F.A.Q.

The history of animal experimentation began as early as the second century in Rome, when the Roman Catholic Church issued a decree prohibiting human autopsy. As a result of this prohibition, Galen, who was physician to the gladiators and to the household of the Roman emperor Marcus Aurelius, abandoned his own investigations of the humans, usually injured gladiators, in favor of cutting into goats, pigs and monkeys brought from the Barbary Coast. Initially, animals did lead to some discovers that were applicable to humans. Especially in the 19th century. Based on animal experiments, among other things, researchers concluded the heart circulated blood and discovered other basic functions. Most of these discoveries were not incumbent upon animals but that is where some of the knowledge came from. On the gross level, all mammals do have similarities. Dissect a cow, dog, chimpanzee, human, or mouse and you find essentially the same anatomy and that the anatomy does essentially the same things. This is where we were hundreds of years ago. Today animals are used mainly to study drugs and as models for human diseases. Animal experimentation continues today largely because it is a tradition and like many traditions it financially supports many people. Animal experimenters justify the practice in part because experimenting on animals allows researchers to control many variables they cannot control in humans. This justification fails however as it doesn’t matter how many variables are controlled if there are differences between species that invalidate extrapolation. Drug testing in animals is much less expensive than conducting clinical trials, which is where most side effects are found.

Since ancient times, people have examined animals to learn more about the nature and function of the human body. In the distance past, when people knew so little about life processes, studying animals may have contributed something to the overall body of scientific knowledge. That occurred during times when people were able to observe the obvious similarities between humans and animals. For example, both humans and animals have a heart, a liver, lungs, and kidneys, and biological functions that are similar across many species. In modern times, however, when the vast majority of research is being conducted on a cellular and subcellular level, even the smallest difference between animals and humans at that level is enough to render any data comparison between the two species completely irrelevant.

Equally important, it must be remembered that while animal experimentation led to certain developments, they were not necessary. For example, animals can be used to grow viruses, but so can Petri dishes and human tissue cultures.

When scientists say that animals are “models” for humans, they mean that animals are used as a device for conceptualizing unfamiliar phenomena by analogy to qualitatively different but familiar phenomena. Put more simply, animal researchers presume that what occurs in a mouse will also occur in a human because there is a one-to-one correspondence between these two living systems. Early animal experimenters assumed that if one type of tissue in two different species performs the same function — say, respiration — then the causal mechanism is the same. This concept has led researchers to maintain that animals are acceptable causal analogic models (CAMs), and therefore they can be used to study human disease. In the laboratory, animals are used as CAMs for human disease, test subjects (e.g., drug testing, carcinogen testing), as a way to explore new theories, and for dissection in education. In addition, animal tissue is used to study basic physiological principles.

Rodents (mice and rats) are the most commonly used animals in the laboratory. Millions of mice and rats suffer and die each year, but exact numbers are unknown. Because rodents are not protected under current provisions of the Animal Welfare Act, specific accounting of the numbers that are used are not required by law. As a result, there is not way to know conclusively just how many millions suffer and die each year in publicly and privately funded research. Long ago, rodents became favored “laboratory” animals, not because there were compelling scientific reasons to do so, but rather for reasons of space, economy and convenience. Rodents are small animals, and more of them can be housed in a laboratory than larger animals, such as cats, dogs or monkeys. They also breed faster, and are less expensive to purchase and maintain. Because of the obvious (and not so obvious) biological differences between rodents and humans. Rodents not only have a slower metabolism than humans, they distribute and excrete toxic substances differently. And that’s just the beginning. In rodents, plaque (fatty deposits) is deposited in the liver, whereas in humans, plaque is deposited in blood vessels. Rodents manufacture Vitamin C in their bodies, but humans can only obtain Vitamin C through their diet. Rodents require 3 – 1/2 times more protein than humans. And they cannot tolerate more than 15 minutes of direct sunlight. These and the other ways rodents and humans differ anatomically, metabolically and physiologically create a number of problems in the laboratory. For example, some common tumors such as prostate, colon and rectal tumors are rare in rodents, and when they are artificially induced in mice and rats in the laboratory, the tumors behave much differently than they do in humans. Furthermore, colon cancer in rats kills by obstructing the colon ; human colon cancer kills by metastasizing (spreading) to other places in the body. There are other differences as well. In rats, the small bowl is most often affected ; in humans, it is the larger bowel. At first glance, the fact that mice are highly susceptible to tumors of the mammary glands, liver, pituitary, thyroid, lung and lymph systems would make them suitable models for humans. However, a closer examination reveals that even though they are located in the same regions, they are not the same cancers.

On a gross anatomical level, human and nonhuman animals are similar. All life on earth has characteristics in common because all living things evolved from a single form of life that inhabited the earth 3.5 million years ago. Through a branching process known as speciation, this basic life form evolved into the ten million plant and animal species that exist today. These evolutionary changes occurred on a microscopic level through changes in the organism’s DNA sequence. So, while all plant and animal species share the same genetic material because they are formed from the same DNA units, it is the composition, or arrangement of this genetic material that makes all the difference. Idiosyncrasies at this subcellular level distinguish the way the cells of different species react to food, the environment and medications. And these very small differences can lead to dramatic differences in the organism as a whole.

No. Animals are complicated creatures with multiple organ systems that interact with each other in many subtle ways. Often these complex interactions are not fully known or understood. Dual experiments at Carnegie Mellon University, which tested the ability of 214 compounds to cause cancer in both rats and mice, agreed with each other only 70% of the time. In other words, rats and mice had a different reaction to the tested chemical 30% of the time. Another study revealed that only 54% of chemicals found to be carcinogenic in one species were also carcinogenic in the other. For example, liver tumors can be induced via chemicals in mice, but the same chemicals do not induce cancer in rats or hamsters. Benzedrine causes bladder tumors in humans, liver tumors in hamsters and middle ear tumors in rats. Studies have even shown differences within genders of the same species. Of 33 chemicals that caused cancer in both rats and mice, only 13 caused cancer in both males and females.

Because imposing disease symptoms in an animal during an experiment cannot adequately predict or duplicate human disease. In order for a model to be scientifically acceptable — that is, to have predictive value — it must exhibit the same symptoms, the same assumed origin of disease, the same neurobiological mechanism and the same treatment response. Although certain animals may have some of these characteristics in some instances, no animal consistently fulfills all four criteria. That’s because animals and humans are different in many ways — anatomically, physiologically and metabolically.

It is true that in vitro (test tube) research methodologies, though tremendously valuable, cannot predict what will happen in a whole living system. But history has proven that laboratory results in animals are even more inadequate. Although successful in predicting what happens in a particular animal tested, animal studies do not predict what will happen in humans. Very often, substances that have proven effective in animals do not demonstrate curative value in humans, and may even harm them. (Just as often, animal testing often works at cross-purposes to discovery, when poor results prevent medications that could alleviate pain and save lives from being introduced into the market.) Because animal tests lack predictive value, all drugs must eventually be tested on humans in “clinical phases” of drug testing.

Harm to Humans from Experiments on Animals
Smoking thought noncarcinogenic secondary to research in animals so many continued to smoke.
Asbestos thought noncarcinogenic so many continued to be exposed.
The cause of numerous environmental induced cancers (arsenic, glass fibers, etc.) were shown to be false according to animal research, but eventually proved true. Many continued to be exposed and injured/killed.
Animal models of heart disease failed to show that a high cholesterol/high fat diet increased the risk of coronary artery disease thus lulling many into a false sense of security
Animal models of stroke and sepsis resulted in patients receiving medications which were dangerous and harmful and that were not efficacious.
Animal models of transplant surgery, cardiopulmonary-bypass surgery, radial keratotomies, artificial heart surgery and many others led to disaster when applied to human patients.
Anti-rejection medications now used for transplant patients were delayed because they did not work in animals.
Multiple side effects from medications that tested negative in animals. There are also far too many examples of good medications i.e., penicillin that were delayed because of adverse reactions in animals that did not occur in human.
Misinformed researchers about how rapidly HIV replicates resulting in mistreatment and lost lives.
Delayed polio vaccine.
Wasted time, money, and resources that could have gone to research that historically yielded results that benefited humans

Almost every chemical commonly in use today has been tested on animals. Water, table salt, antibiotics and so forth have all been tested on animals. The ethical issue, for those opposed to animal experimentation on ethical grounds, is moot as society uses, daily, procedures and knowledge derived the experiments on Jews in Nazi concentration camps and knowledge obtained through other unethical means. While a few question the ethics of using such knowledge, the fact is society has decided it is morally acceptable. If those who accuse anti-vivisectionists of being hypocrites are, themselves, going to be consistent, they should dramatically change the way they live as much of this knowledge has been obtained via immoral means. The real question is, “Were animals necessary for this knowledge?” An even better question would be, “Are animals necessary for tomorrows discoveries?” The answer to both is no. People concerned about humans and easing their suffering should support the research methods that are viable today : epidemiology, in vitro research, autopsies, post-marketing drug surveillance, pathology research, genetics research, pharmacology research such as combinatorial chemistry and high-throughput drug screening, research in physics and chemistry that will lead to advances in technology, clinical research and human observation, research with human tissue, mathematical and computer modeling, research with artificial neural networks, stem cell research, research with DNA chips, research into prevention and so forth.

This implies that poeple do not differentiate between the drug development stage which is frequently done without animal models and the actual tox testing which has less relevance and less degrees of freedom to extrapolate results, of course.

Wouldn’t the tragedy of thalidomide have been avoided if more animal studies had been done ?
In fact, animal testing delayed the withdrawal of this drug and resulted in thousands of children born with phocomelia (the lack of developed limbs). Thalidomide was prescribed to pregnant women to prevent miscarriage and also to relieve morning sickness. The first case of phocomelia in infants of mothers taking thalidomide was reported in 1956, yet the drug was released in 1957 anyway. (Toxicity tests on animals had been conducted, including some on pregnant rodents, where phocomelia did not occur.) As the incidence of phocomelia increased, scientists attempted to reproduce the phenomenon in a wide range of animal species, looking for proof in animals of what they already knew was occurring in humans — that thalidomide was drastically damaging unborn offspring. Eventually, one breed of rabbit, the White New Zealand rabbit, was affected, but only at a dose between 25 and 300 times that given to humans. Some monkeys gave birth to deformed offspring, but it took ten times the normal dose to make this happen. The drug was not withdrawn until 1962, five years after obvious and graphic epidemiological evidence in the form of hundreds of babies born with flippers or no limbs at all was available, but largely ignored. In the end, more than 10,000 additional children were born with phocomelia.

Finding medications that will be safe for everyone is indeed difficult. But the question is based on the false assumption that pharmaceutical companies are trying as hard as they can to find the adverse side effects. The most trusted means of finding side effects in human clinical trials. This is also the most expensive testing a drug goes through. Testing on animals is cheap compared to clinical trials

Because reaction to a drug can vary by species, animal tests cannot predict response in humans. Because they cannot reliably predict a human response, data from animal studies cannot be reliably extrapolated to humans. No amount of animal testing, and no matter how many different animal species are tested, can change this fact. There is simply no guarantee that the medications will behave the same way in humans as they do in animals.

A principle called Karnofsky’s Law states that any substance can be teratogenic (causing birth defects) if given to the right species, at the right stage in development and in the right dose. In other words, all medications can cause birth defects in all creatures — and a vast amount of experimental data support this rule. The problem with animal testing drugs for teratogenicity is the fact that not all species are equally susceptible to teratogenic influences by any given chemical. Likewise, an agent that is teratogenic in some species may have little or no teratogenic effect in others. For example, according to the New England Journal of Medicine, out of more than 1,200 tested chemicals that cause birth defects in animals, only 30 cause them in humans. Thus, animal tests have no predictive value, except for the species being tested. Because they cannot reliably predict teratogenicity in humans, animal tests fail miserably as a way to evaluate the safety of a drug.

Researchers have not been successful in reproducing birth defects in animals for the following drugs, which cause birth defects in humans : Captopril, Enalapril, Minoxidil, CCBs, Warfarin. Many safe and useful drugs have been shown to cause birth defects in animals. These include :

Lovastatin / Chondroitin sulfate / Acetazolamide / Dichlorphenamide / Ethoxzolamide / Methazolamide / Furosemide / Clonidine / Diazoxide / Hydralazine / Reserpine / Guanabenz / Diltiazem / Nifedipine / Codeine / Hydrocodone / Hydromorphone / Meperidine (Demerol) / Morphine / Oxymorphine / Phenazocine / Propoxyphene / Colchicine / Allopurinol / Aspirin / Acetaminophen / Enflurane / Ether / Halothane / Isoflurane / Methoxyflurane / Nitrous oxide / Sevoflurane / Procaine / Corticosteroids / Ampicillin /Cephalothin
ETC

Most of the medications used to treat nausea, vomiting, allergic conditions, and respiratory ailments, as well as many antibiotics, antifungal medications and antiviral medications, and a number of non-steroidal anti-inflammatory drugs, cause birth defects in animals, but not humans.

The list, unfortunately, is a long (and devastating) one. Here are a few examples, which represent a mere fraction of the medications that passed animal tests, and then went on to produce severe to life-threatening problems, and even death, in humans :

• Diethylstilbestrol (DES), prescribed to pregnant women to prevent miscarriages, caused spontaneous abortions, premature birth and neonatal death, and increased the risk of vaginal and cervical cancer in the patients’ daughters.
• Rexar, an antibiotic, was withdrawn after it was linked to severe cardiovascular events and seven deaths.
• Celebrex, an arthritis drug, was linked to ten deaths and 11 cases of gastrointestinal hemorrhage in its first three months on the market.
• Zimeldine, the first SSRI (selective serotonin reuptake inhibitor), was withdrawn after causing a paralyzing illness known as Guillain-Barre syndrome.
• Zafirlukast (Accolate), a common medication used to treat asthma, has recently been linked through human studies to a rare and sometimes fatal condition known as Churg-Strauss syndrome.
• Chloramphenicol, an antibiotic, caused life threatening aplastic anemia, which could have been predicted by in vitro testing with human cells.
• Fialuridine, designed to counteract hepatitis B, caused liver damage in seven out of 15 people, five of whom eventually died and two more needed liver transplants.
• Isuprel (isoporterenol), a drug used to treat asthma, proved highly toxic for humans in the dosages recommended for humans based on animal studies, with 3,500 deaths of asthmatics in Great Britain.
• Methysergide, a migraine medication, led to retroperitoneal fibrosis (severe scarring of the heart, kidneys and blood vessels in the abdomen).
• Suprofen, an arthritis drug, was withdrawn from the market when patients suffered kidney toxicity.
• Selacryn, a diuretic, was withdrawn after 24 people died from drug-induced liver failure.
• Perhexiline, a heart medication, was withdrawn when it produced liver failure.
• Domperidone, designed for nausea and vomiting, was withdrawn because it made patients’ hearts beat irregularly.
• Novantrone (Mitoxantrone), a cancer treatment, produced heart failure in humans.
• Carbenoxalone, designed to prevent the formation of gastric ulcers, caused people to retain water to the point of heart failure.
• Cleocin (Clindamycin), an antibiotic, causes pseudomembranous colitis (a bowel condition).
• Linomide (roquinimex), for the treatment of multiple sclerosis, was withdrawn from clinical trials after several patients suffered heart attacks.
• Cylert (pemoline), used to treat Attention Deficit Hyperactivity Disorder in children, caused liver failure in 13 children, 11 of whom either died or needed a liver transplant.
• Eldepryl (selegiline), used to treat Parkinson’s disease, induced very high blood pressure in patients.
• The combination of fenfluramine and dexfenfluramine, a diet drug, was withdrawn when it was linked to heart-valve abnormalities. (Physicians in Belgium reported heart abnormalities in patients using the medications as early as 1994.)
• Troglitazone (Rezulin), a diabetes medication, has caused death due to liver failure in as many as 155 people.
• Seldane (terfenadine), an allergy drug, caused life-threatening heartbeat abnormalities in humans before it was withdrawn from the market.
• Duract (bromfenac sodium), a non-steroidal anti-inflammatory, has caused fulminant hepatitis and liver failure.
• Omniflox, an antibiotic, was recalled after several deaths.
• Floxin, an antibiotic, was found to cause seizures and psychosis in humans.

There are many cases in which the mandate for animal testing prevented the development and distribution of valuable medications, thus initially depriving American patients of much-needed treatments and cures. Here are just a few :

• The contraceptive Depo-Provera was barred in the U.S. from 1973 to 1993, even though it was used by women and found safe elsewhere in the world, because it caused cancer in dogs and baboons.
• Clinical trials of the drug digitalis, used to treat heart disorders, was delayed when it caused high blood pressure in animals.
• FK 506, now marketed as Tacromilus, an antirejection agent, was almost shelved before proceeding to clinical trials because of severe toxicity in dogs.
• Prilosec (Omeprazole), a widely used gastrointestinal medication, was delayed for years and almost canceled because of an effect in animals that did not occur in humans.
• Furosemide (Lasix), a diuretic used to treat high blood pressure and heart disease, was almost lost to the public because it was found to cause liver damage in mice, rats and hamsters.
• Fluoride, which provides protection against cavities, was initially withheld from dental use because it causes cancer in rats.

This is fallacious reasoning. We do not know how to design a time travel machine but that does not mean that we condone flying in unsafe airplanes or riding in unsafe cars. It is not incumbent upon us to do biomedical research that will result in cures for cancer or safer new drugs. It would be unethical however if we were to ignore the fact that the current system of using animal models is a failure.

If a technology or model does not work it should be abandoned. Treating brain cancers with bullets fired from guns is not effective therefore it should be abandoned/not begun. It is not incumbent upon us to find a cure for brain cancer even though we suggest that guns are not the answer. Likewise if animal models are not predictive or effective they should be abandoned. We do not have to find technologies that are effective in order to justify abandoning the ones that are not. We have no cure for brain cancer and arguably there have been case reports of a patient using a gun to shoot a bullet into his head, killing all the cancer and leading a life perhaps not that much worse than would have otherwise been. We do however, offer here, what we think researchers should be focusing on :

Advances in in vitro, molecular, and cellular assays as well as DNA microarrays, to name but a few, are beginning to reshape the drug development process by enabling researchers to predict a lead compound’s ADMET characteristics during the discovery phase, well before the preclinical phase. There is a flood of data for new drug development. Many companies are focusing on human-based ADMET tests. Camitro of Menlo Park, CA is developing computer models and simulation of drug metabolism, Lion Bioscience of Dan Diego and Heidelberg, is developing computer models from in vitro data, Genmatics of San Francisco is developing in silica modeling, Amedis of the UK is developing software for ADMET studies, D‑Pharm/Pharma Logic of Israel is developing computer models, Cyprotex of the UK is developing high-throughput ADMET testing facilities and methods, Pharmagene of the UK, Cell Technologies of Houston and Gene Trace Systems of Alameda are using human tissue for ADMET studies, Amphioxus Quintiles of Durham, MDS Pharma Services of Canada, Quest Diagnostics Clinical Trials of New Jersey and many more.

Screening in silica is taking the place of many animal tests. ComGenex of South San Francisco and Hungary is developing computer technology based on in vitro tests using human tissue to predict important properties of new chemical like pKa, log P and log D. Ferenc Darvas, ComGenex president and chairman said in Nature Biotechnology, “that the most promising use of data is to ‘calculate structure-activity relationships, convert those into rules, and then reintroduce those rules in a rule-based system for the design and selection of compounds or libraries.’ ” Along the same lines, Amedis of the UK has developed a structure-activity-based predictive test for carcinogenesis. Bains states, “The prototype software can predict carcinogenicity far more accurately then the Ames test can do.”

DNA microarrays are also taking the place of animals in toxicology studies. DNA microarrays allow an intersection of computers and biology. Thousands of genes interact in order to create proteins and indeed life as we experience it. They do not act alone but in combination with each other. DNA microarrays allow scientists to monitor the entire genome, or at least a very large percentage of it on a single chip. Thus scientists are able to look at how a chemical will influence genes, the proteins they make, and how the gene-gene interactions are effected. Numerous DNA chips are available : Biochip, DNA chip, DNA microarray, GeneChip, and gene array. Microarrays require sophisticated robotics and imaging technology. Several thousand genes can be analyzed simultaneously. They can be used to identify gene sequences, gene mutations, determine how active a gene is, analyze gene expression patterns induced by environmental factors or medications, create a profile for an individual patient, and to discovery new genes. Genes can be exposed to medications and analyzed to see if they are more or less active after exposure.

Caco‑2 cells have become the standard for predicting drug absorption. A human liver cell line, ACTIVTOX has been used to predict toxicity and metabolism of drugs that were approved based on animals studies, terfenadine (Seldane) and astemizole Hismanal), that went on the harm humans.

Rather than safeguarding consumers, animal tests create a false sense of security with regard to the safety and effectiveness of drugs, working against the health interests of the public and diverting precious research dollars away from solid, human-based testing methodologies.

Animal studies provide only two sure things : a very accurate picture of the effects of a drug on animals in the laboratory, and a legal safety net for the government and pharmaceutical companies. Beyond that, drugs that have been released to the public based on misleading animal studies have caused harm and even death to tens of thousands of people.
Animal testing in no way provides any real indication of how a drug will affect humans because animal models are an ineffective way to extrapolate data for human reactions. Although subjecting the substances to animal testing is designed to reveal anticipated effects and side effects in humans, very often the results differ dramatically between species. Substances that could save many human lives are not approved because they are harmful to animals, thus preventing ill patients from receiving the medicine they need. Likewise, substances that are therapeutic to animals get approved, but then sometimes harm and kill humans.

An astonishing number of animal-tested drugs make it to market, only to cause problems later. It is well accepted that about 100,000 deaths per year and about 15% of all hospital admissions are caused by adverse reactions to medications. Between 1976 and 1985, 102 of the 198 new medications that had undergone extensive animal testing were either withdrawn or relabeled by the FDA due to severe and unpredicted side effects.

In vitro testing, computer modeling, epidemiology, clinical observation (monitoring human patients), and autopsy of humans are the only truly accurate methods for obtaining knowledge about the positive and negative effects of medications on humans. More extensive preclinical testing on human tissue, more extensive clinical trials and mandatory postmarketing drug surveillance would offer the public much safer medications.

A research team composed of Drs. Swan and Ganz improved the PAC. The problem was getting the catheter to go in the proper direction ; the way the blood is flowing. One day while observing sailboats, Dr. Swan had the idea of attaching a sail onto their catheter and letting it float into the heart with the blood. Since a sail seemed impractical, he used a tiny balloon that successfully carried the catheter to the correct location.

Amblyopia is one of the leading causes of monocular blindness. According to Burton J Kushner, MD of the University of Wisconsin, the treatment for amblyopia, occluding the unaffected eye with a patch, has not changed since 1750. Placing atropine in the unaffected eye is currently being touted as an alternative for children suffering from moderate amblyopia. The idea to do so was based on basic pharmacology and physiology, not animal studies.

Most of them did, but in no case does that mean the discoveries would not have been made without animals. It only means that the market for “laboratory” animals was thriving, and using them was the easiest, most convenient method. Beginning in the 1850’s, experimentation on animals became part of all medical curricula, and researchers were obliged to perform animal experiments to obtain their degrees. However, it is incorrect to assume that those experiments bore directly on the Nobel-winning results. In those instances where animals were used for Nobel-winning results, they were not necessary. Although animal tissue research was the convention, human tissue was available and more viable, as many Nobel Prize winners have since admitted. (Who?)

Over the last 20 years, billions of dollars have been spent trying to infect animals with AIDS, and these efforts have been entirely futile. It is true that researchers have succeeded in infecting chimpanzees with HIV ; however, none has progressed to AIDS. The inability for researchers to produce an adequate animal model — despite years of effort and billions of dollars — makes it extremely unlikely that animal experimentation will lead us to therapies and cures for this terrible disease. Investing AIDS research money in animal research is therefore wasteful. With as many as 34 million people infected with HIV worldwide, blood cells from those already afflicted will serve as our most illuminating research material.

In fact, in vitro research on human blood cells — not research on animals — has revealed a number of idiosyncrasies that allow HIV to proliferate freely and progress to AIDS in humans. The efficiency of the virus relies on very specific and minuscule aspects of human white blood cells called helper T‑cells. These cells have portals on their surface called receptors. These receptors work in tandem with precise proteins to invite HIV into the white blood cell, where the virus then reproduces. Receptors can be very species-specific and sometimes vary even within a species, which explains why chimpanzees and even some people who are exposed to HIV never progress to AIDS. That is also how HIV-infected humans who do not progress to AIDS offer valuable insights into possible ways of countermanding the disease.

Furthermore, the identity of those HIV-infected humans who do not progress to AIDS was derived through epidemiological studies, and in vitro research has isolated the human gene believed responsible for their immunity. The sequencing of the HIV genome was also accomplished through in vitro research. And the development of AZT and other anti-AIDS medications was not dependent on animal experimentation.

In short, it has been human data, not animal research, that has reliably informed the development of HIV medications and the effort to produce a vaccine.

Despite the fact that hundreds of millions of animals have been sacrificed, and billions of dollars invested, researchers appear to be losing the “War on Cancer” declared by the Nixon Administration more than 20 years ago. In fact, deaths from cancer are higher than ever. On the surface, that may lead one to believe that we should do more animal research. In fact, though, the opposite is true. Cancer research that relies on the animal model will almost certainly not lead us to the answers we need to eradicate cancer.

Why ? Because animal cancer is not the same as human cancer. While researchers have been highly successful in curing cancer in mice, those cures have not been translated to humans.
That is not surprising, given the fact that there are over 200 different forms of cancer afflicting different organs, tissues and cells in humans, and although comparable animal organs, tissues and cells may become cancerous, the cancers are never identical to human carcinomas. As a result, data from animal cancers do not help us predict cancer (and its treatment and cure) in humans, thereby wasting valuable time and money — even while human cancer patients suffer and die.

Another reason animal research has not helped bring about a cure for cancer is the fact that susceptibility to cancer may be genetic. In addition, diet, lifestyle and exposure to certain chemical elements are also contributing factors to the occurrence of cancer. In an effort to turn animals into adequate research models, researchers implant them with human genes, and then expose them to known human carcinogens. If we already have significant human evidence that a substance, diet or lifestyle is carcinogenic, why do we tool up to repeat that episode in animals ?

In any event, different substances are not necessarily carcinogenic to all species. Although one would expect rats and mice to acquire cancers similarly, studies conducted on both species found that 46% of chemicals found to cause cancer in rats were not cancer-causing in mice. Since species as closely related as mice and rats do not acquire cancer identically, it is not surprising that 19 out of 20 compounds known not to cause cancer in humans did cause cancer in animals. The National Cancer Institute treated mice that were growing 48 different “human” cancers with a dozen different drugs that were already used successfully in humans. The drugs did not work in 30 out of the 48 cancers ; 63% of the time, the mouse models were wrong.

While it is true that animals have figured largely in the history of research and therapy for diabetes, their use has not been necessary and has not always advanced science.
Diabetes is a very serious disease. It affects up to 14 million Americans and is a leading cause of blindness, amputation, kidney failure and premature death. Although the clinical signs of diabetes have been known since the first century AD, it was not until the 1700s that physicians using autopsy studies were able to associate the disease with changes to the pancreas. But because these pancreatic changes were difficult to reproduce in animals, many scientists continued to dispute the role of the pancreas in the disease.

Nearly a century later, in 1869, scientists identified insulin-producing pancreatic cells that malfunction in diabetic patients. Other human pancreatic conditions, such as pancreatic cancer and pancreatitis (inflammation of the pancreas) were seen to produce diabetic symptoms, thus reinforcing the link between diabetes and the pancreas.

However, animal experimenters continued to interrupt developing knowledge about this link. When they removed pancreases from dogs, cats and pigs, the animals did become diabetic, but the animals’ symptoms led to conjecture that diabetes was a liver disease. These animal studies threw diabetes research off track for many years.

Defenders of animal research often point to the development of insulin as support for continued animal testing. In the early 1920s, two scientists, Macleod and Banting, isolated insulin by extracting it from a dog. They received a Nobel Prize for this accomplishment, but Macleod later admitted that their contribution was not the discovery of insulin, but rather the reproduction in the dog lab what had already been demonstrated in humans. They were not obliged to extract insulin from dogs, because ample human tissue was available. They did so merely because it was convenient.

Later, Banting and other scientists modified the process of extracting animal insulin using in vitro techniques and mass-produced insulin from pigs and cattle by obtaining insulin from slaughterhouses. In coming years, scientists continued to refine the animal-derived substance. And although it is true that beef and pork insulin saved lives, it also created an allergic reaction in some patients. Injecting animal-derived insulin also presented the sizable danger of contracting viruses that cross from one species to another. Had researchers recognized these potentialities early on, particularly in view of the gulf of differences between humans and farm animals, they would have hastened to develop human insulin more quickly.

The ability to treat patients suffering from diabetes without giving them insulin injections was discovered by chance on humans. Today, the administration of oral anti-hyperglycemics, which arose from serendipity (chance discovery) and self-experimentation, eliminates the need for insulin injections in many patients.

Nevertheless, diabetes remains a stunningly enigmatic disease, in large part due to a continued reliance on animal models. Insulin is a treatment, not a cure, for this disease. The exact biochemical process through which insulin regulates blood sugar is not yet known. But in light of the differences between humans and animals on a cellular level, it is extremely unlikely that any revelations will come through animal research.

Animal tests sidetracked the development of this important drug. In 1929, Alexander Fleming observed penicillin-killing bacteria in a petri dish. Intrigued, he administered the compound to bacteria-infected rabbits, hoping that it would do the same thing. Unfortunately, penicillin was ineffective against the rabbit’s infection. (We now know that rabbits excrete penicillin into their urine so rapidly that the drug does not have a chance to take effect before it is eliminated.)

Disappointed, Fleming set the drug aside for a decade, because, in his mind, the rabbits had “proven” the drug to be useless as a systematic medication. Years later, he recalled the drug when he had a patient near death, for whom all other treatments had proved ineffectual. In desperation, he reached for the penicillin. The patient survived, and the rest is history.
It is fortunate that we didn’t have animal tests in the 1940s, for penicillin would probably never have been granted a license, and possibly the whole field of antibiotics might never have been realized.

In fact, animal experimentation delayed this much-needed vaccine throughout the first half of the 1900s.

• In 1908 — 73 years after the first polio outbreak — scientists suggested that a virus was responsible for the disease, and that a vaccine could be developed to eradicate it. In 1912, pathologists discovered the poliovirus in human intestines, which suggested it might enter humans through the digestive track. This was a critical discovery, because in developing a vaccine, it is very important to determine how the infection enters the body and takes hold. Its contagion cannot be interrupted without first determining its path.
• Meanwhile, researchers successfully infected monkeys with polio. However, monkeys contract polio nasally (through the nose), and the virus moves directly to the brain. Incredibly, scientists working on the vaccine chose to ignore the human digestive data in favor of the monkey data, thereby postponing the development of a vaccine by decades.
• In 1934, a polio vaccine manufactured from monkey tissues was released, and it resulted in the paralysis of 12 people, and the deaths of six others. In 1937, animal experiments led scientists to spray zinc sulfate and picric acid alum into the noses of children. These scientists reasoned that if the human transmission route was through the nose, as it was in monkeys, that this would kill the virus in the nose. The only result was that some children permanently lost their sense of smell.
• In 1941, 30 years after the original animal experiments, Dr. Albert Sabin worked with autopsy findings to demonstrate that the human nasal mucosa did not have virus. What he did find was that the virus was confined to the gastrointestinal tract, as had been determined near 30 years earlier.
• In 1949, John Enders grew the virus in tissue culture, thus paving the way for a vaccine, and in 1954 received the Nobel Prize in Physiology or Medicine for his achievement. The vaccine could have been produced from non-animal tissue ; however, manufacturers opted for monkey kidney tissue instead. The first animal-based vaccine contained live virus, killing 11 people and causing 204 others to contract polio. Today, the polio vaccine is grown in human diploid-cell culture, rather than animal tissue.

Transgenic animals are mutants that have selected human genes in their bodies, which make them more susceptible to certain human diseases or enable them to produce certain human antibodies, tissues, or even whole animals. These new species are created in the laboratory by manipulating an animal’s genes in several different ways, such as cutting or recombining an animal’s DNA, by adding or deleting segments of DNA, by injecting human genes into animals, or by transferring genes from one species to another.

Transgenic animals, also called genetically engineered animals, are seen by researchers as an improved animal model for studying specific diseases because they are more “human.” For example, there are transgenic mice who have been specifically designed to have weakened immune systems, so that their bodies are more prone to develop cancer quickly (and develop larger tumors) in the laboratory.

The best methods for screening chemicals for carcinogenicity and curative potential lie in in vitro, or test tube, technology. A combination of in vitro techniques and epidemiology (the study of disease incidence) is ideal for testing chemicals already in the marketplace.

In vitro testing has also revolutionized diagnostic science. For example, the Pap smear, one of the oldest and most successful forms of in vitro testing, is now used in 97 percent of all cervical cancer diagnoses.

Tremendous progress in cancer research has come through epidemiological studies that have linked populations of people lifestyle to disease. For example, it was through epidemiological studies that we learned the association between diet and cancer.

Perhaps most significantly, by studying patients who have already developed cancer, researchers have been able to determine that some genes activate and deactivate the uncontrolled growth of cancer cells.

Over the past 30 years, techniques for detecting early cancers — colonoscopy, breast examination and prostate examination among them — have improved the prognosis for many cancer patients. None of these benefited from animal experimentation.

Following are just a few examples of the many medical advances made throughout the ages that did not involve animal research : 

• Discovery of how blood circulates from the right heart through the lungs back to the left heart and into the arteries and veins.
• The germ theory of disease, the sterilization process and the pasteurization process.
• Isolation of the HIV (human immunodeficiency virus).
• Discovery of the mechanism of AIDS transmission.
• Development of x‑rays.
• Interpretation of the genetic code.
• Production of Humulin, a synthetic copy of human insulin which causes fewer allergic reactions than animal-based insulin.
• Development of a vaccine against yellow fever.
• Understanding of cholesterol biochemistry and familial hypercholesterolemia.
• Discovery of the chemical and physiological visual process in the eye.
• Development of anti-depressant and anti-psychotic drugs.
• Discovery of human blood groups.
• Discovery of the relationship between chemical exposure and birth defects.
• Discovery of the effectiveness of digoxin (digitalis) in treating heart failure and irregular heartbeat.
• Discovery of the anti-malarial drug quinine.
• Discovery of aspirin.
• Discovery of penicillin.
• Use of nitrogen mustard, prednisone and acinomycin D as cancer treatments.
• Discovery of potassium bromide as an epilepsy treatment.

Xenotransplantation is a procedure in which the cells, tissue and organs of nonhuman animals are implanted into humans. Xeno in the word xenotransplantation comes from the Greek word meaning strange or foreign.

Cross-species transplant experiments have been conducted since 1963, when a human patient received a baboon kidney at Hennepin County Medical Center in Minneapolis, MN. The organ functioned four days.

Anti-vivisectionists object to using animals as “factories” for spare parts in cases where human organs no longer function. In addition, xenotransplantation has the potential to threaten public health and safety by enabling dangerous infectious diseases and viruses to cross the species barrier and spread disease among the human population.
Transplanting living animal organs into humans bypasses natural barriers that prevent infection. This process makes it easier for infectious diseases and deadly viruses to pass from animals to humans, which could cause illness and death of the recipient, as well as the spread of disease to epidemic levels. With the very real possibility that deadly infectious agents could find a compatible home in a human, then transmit itself from human to human, mutating along the way, xenotransplantation could very well unleash an epidemic that could outstrip AIDS in its devastation.

Even the most careful screening of a donor animal is no guarantee of safety. There is no such thing as a “virus free” animal. Moreover, scientists can only screen for known viruses and other diseases agents. They have no way of screening for disease agents that have yet to be discovered. Consider prions, an entirely different form of infectious substances, which were not discovered until 1982. (Prions are responsible for Mad Cow Disease and other transmissible spongiform encephalopathies.) These infectious substances lie dormant in living systems for years before bringing on lethal disease. So far, they cannot be killed or controlled. And prions may be found in pigs, which are now the favored animal for experimental xenografts.
At first glance, it may seem that primates would be the logical choice for organ cultivation, because of their genetic similarity to humans. But that proximity creates a potentially deadly problem, because the closer the donor species, the more likely it is to transmit lethal diseases. In the past, baboons have been used in experimental xenotransplant operations. Recently, however, scientists have switched to genetically-engineered pigs. These are pigs that have had human DNA injected into them as fetuses. (The fetus’s system does not attack the foreign DNA, because immune response is unformed in fetuses.) Once born, pigs mature and reproduce quickly, and each succeeding generation has more human DNA introduced into their fetuses. As time goes on, the pig organs become more like human organs in terms of immune recognition.

Absolutely not. Yes, there is a severe shortage of human donor organs in the U.S. today. But if more human organs were available, there would be no need to pursue the highly questionable and potentially dangerous xenotransplantation experiments. A relatively small increase in organ donations, combined with an improvement in the way organs are procured, would provide a sufficient number of organs to meet the demand.

The U.S. should consider following the lead of many European countries, including France, Austria, Belgium, Denmark and Sweden, which have passed “presumed-exempt” laws. These laws presume that an individual’s organs are available for clinical use unless the individual specifically states otherwise. When Belgium passed its presumed-exempt law, organ donation increased by 183 percent.

Yes, several humans have received experimental xenografts. In 1963, six humans received a baboon kidney. In 1964, researchers attempted to transplant a chimpanzee heart into a human. Between 1969 and 1974, three children received transplanted livers from chimpanzees. In 1993, researchers tried a baboon-to-human kidney transplant, as well as a bone marrow transplant from a baboon to a human patient with AIDS. Perhaps the best known human xenograft patient is Baby Fae, who received a baboon heart in 1984.

None of these procedures were successful. In 1999, the U.S. Food and Drug Administration (FDA) announced a de facto ban on clinical trials of xenotransplants from nonhuman primates to humans.

There are many non-animal alternatives to dissection that teach children about life processes far more effectively than cutting up an animal. Using a non-animal alternative provides the necessary learning experience while also teaching young people that a healthy respect for all life. Dissection, on the other hand, conveys the message that life is cheap and expendable.
Innovative technology has produced a wide range of non-animal alternatives that teach children valuable computer skills while they learn about life processes. These alternatives include interactive, virtual reality programs on CD-ROM and DVD.

There are also a multitude of anatomical charts, transparencies and videotapes available. Three-dimensional replicas made of species ranging from frogs to fetal pigs and human torsos illustrate organs and processes with remarkable detail.

All these materials are available from kindergarten through the post-graduate level.

In these days of budget cuts and teachers being asked to do more with less, non-animal alternatives to dissection should be welcomed by school districts because a one-time investment in these materials pays off in many ways. Non-animal alternatives will last many years, and teachers don’t have to keep replenishing their supply of dead frogs, cats and fetal pigs, which can be very costly. Non-animal alternatives are often less expensive on a short-term basis, and are always less expensive on a long-term basis.

Many science teachers defend classroom dissection because they believe it is the best way to teach students about life processes. Others insist that allowing students to choose a non-animal alternative will erode discipline in the classroom. Still others resist using alternatives because it represents a new teaching method, and they simply don’t have the time or inclination to learn something new. Some even believe that it is an important “rite of passage” in a student’s development.

There are biology teachers who, believing that students pursuing an advanced degree will have to dissect in college, insist that high school dissection exercises are a way for them to “get over it” early on. Unfortunately, these teachers are not keeping up with revised university curriculum requirements, which in many cases have been modified to exclude dissection.
Studies have shown that students who have used a non-animal alternative perform at least as well — and often better — in their coursework. It is not the best way to learn anatomy, but it does seem to be the best way to discourage students from pursuing careers in the life sciences. While there are no specific numbers available, it is likely that many of our best and brightest young people, believing that they must dissect in order to successfully complete their education, turn away from a career in science and medicine because of ethical concerns.

No. Medical students and physicians have been surveyed and asked if they think learning techniques, procedures and basic physiology is best obtained from animals or humans. The overwhelming response has been that human observation is the best teacher.
Medical students observe numerous procedures, such as chest tube insertions, before ever doing one. When it is time for them to perform the procedure on a human, they will not be alone, but will have two or three physicians watching them to make sure they are performing the technique properly. Only after multiple insertions, under direct supervision, will the student, who is by then a resident, be allowed to do one alone.

There are many differences between inserting a chest tube in a dog and a human, who has a different anatomy than a dog.
Surgeons learn how to be surgeons by watching other surgeons. There are also many ways to practice an operation without using a living human or animal. Simulab Corporation of Seattle manufactures simulators for teaching laparoscopic surgical skills, chest tube insertion and other procedures.
Here are some other examples of the non-animal alternatives which have proven to be more effective in training medical and other post-graduate students than practicing on live animals :

• “Sniffy” is a computer rat from Brooks/Cole Publishing who can teach basic operant conditioning principles to psychology students.
• “PracticeRat” from Sharpoint is a synthetic simulation of blood vessels and nerves which can be used by students as well as experienced surgeons who would like to perfect their microsurgical skills.
• A canine spinal surgery model, which is actually a foam replication of the back and upper hindquarters of a dog, has been developed by Dr. Robert Leighton of the University of California, Davis.
• Koken Rabbit, manufactured by the Koken Co., Ltd. of Japan, is a model of a female New Zealand white rabbit which simulates a rabbit’s anatomy. Constructed of silicone and soft, fur-like material, Koken Rabbit was designed to assist in the training for handling peroral dosage, intravenous injections and blood collection, urethral catheterization and orotracheal intubation.

To date, over 85 of 126 U.S. medical schools have discontinued the practice of using animals for training doctors. These include : 

• Harvard University
• Stanford University
• Columbia University
• Yale University
• Tufts University
• New York university
• Ohio State University
• Michigan State University
• State University of New York, Stony Brook
• University of Michigan
• University of Washington
• Hahnemann University
• Louisiana State University
• Mercer University
• University of Maryland
• University of New England College of Osteopathic Medicine

All but two medical schools in the entire country offer their students non-animal alternatives — the Uniformed Services University of the Health Sciences, Bethesda, MD and the University of Colorado, Denver.
In 1986, the American Medical Student Association adopted a resolution supporting a student’s right to choose an alternative activity to dissection and to be free from penalties or faculty intimidation when they refuse to dissect.

Surgeons-in-training have long “practiced” on pigs and other animals, yet many have admitted that work on animals confuses procedures, and there are many examples to support their concern, including the following :
Ophthalmologists perfected radial keratotomy on rabbits, then tried it on humans. Only after completely blinding several humans did they finally correct the procedure.
Extracranial-intracranial (EC-IC) bypass procedures for inoperable carotid artery disease were tested and perfected on dogs and rabbits. Neurosurgeons performed thousands of EC-ICs before it was discovered that the operation did more harm than good. More patients died or suffered strokes because of the operation than were saved as a result of it.
No matter how many practice surgeries on animals in which organs are transplanted from one creature to another, the first human operations have always failed.

Research methods that do not use animals have been advancing medical knowledge since ancient times, and are still in use today. These include autopsy studies and clinical research, which involves the observation of human patients.
Epidemiology, which is the study of the incidence of disease within a population group, has been around since the 1600s. The development of sophisticated technology in recent years has enabled epidemiologists to maintain large databases of information and analyze the data quickly, with pinpoint accuracy.

Autopsies are an essential source of medical knowledge because if you want to know what caused a failure, you must study the failed entity. In the past, when autopsies were perfor