Quotes from Doctors & Researchers:
It is often claimed that scientists and doctors are united in their belief in the value of, and necessity for, animal experiments to protect human health. This stream of quotes from scientists and doctors, stretching from as far back as the early 20th Century right up to today, shows that there has been a long tradition of scepticism about this issue. Many of the quotes are from scientists who support or conduct animal research; far from diminishing the impact of their words, this fact ought to give them extra weight.
Note: FDA stands for Food and Drug Administration, the US drug regulatory body.
Cancer | Neurological diseases/ conditions | Teratogenicity and thalidomide | Immunology & AIDS & TGN1412 | Miscellaneous
Immunology & AIDS & TGN1412
2009
If you make a drug that's
effective against HIV, sometimes it works against SIV and sometimes it doesn't.
So that basically devalues SIV as an animal model for doing experiments
involved with developing drugs…The slight problem (with using monkeys as an
animal model for AIDS in humans) is the monkeys don't go on to develop AIDS,
they don't get sick. Dr Paul Bieniasz of the Rockefeller University in New York. Quoted in Scientists make HIV that can infect monkeys, Reuters, 3rd March.
2008
We've learnt a few
important things [from the clinical trial]. We've learnt that one of the animal
models, the SHIV [an artificial virus meant to mimic the human virus but
capable of infecting monkeys] model, really doesn't predict very well at all. At least we now know that you can get a situation where it looks like you
are protecting against SHIV and you're not protecting at all in the human model
– that's important. Anthony
Fauci, director of the US National Institute of Allergy and Infectious
Diseases, quoted in the Independent, 24th April.
The following quotes are
all taken from Catherine Guthrie, Putting
Immunity in a Test Tube, Time, 27th
March.
- In the end, you can only extrapolate so much from a monkey model. Wayne Koff, senior vice president of research
and development at the International AIDS Vaccine Initiative.
- Best yet, researchers can test hundreds of different donors from
a diverse genetic pool, a feat that's impossible to replicate with lab animals
since they are bred to be genetically similar. "The information you get
from this type of test is far and beyond what you'd get out of a mouse study,
both because it's humans and because you can see the effect across a spectrum
of genotypes." Michael Rivard, vice
president of corporate development at VaxDesign.
- As
things stand, it takes months for potential AIDS vaccines to graduate from
small-animal trials to monkey studies. "That takes a lot of time, and,
with HIV, we don't have a lot of time. We asked the question is there a way to
do it faster and take it to humans more quickly?" Wayne Koff, senior vice president of research and development at the
International AIDS Vaccine Initiative.
- Compared
to what's available, MIMIC offers a dramatic increase in scale and speed, says
Koff. "What's more, by collecting immune cells from different donors,
promising vaccine candidates can be tested in diverse populations before they
enter humans."
- From
our point of view, [VaxDesign is] further advanced than anyone in the field in
terms of tissue engineering and vaccine design. If they are successful it will
revolutionize all of vaccinology. Wayne Koff,
senior vice president of research and development at the International AIDS
Vaccine Initiative.
- The
possibilities for medical breakthroughs don't end at vaccines. VaxDesign hopes
to use the MIMIC system to study autoimmune diseases... as well as inflammatory
conditions. The aim is to better understand both how these diseases impact
immune function as well as help design smarter drugs. Says Koff, "the
opportunities are endless."
Many
vaccines that are safe and highly immunogenic in mice have shown very little
immunogenicity in humans and non-human primates. Weatherall, The use of non-human primates in research., Academy of Medical Science.
2007
Progress is further hampered
by the lack of a reliable animal model to road test candidate vaccines. Monkeys
with simian immunodeficiency virus (SIV) are the lab rats of HIV vaccine
research, but important differences between monkeys with SIV and humans with
HIV have misled researchers at least once. The gp120 vaccine worked well in
chimpanzees. When
it comes to testing HIV vaccines, only humans will do. Tonks, British
Medical Journal,
334;1346-1348.
While we find
the Adeno Associated Virus study... very interesting and we'll consider whether
it can inform our future studies, their study was conducted in mice and there
are fundamental differences between mice and humans in their respective immune
responses, particularly with regard to the immune response against HIV. Dr Pat Fast of the International AIDS Vaccine
Initiative. (Fox, Reuters, 11/15). http://aidswarning.blogspot.com/2007/11/several-vaccine-trials-affected-by-halt.html
Mice lie, monkeys sometimes lie, and humans never lie. Some monkeys
have lied to us this time. Peggy Johnston, head
of NIH’s AIDS vaccine program, quoted in: AIDS Research: Did Merck's Failed HIV
Vaccine Cause Harm? Cohen, Science, 318: 1048-1049.
2006
The more we
learn about the immune system, the more we realise that the mouse is not a good
model for humans. This mismatch may be a particular problem with CD28, where
there is little or no cross reactivity between a human antibody and the mouse
immune system. Dr Camilo Colaco, quoted in The
Telegraph, 13th March
2006.
(Some scientists)
question whether cynomolgus monkeys were an appropriate species for preclinical
TGN1412 safety studies and refer to differences in the primary structure of
human and rhesus monkey CD28. However, TeGenero chose cynomolgus monkeys,
rather than rhesus monkeys, because the aminoacid sequences of the
extracellular and intracellular domains of cynomolgus monkey CD28 are 100%
identical to those of the human molecule. The Lancet 2006; 368:1387-1391.
Safety of
drugs in animals can never guarantee the same for humans. Khan & Rodrigues, rapid response to Goodyear, Learning from the TGN1412 trial, British
Medical Journal, 332: 677-678.
Whilst it is
plausible that the development of a humanised monoclonal antibody might not be
recognised in lower animals, no stone should be left unturned in the search for
the cause of the alleged cytokine storm at Northwick Park. Apart from the
species difference between humans and the animals used for testing TGN1412,
there would also have been a huge difference in the background diets between
the humans and the test animals, and hence immune behaviour which should not be
overlooked in the search for answers. Indeed from what we know about the cell
membrane and the lipid domains for the receptors, the binding of these antibodies
to a specific part of the CD28 or indeed to other molecules would be expected
to be influenced by the membrane lipid domain which will be very different in a
human and a rat. Michael Crawford, rapid
response to Goodyear, Learning from
the TGN1412 trial, British Medical Journal, 332:
677-678.
2004
...animal studies, even those conducted in non-human
primates, have limited predictive power for immunogenicity in humans. Bugelski and Treacy, Current Opinions
in Molecular Therapeutics,
6:10-16.
...it was generally accepted that predicting
human immunogenicity, even in non-human primates was rare and thus, the
predictive power of preclinical immunogenicity is low. Bugelski & collaborators from
Centocor, US FDA, GlaxoSmithKline, Amgen & Pfizer. Predictive Power of
Preclinical Data for Human Immunogenicity of Macromolecules: Proceedings of a
Roundtable Discussion. (Discussion sponsored by the Immunotoxicology Technical
Committee Health & Environmental Sciences Institute/ International Life
Sciences Institute)
The discussants also felt that transgenics,
SCID-human reconstituted and knock-out mice should be used with caution.
Concern was expressed that use of a “manipulated system” can yield
“manipulated data” of potentially little relevance to clinical immunogenicity. Bugelski & collaborators from
Centocor, US FDA, GlaxoSmithKline, Amgen & Pfizer. Predictive Power of
Preclinical Data for Human Immunogenicity of Macromolecules: Proceedings of a
Roundtable Discussion. (Discussion sponsored by the Immunotoxicology Technical
Committee Health & Environmental Sciences Institute/ International Life
Sciences Institute)
2002
If you want
your vaccine to work in a human, you’d better get it into a human, quickly.
Otherwise you’re going to spend a lot of time with animal studies and never be
able to predict what it will do in people. Prof.
Bob Edelman, June 2002. http://www.antigenics.com/whitepapers/qs21_adjuvant.html
2001
A few labs
have been plugging away for years to develop cheap, malleable animal models for
AIDS, say, a rat or a mouse, to help speed up research, but HIV stubbornly
refuses to infect animals other than humans and chimpanzees. Recent findings
have brought the goal closer, but some AIDS researchers remain skeptical that
it can be done. Some even argue that the whole effort is an exercise in
futility, because by the time researchers engineer both the animal and the
virus to produce a model, it will no longer bear enough resemblance to the
actual disease. Jon
Cohen, Science, Vol.
293. no. 5532, pp. 1034 – 1036.
More recently, researchers have used much more plentiful
and cheaper rhesus macaque monkeys, originally from India. These monkeys
develop an AIDS-like disease when infected with either SIV, a simian cousin of
HIV, or a laboratory-made SIV/HIV hybrid called SHIV. The monkey model is a big
improvement, but it has serious drawbacks of its own: SIV and SHIV are not HIV,
one animal costs up to $5000, breeding takes years, and now Indian rhesus
macaques are in short supply (Science,
11 February 2000, p. 959). Jon Cohen, Science, Vol. 293. no. 5532, pp. 1034 – 1036.
Some researchers even argue that
the whole effort is an exercise in futility. “They’re wasting their time,” says
Malcolm Martin of NIH’s National Institute of Allergy and Infectious Diseases
(NIAID), who once worked on the mouse model. By the time researchers engineer
both the mouse and the virus to produce a model, he says, “you’re going to wind
up with an animal that’s no longer a mouse or a virus that’s no longer HIV.” Jon Cohen, Science, Vol. 293. no. 5532, pp. 1034 – 1036.
1999
One must be aware of the many limitations of using
laboratory animals to model infectious processes… limited genetic diversity;
one must recognize that observations made in a group of nearly isogeneic hosts
with a single or a few strains of a specific pathogen may not represent the
actual disease process seen in [human patients]. Few animal models are exact
duplicates of human infection.” Handbook of Animal Models of Infection (publ. Academic Press), p9-10.
Up to this very day, all infectious diseases affecting
humans are far from having appropriate animal models and, even in those cases
where such infections are possible, the symptoms observed in animals and the
course of the disease are often very different from those encountered in
humans.” Handbook of
Animal Models of Infection (publ.
Academic Press), p7.
The
pharmacokinetics of antibiotics in experimental animals can often differ
markedly from those of humans. This is a consequence of differences in
absorption, distribution, metabolism and excretion. Handbook of Animal Models of Infection (publ. Academic Press).
1997
What good does it do you to test something [a vaccine] in a
monkey? You find five or six years from now that it works in the monkey, and
then you test it in humans and you realise that humans behave totally
differently from monkeys, so you've wasted five years. Dr. Mark Feinberg, leading AIDS researcher
and now director of pharmaceutical
company Merck's HIV vaccine development, Atlanta
Journal Constitution, 21st September.
1994
The fact that most of the existing animal models in vaccine
potency are artificial, poorly understood, and in fact do not always reflect
vaccine-induced protective immunity in humans is all too often overlooked. Many
of the traditional [animal] tests are highly variable, despite the use of a
reference preparation, and the relevance of these tests may be questionable. Dr. Hendrickson, Lab Animal March, p24-30.
1992
The critical
events in the progression of AIDS occur in human lymphoid tissue... Primary
cultures and cocultures of isolated cells cannot mimic the full cellular
repertoire within lymph tissue, nor their functional relationship to lymphoid
tissue structures. Animal models do not fully mimic the characteristic tissue
pathology of human HIV infection. For this reason, we have developed a tissue
culture method that retains the complex three-dimensional spatial, cellular
organization found in normal human lymphoid tissue. Science, vol. 256, p
1630-1631.
Candidate
antivirals have been screened using in vitro systems and those with acceptable
safety profiles have gone directly into humans with little supporting efficacy
data in any in vivo system. AIDS research and
human retroviruses 8: 349-356.
1987
I think we've already waited too long. The sooner we beging testing on
humans, the sooner we'll hopefully be able to develop a vaccine. Dr. Allan Goldstein, George Washington University
Medical Center, quoted in U.S. Said to Back AIDS Vaccine Test on Humans, the
New York Times, 18th August 1987.
1985
The
immunological system too shows species differences which may have a role in the
immunotoxic or immunostimulant effects of chemicals. Silvio Garattini, Toxic Effects of Chemicals: Difficulties in
extrapolating data from animals to man, Critical Reviews in Toxicology, vol 16, issue 1, p1-29.
1984
Work
on prevention [the vaccine] was long delayed by the erroneous conception of the
nature of the human disease, based on misleading experimental models of the
disease in monkeys. Inventor of the polio
vaccine, Albert Sabin MD. Statement before the subcommittee on Hospitals and
Health Care, Committee on Veterans Affair’s, House of Representatives, April 26, serial no. 98-48. |
