Discussions on the use of non-human primates (NHPs) in biomedical research most commonly center on the philosophical or ethical issues surrounding their use. The second and less explored issue is whether NHP experimentation is necessary for medical science to advance or if it is scientifically accurate. This essay addresses the latter scientific issue only, and argues that for the purpose of explaining or treating human disease.

1. Discrepancies on the cellular level between NHPs and humans make extrapolation of data from NHPs to humans highly suspect.
2. Very small differences between humans and NHPs lead to lethal errors when extrapolating NHP-derived data to humans. We know that non-human primates share up to 99% of their DNA with humans. We have watched Jane Goodall and others on television showing us how similar we are to our non-human primate "cousins." So much similarity must mean that laboratory experiments on chimpanzees, monkeys and other non-human primates provides results reliable enough to be extrapolated to humans, right? Maybe not.

Clearly, NHPs are composed of cells, metabolize medications, have hearts that pump blood and immune systems to resist disease. In that regard, we are all the same. However, if we were identical, extrapolation of experimental results on NHPs to humans would be reliably accurate. We will compare the results of experiments on NHPs with the results in humans.

Compare the track record of safety testing of medications for humans on non-human primates. Primates have been very disappointing with regards to their ability to predict dangerous side effects of medications, especially pertaining to the induction of birth defects. Perhaps the most infamous example is thalidomide, which cause birth defects in some but not many non-human primates. Aspirin produces birth defects in primates, but not babies.

PCP, better known as angel dust, sedates chimpanzees but causes humans to have severe and untoward experiences including paranoia. Nitrobenzene is toxic to humans but not monkeys. Isoproterenol doses were worked out on animals, but proved too high for humans. Peopled died as a result. Even when the researchers knew what to look for, they were unable to reproduce this effect n monkeys. Carbenoxalone caused people to retain water to the point of heart failure. Scientists retrospectively tested it on monkeys, but could not reproduce this effect.

Flosint, an arthritis medication, was tested on monkeys that tolerated the medication well. In humans, however, it caused deaths. Amrinone, a medication used for heart failure was tested on numerous non-human primates and released without trepidation. Humans hemorrhaged, as the drug caused failure in their blood cells responsible for clotting. This side effect occurred in a startling 20% of patients taking the medication on a long-term basis.

Opren killed 61 people. Over 3,500 cases of sever reactions have been documented. Opren was tested on monkeys without problem.

What about infectious diseases? Are we able to draw results about viruses from primates? Chimpanzees harbor Hepatitis B asymptomatically. Humans die from it. The initial polio, rabies and other vaccines were tested safe in primates but killed humans. Even the inventor of the polio vaccine, Dr. Albert Sabin stated under oath that the polio vaccine was long delayed because of misleading results in primates.

AIDS researchers have fared no better. The huge number of differences between the immune system of humans and non-human primates invalidates any experimental results. Dr. Mark Feinberg, a leading AIDS researcher stated: "What good does it do you to test something [a vaccine] in a monkey? You find five or six y ears from now that it works in the monkey, and then you test it in humans and you realized that humans behave totally differently from monkeys, so you've wasted five years." Monkeys do not die of AIDS. Humans do.

The Scientist published an article in 1999 wherein Steven Bende, coordinator of funding for preclinical AIDS vaccine studies at the National Institute of Allergy and Infection Diseases, admitted that HIV replicates differently in chimp cells than in human cells. Thomas Insel, director of the large Yerkes Regional Primate Center, said, "I just don't see much coming out of the chimp work that has convinced us that that is a particularly useful model."

Heart disease is the leading killer of Americans, but non-human primates do not form atherosclerotic plaque like humans. Monkeys, chimpanzees, baboons, and gorillas have all been studied, and none were found to form atherosclerotic plaques like humans.

Our blood typing system bears testament to the fallacy of extrapolating monkey research to man. The Rh factor in human blood was named after rhesus monkeys. Later research in humans showed that the factors were quite different in man and monkey. By that time, the mistake was so ingrained in medical lore they didn't bother to change the name!

Studying the brain has long challenged scientists because of the inaccessibility and because any manipulation usually results in harm. Hence researchers like Daniel Casey have reported the results from NHPs as relevant to humans. Many people have died or been injured as result of extrapolating the results of neurological research on animals. Because it is simply unreliable, using animals as models for humans should be stopped. With the new brain imaging machines there is no excuse whatsoever to use animals.

Electroencephalograms (EEG), magnetoencephalography (MEG), magnetic resonance imaging (MRI), functional MRI (fMRI), magnetic resonance spectroscopy (MRS), Positron emission topography (PET), single photon emission computed tomography (SPECT), event-related optical signals (EROS) and transcranial magnetic stimulation (TMS) allow insights to the brain animal models never could. And most of these are still improving.

Research for causes of disease like those Casey is researching are ideal for these new technologies. Medications can be given to volunteers, as they are already when any new drug goes to phase I clinical trials, in very small amounts, much smaller than now. And, these imaging techniques can visualize where in the brain the drug goes and how it interacts with receptors.

PET scans using radiolabeled ligands allow scientists to see which neurotransmitters are being used when a human performs a certain activity. Neuronal connections between brain areas can now be traced using MRI that tracks the direction of water diffusion.

The combination of these technologies is even more powerful. Functional MRI can isolate the area of the brain involved in an activity, and MEG can then be used to determine which very small areas are activated and in what order. TMS can also be combined with PET and fMRI in order to identify how areas of the brain are related and how they communicate, as well as how brain damaged patients recover. When these technologies are combined with autopsies, we can finally come to understand the human brain.

Researchers reported in February of 2000 the discovery of a genetic mutation that may be associated with an increased risk of suicide. They accomplished this by studying humans. Two drug companies isolated a gene linked to Alzheimer's disease, again by studying humans. The medical textbook, Non-human Primates in Biomedical Research: Biology and Management states: "Despite the enormous number of human diseases caused by single gene defects, a 1986 review of the literature revealed non instances in which research with non-human primates had revealed a well-defined hereditary disease controlled by a single gene."

Receptors and genes differ across species lines. Casey is going to find nothing in monkeys that will be applicable to humans.

Only 1% difference in our DNA - but what a difference 1% can make when seen on a cellular level

Evolutionary biology lies at the heart of our argument that animal models of human disease are scientifically untenable. Speciation is both the reason why it appears that we can use animal models, as well as the reason why in reality we cannot.

Lafollette and Shanks state in Brute Science, "Since phylogenetically related species, say mammals, have all evolved from the same ancestral species, we would expect them to be, in some respects, biologically similar. Nonetheless, evolution also leads us to expect important biological differences between species; after all, the species have adapted to different ecological niches. However, Darwin's theory does not tell us how pervasive or significant those differences will be. This again brings the ontological problem of relevance to the fore. Will the similarities between species be pervasive and deep enough to justify extrapolation from animal test subjects to humans? Or will the biological differences be quantitatively or qualitatively substantial enough to make such extrapolations scientifically dubious?"

Lewis Wolpert summarized this: "Compare one's body to that of a chimpanzee - there are many similarities. Look, for example, at its arms or legs, which have rather different proportion from our own, but are basically the same. If we look at the internal organs there is not much to distinguish a chimpanzee's heart or liver from our own. Even if we examined the cells in these organs, we will again find that they are very similar to ours. Yet we are different, very different from chimpanzees … We possess non cell types that the chimpanzee does not, nor does the chimpanzee have any cell that we do not have. The difference between use and the chimpanzee lies in the spatial organization of the cells."

Lafollette and Shanks go on to say that: "Profound differences between species need not indicated any large quantitative genetic differences between them. Instead, even very small differences, allowed to propagate in developmental time, can have dramatic morphological and physiological consequences."

This is the crux of our argument. Small differences between species vis-à-vis regulatory genes lead to huge differences at the cellular level which is where we focus when treating diseases today.

We judge whether an endeavor is science or pseudoscience based on numerous principles, including predictability. Predictability distinguishes between science and pseudoscience. Weighing the study of NHPs in terms of predictability, we find significant problems. After a condition or side-effect appears in humans, NHPs can usually, though not always, be found that will demonstrate the same concept. But, retrospective confirmation, which is what this is, is not predictive. It is like knowing the outcome of a ball game before betting on it. NHPs occasionally accurately predict human response; so does your horoscope. But, neither is science.

For too long, arguments against NHP experimentation have focussed only on the philosophical and ethical issues of cruelty. By overlooking the scientific credibility issue, this point of view leaves room for the possibility that NHP study may actually provide necessary, consistently predictive results applicable to humans. It suggests that the NHPs are the only losers. It turns out that humans also suffer. They suffer when treatments for disease are based on animal models. They suffer when limited resources are diverted away from the credible search for cures. And, they suffer when dangerous drugs are approved based on NHP research.

Animals and humans share superficial similarities, but today we are studying diseases and life processes at the very level that separates species - the cellular level. Extrapolating results from animal models has harmed humans, and discoveries made via past experiments on animals could have been found without them.

The great advances in science that have given us the high standard of medical care we enjoy today have come from clinical observation, in vitro research, epidemiology, autopsies, serendipity, computer and mathematical modeling, technology, human tissue research, genetics, pathology, post-marketing drug surveillance, the specialization of medical care, e.g. physicians, nurses, and areas of the hospital. Funding experiments on NHPs and other animals has only diverted funds from areas of medical research that have a tried and proven record of success.

So, why does this practice continue? There are many reasons. People always resist change. Imagine researchers who have spent a lifetime studying in one way having to admit they have wasted their time and the taxpayers' money. Many who do this type of research are so isolated in their ivory towers that they are able to afford the privilege to remain ignorant of the uselessness of their work as applied to human patients. Also, it behooves us to follow the money.

The animal experimentation lobby spends millions annually to convince the public that all medical advances are a direct result of animal experimentation. Of course, the facts do not support this outlandish claim. Millions of tax dollars are given to non-human primate researchers every year, supposedly to find a cure for cancer, AIDS, or to make our medications safer. Universities profit; those who manufacture and sell equipment to conduct the experiments profit, and, of course, the researchers themselves earn their livelihood. Many have long believed that the animals were the only losers. It turns out that patients also suffer as limited resources are diverted away from the true search for cures.