown is always
completely different. Drug development is my field, what is your point, Dr
Bross? Furthermore, many surgical techniques have been developed using
animals.

If Dr Bross seriously thinks that lawyers are the driving force
behind animal testing, then he should be criticizing lawyers, and not
doctors, scientists and the pharmaceutical industry.

The crux of Carey’s argument is this: "I repeat the point I made in a
previous posting: animal studies are needed to provide enough valid data
to allow doctors to give cautiously new chemicals to humans. This animal
studies do, which is why it is done with excellent safety records." The
trouble with this argument is that the safety record for drug testing is
not "excellent", massive factual evidence suggests that a more accurate
description would be "a system in failure". These facts clearly show that
neither animal testing nor clinical trials nor the combination of the two
have produced "excellent safety records".

I spoke of excellent safety results in context of Phase 1 studies, ie
those in which a new chemical is given to humans for the first time. The
results are excellent as the number of serious problems is amazingly small
given how many are done globally each year.

Even for marketed drugs, the picture OVERALL is good, given how many
millions of tablets people take every day. It is important to the
undecided to understand the nature of side effects. They can be classified
broadly as follows:

1. Most are mild and self-limiting, eg headaches, nausea etc which
resolve after taking stopping the drug.

2. Severe and/or fatal. Those can be ones which are unpredictable and no
methods at present will pick them up 100%, eg anaphylaxis. Fortunately
they are rare, but methods are being developed to try and predict them.
Because they are rare, they will only become apparent after huge numbers
of people are studied.

3. Predictable ones. They can be predicted from eg their pharmacology
and can be allowed for by appropriate use of the drug.

4. Drugs which are known to have severe side effects. Those are drugs
which are used in desperate situations, eg cancer, where there are no good
alternatives. Patients are warned about those side effects, and they can
choose whether or not to take the drug.

5. Other side effect problems arise because of interfering factors such as
concomitant disease and other drugs. This is a problem, which is one
reason why pharmacovigilance is undertaken; but to do trials to allow for
every eventuality is not feasible.

6. Sometimes drugs are incorrectly taken by patients.

7. Side effects resulting from deliberate overdoses of drugs.

8. Side effects arising from prescribing errors.

9. Errors in drug development.

Of course, we come to the problem of language, and in a discussion we
have to operate on the basis of a shared and tacitly agreed use of
language. The phrase ‘excellent safety records’ does not mean 100% safety,
and I did not intend it to mean that, since as I am a doctor I know that
side effects are a problem. Commercial flying has an excellent safety
record. That does not mean that planes never crash, and that people never
die as a result of flying in a commercial flight. What it does mean is
that people are willing to fly on such flights acknowledging that planes
do crash, but knowing that the risk is very small, and that the airline
industry does its best to ensure the best safety possible.

Carey does not seem to realize that he is in an extreme conflict of
interest situation here–this issue directly effects his own livelihood.
Courts discount testimony given in conflict of interest situations–and the
public should do this too.

I am sorry Dr Bross thinks I am so stupid not to understand that
first statement. I should point out that on my first posting I stated:
Competing interests: I work in a CRO doing Phase 1 and 2 studies.

I do not understand his second point: is he suggesting that people
involved in drug development should not be allowed to defend what they do?
Would that be natural justice?

Mr Johnson wrote:

Mr. Carey does a magnificent job of destroying his own argument. His
first statement: "How is it that smallpox, known for at least 3,000 years,
responsible for the deaths of millions of people, with 50m cases annually
in the early 1950s, disappeared in 1979"?

The undecided will notice that Mr Johnson does not answer my
question.

How is it that Bubonic Plague and leprosy declined Mr. Carey?

As in any human endeavour, the path to success is filled with
problems and set backs. The development of vaccines is no exception. This
is the point that Mr Johnson illustrates. It does not prove that vaccines
do not work, which I think is the one he wishes to make. (Modern
epidemiologists know that vaccinations cannot prevent the spread of any
disease whatever [Which epidemiologists?]) This is interesting. No doctor
would deny that vaccines, like any other treatments, have problems. Like
everything in life, it is a risk-benefit balance. Because smallpox is no
longer in the community, we no longer routinely give it.

The plague (one form being bubonic) still exists (cf smallpox), the
major source of the bacterium responsible being woodland rodents. Such
chemicals as aldrin are used for prevention, antibiotics for treatment,
and there is a partially effective vaccine. (yes, I acknowledge not all
vaccines are 100% effective.) Thus medical science has helped control this
disease. Millions of people still have leprosy – hardly a significant
decline. Treatment involves the use of drugs. We do not yet have an
effective vaccine, though work is continuing.

What is your point, Mr Johnson? If you are trying to analogize
between smallpox, and bubonic plague and leprosy to prove that the
smallpox vaccine does and did not work, then you simply do not understand
the diseases you mention. We have a vaccine against smallpox, and it is no
longer in the community. We do not have good vaccines against the plague,
leprosy, malaria etc and they still exist, kill and maim.

I wonder if he can explain the fact that the World Health
Organisation study in India which involved over 260,000 people, came to
the embarrassing conclusion that the BCG vaccine was ineffective against
TB in that country.

As vaccines have been developed and used, we have, like any other
treatment, learnt more about their uses and limitations. When vaccines
first came out, people did naively and over optimistically think that they
would provide and simple, magical prevention of disease. But we learn. We
now realize that for vaccines to be fully effective they need to fulfill
certain requirements. For example:

1. Appropriate to the variation of bug involved, eg influenza.

2. That patients should have sufficiently good nutritional status so that
they can amount a sufficiently good immune response.

3. The drug should be correctly stored, distributed and administered.

4. Etc.

From such experiences as the use of the BCG vaccine in India, it was
realized that for a vaccine to be fully effective it was necessary for
patients to be sufficiently well nourished which was (one reason) why the
vaccine did not work. It did not prove that vaccines do not work, which is
what AV try and purport it does. This is one of common arguments that AV
use to fool people (whether individual AV realizes that or not), ie a
vaccine does not work in a particular example (eg because of poor
nutritional status), therefore no vaccines work, therefore animal studies
are misleading.

Carey wrote: “And in any case, smallpox killed the rich as well”

In this statement I was referring to those people in the past who
succumbed to the disease, eg Queen Mary II of England, Emperor Joseph I of
Austria and George Washington etc

Again Mr. Carey is splitting hairs…and missing the point, the whole
tenant of my argument is that animal tests do not ensure safety

I agree; please read again what I have written.

In making this statement, Mr Johnson has demonstrated that he does
not understand the arguments. I repeat again what I said: ANIMAL STUDIES
DO NOT PROVE THAT DRUGS ARE SAFE AND EFFECTIVE IN HUMANS; NOR ARE THEY
DESIGNED TO DO THAT SINCE CLEARLY THEY CANNOT.

Repeating erroneous or irrelevant statements does not constitute
debate.

No matter how many times I state that printing and distributing more
money will cure world poverty, it will never be true, as any economist
will tell you.

In my previous postings I asked the following:

1. A question relating to 4 drugs A, B, C and D.
2. Details of what studies should be done to replace animal studies to
acquire the information we need to test a new chemical before giving it
humans for the first time.

No-one so far as even referred to those questions, let alone answer
them. I do not expect Nobis, Johnson etc to answer number 2 as that would
require a detailed technical analysis. Perhaps they were hoping Dr Greek
would answer it. I do not expect him to as I know he cannot.

Question 1 is a simple one to understand. But the undecided will
observe that none was prepared to answer it. I will let the undecided
ponder why this is.

Above I noted that it was interesting that Mr Johnson thinks that
vaccines do not work. This is a point that many AV make, since it would,
if true, provide evidence that animal testing does not work. The undecided
will recall that this current debate began with the letter from Drs Greek
and Pound in which they were calling for the development of a vaccine for
HIV (and drugs, by non-animal methods). What is also interesting is that
both Pound and Greek are worried, as we all are, of the potential scale of
the horror that HIV could wreak on humanity. Perhaps now they can begin to
understand the fear that previous generations had for smallpox, something
we do not have to face. Unless some bioterrorists inflict it on us all.
But fortunately we do have a vaccine – I advise Mr Johnson and his family
to take it were that eventuality to arise.

I do not have the time to answer every point raised, but I hope I
have answered enough to help the undecided understand the issues involved,
and why animal studies are still needed. The thrust of my discussions have
been centred around drug development. Similar arguments apply to
experimentation designed to answer questions of animal (including man)
physiology etc.

I add one more question to the above 2: Could the AV come to a
consensus – do or don’t vaccines work?

Yours faithfully

William D H Carey

Conflict of interest: I work in a Phase 1 and 2 CRO.

PS My livelihood does not depend on animal studies in that if and when
animal studies are no longer required, I would still have a job.