Week 5. Human and Animal Experimentation

Human Subjects / Clinical Research

(From “Teaching the Responsible Conduct of Research through a Case Study Approach:” AAMC, 1994. Reprinted with permission of the Association of American Medical Colleges) 

Research involving humans entails a rigorous responsibility for the well-being of the research subjects, as well as a delicacy and sensitivity not required when working strictly with test tubes and reagents. Patients make an important contribution to science and society by participating in research protocols. This commitment must invite in return the utmost in respect and diligence from the researcher. In practice, that respect and diligence should include planning studies so that the potential benefits (to both the subject and society) outweigh the potential risks. In addition, steps must be taken to guarantee that subjects are selected equitably and that they make an informed decision about participating. This last concept is known as the principle of informed consent. Informed consent requires that patients be fully informed of the risks and benefits of the protocol and be competent to evaluate this information. Not only must consent be informed, it must also be free of coercion. 

Obtaining informed consent is not always a straightforward issue. For example, the most appropriate method of obtaining informed consent may not be clear. Ensuring that patients fully understand the risks and benefits of a procedure can be a complicated matter as well, particularly where the competency of the patient is in doubt. 

Although there is general agreement that a patient’s well-being should be paramount, the level of risk to which he or she may be subjected is less clear. Even under the best of circumstances, researchers may not be able to anticipate every eventuality of the study. Thus, although patients have been informed at the outset of possible events, unanticipated risks or benefits may arise during the course of the protocol. Researchers must inform patients of these events and make appropriate determinations about whether and how to proceed. For example, even in a double-blinded study, the experimental drug may prove so promising that its therapeutic effects break the blind. At that point physicians must consider whether it is ethical to continue to utilize a placebo in seriously ill patients, when an apparent effective agent is available. 

Animals in Research

(From “Teaching the Responsible Conduct of Research through a Case Study Approach:” AAMC, 1994. Reprinted with permission of the Association of American Medical Colleges) 

Research utilizing animals has contributed greatly to our understanding of nature and the pathophysiology of disease. Animal research not only plays an essential role in improving human health, but in many cases benefits the care and treatment of the animals themselves. Yet the use of animals in research is a matter of significant controversy. Animals rights groups, many of who consider the life of an animal as morally equivalent to that of a human, eschew all animal research no matter what the apparent justification. 

By contrast most scientists and much of the public supports animal research if it is carried out humanely and if research animals are treated well. Often, the priority that these individuals accord animal life is based on distinctions between species and their proximity to humans in the evolutionary ladder. 

Finally, there is general agreement among those who advocate the use of animals in research that there must be appropriate scientific support to justify experiments using animals and the number of animals to be studied. This is accomplished at research institutions through a mechanism known as the Institutional Animal Care and Use Committee (IACUC). The IACUC reviews proposed projects involving animals to ensure they are meeting certain scientific and humane standards. These standards are articulated in part by the principles of humane research on animals as defined by the U.S. Public Health Service (PHS) and the U.S. Department of Agriculture. According to the PHS principles:

  • procedures must avoid or minimize discomfort, distress, and pain to animals, consistent with sound research design;
  • procedures that may cause more than momentary discomfort or slight pain or distress must be performed with appropriate sedation, analgesia, or anesthesia;
  • animals that would otherwise experience severe or chronic pain or distress must be painlessly sacrificed using approved methods of euthanasia during or at the end of the experiment; and
  • the living conditions of laboratory animals must be professionally supervised, appropriate for the species, and contribute to the animals’ health and comfort.
 
Just as with the use of human subjects, the use of animals can present difficult choices and ethical dilemmas. Some questions that scientists may face in animal research include the following:
  • Is it appropriate to use an animal model if an alternative, nonliving system would work, albeit less well?
  • If the use of an analgesic or anesthetic would alter body chemistry in a way to compromise the data obtained, should the need for accurate data outweigh the concern for alleviating pain and suffering?
  • If an animal can survive an experiment, what is one’s obligation to sustain its life after the experiment is completed? Should the species of animal involved weigh in to the decision (i.e., should one feel differently about preserving the life of a rat versus a chimpanzee?)
  • Is repeated experimentation on a single animal justified if it means sacrificing fewer animals overall?

Sample Scenarios

1. From: HHMI Ethics in Biomedical Research
Case Study: Research Using Awake, Behaving Monkeys


Prepared by Denis A. Baylor, Ph.D.
HHMI Senior Scientific Officer

Rita is a first-year graduate student fascinated by neuroscience. She had planned to do her thesis on the neural basis of decision-making, but now she faces a dilemma. Originally, she had hoped to work with a senior faculty member with a superb reputation for research in systems neuroscience. She visited the faculty member's lab and observed the procedures for making electrical recordings and behavioral measurements in awake, behaving monkeys. She came away from this experience profoundly upset — not about whether the animals "suffer" during the measurements, but whether the knowledge gained justifies using the lives of such magnificent creatures. She now wonders how to proceed — whether to pursue this kind of work for her thesis. What should she do?


2. From: Onlineethics.org (http://www.onlineethics.org/Resources.aspx?resource-type=29_772)
Interpreting Consent for Research on Archived Tissue

by Thomas H. Murray, Ph.D.

A researcher believes that breast cancer occurs only when a combination of inherited and acquired genetic mutations occur, and theorizes that biopsied breast tissue might be used to detect earlier pre-cancerous mutations that might help predict who is at increased risk of cancer. The scientist wants to use archived tissue samples and correlate them with later medical records indicating whether the person went on to develop breast cancer. The scientist wants to know whether certain early mutations are especially likely to predict later cancers, or alternatively whether the sheer number of mutations in key sites in the genome might be used as an index of risk.

Given the latency of breast cancer, the scientist prefers tissue at least ten to thirty years old, for which there is accurate and complete medical follow up. Unfortunately, at the time the tissues were obtained, informed consent for their use in research was either not asked at all, or was obtained through a very brief and general consent form. Neither researchers nor patients anticipated this kind of research when the tissues were gathered.

    • Were the consents given then adequate to use the tissue for research today?
    • What if no record of consent exists for a particular sample?
    • Should the persons be tracked down and asked to consent specifically for this study?
    • What are the reasons for or against this course?

3. When the Proposed Research May be Objectionable to the Source of the Tissue

by Thomas H. Murray, Ph.D.

A researcher interested in the genetics of alcoholism has identified what she believes is a candidate gene for susceptibility. Knowing the prevalence of alcoholism is especially high in certain ethnic groups, she asks a tissue repository for samples of tissue from Native Americans living in the Southwest, and from a control group of non-Native Americans from the same region. She neither requests nor needs any identifying information with each sample other than whether it is from a Native American, so that the samples could be taken from unlinked samples.

    • Is it likely that at least some people whose specimens might be used in this study might object to it? If so, what objections might they offer?
    • What arguments might the scientist proposing the study give in favor of obtaining the samples even if some of the sample sources might object if they knew the use to which it was being put?
    • Should institutions or funders of research require that potentially objectionable research be subject to special review? How might such a review be conducted, and by whom?

Readings

Human:

Marshall E. Procedures faulted in fatal asthma trial. Science 293:405-407, 2001.

http://www.sciencemag.org/cgi/content/full/293/5529/405b

Marshall E. Shutdown at Hopkins Sparks a Debate. Science 293:587-589, 2001.
http://www.sciencemag.org/cgi/content/full/293/5530/587

Animal:

Retraction of a paper for failure to have an approved animal protocol.
Case: ICOS and arthritis. JCI 111:701-706, 2003.
http://www.ncbi.nlm.nih.gov/pubmed/?term=JCI+111%3A701-706%2C+2003

Retraction: JCI 112:1597,2003.
http://www.ncbi.nlm.nih.gov/pubmed/?term=JCI+112%3A1597%2C2003

Editorial: JCI 112:1456, 2003.
http://www.ncbi.nlm.nih.gov/pubmed/?term=JCI+112%3A1456%2C+2003​

Reference

Rutgers University School of Law Animal Rights Law Project
http://www.animal-law.org/

National Institute of Environmental Health Sciences: Why Animal Research (Information for nonscientists)
http://www.niehs.nih.gov/health/topics/

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