We are all aware of times when the best path for public health or the environment has been ignored in favor of industrial profit. Unfortunately the money which is made from animal experimentation has far outgrown its scientific usefulness. Since 1847 – 1878, the period when Claude Bernard first established the modern use of animal experiments, a massive financial infrastructure has arisen built on the laboratory animal model, upon which very many research centres, universities and scientists now rely. A realistic appreciation of this finance is key to understanding why experiments on animals still persist.
The Editor in Chief at the British Medical Journal made this the concluding focus of her recent Editors Choice in June 2014, How predictive and productive is animal research? This article concluded by quoting from the paper it cited:
“If research conducted on animals continues to be unable to reasonably predict what can be expected in humans, the public’s continuing endorsement and funding of preclinical animal research seems misplaced.” Where would you place the balance of effort: investment in better animal research or a shift in funding to more clinical research? Read the article here.
Senior scientists involved in medical research are also speaking out about this financial aspect and the pressure placed on them to blur the distinction between ‘basic research’ which is curiosity driven and makes no claim to apply to human patients, and ‘applied research’ which is funded on the premise that it will lead to effective new treatments for human patients. Senior investigator and Director of Research of the Samuel Lunenfeld Research Institute, Dr Jim Woodgett comments on this following an article in Nature: (scroll down to 5th comment):
When we publish our studies in mouse models, we are encouraged to extrapolate to human relevance. This is almost a requirement of some funding agencies and certainly a pressure from the press in reporting research progress. When will this enter the clinic? The problem is an obvious one. If the scientific (most notably, biomedical community) does not take ownership of the problem, then we will be held to account. If we break the “contract” with the funders (a.k.a. tax payers), we will lose not only credibility but also funding...Building only on solid foundations was a principle understood by the ancient Greeks and Egyptians yet we are building castles on the equivalent of swampland. No wonder clinical translation fails so often.
Animal models of human disease still receive the lion’s share of research funding, despite pharmaceutical companies and the wider scientific community openly acknowledging the fact laboratory animal models fail human patients.
Given that finding cures and effective treatments is the issue, we are surprised that no scientist has come forward to represent the animal model community in the vital debate hearing called for by Parliamentary EDM 400.
For more details on the exact sums of money which still drive this outdated and deeply misleading practice in medical research, please read the excellent blog below, written by American doctor Ray Greek, 25th August 2010
A press release from Johns Hopkins:
Researchers at Johns Hopkins have shown that using specific drugs can protect nerve cells in mice from the lethal effects of Parkinson’s disease.
(The scientific article can be read in Nature Medicine.)
There are numerous problems with this statement. I will list only two.
- Mice do not suffer from Parkinson’s disease. Scientists can induce as Parkinson’s-like symptoms, but that is not the same thing as Parkinson’s disease. Mice cannot predict drug and disease response for humans. (See Animal Models in Light of Evolution for more.) This is yet another example of those with a vested interest in using animals misrepresenting the importance of such models. Why do they misrepresent the importance of what they do? Money.
To begin with, universities make money from research that uses animals. With every NIH grant that a researcher receives, the university takes a percentage. The average that the university receives is probably well over 50%. So if a researcher needs $1 million for a research project, he must apply for at least $2 million so the university can take their cut. Ahrens:
No matter how many extramural scientists and other personnel are paid on any one NIH grant, there is only one PI [primary investigator] per grant; and all transfers of funds are made not to PIs personally, but to the institutions in which they are employed. All NIH awards consist of direct cost allowances for salaries, permanent equipment, supplies, travel, and publication costs, but also of indirect cost allowances for administration, energy, security, library, and custodial services. Thus, direct costs support the research institution of the PI, while indirect costs are paid to meet the overhead costs of the institution in which the PI works. (Ahrens 1992)
Where does all this money go? Ahrens continues:
By far the largest percentage of NIH support for new R01’s… is awarded to applicants for studies of animal (or microbial) models of human disease. Yet, most experienced investigators realize that animal models of arteriosclerosis, diabetes, hypertension, and cancer are different in important ways from the human condition they are intended to simulate.
Between 1977 and 1987 only 7.4 per cent of the NIH’s R01 funding went to basic patient-oriented research.
But isn’t all animal use overseen by animal care and use committees?
Since most overhead is brought into the university by a small number of research professors (at Stanford, 5% of the faculty bring in over one-half of the indirect cost dollars), proposals to reduce research output are not looked on with favor by many university administrators. (US_Congress_Office_of_Technology_Assessment 1991)
In 1988, the president of the Institute of Medicine (IOM) cautioned that medical research was leaning too heavily on basic animal experiments and not enough toward clinical observation. He called it an “emperor has no clothes” scenario. (Smith 1988) An IOM survey revealed that NIH gave only 15-17% of total grant money from 1990-1991 to research which could be regarded as human clinical research. This included research with human cells and tissues. Only 4.5% went to lab research involving humans. (Marshall 1994) In 1993, the National Cancer Advisory Board declared that clinical research was in “crisis.” The next year the National Cancer Institute (NCI), a division of NIH, allocated only 1% of its total R01 funds to clinical research. (No_Authors_Listed 1996)
Here are three quotes from The Politics of Pure Science by Daniel S. Greenberg (Greenberg. 1999) that tie into the above.
1) Greenberg quotes from a Report of the Task Force on the Health of Research, Science, Space, and Technology Committee, U.S. House of Representatives, 1992:
. . . the community of federally funded researchers shares many attributes with other interest groups that receive federal support: it resists change; it seeks additional resources as a cure for internal stress; it develops political (i.e., subjective and partisan) strategies to promote its agenda and demonstrate the need for special treatment; it unselfconsciously gives its own values primacy; and, in particular, it strives to show that it is an essential contributor to the national interest.
2) Greenberg quotes from a congressional hearing, (House Committee on Science, Restructuring the Federal Science Establishment: Hearings before the House Science Committee, 104th Cong., 1st sess., June 28, 1995.) where George A. Keyworth II, White House science adviser in the Reagan administration, stated: American science has become a bureaucracy. As with all bureaucracies, preserving the status quo has become the overarching goal, replacing the pursuit of excellence.
However, success in the politics of science has been accompanied by ethical doubts and contention. Failings in openness, collegiality, respect for human and animal experimental subjects, and scientific and financial integrity are common topics in scientific journals and on a thriving conference circuit. The hand wringing, arguments, and recriminations go on, within and beyond the boundaries of science. But ethical concerns are a sideshow of science, providing grist for the press and moralizing politicians, though with little actual effect on the conduct of the research enterprise. Within science, the ethical issues are overshadowed by material concerns. These concerns consume more energy than any attempts to rectify ethical shortcomings. More money for more science is the commanding passion of the politics of science. More is deemed better, including the production of more scientists from a university system that is well supported by, but ingeniously decoupled from, the general economy. Even in these prosperous times, young Ph.D. graduates, once hopeful but now often embittered, stack up in low-wage postdoctoral holding patterns. The growing corporate presence in science arouses unease-as did the military presence, huge and pervasive during the Cold War but now receded, and, strangely enough, mourned in academic quarters for the loss of its money. Nonetheless, the courtship between university-based science and industry persistently intensifies, with academe often the suitor, in single-minded pursuit of more money for science.
In order to understand why the animal model persists, I suggest that you also read Science, Money, and Politics by Greenberg and Trust Us! We’re Experts and Toxic Sludge Is Good For You both by Rampton and Stauber. The scientific value using animals to predict human response to drugs and disease was lost long ago; unfortunately the monetary value was not. Scientists have biases just like everyone else. And, just like everyone else, they like money and some will compromise the search for truth to obtain it.
Ahrens, EH. 1992. The Crisis in Clinical Research: Overcoming Institutional Obstacles. New York: Oxford University Press.
Greenberg., Daniel S. 1999. The Politics of Pure Science: University of Chicago Press.
Marshall, E. 1994. Does NIH shortchange clinicians? Science (5168):20-21.
No_Authors_Listed. 1996. Funding for clinical (patient-oriented) oncology research: current status and recommendations for improvement. American Society of Clinical Oncology. J Clin Oncol. 14 (2):666-70.
Smith, Richard. 1988. News. From the Royal Society’s meeting on the funding of science BMJ 297 (6657):1149-1154.
US_Congress_Office_of_Technology_Assessment. 1991. Federally Funded Research: Decisions for a Decade (OTA-SET-490). Washington, DC: U.S. Government Printing Office. As quoted in Bell, Robert. “Impure Science.” John Wiley and Sons. 1992.
Animal models have misled scientists in the past and this has resulted in human deaths.
Penicillin stayed on the shelf for over a decade because the rabbits Fleming tested it on led him to believe it would be ineffective in humans. Scientists were misled about HIV enters the human cell because of studies on monkeys. The polio vaccine was delayed by decades because the way monkeys responded turned out to be very different from the way humans reacted. The cardiopulmonary bypass machine killed the first patients it was used on and it was only after human data was used that the machine turned was safe. Studying strokes and brain hemorrhage in animals has led to multiple medical treatments that worked in animals but that resulted in harm to human patients. HIV vaccines that protected monkeys have actually increased the risk of contracting HIV in the volunteers that took the vaccine. The flip side of all this is the fact that society has also lost cures and treatments because scientists believed the results from animals: the National Cancer Institute has said that we have lost cures for cancer because studies in rodents have been believed.
Animals simply do not react the same as humans in a reliable manner. More examples:
Cancers in mice have been cured but the cures did not work in humans. Humans respond to tobacco and asbestos by suffering from cancer while most animals do not. Smoking leads to heart disease in humans not animals. High chol leads to heart disease in humans not animals. Babies of mothers who took thalidomide in the late 1950s early 1960s suffered severe birth defects but animals for the most part did not. Rabbits reacted to the penicillin PCN administered by Fleming in 1929 very differently than humans. HRT was administered to women based on animal studies. Every drug that kills people tested safe on animals. (Melanoma in dogs is malignant in nailbed, eye, and mouth.)
Plavix is an anticlotting drugs that is not effective in some people. Plavix is converted by a CYP enzyme in the liver to another chemical that actually does the work of preventing blood clots. If the patient has 2 copies of a variant of the gene coding for this particular CYP enzyme then the drug will not be converted into the active chemical and about 14% of Chinese patients have this variant. However, even patients that have only 1 copy of the variant can also be affected.
Other drugs that are metabolized or processed differently in some way by the body include Iressa, methotrexate, 6-mercaptopurine, codeine, tamoxifen, warfarin aka Coumadin, and succinylcholine. We also know that drugs like 5-FU-based chemotherapies, aspirin, and opiates or other drugs that act on Kappa receptors have effects that vary between the sexes. All of this at least in part explains why 90% of drugs work in only 30 to 50% of the people.
Physicians have realized for decades that people respond differently to drugs. Because of the Human Genome Project and various spinoffs we now have a lot more data about this.
Men are affected differently than women by diseases like cardiovascular diseases and myocardial infarction. But there are a lot more examples.
Caucasians and African-Americans have a similar prevalence of early age-related macular degeneration. However, the progression to the late form of this disease is very rare for African-Americans while being common in Caucasians. Similarly, infantile hemangiomas of the skin are commonly seen in Caucasians but are rare in African-Americans. Certain breast cancers are less common in young black women but usually much more lethal than in young white women even when socioeconomic factors are taken into account. Among cigarette smokers, African Americans and Native Hawaiians are more susceptible to lung cancer than whites, Japanese Americans, and Latinos.
Breast cancer is a good example of a disease that is now treated based on the genotype of the patient and the tumor. It seems like every week I see another study that links a gene to a disease.
Experts in the wider scientific community – outside the animal-based research sector – acknowledge the lack of predictive value animal experiments have for human patients. These experts include pharmaceutical companies, who write about the failure of animal models in their drug development process often and openly in the scientific literature, and the BMJ which published its Editor’s Choice in June 2014, titled How Predictive and Productive is Animal Research?
The president of our medical Board, Dr Ray Greek, speaks about personalized medicine and the life saving significance gene-based medical research and systems biology holds for treating disease in individual patients:
Visit the new PR organisation Speaking of Human-Based Research, ready to help you with your discovery of up-to-the minute valid research methods, viable for patients and urgently in need of all the funding.
Watch the Wyss Institute’s TED talk on personalized medicine and the potential of funding this instead of animal models – which still continue to receive the lion’s share of research funding despite pharma and the wider scientific community acknowledging lab animals fail human patients.
There are many valid research methods that are providing scientists the answers they need in the search for treatments and cures for human disease. Here are just a few:
In vitro (test tube) research on living tissue has been instrumental for many of the great discoveries that have advanced medicine. Though human tissue has not always been employed, it could have been because it has always been in ample supply. Blood, tissues, and organ cultures are ideal test-beds.
Epidemiology is the study of populations of humans to determine factors that could account for the prevalence of the disease within a population or for their disease immunity. Combined with genetic research and other nonanimal methods enumerated here, it provides very accurate information about whole systems.
Bacteria, viruses, and fungi reveal basic cellular and genetic properties.
Autopsy and cadavers are used for clarifying disease and teaching operating techniques such as fracture fixation, spine stabilization, ligament reconstruction, and other procedures. Physical models can be made for studying the wear on joints and other physiological matters of interest.
Genetic research has elucidated many genes that are responsible for specific diseases. Physicians can now ascertain their patients’ predisposition to certain diseases, which allows them to monitor individuals with greater focus and suggest optimal nutrition, lifestyle changes, and medications.
Clinical research on patients shows how humans respond to different treatments and determines whether or not one treatment is superior to another. We can attribute our fundamental knowledge of disease and hospital care to clinical research.
Post-marketing drug surveillance (PMDS) is the reporting process whereby every effect and side effect of a new medication is reported to a monitoring agency, such as the FDA. Despite its obvious benefits, PMDS is practiced rather erratically at the present time, as reporting methods are neither easy to implement nor enforced by the government. It is an underutilized opportunity that should be further explored.
Mathematical and computer modeling is a complex research method that employs mathematics to simulate living systems and chemical reactions.
Technology is largely responsible for the high standard of care we receive today. MRI scanners, CT scanners, PET scanners, X-rays, ultrasound, blood gas analysis machines, blood chemistry analysis machines, pulmonary artery catheters, arterial catheters, microscopes, monitoring devices, lasers, anesthesia machines and monitors, operating room equipment, computer based equipment, sutures, the heart-lung machine, pacemakers, electrocardiograms, electroencephalograms, bone and joint replacements, surgical staplers, laparoscopic surgery, the artificial kidney machine, and many more are examples of technological breakthroughs.
Today we also have stem cell research, gene-based medical research such as pharmacogenetics, toxicogenomics, systems biology, and other areas to study. Another important but oft-overlooked area of study is evolutionary biology. More emphasis needs to be placed on the study of evolution, the place of evolution in disease, and the implications of evolution for disease research and treatment.
When discussing animals as surrogates for humans in drug testing and disease research, society needs ways to test and conduct research that have a high predictive value for humans. We refer to these research methods and tests as predictive modalities. To call these predictive modalities alternatives is to misuse the word.
Animal models are actually a very minor part of research. However, despite not allowing scientists to predict human response, they receive the lion’s share of the research funding. There are 2 points that need to be made:
1. Society does not need new research methods it simply needs to fund the ones we already have. For example, performing research on animals is not going to solve the problem of drug resistant infections. Research in physics on the other hand might because physics offers society the chance to design nanomachines that will mechanically destroy the bacteria. Regardless of the bacteria’s genetic makeup it can be mechanically crushed or chewed up. So society needs the knowledge that would come from underfunded research areas like physics, chemistry, genetics, epidemiology, clinical research and so forth.
- 2. Society needs to make a fundamental change from animal-based research to human-based research. If it is humans we are trying to help then scientists must study diseases and drug reactions in humans. This is already being done but again funding needs to be increased to these areas. The way to accomplish both number 1 and 2 is to stop funding research that does not work, thus freeing up the money that needs to be spent on the research where future cures will come from!
Because an alternative implies that the original modality is a viable one, and that the alternative simply offers a different route to the same destination. This is not true when considering the animal model, because it is not a viable modality.
Many use the word alternative to mean any test that does not harm animals. The problem with this is that it validates using animals as predictive models for humans. Looking for alternatives to tests that don’t work in the first place has been primarily a subterfuge for more funding for animal-based studies.
So how does one properly define the word alternative?
The word alternative comes from the Latin alternare—meaning to interchange. According to The New Oxford American Dictionary it means: “One of two or more available possibilities.” The important thing here is that it implies viability.
A scientifically invalid practice cannot be replaced with an alternative. Consider this example: Eating broccoli is not an alternative to eating rocks for nutrition, but it is an alternative to eating asparagus.
The Encarta Dictionary defines alternative as follows:
Other possibility: something different from, and able to serve as a substitute for, something else.
Example: You could take the bus as an alternative to driving. Note that the original choice in this example—taking the bus—is viable.
Possibility of choosing: the possibility of choosing between two different things or courses of action.
Example: We gave you the alternative; you decided to stay. Again, the original choice—leaving, presumably—is the original and viable choice.
Option: either one of two or one of several things or courses of action to choose between.
Example: I can’t decide which of the two alternatives is worse. Both are viable, just not great.
The Cambridge Dictionary defines alternative as follows: “Something that is different from something else, especially from what is usual, and offering the possibility of choice: an alternative to coffee.” The original choice is viable—in this case, coffee.
Another example: There must be an alternative to people sleeping on the streets. The original is viable; in this case, people are actually sleeping on the streets.
I’m afraid I have no alternative but to ask you to leave (that is what I have to do). Again, the original is viable; in this case, staying is viable if the person behaved better.
The opposition parties have so far failed to set out an alternative strategy. The original is viable; in this case, the original strategy is viable, just not acceptable to all.
An alternative venue for the concert is being sought. The original is viable; in this case, the concert was scheduled for a certain venue and could have been held there, but now needs to be changed.
We could go to the Indian restaurant or, alternatively, we could try Italian. Again, the original choice is viable because indeed the Indian restaurant serves food.
The Three Rs is a concept that has been embraced by groups that would seemingly be on opposite sides of the issue: the animal experimentation community and many in the animal protection community. That fact alone should give one pause: one must question the motivation of groups that support the Three Rs when the very people whose conduct they supposedly oppose also support this concept. This does not prove malfeasance but it suggests closer examination is needed.
The Three Rs has been around for almost 50 years. In 1959, two British scientists, William Russell and Rex Burch, published the results of a systematic study they conducted on the ethical aspects of animal research and the development and progress of humane techniques in the laboratory. This study launched the concept of the Three Rs: Reducing the number of animals used; Refining techniques so the animals suffer less; and Replacing animal-based tests as alternatives are invented.
In the ensuing years, finding alternatives to animal tests—the Replacement component of the Three Rs—has become a cottage industry consuming billions of dollars and employing thousands of people. Yet the Three Rs has been a dismal failure. More animals are used in research and testing now, and more money goes to animal-based studies, than in the 1950s and 1960s when Russell and Burch were popularizing the concept. Additionally, more animals are used now than when the Three Rs groups—the European Centre for the Validation of Alternative Methods (ECCVAM) and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)—were organized.
Why? Because the Three Rs have been applied to animal use that purports to predict human response. As we have discussed earlier, most animal use is justified by scientists to society-at-large on the grounds that it is predictive for humans. If one considers the number of people whose employment hinges on the search for alternatives to tests that don’t work in the first place, it’s no surprise that they are outraged whenever it is pointed out to them that if a test does not fulfill the function it was designed to fill, it should be abandoned for that purpose regardless of what else is or isn’t available.
Waiting to abandon a test that does not work until we can find one that does (finding an “alternative”) is not just a misuse of the word but utter nonsense as well. The Three Rs should never have been applied to animal use that purports to predict human response. But there are more problems with this failed concept.
Q: What other problems do you see with the Three Rs?
To answer that, let’s examine who defends the animals as predictive models industry. They can generally be divided into two groups. The first group is made up of the animal experimenters themselves—those who use animals in research or their representatives. They have their incomes directly linked to animal experiments. The second group is the people involved in the Three Rs industry who, like the animal experimenters themselves, have their incomes linked to strong claims about the predictive utility of animal models. Indeed, the director of the UK’s main lobbyist for the 3Rs: FRAME’s ‘alternatives’ laboratory is an active animal experimenter, Dr Andrew Bennett. Included in this latter group are those who profess to be advocates for animals but who say: “Gosh darn we just have to experiment on animals. We just have to.” (This is a direct quote from the current chairman of the board of a large, prominent animal protection organization.)
What both groups have in common is the difficult problem of saying animals are capable of predicting human response while simultaneously saying that is not why they are used, since the evidence that animals cannot be used to predict human response is overwhelming.
YES. Seven out of the nine main accepted ways animals are used in science are scientifically viable, as outlined below. Our concern is solely with the first 2 categories, highlighted in red, which are not valid uses and fail human patients. The remaining 7 categories are viable, for which there are more efficient, less expensive human-biology based methods which can correctly be referred to as ‘alternatives’, because the original did actually work in the first place.
Animals are used in science today in at least nine different ways:
- 1. Animals are used as predictive models of humans for research into such diseases as cancer and AIDS.
- 2. Animals are used as predictive models of humans for testing drugs or other chemicals.
- 3. Animals are used as “spare parts”, such as when a person receives an aortic valve from a pig.
- 4. Animals are used as bioreactorsor factories, such as for the production of insulin or monoclonal antibodies, or to maintain the supply of a virus.
- 5. Animals and animal tissues are used to study basic physiological principles.
- 6. Animals are used in education to educate and train medical students and to teach basic principles of anatomy in high school biology classes.
- 7. Animals are used as a modality for ideas or as a heuristic device, which is a component of basic science research.
- 8. Animals are used in research designed to benefit other animals of the same species or breed.
- 9. Animals are used in research in order to gain knowledge for knowledge sake.