Clioquinol

"One of my animals is sick. I think it's having respiratory problems," a researcher told John McArdle, hoping that he might know what to do. McArdle rushed over to the test subject, a common house cat, only to find that the kitty was not sick but purring. The researcher was unaware that cats do that.

Scientists historically have depended on animals to help them understand and explain the human condition. Around one-half of all grants awarded by the National Institutes of Health (NIH) fund animal experiments. That means each year several billion dollars are allocated for what some scientists call a dangerous waste of time. But not everyone puts it this way.

In the years since that evening when two men raced across campus to save a purring kitten, McArdle has continued to see cases that demonstrate the gap between what experimental science is and what it should be. As director of the Alternatives Research and Development Foundation, he supports in-vitro biomedical research, or research that takes place in an artificial environment instead of in a living body. "The cat was an extreme case, but represents a problem," McArdle tells INSIGHT. He claims experiments regularly are conducted by unqualified personnel. "Many biomedical researchers never took evolution, ecology or comparative anatomy," he says. These classes, often electives at the graduate and undergraduate levels, are deemed unnecessary by some universities. "You produce a highly trained technician rather than a broadly trained biologist who can ask the right questions," McArdle says.

The right question may be: Can experiments on animals be relied upon to teach us about ourselves?

A legal drug doesn't exist--and hardly an illicit one--that hasn't been tested on animals. Does this make people any safer? Clioquinol, an antidiuretic, caused blindness and paralysis. Thalidomide, marketed for insomnia and morning sickness, caused severe birth defects. These drugs had been tested on animals.

Adrian R. Morrison, a researcher who has written on this subject for Scientific American, stands by the in-vivo methods, which take place in the living bodies of animals.

"Why don't they go on to say that twice the numbers of humans are tested on a drug as animals? Only after it is marketed to millions do we see the side effects of a drug," Morrison says. He admits one may miss something in the process. "But who will stand in front of the first mouse?" he asks, adding that thalidomide was not tested on pregnant animals until too late.

"The proper study of mankind is man," McArdle maintains. "Scientists are engaged in a phylogenetic fallacy--the belief that we [animals and humans] are so similar that we can make comparisons."

Is in-vivo research obsolete? When science first made experimental comparisons between man and beast it was at a functional level, but today's questions are more complicated.

If we are asking questions about our genetic makeup, how can we get answers from another species whose genes are the very thing that make them different? Do special disparities become more serious at a macro level? These are questions posed by modern animal-rights groups.

"People are afraid to die. We have an emotional need to believe in animal experimentation," says Ray Greek, director of Americans for Medical Advancement. His book, Specious Science, was published in May. "Animals may be 99.9 percent similar to humans, but it is not good enough. At the cellular level, .1 percent is a big deal." He claims using animal models is not only a waste of time but inherently harmful. "For 10 years, in-vivo methods misled AIDS researchers. No result obtained from primate studies can be seriously considered valid in humans as long as the observation has not been made in man also."

McArdle doesn't push the argument this far. He is, after all, still on speaking terms with such organizations as the American Association for the Advancement of Science. "What works depends on whether it is for testing, education or basic research," McArdle says. "It is not so simple to say in vivo is better."

Greek and McArdle do agree that animal models aren't perfect: Of 11,000 anticancer chemicals developed in mice, none help humans. While 5 milligrams of botulinum kills man, 10 grams has no effect on dogs or cats. Rodents live three years while humans average 72. The differences can be both unknown and very great, researchers say. Some animal tests indeed have led to erroneous conclusions: that smoking is noncarcinogenic and that benzene is safe, for instance. Animal activists say animal research delayed pacemakers and transplants and note that scientists have yet to infect another species with the human AIDS virus.

The basic claim of these critics is that animal research is bad science; that animals don't accurately represent humans, that naturally occurring diseases cannot be artificially induced and that one cannot safely assume a correlation between animal reaction to a drug and that of humans. They worry that where animal tests are the basis for approval, bad drugs may be approved and good drugs discounted. But how serious are these widely publicized concerns?

A 1990 Government Accounting Office report often is cited: the Drug Review and Approval Times of the Food and Drug Administration (FDA). Animal-rights groups point out that, between 1976 and 1985, 52 percent of animal-tested drugs had harmful or deadly side effects in humans. But not mentioned is that the report demonstrated a correlation between the amount of time the FDA took to review a new drug and that drug's safety.

There are other mistakes. While it is true that no animal ever has had HIV, primates and felines have contracted their own forms of the virus. Studies conducted on primates, animal researchers say, didn't slow down transplants--they provided the background for such procedures.

Some tests no longer need animals. A few years ago mice were used as though they were living factories to produce monoclonals (antibodies). McArdle and his organization helped spearhead in-vitro production. Today it is illegal to use animals for this unless one can prove there is no alternative. Europe goes a step further: one must show there isn't an alternative to any animal experiment, or else use an in-vitro method. The United States has been behind the curve on using alternatives.

While 40 percent of NIH grants go to in-vitro methods, an overwhelming majority of applications are for in-vivo studies. There are several explanations for this. Greek accuses scientists, universities, lab companies and the funding community of collusion. "Manufacturers of drugs and food products have a legal obligation to protect their consumers. They just want an easy stamp of approval to say `Look, we did our part,'" he says.

According to McArdle, "These practices have more to do with tradition than anything. The scientists want us to believe what they are doing works, but this use of animals is not deception." He cites the In Defense of Animals (IDA) reallocation plan as an example of habit. IDA submitted a plan to universities and the NIH to encourage a shift from in vivo to in vitro. "People are afraid of losing their jobs. They need to be retrained to use in-vitro methods," says an IDA spokesman. He says alternative methods include:

* epidemiology (control of disease in a population);

* autopsy & biopsy;

* physical models;

* genetic research;

* clinical research;

* post-marketing drug surveillance; and

* mathematical and computer modeling.

How much retraining would benefit American scientists is unclear considering that many of these alternatives already are quite commonly used. It is certain though that there is resistance. The Animals (Scientific Procedures) Act of 1986 requires scientists to weigh the potential animal suffering against potential benefits of research. But American scientists still don't have to opt for in vivo over in vitro like Europeans.

McArdle suggests the clash between the Environmental Protection Agency (EPA) and the Organization for Economic Cooperation and Development (OECD) is an example of resistance. For years the OECD has tried to eliminate or restrict the use of the LD50--a test that force-feeds animals until one-half die from a lethal dose of a substance. While the OECD generally works by consensus, McArdle claims a vote was taken to override the EPP's resistance to other toxicity tests.

William Stokes, director of the National Toxicology Program, addressed this issue. His organization is considering alternatives to toxicity tests for the NIH. "The EPA has to get approval for any new methods of testing. They can't use an alternative until it is approved of by the NIH for regulatory agencies," Stokes says. He believes the resistance was just a matter of following established procedures.

Is it really time for animal models to take a backseat? Is McArdle correct when he says that it is impossible to recreate naturally occurring diseases in lab animals? Are cancer and AIDs species-specific?

The first thing Morrison will tell you is that we can learn a lot from animal diseases and that we have done just that. "We found that the same brain area was deficient when comparing narcoleptic Dobermans to humans," he says. "We have learned most of what we know about cancer and AIDS from animals. Animals have similar cancers; their cellular mechanisms are the same."

Morrison does agree that humans are better models for humans. "But you [have to] come up with a society willing to experiment on humans," Morrison challenges. "One can learn a lot studying cells in tissue cultures, but to study cancer in various parts of the body, you need a whole organism."

According to Morrison, "Animals give us clues about what is going on. It is like wind tunnels. They aren't the sky--ultimately someone brave enough has to get in a plane that's never been flown before. Sometimes it crashes."

Animal Rights

The 30-year assault on animal research has matured--evolved if you will.

In the 1940s after World War II, in-vivo (animal) research came into vogue and a record number of students were learning its techniques. The GI Bill provided the incentive for many who focused on what seemed most promising.

It was the late 1970s before the animal-rights movements gained real momentum. Since then, animal research has been reduced by as much as 50 percent, but mostly because alternatives have become cheaper. Advocacy groups did raise awareness in the scientific community though, and today researchers tend to look for cheaper, more effective alternatives.

Because of this, today's successful animal-rights advocates no longer depend on moral leverage. "We try not to attack the researcher, we attack the tools," says activist John McArdle. This revolution in advocacy has spawned a whole new generation of contrary opinion:

* "We would be in absolute darkness about AIDS if we hadn't done decades of basic research on animal retroviruses."--former surgeon general C. Everett Koop

* "None of this could have been done without animal experimentation. It's a tragedy and a waste of resources that scientists have to combat the antivivisectionists."--Dr. Joseph Murray

* "A lot of medical experimentation, perhaps all of it, is a sham.... I know that it's kind of ludicrous to continue this charade, this kind of lazy, outdated science as an answer."--Alec Baldwin, actor and celebrity spokesman for People for the Ethical Treatment of Animals.

* "Animal experimentation has not cured a single human disease--if the death of one rat cured all diseases, it wouldn't make any difference to me."--Humane Society activist Chris DeRose in Last Chance for Animals.

Research for Which Animals Are Being Used.

Rabbits: cardiovascular disease (hypertension and arteriosclerosis)

Guinea pigs: anthrax

Pigs: healing skin

Sheep: orthopedic research, joints and bones, muscles

Fish: chemical exposure and toxicity Octopus, squid, snails: neurological studies

Armadillos: leprosy

Leeches: memory

Nonhuman primates: HIV, hepatitis B and C, malaria, periodontal disease, Parkinson's, Alzheimer's

Mice: cystic fibrosis, spinal chord, heart attack

Dogs: heart-valve artery replacement, organ transplants, hip-joint replacements, traumatic injuries, diabetes, narcolepsy, blindness

Cats: neurons, chemical transition of impulses, HIV

To see what animals have done for human-health research see www.rdsonline.org.uk/milestones/index.html.

BRANDON SPUN IS A REPORTER FOR Insight.

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COPYRIGHT 2002 Gale Group