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Animals in Scientific Research

Medical Research

Medical research is what most people think of when they hear the phrase animal experimentation or animal research. Animals used in medical research are used to model human disease, and in what is called translational research.

Everyone wants to see cures for diseases like Alzheimer’s, Parkinson’s, cancer, stroke, heart attack, AIDS, and so forth. Many people envision these cures happening by using animals to model human disease. Is that such a bad idea?

In the old days, animals were used to prove very basic things about the mammalian body: arteries carry blood away from the heart and veins carry it back; the immune system is involved in fighting infection and so forth. So, for a hundred or so years using animals to model human beings appeared promising.

But today we are studying human disease and human physiology on a much more fine-grained level. For example, today we know that even members of the same species react differently to the same drug and disease. (For more on why genetics is so important in biomedical research, view the Medical Research.pdf at the bottom of this section).

Is there objective empirical evidence that the use of animals as models for humans in biomedical research is hopelessly flawed and has often worked to the detriment, of human health?

Consider the following:

The National Cancer Institute (NCI) tested 12 anti-cancer drugs (on mice) that are currently being used successfully in humans. The scientists studied mice that were growing 48 different kinds of human cancers and treated them with the 12 drugs. They found that 30/48 times, the drugs were ineffective in the mice. In other words, 63 percent of the time, the mouse models with human tumors inaccurately predicted human response. 

In a study that spanned over ten years and has not yet been repeated, the Food and Drug Administration (FDA) began in 1976 to follow all the new medications it released for side effects. In that study, the FDA found that out of 198 new medications, 102 (52 percent) were either recalled or relabeled secondary to side effects not predicted in animal tests. 

A similar study examined six drugs, the side effects of which were already known in humans. The study found that animals correctly predicted 22 side effects, but incorrectly identified 48 side effects that did not occur in humans, while missing 20 side effects that did occur in humans. This means that the animal models were incorrect 68/90 times, or 76 percent of the time. 

In August 2001, Mark Levin, Ph.D. and CEO of Millenium Pharmaceuticals, presented data at the Drug Discovery Technology Conference in Boston, MA regarding the inadequacy of current animal models in drug testing.

In the study he presented, 28 potential new drugs were tested in rats for liver toxicity. Eleven of these drugs were shown to be toxic, while 17 were shown to be safe. Twenty-two of the 28 potential drugs advanced into human clinical trials, and the results revealed that of the 11 drugs that had been shown to be toxic in rats only two were toxic in humans, while six were safe. Of the 17 drugs that were safe in rats, eight were found to be safe in humans, while six were found to be toxic to humans.

Levin concluded that this basically means the animals were about as accurate as "a coin toss." 

In the Handbook of Laboratory Animal Science Volume II: Animal Models, the authors state:

The case of the huge 25-year screening program, undertaken by the prestigious U.S. National Cancer Institute, illustrates the kind of dilemma possible: in this program, 40,000 plant species were tested for anti-tumor activity. Several of the plants proved effective and safe enough in the chosen animal model to justify clinical trials in humans. In the end, none of these drugs was found useful for therapy because of too high toxicity or ineffectivity in humans. This means that despite 25 years of intensive research and positive results in animal models, not a single antitumor drug emerged from this work. As a consequence, the NCI now uses human cancer cell lines for the screening of cytotoxins.

Of 20 compounds known not to cause cancer in humans, 19 did cause cancer in animals  while of 19 compounds known to cause oral cancer in humans, only seven caused cancer in mice and rats using standard NCI protocol. 

Further, of 22 drugs tested on animals and shown to be therapeutic in spinal cord injury, none were effective in humans.

Although aptiganel (a n-methyl-D-aspartate (NMDA) receptor blocker, manufactured under the brand name Cerestat), was effective at providing brain protection against stroke in animal models, large clinical studies revealed no positive effects and possibly some harm when it was given to humans. 

More patients who received the drug died than those who did not, and more side effects were observed in the group receiving aptiganel than in the control group. No benefits were seen in patients treated with aptiganel. In contrast to humans, rats given aptiganel showed a decrease in brain damage by up to 70 percent. According to the Associated Press,

Yet another experimental stroke drug that showed great promise in animals has failed in humans, with the study cut short because patients were dying or showing no improvement.

The animal model-based medical decision to give women past their reproductive years hormone replacement therapy (HRT) did not work out as the animal models had predicted.  As we all know by now, women receiving HRT suffered more strokes and heart attacks than their counterparts who were not taking HRT.

Medical care costs continue to rise. Spending money on drugs that don’t work, and that even are potentially dangerous, just because they looked promising in animals is a waste of resources and a danger to human patients. This report was in USNews:

Marcia Stefanick knows she will not get through this October day without hearing about monkeys. The Stanford University medical professor is addressing a major meeting of researchers and physicians at the National Institutes of Health, detailing the recent results of what everyone calls simply "The Study." The Study is part of the massive Women's Health Initiative, and the findings are not good news. The hoped-for health benefits of hormone replacement therapy, known universally as HRT, are not turning up. "It's clear now that there is no cardiovascular benefit," she tells her audience.

A physician approaches the microphone. He has a bone to pick: "In the monkey trials," he says, "hormones reduce heart risk and atherosclerosis if the monkeys are started on hormones early enough. Don't you think you would have found long-term benefits if the women in the trial had been younger and started hormones earlier? Are you aware of the monkey data?"

Stefanick, who has worked on most of the recent hormone trials, is struggling to conceal her annoyance. "Yes, I'm familiar with the monkey data," she says evenly. She once again goes over her newest analysis of the WHI results, showing that younger women had more risks and fewer benefits than the average women in The Study. "We've got to get our arms around this: HRT does not provide cardiovascular protection. We were wrong. We were just wrong."

The journal Science had this to say about HRT and data obtained from animals:

The study was supposed to prove what people thought they already knew: Hormones taken by millions of postmenopausal women protect against heart disease. Instead, in July 2002 the Women’s Health Initiative (WHI) abruptly ended its flagship experiment of 16,600 participants, half of whom were taking a popular estrogen and progestin combination pill and half a placebo. Those on hormones were slightly more likely to be felled by a heart attack than those on dummy pills. The headlines sent a quake through doctors’ offices. An aftershock is now spreading through research labs devoted to the study of estrogen and the heart. Decades of research and hundreds of scientific papers had consistently shown that estrogen was the heart’s guardian. Mice, rabbits, pigs, and monkeys displayed reduced signs of vascular damage after receiving the hormone, and genetically susceptible animals given estrogen never got heart disease. The hormone’s effects on the brain and cognition appeared no less remarkable. These, too, were upended by a related WHI study… This new disconnect between patient and researcher interests has scientists jittery—nearly as jittery, in fact, as they are over the apparent contradictions between basic research and clinical data. … Prempro, however, contains not estradiol but different estrogens from horses. (Some studies on monkeys and rabbits have found protection from heart disease with equine estrogens.) Hormone experts can’t agree on whether the different compounds have different cardiac effects. There’s much debate, too, about the role of progestin, the hormone added to avert the risk of uterine cancer. Until about 5 years ago, it was rarely studied in combination with estrogen in animals. Some work hints that progestin may blunt estrogen’s positive effect on vascular cells, which could render the combination useless. But studies in monkeys suggest that “it doesn’t seem to be a large issue,” says Thomas Clarkson of Wake Forest. Modeling heart disease in animals is an imperfect science. To mimic early-stage disease, scientists can injure a major artery. They sometimes feed monkeys extremely high-fat diets. Or they rely on genetically altered mice deficient in the enzyme ApoE. These animals develop a form of atherosclerosis, but it’s unclear how closely their disease hews to the human version. Oddly enough, even mice with serious disease rarely die of it. “Most of these animals don’t drop dead of heart attacks,” says Banka. So researchers rely on other measures, such as improvements in arterial lesions or carotid thickness, to assess estrogen’s benefits. Still, lesions aren’t a surefire way to predict death from atherosclerosis in humans, who normally succumb when an arterial plaque ruptures. “These are highly artificial systems,” says Jan-Åke Gustafsson, a molecular endocrinologist at the Karolinska Institute in Stockholm, Sweden.

Researchers struggling to develop an animal model for prostate cancer admit the limitations of the paradigm. Tom Rosol, DVM, a veterinarian at the Ohio State University’s Comprehensive Cancer Center, who has spent almost 20 years studying the molecular intricacies of cancer metastasis, has stated, “…every time we put human prostate cancer cells in animals, they stop acting like they do in humans.”

As we discussed earlier, science is largely about predictability and as we learned from the above, animals are not predictive for human response. (For more on predictability in drug response see Drug Testing and Development.)

Studying one species in order to understand the drug or disease response of a different species is an archaic and scientifically invalid idea. What biomedical research has advanced towards and what society should be funding is personalized medicine: treatment tailor-made for your genetic makeup; not the one-size-fits-all approach that has historically been used.

For example, if you and your twin sister are diagnosed with the same type of breast cancer on the same day, because of your unique genetic profile, you each may receive a very different chemotherapy regime.

Even though you and your sister have far more genes in common than you and a genetically modified mouse or even a chimpanzee, she may have a gene that would cause a severe adverse reaction to one of the medications you will receive, hence another will be substituted.

Or, you may receive a larger and more frequent dose of the same medication as she receives, because you are a rapid metabolizer of that drug. Or, you may both receive very different treatment regimes because, even though the cancer is of the same type, you have genes that will allow it to progress more rapidly than your sister’s and hence you need more aggressive therapy.

This is not science fiction. These advances are taking place even as you read this, and many are already in clinical use. If we are to expand what is currently being done, more human-based research must be done rather than research with entirely different species.

More on Personalized Medicine

Subsections of Medical Research

Further in depth analysis of Medical Research is below.  You must have Adobe Acrobat Reader to view this file.

Medical Research