Alternatives In Research

“If we are to use a criterion for choosing experiments to perform, the criterion of humanity is the best we could possibly invent.”

There are scientifically validated alternatives that are better than using animals in research. In 1959, Russell and Burch published The Principles of Humane Experimental Technique, which introduced the “3Rs” of alternative experimental methods.1 In addition to elucidating the concepts of humane research and the importance of alternatives, the 3Rs advocate for test methods that

  • Refine animal use by lessening or eliminating pain or distress in animals, or enhancing animal well-being
  • Reduce animal use by decreasing the number of animals required for testing while still obtaining the testing objectives
  • Replace animal use with either non-animal methods or a less developed animal species (for example, replacing a mouse with a fish)

Simply stated, these alternatives exemplify a scale of varying degrees of decreased animal use and suffering and have come to be applied, not just in regulatory toxicity testing, but in all areas of research and testing. Replacement methods represent the ultimate goal of the alternatives approach to basic biomedical research, testing, and education—and it is the alternative that NEAVS is committed to realizing.

Today, there is a vast range of non-animal research methods available to researchers. Russell and Burch, Ethel Thurston, and others placed the concept of alternatives squarely on the doable scientific map. Alternatives are proving not only more humane, but more cost-effective, faster, and more relevant to humans.  Some alternatives to the use of animals in research include:

Epidemiological studies

Epidemiology is the study of naturally occurring (versus experimentally induced) disease and health in human populations. Results of epidemiological data collected over years (longitudinal studies) have provided researchers and health practitioners with the understanding of causes, treatments, and preventions of a range of human illnesses. Epidemiology exists in the interest of individual and public health. Epidemiological researchers are committed to the dissemination of preventative information, changes in policy that will affect health and well-being, and other aspects of public health medicine. Epidemiology is an extremely important method to identify risk factors for disease and to determine optimal treatment approaches to clinical practice, which typically will include lifestyle changes, and understanding of the role of genetics and potential environmental contributors to illness.

Epidemiological studies, for example, revealed that smoking is associated with lung cancer, and it was the first area of research to identify AIDS when rare infections and malignancies surfaced in patients in the late 1970s. Further, the famous Framingham Heart Study, ongoing for the last 60+ years, has given us more information about the causes, preventions, symptoms, and evidences of heart disease than any other single area of heart research.

Some recent research milestones discovered without animal testing from the Framingham Heart Study include

  • Learning that sleep apnea is tied to increased risk of stroke
  • Pinpointing additional genes that may play a role in Alzheimer's
  • Finding that fat around the abdomen associates with smaller, older brains in middle-aged adults
  • Detecting that genes link puberty timing and body fat in women
  • Determining that having a first-degree relative with atrial fibrillation is associated with increased risk for this disorder
  • Discovering hundreds of new genes underlying the major heart disease risk factors—body mass index, blood cholesterol, cigarette smoking, blood pressure, and glucose/diabetes
  • Identifying first definitive evidence that occurrence of stroke by age 65 years in a parent increases risk of stroke in offspring by 3-fold

In vitro research and human cell and tissue cultures

In vitro (test tube or “in glass”) research and human cell cultures have proven superior to animal tests for a multitude of purposes. Human cells and tissue cultures studied “in glass” have advanced our knowledge of human disease. Some significant findings from in vitro testing include cancer-screening treatments, testing drugs with biochips, and replicating human skin for research. The primary advantage of in vitro research is that it permits simplification of the system or disease under study, allowing the investigator to focus on a small number of components. In vitro models of the brain and the blood-brain barrier are being used for studies of neurotransmitter pathways, electrophysiological characteristics, morphological associations of human diseases (i.e., Alzheimer's, Parkinson's, Huntington's, and epilepsy), new drug designs, receptor targets, and modes of action of new pharmaceuticals.

In the lab, researchers culture cells or tissues obtained from human volunteers, surgical operations, biopsies, and post-mortem specimens and use them for in vitro studies. Tissue culturing is an important tool for the study of the biology of cells from multi-cellular organisms. It provides an in vitro model of the tissue in a defined environment for analysis.

Though surrounded by controversy because of potentially unethical procurement and uncompensated commercial use of the human cells, there are infinite possibilities of using human cell lines. For example, in 1951 Henrietta Lacks died of an aggressive form of cervical cancer. Researchers harvested her cells, called HeLa cells after (He)nrietta (La)cks, without family approval or knowledge. Henrietta’s “immortal life” through her cells has been

…part of researching the genes that cause cancer and those that suppress it; they helped develop drugs for treating herpes, leukemia, influenza, hemophilia and Parkinson’s disease, and they’ve been used to study lactose digestion, sexually transmitted diseases, appendicitis, human longevity, mosquito mating, and the negative effects of working in sewers. Their chromosomes and proteins have been studied with such detail and precision that scientists know their every quirk. … Henrietta’s cells have become the standard laboratory workhorse.2

Clinical studies

We cannot rule out the value of human volunteers in research, and carefully designed and managed clinical studies can yield significant results without the use of animals, or harm to humans. Many individuals with both ordinary and terminal illnesses are willing to volunteer for new drug or treatment trials, or be part of a study collecting data on their illness. The numbers of ongoing human clinical studies testify to the fact that there is no shortage of volunteers. Studies with humans—both clinical non-invasive research performed with the highest ethical standards, and longitudinal epidemiological research—may in fact be two of the best alternatives to animals.

For example, if we want to know how healthy aging brains function and how cognitive impairments affect real individuals and families, it is best to study people in different stages of their lives—from 18 to 80 and beyond, as is done in clinical and epidemiological studies. In fact, more than 300 human clinical studies of aging, cognition, and memory were underway in 2007. While some research programs conduct memory and cognitive testing, others help seniors figure out how they are doing and then engage them in appropriate support programs. The University of Illinois has developed one such program called Senior Odyssey, where group problem solving and puzzles help seniors learn coping skills and get a mental workout.3 Sadly, Yerkes National Primate Research Center is also conducting aging studies on a population of humans, chimpanzees, and monkeys—species who will contribute little to the data garnered from the humans in the study, but will contribute to Yerkes’ justification of its animal laboratories and the research dollars they bring in.

Autopsies and post-mortem studies

Human autopsy is the examination, after death, of the tissues and organs of the human body to determine the cause of death or existence of pathological conditions.4 Autopsy research has been responsible for the discovery and description of thousands of diseases, including Legionnaire’s disease, viral hepatitis, aplastic anemia, and fetal alcohol syndrome. The principal aim of an autopsy is to determine the cause of death, the state of health of the person before he or she died, and whether any medical diagnosis and treatment before death was appropriate.

As a result of people donating their bodies to research, organ banks now exist, giving researchers’ access to the supply along with detailed information about the person’s medical history. McLean Hospital in MA, for example, houses the Harvard Brain Tissue Resource Center. First funded by the National Institutes of Health (NIH) in 1978, their “Brain Bank” is now the largest brain tissue research center in the world. It currently has over 6,000 donated human brain specimens, most from donors who had neurological disorders. The center serves as an important resource for studying neurological diseases like Alzheimer’s, Parkinson’s, etc.

Computerized patient-drug databases and post-marketing surveillance

Computer technology can collect detailed comprehensive records and maintain cross references on the side effects of drugs, treatments, etc. Once stored in a central database, researchers can rapidly identify dangerous drugs or interactions. Post-marketing surveillance of patients can also identify unexpected beneficial side effects. In fact, clinical observation of patient side effects led to the discovery of the anti-cancer properties of nitrogen mustard and actinomycin D, and the mood-elevating effects of tricyclic antidepressants.

Mathematical models and computer simulations

Computer-based alternative methods produce computational disease and treatment models, collect and manage millions of human research data points, and carry out human clinical trials virtually. Computer model programs are able to simulate sophisticated anatomical functions such as heart rate and, along with other data, can be used to determine disease or predisposition to certain illnesses. For example, computer simulations of cancer cells are now used to test drug targets within them, and “mathematical models have helped to further our understanding of HCV [hepatitis C] dynamics and clinical trial results in humans.”5

Non-invasive imaging techniques

Non-invasive imaging is the method used to create images of the body for clinical purposes (medical procedures seeking to reveal, diagnose, or examine disease) or medical science (including the study of normal anatomy and physiology). Imaging technology such as the CT scan (computed tomography), MRI (magnetic resonance imaging), AMS (accelerator mass spectroscopy), MEG (magnetoencephalography), DTI (diffusion tensor imaging), ultrasound, and nuclear imaging are all alternatives to utilizing unreliable animal models to produce results specific to humans. These non-invasive techniques allow very sophisticated, real-time measurements of associations between structure and function in humans and are accurate with resolutions possible down to single cells. These imaging options have had their most extensive applications in the neurosciences, allowing direct, noninvasive studies of human neurophysiology.

Chromatography and spectroscopy

These are physical and chemical techniques that identify, isolate, and measure compounds in drugs, toxins, and bodily fluids, such as blood, urine, or saliva.

Conclusion

We cannot afford—in human health, tax dollars, and animal suffering—to repeat the past failures of animal experiments. Rather than wasting millions of dollars and precious time, and bearing the ethical costs of experimenting on so many sentient and intelligent beings, we can and should turn to humane, human-based science that is more promising, effective, and reliable.

A compelling example is our war on obesity in the U.S. The federal government is currently funding an obesity study involving rhesus monkeys. Researchers, since February 2011, intentionally over-feed the monkeys with rich, fattening foods, and lock them in cages, allowing them no access to exercise or other stimulation. This unnatural diet and severe physical restrictions cause extreme stress in the animals, especially since they are typically very active by nature. The intent of the study is to examine obesity’s causes and effects on the body, and potentially related diseases such as heart disease or diabetes. Instead, obesity solutions for humans should come from active medical and policy intervention (e.g. healthy meals at all publicly funded schools, regulation prohibiting  additives known to be related to unhealthy diets, etc.) to help reduce or eliminate the psychosocial causes of obesity in our society. Further, the development of effective public health education programs regarding better food choices and healthier lifestyles should be a federal funding priority—not animal models of obesity. Thankfully, the federal government is making changes by stepping in to educate people and fund obesity programs on the local level in schools—a far better solution to the current obesity epidemic.

According to a July 2011 report by the Trust for America’s Health Executive Director, Jeff Levi, “’We can’t afford to ignore the impact obesity has on our health and corresponding health-care spending,’ … A combination of fewer calories, healthier foods and more physical activity is needed to start cutting pounds, researchers report. Drastic solutions like weight-loss surgery and prescription drugs are costly, last-ditch efforts meant only for people already suffering complications from their weight—not a society-wide solution.”6 As more and more clinical data confirms the short and long-term negative effects of lifestyle choices and sociocultural values that lead to things like obesity and smoking, the government and researchers need to prioritize routes to prevent the spread of these problems and treat those already suffering from them. Continued funding of “animal models” will not, because it cannot, decrease the ever-increasing risk of major and life-threatening complications that result from choices which can and should change.


[1] Russell, W., & Burch, R. (1959). The Principles of Humane Experimental Technique.

[2] Skloot, R. (2010). The Immortal Life of Henrietta Lacks. New York: Crown Publishers.

[3] Bailey, J. (2011). Bad medicine: Using elder chimpanzees in human aging research. Project R&R.

[4] Kapis, M. B. (1993). Human autopsies in biomedical research. In M.B. Kapis,  & S.C. Gad, (Eds.), Non-Animal Techniques in Biomedical and Behavioral Research and Testing. Ann Arbor, MI: Lewis Publishers.

[5] Bailey, J. (2010). An Assessment of Chimpanzee Use in Hepatitis C Research: 2. Alternative Research Methods. ATLA, 38(6), 471-494.

[6] Metro News. (2011, July 7). Fat rising: obesity up by 90% in many U.S. states.

 

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