Drug Safety: An Argument to Ban Animal Testing

Abstract

The U.S. Food and Drug Administration (FDA) mandates that drugs under development go through a preclinical testing phase that includes animal testing. Unfortunately, animals and humans differ greatly biologically. Many drugs are safe for animals but not safe for humans. Therefore, when the drugs are placed on the market and used by humans, many times those drugs harm people. In addition, courts are reluctant to allow the admittance of animal testing as evidence, stating that the tests are not reliable. People rely on FDA approval of drugs to their detriment. They assume that if the FDA approved the drug, it is safe for use. In many documented incidences, this is not the case. There are many alternative methods available other then animal testing that can make drugs more efficient and safe for human use. Therefore, the FDA should not mandate animal testing and should look to the alternative methods for evidence that supports drug approval. [PUBLICATION ABSTRACT]

Headnote

The U.S. Food and Drug Administration (FDA) mandates that drugs under development go through a preclinical testing phase that includes animal testing. Unfortunately, animals and humans differ greatly biologically. Many drugs are safe for animals but not safe for humans. Therefore, when the drugs are placed on the market and used by humans, many times those drugs harm people. In addition, courts are reluctant to allow the admittance of animal testing as evidence, stating that the tests are not reliable. People rely on FDA approval of drugs to their detriment. They assume that if the FDA approved the drug, it is safe for use. In many documented incidences, this is not the case. There are many alternative methods available other then animal testing that can make drugs more efficient and safe for human use. Therefore, the FDA should not mandate animal testing and should look to the alternative methods for evidence that supports drug approval.

Keywords: animal testing; drug safety; medications; Daubert standard

The statistics are staggering. Every year, thousands of people are hurt or killed as a result of using prescription drugs that were approved by the U.S. Food and Drug Administration (FDA); 5.34% of newly approved drugs were pulled from the market by the FDA from 1997 to 2000. 1 Approximately 125,000 Americans have died from FDA-approved medications. 2 Just recently, Vioxx, a medication manufactured by Merck and approved by the FDA, was pulled from the market. The medication caused 25% of 239 patients taking it to have heart attacks within 13 days of starting the drug. 3 How does this happen? How does a drug that goes through the process mandated by the FDA injure or kill people as soon as it is released to the public? Because the method by which the drugs are declared safe for human consumption is outdated and obviously detrimental to humans.

Animal testing is mandated by the FDA for certain drugs to receive approval for distribution to the public: 4

Scientists have to test those compounds that have shown at least some desired effects in living animals. In animal testing, drug companies make every effort to use as few animals as possible and to ensure their humane and proper care. Two or more species are typically tested because a drug may affect one differently from another. Such tests show whether a potential drug has toxic side effects and what its safety is at different doses. 5

If animal testing is an accurate indicator that medications are safe, why are so many drugs pulled from the shelves once humans start taking them? There is a much evidence that animal tests are not reliable. The results are sometimes discarded if the desired effect is not achieved. 6 In fact, 95% of drugs that pass the animal testing stage are immediately discarded because they are useless or harmful to humans. 7 Human consumers need drugs that are proven to be safe and effective before they are prescribed. Because animal testing is unreliable and not indicative to human response, animal testing should be banned and alternatives utilized so that drugs are safer and useful.

HISTORY OF ANIMAL TESTING AND ITS REGULATING LAW

The first record of animal testing can be traced back to early Greece. Aristotle was the first person to dissect animals to reveal internal differences. 8 But it was not until the 19th century that animal testing gained widespread popularity. This movement was made popular by the leading scholars of that time. For example, in 1865, the so-called father of experimental science, Claude Bernard, a French physiologist, published An Introduction to the Study of Experimental Medicine, which in essence stated that information gleaned from laboratory studies far exceeded that gained in human clinical trials and investigation. 9 He concluded, "Experiments on animals, with deleterious substances or in harmful circumstances, are very useful and entirely conclusive for the toxicity and hygiene of man. Investigations of medicinal or of toxic substances also are wholly applicable to man from the therapeutic point of view." 10 He also "succeeded in persuading the scientific community that if any disease could not be reproduced on animals in the laboratory, it simply did not exist-despite accumulated clinical (human) data to the contrary." 11

Other key 19th-century figures in the popularization of animal studies included the renowned microbiologist Louis Pasteur and the noted German physician Robert Koch. Both had limited successes with animal studies that can be attributed to other causal factors. 12 Pasteur was studying rabies and was able to infect the brains of animals and inject this "vaccine" into humans who were bit by a rabid animal. Many of these people did not develop rabies, but clinically, very few humans ever develop the disease after being bitten. Therefore, the people that "recovered" were more than likely never infected in the first place. 13

Koch had similar limited success. He was studying cholera. Previous animal studies he had conducted consisted of giving diseases to animal models. He stated that the microbe reproduced the same in this animal model as in humans. Unfortunately, he had to discredit himself when he was unable to produce cholera in any animal model. 14 Because he had to give up on the animal study and focus solely on human investigation, he was able to isolate the microbe and determine its mode of transmission. This information led to preventive actions to help stop the spread of the devastating disease. 15 His work and study led to the credibility of animal testing despite his reversal later in his career.

Despite dubious laboratory results of the past, animal testing has continued on through the years and is now a mandatory process for drug approval by the FDA. Congress granted authority to the FDA under the federal Food, Drug and Cosmetic Act (FDCA) and the Public Health Service Act. 16 Over the years, many changes have occurred in the FDCA that increased the government's control over medications, labeling, and development processes. 17 One of the requirements of any drug before premarket approval is that the manufacturer has to show that the drug has had proper preclinical investigation. 18 This includes animal studies 19 "before any clinical testing of a new drug is undertaken, of reports, by the manufacturer or the sponsor of the investigation of such drug, of preclinical tests (including tests on animals) of such drug adequate to justify the proposed clinical testing." 20

Therefore, regardless of the rocky beginnings of such science, the government mandates that all drugs go through animal testing to demonstrate a basis for safety and efficiency of the drug.

ANIMALS ARE BIOLOGICALLY AND PHYSIOLOGICALLY DIFFERENT FROM HUMANS

Animals are biologically different from human beings. Animal bodies and their systems react very differently from humans. In fact, animal tests and human results are the same only 5% to 25% of the time. 21 Eighty-eight percent of doctors agreed that animal experiments can be misleading "because of anatomical and physiological differences between animals and humans." 22 When comparing certain drugs and their different effects on humans and then on animals, the results are startling. For example, the drug Thalidomide was found safe in mice and approved for distribution from the German government. It was later found to cause severe birth defects in humans after thousands of babies were born with debilitating defects. Many of those children died before the age of 1. 23 When the manufacturer was sued, it ultimately settled, and there was no judgment made. Many of the experts testifying agreed that the animal tests could not be relied on. 24

More recently, the drug Vioxx was withdrawn from the market. It was manufactured to be an anti- inflammatory medication. It passed animal studies on mice, rats, and African green monkeys. 25 The medication was withdrawn in the fall of 2004. The drug caused cardiac and vascular disease when used in humans. 26 It is estimated that as many as 60,000 Americans have died from the drug and that more than 100,000 Americans have been injured. 27 After an investigation, William G. Bowen, the chairman of the Special Committee of Merck & Co., Inc., concluded "that management acted with integrity and had legitimate reasons for making the decisions that it made, in light of the knowledge available at the time." 28

There are many other drugs that also have had devastating effects on humans after they had been found safe in animal testing. Arsenic is safe in large quantities when given to sheep but is fatal in humans. 29 Chloramphenicol, an antibiotic, was safe in animal testing but caused irreversible damage to the bone marrow of humans. 30 Encainide and flecainide were found safe when tested on animals, and when given to humans, they caused heart attack and death. 31 It is estimated that as many as 3,000 people died from using the drugs. It was withdrawn in 1989. 32 Ibufenac, an anti-inflammatory, caused no liver damage to animal subjects but caused liver damage and death in humans. It was also withdrawn from the market. 33 Domperidone, a drug that was used to help with nausea and vomiting associated with anticancer drugs, caused no heart rhythm changes in animals but caused serious heart arrhythmias in human. 34 These are just a handful of documented drugs that showed safe administration in animals and serious side effects in humans.

In contrast, there are plenty of drugs that are unsafe or deadly to animals while having a beneficial effect on humans. For example, aspirin is deadly in cats and can cause birth defects in dogs, monkeys, and rats. In humans ,it is an analgesic and a therapeutic blood thinner. 35 Penicillin, a great antibiotic for humans, kills guinea pigs. 36 Depo-Provera, a long-acting contraceptive in humans, causes cancer in animals and breast and uterine infections in dogs. 37 Lasix, a common and effective diuretic, causes liver damage in mice but does not affect the human liver. 38 Digitalis, a drug that is used for heart failure and arrhythmias, causes high blood pressure in dogs but does not raise blood pressure when given to human patients. 39 Iron sorbitol, which is used for anemia, causes cancer at the injections site when given to animal subjects but does not when given to humans. 40 If animal tests were reliable and relied on, none of these beneficial drugs would be available for human use.

The FDA claims that they also use animal testing to determine the metabolism of the drugs. "In animal testing, scientists measure how much of a drug is absorbed into the blood, how it is broken down chemically in the body, the toxicity of its breakdown products (metabolites), and how quickly the drug and its metabolites are excreted from the body." 41 Because the systems of animals and humans are different, there is little to be gained from these tests. For example, the drug Digoxin is metabolized in 44 hours in a human and in only 9 hours in rats. 42 Demerol is metabolized in 1.2 hours in rhesus monkeys, 0.9 hours in dogs, and 5.5 hours in humans. 43 It takes Digitoxin 216 hours to be metabolized by humans and only 14 hours in dogs and 18 hours in rats. 44

Not only does the absorption rate needed to metabolize drugs differ between humans and animal subjects, but the lethal doses are also significantly different. Amytal causes death in humans when the concentration reaches 42 mg/kg. In rats, the dose that would cause death is 560 mg/kg. 45 Boric acid is lethal to humans when the dose is 640 mg/kg. In rats, the number rises to 2,660 mg/kg, and the number rises still when given to mice, 3,450 mg/kg. 46 For Lindane, a human lethal dose would be 840 mg/kg, while a rat's lethal dose is significantly smaller, 125 mg/kg. 47

All animals differ from humans when it comes to basic physiological functions. Basic human physiology is as follows: normal breaths per minute are 12 to 20, respiratory tidal volume is 500 ml, heart rate is 60 to 100 beats per minute, and normal body temperature is 98.6 degrees Fahrenheit. Normal breaths per minute for a guinea pig is 120, a mouse 180, a primate 35, and a rat 90. 48 Tidal volumes are also very different. The normal tidal volume in a cat is 30 ml, a guinea pig 2.5 ml, a rat 1.6 ml, and a mouse 0.15 ml. 49 A normal heart rate for a guinea pig is 155 beats per minute, a mouse 570, a gerbil anywhere from 260 to 600, and a normal rat 350. 50 Body temperature also varies. For a gerbil, the normal body temperature is 102.2 degrees Fahrenheit. A mouse's normal body temperature is 99.3 degrees Fahrenheit, and a rat's is 100.4 degrees Fahrenheit. 51 Given all the basic differences, it is impossible to see how a drug meant for a specific body system can be accurately tested when each body system is so different.

Rodents are the most commonly used animals for experiments, but they differ drastically from humans biologically. In humans, plaque is deposited in blood vessels, and this leads to heart attacks and strokes. In rodents, plaque is deposited in the liver. 52 A rodent's life span is only 3 years, while a human has a life span of 72 years. Therefore, a rodent must be given massive doses of drugs to make comparisons, much more then a human will ever use. 53 A rodent can manufacture vitamin C in its body, while a human cannot. A human must obtain vitamin C through diet. 54 A rodent can eliminate drugs from its body in 3 hours; a human eliminates the drug in 72 hours. This increases the danger of a drug when given to the elderly because the elderly take even longer to eliminate drugs because of the aging process of the kidneys and livers. Therefore, the drug stays in their bodies even longer. 55 Rats do not have a gallbladder; humans do. Therefore, the metabolism of fats is completely different. 56 Looking at such varying data, it is hard to imagine what knowledge can be gained about human safety when testing drug effects on these animals.

In addition to biological differences leading to inconsistent data, the environment the animals are kept in affects the way they react to medications and disease processes:

Routine handling, venipuncture, and gavage (the administration of test compounds through an oral tube) elicit striking elevations in pulse, blood pressure, and steroid hormone release that can persist for an hour or more after the event. Similarly, routine features of the laboratory environment-isolation, confinement, social disruption, noise, and restrictions on physical movement-have been shown to be noxious for animals. Together, these bodies of evidence indicate that even routine experiments that appear to be minimally invasive can be highly stressful for the animal subjects, and this finding applies to commonly used rodent species as well as larger and less frequently used animals. Stress effects are relevant to humane concerns as well as to the interpretation of scientific findings. Research on immune function, endocrine and cardiovascular disorders, neoplasms, developmental defects, and psychological phenomena are particularly vulnerable to stress effects. 57

Being that stress itself exerts such an effect on animals, the results of any test performed in this arena are skewed at best. Sometimes simple environment changes, such as bedding and diet changes, have affected disease processes in animals. 58 And yet these are the results that are being relied on for human safety.

ANIMALS DO NOT HAVE THE SAME DISEASES AS HUMANS

When producing drugs, manufacturers are trying to cure a certain disease or aliment. The fact remains that animals do not get the same diseases that humans have. Only 1.16% of human illnesses are seen in animals. 59 "Different species have different biological reactions to disease, viruses, compounds, and so on. Experimental results between dogs and cats differ, as do some results between different strains of mice; therefore it is not practical to apply nonhuman animal results to humans." 60

Animal models for diseases are created by the researcher to be as close to the human disease process as possible. But this can rarely be done. For example, arteriosclerosis is a disease process in which plaque is deposited on blood vessel walls. In humans, this is the main cause for heart attacks and strokes. One of the most widely used animals for these studies are rabbits. They are fed a high-cholesterol diet, and their vessels become blocked. The difference between humans and rabbits is that the rabbit's plaque lesions do not develop fibrosis, hemorrhaging ulceration, or thrombosis. The primary reason for the study is to study these properties. These are the properties that cause complications in humans, and they cannot be replicated in animal models. 61

Cancer is another disease that cannot be replicated in animal studies. Animals are given artificial tumors that differ greatly from spontaneous ones that arise in humans:

Indeed the Lancet (1972) warned that, since no animal tumour is closely related to a cancer in human beings, an agent which is active in the laboratory may well prove useless clinically. This was certainly the case with the US National Cancer Institute's 25-year screening programme in which 40,000 plant species were tested for antitumour activity. As a result of the programme several materials proved sufficiently safe and effective on the basis of animal tests to be considered for clinical trials. 62

Some of the agents produced showed promising results with animal testing, but they were ineffective in humans or too exotic for use. After 25 years of this expansive and expensive program, not one antitumor drug emerged. 63 The National Cancer Institute now uses human cancer cells to accurately screen new drugs. 64

The world of psychotropic drugs gives rise to a completely different issue. There are no animal models for schizophrenia, mania, depression, and other mental illnesses. The drugs that are used to treat these disorders are created from drugs that have had a particular side effect. For example, when trying to find a drug that increases a certain neurotransmitter, they test for the drugs that have that as a side effect. The result is that the drugs are made with serious known built-in side effects from the beginning. Many of the drugs used for mental disorders to block dopamine receptors have side effects such as catalepsy, Parkinsonism, and tardive dyskinesia. 65 Therefore, the medications for these individuals are already set up with devastating, life-altering side effects.

Because animals cannot "catch" human diseases, testing effectiveness of medications is impossible. The results are naturally not able to be transferred to humans suffering from the disorder. These models are set up for failure, and humans who rely on drugs that are tested in this manner are taking risks with their own lives.

THERE IS A LACK OF INTEREST IN DEVELOPING ALTERNATIVE METHODS

Animal testing is big business. It is estimated that trillions of taxpayer dollars along with charity donations fund animal testing. 66 The subjects are relatively cheap and the regulations for their welfare quite broad:

Private institutions, such as facilities that breed animals for research and those companies that make equipment and caging for animals, depend on animal research in order to stay in business. Finally, many of the people who receive federal funding and perform research depend on that money for a living, and for the future success of their career. With all of this money at stake, there is not much incentive for finding alternatives to animal research. 67

And, not surprisingly, the funds needed to develop alternatives are minimal. 68

Government grants, which are essential for research institutions, are influenced by the amount of publishing a researcher can do. Animal testing is quick because animals have a shorter life span than humans, and they can also be euthanized to obtain results. Researchers also find it easier to control the test subjects, unlike clinical testing, where the subjects are human: 69

The more animal experiments the researcher does, the more articles get published. The more articles he gets published, the more grant money he receives. The more grant money he receives, the more money the university receives. The more money the university receives, the better its reputation. The better its reputation, the less liable big business is when the university safely tests its new product and hence the more products they can sell. The more big business sells the more money for advertising and hence the more compliant is the media. And on the other side of this cabal is the unwitting American consumer, paying through the nose for, at best, nothing and worse, ill health. 70

There are many individuals who profit from animal testing and they will not willingly allow the money wheel stop.

In addition to funding issues, the FDA mandates that animal testing be completed prior to approval. 71 Interestingly enough, a new bill, the ICCVAM, has been passed that has looked into alternatives:

An important stride in the use of alternative methods occurred at the end of 2000, when a bill known as the ICCVAM Authorization Act was passed. This bill made the Interagency Coordinating Committee for the Validation of Alternative Methods ( ICCVAM ) an official standing body of the government. ICCVAM validates alternative methods and subsequently recommends these validated alternatives to government agencies (such as the Food and Drug Administration). It is then the responsibility of the government agencies to strongly recommend that the alternatives be used by the institutions that receive funding from that agency. It is important to point out that animal tests have never undergone the vigorous validation process that alternatives must go through. Furthermore, the results of alternative methods are most often compared to animal results. 72

It is hoped that, with the passage of this new bill, alternatives will be seen more seriously and that safer methods can be developed. The next hurdle is whether institutions that do research will embrace the change, which historically has not been the case. 73

ANIMAL TESTING IS DANGEROUS TO HUMANS

Animal testing is relied on to the detriment of humans. Drugs are being produced and given to humans without being truly tested for humans. Therefore, real testing is occurring in human subjects who are given the medication as if it were safe. The FDA approval for safety is a facade. It gives the allusion that the manufacturer has produced a safe product that works the way it was intended to work and that the government agrees. The public accepts that approval as truth and rely on it. When humans are used for experimentation, the FDA requires they be given an extensive informed consent form that outlines the risks involved in participation. 74 Patients who died from taking Vioxx were never given that consideration, but they were, in essence, being experimented on, as are all humans who take a new drug. The researchers do not really know for sure what the human reaction to a drug is until humans start taking it. When humans start taking the drug, the manufacturer really learns if the drug is effective and safe. The people taking the drug do not know that they are being tested on. They do not know the risks associated with the drug because the manufacturer does not even know.

When animal testing is the basis for safety and efficiency, the humans are the one's truly being experimented on. Their reactions to the "safe" drug are the true side effects and toxicity levels.

PROPONENTS FOR ANIMAL TESTING

There are many who, even after seeing the evidence, still believe that animal testing is necessary and essential to human medical innovation. 75 One argument is that animal studies have saved thousands of human lives. 76 The believers look to the advances made in medicine and attribute them to animal research. But the research has indicated that misleading information acquired and relied on from animal studies has injured and killed humans. And there are alternative methods to animal testing that are more accurate in determining efficiency and safety of drugs. 77 These alternative methods can save many more lives.

Proponents also argue that there has been medical knowledge gained through animal testing. But the fact remains that it is impossible to say that those gains would not have been made without animal studies. In fact, the innovation may have occurred more quickly if animal testing were not utilized to mislead the researcher. 78 For example, the researcher who developed the polio vaccine won the Nobel Peace Prize based on his work with in vitro studies on the virus, not the animal studies. "Nobel Laureate Arthur Kornberg noted that for 40 years, experiments on monkeys who had been infected with polio generated 'limited progress' toward a cure. The breakthrough came when scientists learned how to grow the virus from human and monkey cells." 79

Another argument is that testing on animals will show how safe a drug is. This is clearly erroneous. There is an abundance of research that shows that animal testing does not ensure that a drug is safe for human consumption. 80 Many people have died or have been seriously injured after they took a drug that had passed animal testing. The evidence presented here, along with the statistics of medications that are withdrawn from the market, clearly show that animal studies do not guarantee that a drug is safe.

Proponents also argue that if testing is not done on animals, then the drugs have to be tested on humans and that testing on humans is unethical. 81 This reasoning is simply untrue. Because the drugs are not being tested on animals does not mean that they will be tested on humans either. There are not just two options. There are many others. In vitro studies examine study cells in a test tube to see the reaction that the cells have to a chemical. Computers can also be used as models to determine safety. 82 These are just a few of the options that are available.

COMMON-LAW ISSUES AND ANIMAL TESTING

The case law regarding animal testing admittance in trials is shrouded by discussion regarding the rules of evidence and the Daubert standards. The first standard used when looking whether to admit evidence in a trial was made in 1923 in Frye v. United States, the Supreme Court held that as to scientific evidence, the method must be generally accepted in the field where it has come from. 83 This standard was changed in Daubert v. Merrell Dow Pharmaceuticals, Inc. in some jurisdictions. 84 The Court looked to Rule 702 of the Federal Rules of Evidence (FRE 702) and concluded that FRE 702 superseded the Frye standard. 85 The Court stated that FRE 702 was not meant to allow the admittance of all scientific evidence. Thus, the Daubert standard was developed.

The Court held that the trial court is the gatekeeper in regard to expert testimony. All scientific testimony that is admitted as evidence should be both reliable and relevant. 86 To be reliable, the testimony must be "based on recognized methodology and supported by appropriate validation based on what is known." 87 The Supreme Court laid out five factors that are considered when determining the reliability of testimony.

These factors are: (1) whether the theory has been tested; (2) whether the theory has been subject to peer review and publication; (3) the known or potential rate of error; (4) whether standards and controls exist and have been maintained with respect to the technique; and (5) the general acceptance of the methodology in the scientific community. 88

The facts of the case determine which of these factors apply. In addition to these, there are other factors that a court can consider when assessing the reliability of expert testimony:

(1) whether the expert's opinion is based on incomplete or inaccurate dosage or duration data; (2) whether the expert has identified the specific mechanism by which the drug supposedly causes the alleged disease; (3) whether the expert has unjustifiably extrapolated from an accepted premise to an unfounded conclusion; (4) whether the expert has adequately accounted for alternative explanations; and (5) whether the expert proposes to testify about matters growing directly out of research he or she has conducted independent of the litigation. 89

Relevancy is established "only if the expert's reasoning or methodology can be properly applied to the facts in issue, meaning that there is an appropriate fit between the scientific testimony and the specific facts of the case." 90 Therefore, the evidence is irrelevant when there is too great of a gap between the data that are shown and the opinion being offered. 91

As the gatekeeper, the court has a duty to look at the qualifications of the expert and at the methodology used to reach the opinion but not to determine if the opinion is correct. The determination of correctness is left to the fact finder. 92

This is the standard most often used in courts when determining whether animal research is admissible as evidence. In many cases, both the plaintiff and the defendant will file motions to exclude testimony of experts, and the court looks to the Daubert standards in allowing or denying the testimony.

When looking at whether animal testing can be extrapolated to humans, the court looks to the "leap" that has to be made from the purpose or the method of the animal study to the conclusion of the expert. 93 In Re: Baycol is a case involving the prescription drug Cerivastatin, which was marketed under the brand name Baycol. The drug was meant to lower cholesterol levels for people with high cholesterol. 94 The FDA approved it in June 1997. It was withdrawn from the market in August 2001 after it was linked to 31 deaths. 95 When the court in In Re: Baycol was faced with testimony stating that a drug could have long-term effects based on an animal study, it held that the testimony was not admissible because the study was on the animals generally, not specifically on results involving statins. They held that the gap was too great between the animal study and the results of the opinion. 96 Seeing the evidence presented here regarding basic biological and physiological differences in humans and animals, it seems that the argument can always be made that the leap is too large.

Experts themselves have admitted that extrapolating results from small animals is not reliable. 97 The Glastetter case involves a woman who experienced an intracerebral hemorrhage after taking Parlodel. Parlodel had been approved by the FDA for use in women after giving birth to prevent postpartum lactation. 98 The FDA revoked its approval for Parlodel's use in inhibiting lactation approximately 6 months after Glastetter had the intracerebral hemorrhage. 99 In the Glastetter case, after the court denied the admittance of testimony based on the experts admitting that the results were perhaps unreliable, the court went on to clarify that the ruling did not discount all animal studies per se. 100 But the fact remains that the experts were not saying that only their test might have been unreliable, only that all tests that try to extrapolate results from small animals to larger humans are unreliable. 101

Another way that courts have denied results of animal testing is when the dose of the medication used in the animal study is analyzed. "The Eighth Circuit has recognized that because of the dose-response differential between animals and humans, extrapolating to humans from animal studies can be problematic." 102 This is also the case beyond dosing: "Expert opinion testimony has been excluded when the expert fails to take into account the critical differences in animal data and human experiences." 103 The study cannot be seen as reliable when the differences between animals and people are not accounted for. 104 But looking at the differences between animals and people, it stands to reason that there are always unaccounted-for critical differences.

Courts also have denied animal studies where there was a different possible causal connection between the study methods and the conclusion. The court in In Re: Baycol held that testimony was inadmissible when a study was done that used an anesthetic that could cause the same outcome as the drug being tested. 105 Because there was no control group to look at the anesthetic alone, the scientific method was in question, and the animal study was inadmissible. 106

Using the Daubert standards of reliability and relevancy, it is easy to discount all animal studies. It is impossible to take the reaction of one species and apply it to another species that is completely different. Animals and humans are so biologically and physiologically different that even experts in the field state that extrapolating data from one to another is unreliable. 107 Dosing, study methods, and unaccounted-for critical differences in humans and animal subjects are all reasons that courts find animal studies unreliable. 108 The question that remains to be answered is why animal studies are mandated when the courts can find them unreliable and irrelevant.

ALTERNATIVE METHODS

There are alternative methods that have been shown to be better in predicting outcomes for humans than testing on animal subjects. One of these is in vitro studies. In these studies, cells are used to test properties of drugs. These cells can be cancer cells, blood cells, liver cells, and other tissues that are attempting to be understood. 109 Tissues can also be used to test products and reactions. "The National Disease Research Interchange, a non-profit clearinghouse, provides more than 130 types of human tissue to scientists investigating diabetes, cancer, cystic fibrosis, muscular dystrophy, glaucoma, and more than 50 other diseases." 110

Epidemiological studies also make up an alternative that has already saved human lives. These studies look at the human population and using the scientific method determine the causes of diseases and disorders: 111

The basic approach of epidemiology is to compare groups of people. In doing so, it explores whether an association, or a link, exists between exposures and health effects. The comparisons are usually done by placing people into categories. There are two main categories: exposure and disease. A "cohort" study compares groups of people based on exposure. It tries to determine whether disease occurs more frequently or less frequently among a population (or group of people) which has been exposed than among those who have not been exposed. 112

These types of studies have helped discover the transmission of acquired immunodeficiency syndrome and the risk of infants when X-rays are given to the pregnant mother. 113 These types of studies also reduced the risk of heart disease by showing that diet and lifestyle changes had an effect on decreasing the risk of heart attacks. 114

The European Union (EU) has taken the science behind alternative methods to animal testing very seriously. 115 Combining both the desire for drugs to be safer along with ending animal suffering has allowed Europeans to approve six new alternatives to animal testing. 116 The European Centre for the Validation of Alternative Methods is a group whose purpose is to test and approve alternatives to animal studies. The European Centre for the Validation of Alternative Methods is funded from the EU's Research Framework Program with support from member states, industry, and animal welfare organizations. This group validates the alternative methods and submits their findings to the Scientific Advisory Committee for approval. 117 When approved, the methods are then used all across Europe.

The United States is beginning to look at alternative methods more seriously as well. The Environmental Protection Agency, the National Toxicology Program, and the National Institutes of Health have joined forces in developing alternatives that are going to make drugs and chemicals safer for humans. 118 They have signed a memorandum of understanding that details the movement toward that use of alternatives. 119 They are already validating the use of computers with in vitro studies. The computers are able to test thousands of compounds at one time and use a laser to determine the effect on cells. 120 This is not only more accurate then animal testing but also exponentially quicker. 121

As alternative methods are being used and developed, animal studies will become increasingly archaic and inefficient. With the proper funding and backing, alternates will make medications safer and more efficient for human consumption. These advances will truly increase longevity, decrease suffering, and save human lives.

CONCLUSION

Animal studies have negatively influenced medication approval. The studies have deluded the public into thinking that the medications they are taking are safe and effective. The public is then shocked and confused when the medications that they think are safe are causing injury and death.

The FDA mandates that animal testing be done on all medications prior to approval. Given the evidence that demonstrates that drugs affect animals differently because their body systems are different than that of humans, it is erroneous to assume that these tests do anything in regard to human safety.

In contrast to the mandated testing, courts using the Daubert standards can and do reasonably exclude animal study results in trials. Experts who conduct the tests have testified that the results are unreliable when extrapolated from animals to humans. It does not make sense to mandate a test that can easily be seen as unreliable in court.

Alternative methods are becoming more accepted by the scientific community. Given increased funding, the gains in knowledge that can be made are well within reach. The results will give scientists more accurate indications on how drugs will affect humans rather then mislead them with animal reactions.

Therefore, because of misleading information and alternative methods that are becoming more reliable, animal testing should be banned and alternative methods utilized. This will increase patient safety and make drugs more effective.

Footnote

NOTES

1. Kris Hundley, Drug's Chilling Path to Market: How a Broken FDA Approved a Cold Antibiotic Despite a Wide Trail of Alarms, ST. PETERSBURG TIMES , May 27, 2007, http://www. sptimes.com/2007/05/27/Worldandnation/Drug_s_chilling__ path.shtml (last visited June 28, 2008).

2. Facts and Statistics, http://www.chaada.org/Page3.html (last visited June 28, 2008).

3. Id.

4. See 21 C.F.R. § 314.600 (2000), stating animal testing "applies only to those new drug products for which: Definitive human efficacy studies cannot be conducted because it would be unethical to deliberately expose healthy human volunteers to a lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substance; and field trials to study the product's effectiveness after an accidental or hostile exposure have not been feasible."

5. The Beginnings: Laboratory and Animal Studies, http://www.fda.gov/fdac/special/testtubetopatient/studies. html (last visited June 28, 2008).

6. Does Animal Testing Help Human Medicine? 33 Facts to Consider . . . , http://vivisection-absurd.org.uk/33facts. html (last visited June 28, 2008).

7. Id.

8. Biomed for the Layperson, http://www.lpag.org/lay person/layperson.html#enrichment (last visited June 28, 2008).

9. Dr. Robert Sharpe, The Failure of Vivisection, Part 1 "Animal Experimentation: A Failed Technology," http://vivi section-absurd.org.uk/sharpe.html (last visited July 4, 2008).

10. Id.

11. C. RAY GREEK & JEAN SWINGLE GREEK, SACRED COWS AND GOLDEN GEESE, 28 ( Continuum 2000).

12. Sharpe, supra note 9.

13. Id.

14. Id.

15. Id.

16. 21 U.S.C. § 351-360 (2000).

17. Gail H. Javitt, Drugs and Vaccines for the Common Defense: Refining FDA Regulation to Promote the Availability of Products to Counter Biological Attacks, 19 J. CONTEMP. HEALTH L. & POL ' Y 37, 46-55 (2002).

18. Id.

19. Id.

20. 21 U.S.C. § 355(i)(1)(A) (2000).

21. Does Animal Testing Help Human Medicine? 33 Facts to Consider . . . , supra note 6.

22. Id.

23. Thalidomide, CBCNEWS, November 22, 2007, http:// www.cbc.ca/news/background/health/thalidomide.html (last visited June 28, 2008).

24. HANS RUESCH, SLAUGHTER OF THE INNOCENT, 361-62 (Civitas Publications 1983).

25. Animal Research on Trial: PCRM Sues Merck over Vioxx Animal Tests, 2005, http://www.pcrm.org/magazine/ gm05autumn/vioxx.html (last visited July 5, 2008).

26. Id.

27. Merck Wins Victims Lose, June 5, 2008, http://www. mynippon.com/vioxx/?p=106 (last visited June 28, 2008).

28. Letter from William G. Bowen, Chairman of the Special Comm. of Merck & Co., Inc., Report Concerning the Conduct of Senior Management in the Development and Marketing of Vioxx (September 6, 2006), available at http://www.merck.com/news room/vioxx/pdf/bbowen_to_interested_parties_090606.pdf.

29. M. A. FADALI , ANIMAL EXPERIMENTATION: A HARVEST OF SHAME 44-50 (Hidden Springs Press 1996).

30. Id.

31. Id.

32. Id.

33. Id.

34. Id.

35. Id.

36. Id.

37. Id.

38. Id.

39. Id.

40. Id.

41. The Beginnings: Laboratory and Animal Studies, supra note 5.

42. Fiction and Fact, http://vivisection-absurd.org.uk/facts. html (last visited July 15, 2008) (citing R. LEVINE ET AL., PHARMACOLOGY: DRUG ACTIONS & REACTIONS [Medpharm, 1978]).

43. Id.

44. Id.

45. ANDREW N. ROWAN, OF MICE, MODELS, AND MEN, 209 (State University of New York Press 1984).

46. Id.

47. Id.

48. Fiction and Fact, http://vivisection-absurd.org.uk/facts. html (last visited July 15, 2008) (citing P. A. Flecknell, Anaesthesia of Animals for Biomedical Research, 71 BR. J. OF ANAESTH. 887 [1993]).

49. Id.

50. Id.

51. Id.

52. PIETRO CROCE, VIVISECTION OR SCIENCE?, 28 (Zed Books 1999).

53. TONY PAGE, VIVISECTION UNVEILED, 28 (Jon Carpenter Publishing 1997).

54. Id.

55. PAGE , supra note 53, at 29.

56. Id.

57. PCRM Position Paper on Animal Research, http://www. pcrm.org/resch/anexp/position.html (last visited June 28, 2008).

58. CROCE , supra note 52, at 36.

59. PAGE, supra note 53, at 6.

60. Biomed for the Layperson, supra note 8.

61. Sharpe, supra note 9.

62. Id.

63. Id.

64. Id.

65. Id.

66. GREEK , supra note 11, at 97.

67. Biomed for the Layperson, supra note 8.

68. Id.

69. GREEK , supra note 11, at 79.

70. Id. at 97.

71. 21 U.S.C. § 355(i)(1)(A).

72. Biomed for the Layperson, supra note 8.

73. Id.

74. 21 U.S.C. § 355(i)(4) (2000).

75. Bonita de Boer, HIV Drugs, Vaccines and Animal Testing, AVERT , March 3, 2008, http://www.avert.org/hiv-animal-test ing.htm (last visited July 4, 2008).

76. Id.

77. Id.

78. FADALI , supra note 29, at 25.

79. Animals Used for Experimentation FAQs, http://www. peta.org/about/faq-viv.asp (last visited June 28, 2008).

80. de Boer, supra note 75.

81. Animals Used for Experimentation FAQs, supra note 79.

82. Id.

83. Dije Ndreu, Keeping Bad Science Out of the Courtroom: Why Post-Daubert Courts Are Correct in Excluding Opinions Based on Animal Studies From Birth-Defects Cases, 36 GOLDEN GATE U.L. REV. 459, 461-62 (2006).

84. See Daubert v. Merrell Dow Pharmaceuticals, 516 U.S. 869 (1995).

85. Ndreu, supra note 83, at 464.

86. In Re: Vioxx Prods. Liab. Litig., 401 F. Supp. 2d 565, 573 (E.D. La. 2005).

87. Id.

88. Id.

89. Id.

90. Id.

91. Id.

92. Id. at 574.

93. In re: Baycol Prods. Litig., 532 F. Supp. 2d 1029, 1056-57 (D. Minn. 2007).

94. Id. at 1035.

95. Id.

96. Id. at 1056-57.

97. Glastetter v. Novartis Pharm. Corp., 252 F.3d 986, 991 (8th Cir. 2001).

98. Id. at 987-88.

99. Id.

100. Id. at 991.

101. Id.

102. In re: Baycol Prods. Litig., 532 F. Supp. 2d at 1065.

103. Id.

104. Id.

105. Id.

106. Id.

107. Glastetter, 252 F.3d at 991.

108. In re: Baycol Prods. Litig., 532 F. Supp. 2d at 1065.

109. Sharpe, supra note 9.

110. FADALI , supra note 29, at 139.

111. Epidemiology, Washington State Department of Health Studies, July 16, 2004, http://www.doh.wa.gov/Han ford/pub lications/overview/epidemiology.html (last visited July 5, 2008).

112. Id.

113. Id.

114. FADALI , supra note 29, at 140-41.

115. Press Release, March 21, 2006, http://europa.eu/rapid/ pressReleasesAction.do?reference=IP/06/347&format= HTML&aged=0&language=EN&guiLanguage=en (last visited July 5, 2008).

116. Id.

117. Id.

118. Elizabeth Weise, Three U.S. Agencies Aim to End Animal Testing, USA TODAY , February 14, 2008, http://www.usa today.com/tech/science/2008-02-14-animal-tests_N.htm (last visited July 4, 2008).

119. Id.

120. Id.

121. Id.