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Sunday, November 28, 2010

The Ethics Underpinning Oversight

It is common to hear from those within the vivisection industry that research with humans is considerably less constrained by regulations than research involving other kinds of animals.


The U.S. Department of Agriculture has set rigorous standards for the use of animals in research that are more stringent than those used for human studies." Our Commitment to Ethical Animal Care and Use. (p 7)
Johnson and Johnson
Even though the policies for protecting human participants have been strengthened, the requirements for human subjects investigators and IRB members remain less stringent than those of many other regulatory compliance boards, such as those overseeing radiation safety, biosafety, and animal research.

Regulatory Changes Affecting IRBs and Researchers
APS Observer. The American Psychological Society. Sept. 2001.
Is animal research regulated in any way?

Yes. All animal research is subject to strict federal regulations. The United States Department of Agriculture (USDA) has set forth federal regulations governing the care and use of animals in biomedical research that are considered more extensive than those covering human research subjects. The Animal Welfare Act sets these high standards of care for research animals.

If these claims were accurate they might suggest that American society cares less about humans than about other animals; or, if they were accurate, maybe these claims might mean that people experimenting on animals need the law explained to them in much greater detail than do those studying humans.

These claims do not reflect reality. These claims suggest that those within the industry worry about the potential results of the public’s concern and as a result either manufacture misleading claims or else, and probably more likely, have been duped by their industry’s propaganda. Such duping and willful ignorance – “faith” in the eyes of the believer -- or is a common phenomena throughout society and is discussed at length in Phillip Zimbardo’s The Lucifer Effect.

Previous posts and discussions here and elsewhere have addressed the question of whether or not ethics enters into the decision-making process regarding experiments using animals at the University of Wisconsin-Madison. This discussion has been narrowly focused for the most part on the university’s use of monkeys.

One of the many possible stumbling blocks in this discussion is the meaning of ethics. For some, apparently, ethics means compliance with rules and regulations. For others, like me, ethics in this context is synonymous with morality. When arguing that compliance with rules and regulations assures ethical behavior, it is claimed that ethics is built into the rules. This is sort of true, but it misses the point of the bigger question of whether or not we should use monkeys or other animals in the first place.

If we compare the regulation of the use of humans in biomedical and behavioral research with the regulation of the use of other animals we should be able to draw reasonable fact-based conclusions concerning the way these two enterprises are thought about and controlled.

We can look at the language used in the regulations and in the documents underlying the regulations. We can look at the paperwork required for each, and we can look at what is allowed.

The use of humans and other animals in research in the United States and its territories is regulated by the federal government. The use of humans and the use of other animals are each regulated by different laws and regulations, the differing regulations have different purposes, and the regulations each have different histories.

Human research subjects

Regulations controlling the use of humans grew out of the long history of scientists using humans in ways that they expected could or would harm or kill them. The most well-known and often cited example is the medical research conducted on humans in Nazi Germany. The result was "The Nuremberg Code", a set of ten guidelines written in 1949 by the judges presiding over the “Doctors Trial.”

The Nuremberg Code is a landmark document. It has been called the most important document in the history of the ethics of medical research. It is germane to note that the Nuremberg Code requires experiments on animals prior to experiments on humans but requires no initial consideration concerning the use of animals.

In 1964, the World Medical Association issued its Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects, which begins with the clear statement of purpose and intent:
The World Medical Association has developed the as a statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects. Medical research involving human subjects includes research on identifiable human material or identifiable data.
The clear unambiguous intent of the Nuremberg Code and the Declaration of Helsinki is the protection of people used in scientific research. The Declaration of Helsinki includes the directive that if appropriate, experiments on animals should proceed human experimentations and that “the welfare of animals used for research must be respected.”

In the United States, the National Research Act of 1974 was passed as a result of the political embarrassment over the disclosure that men had been left untreated and had died as a result in the Tuskegee Syphilis Study which was halted in 1973.
SUMMARY: On July 12, 1974, the National Research Act (Pub. L. 93-348) was signed into law, there-by creating the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. One of the charges to the Commission was to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines which should be followed to assure that such research is conducted in accordance with those principles.
The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research the produced the Belmont Report: Ethical Principles and Guidelines for the protection of human subjects of research. “The Belmont Report attempts to summarize the basic ethical principles identified by the Commission in the course of its deliberations.”

In 1981, the Department of Health and Human Services and the Food and Drug Administration issued regulations based on the Belmont Report. DHHS issued the Code of Federal Regulations (CFR) Title 45 (public welfare), Part 46 (protection of human subjects).

In 1991, 45 CFR 46 Protection Of Human Subjects, Subpart A, known as “The Common Rule” was officially adopted by most federal agencies using human research subjects.

“The Common Rule” requires among many other things that an Institutional Review Board (IRB) review, approve, and oversee all research involving humans at each institution:
§46.107 IRB membership.

(a) Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution. The IRB shall be sufficiently qualified through the experience and expertise of its members, and the diversity of the members, including consideration of race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. In addition to possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas. If an IRB regularly reviews research that involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects.
Repeated throughout the regulatory literature mentioned above is the underlying frequently repeated intent to treat human subjects with respect and to keep their individual safety and dignity paramount in any research design. “The IRB shall be sufficiently qualified through the experience and expertise of its members, ..., to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects.”

For more on the regulation of human-based research see:

NIH Regulations and Ethical Guidelines

University of Nevada Las Vegas History of Research Ethics

Non-human research subjects

In the United States, laws governing the use of animals emerged directly from the theft of dogs and their sale to research laboratories. The first regulations were intended to protect the rights of pet owners rather than the animals themselves.

A “Legislative History of the Animal Welfare Act” is available on the National Agricultural Library website. It provides a useful bibliography and history.

Compare this summary of the meaning and intent of the laws and regulations governing the use of animals with the passages above regarding the use of humans:
All of these codes are the philosophical foundation for the development of laws that protect animals as property. They limit liability for the owner or for the animal. They set forth rules regarding the theft of animals, the use of animals in the punishment and execution of criminals or traitors, religious sacrifice, and provide for the legal standing of animals. The predominate rationale in these codes is based on the protection of property, the protection of the owner’s investment, and sanctions imposed by society for violating its notions of justice. These factors are not surprising if one considers the importance of animals to the early agricultural societies.
It is difficult to find among the large body of documents included in the “Legislative History of the Animal Welfare Act” any assertions similar to those found throughout the regulatory history of human experimentation.

There is no Belmont Report addressing the use of animals.

United States Code, Title 7, Chapter 54 § 2143 “Standards and certification process for humane handling, care, treatment, and transportation of animals,” creates the regulatory framework that controls the use of animals in laboratories. It also establishes the requirement of an Institutional Animal Care and Use Committee (IACUC) at each institution, a committee parallel in form to that of the IRB mentioned above:
(b) Research facility Committee; establishment, membership, functions, etc.
(1) The Secretary shall require that each research facility establish at least one Committee. Each Committee shall be appointed by the chief executive officer of each such research facility and shall be composed of not fewer than three members. Such members shall possess sufficient ability to assess animal care, treatment, and practices in experimental research as determined by the needs of the research facility and shall represent society’s concerns regarding the welfare of animal subjects used at such facility.
Notice that “The IRB shall be sufficiently qualified through the experience and expertise of its members, ..., to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects” while the IACUC “shall represent society’s concerns regarding the welfare of animal subjects.” One committee is charged with protecting the research subjects while the other is charged with representing society’s “concerns.” In practice, the results are grossly disparate.

This is because the Act has an escape clause unlke anything found in the regulations governing human-based research:
(6) (A) Nothing in this chapter—
(i) except as provided in paragraphs [1] (7) of this subsection, shall be construed as authorizing the Secretary to promulgate rules, regulations, or orders with regard to the design, outlines, or guidelines of actual research or experimentation by a research facility as determined by such research facility;
(ii) except as provided [2] subparagraphs (A) and (C)(ii) through (v) of paragraph (3) and paragraph (7) of this subsection, shall be construed as authorizing the Secretary to promulgate rules, regulations, or orders with regard to the performance of actual research or experimentation by a research facility as determined by such research facility; and
(iii) shall authorize the Secretary, during inspection, to interrupt the conduct of actual research or experimentation.
In other words, and in actual practice, anything is allowed to be done to animal subjects so long as it is approved by the IACUC and documented.

National Institutes of Health regulations governing the use of animals in research rely heavily on the Guide for the Care and Use of Laboratory Animals. The Introduction to the Guide makes its purpose clear:
The Guide is applicable only after the decision is made to use animals in research, teaching, or testing. Decisions associated with the need to use animals are not within the purview of the Guide,...
The NIH Office of Laboratory Animal Welfare is charged with ensuring that funded institutions and researchers are in compliance with the Guide. Additionally, NIH has promulgated a number of documents addressing the use of animals in the research it funds. One of these is the Public Health Service Policy on Humane Care and Use of Laboratory Animals.

The "U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training" looks superficially like the Nuremberg Code. And, the "Principles" have been offered as evidence by researchers at the UW-Madison that ethical principles are built into the oversight committees’ deliberations. But a glance at each makes clear that one is intended to protect one group of subjects while the other is intended to govern how another group may be imprisoned, harmed, and killed.

If the "Principles" were cited as a guide to the use of humans no one would argue that meaningful ethical deliberation had occurred.

But everything above is academic. The scalpel meets the flesh at the paperwork required by federal law and regulation prior to using either humans or other animals and it is this regulatory burden and the resulting limitations and requisites therein that animal researchers seem to refer to when that they claim to be more regulated than scientists using human subjects.

The form researchers submit to their IRB is the “Application for Initial Review of Research Projects Involving Human Subjects.” The form researchers submit to their IACUC is the “University of Wisconsin - Madison Animal Care and Use Protocol Review Form.”

The Human Subjects form is twenty-one pages long. (The Human Subjects form was recently removed and replaced with a web-based form that is not accessible to the public.)
The Animal Care and Use form is nine pages long.

The Human Subjects form requires a “Submission Cover Sheet for Initial Review and Ongoing Studies,” which is five pages long.
It also requires a one page “Potential Financial Conflict of Interest Assessment Form.”
See too: University of Wisconsin-Madison Health Sciences Institutional Review Boards

Looking at the two forms, it seems clear that one expects the subjects to be seriously harmed and the other expects the subjects to be well protected from harm. The Human Subjects form asks about the length of stay required by subjects; the Animal Care and Use form leaves unsaid that the subjects are incarcerated for their entire lives.

Regulation of human use rests on the idea that the research is voluntary, that the subject can terminate their participation at any time, and that a subject’s best interests must prevail.

In actual practice, regulation of nonhuman use rests on the idea that animals are consumable commodities, that their use is justified by even the most remote and most unlikely possibility that some knowledge will be gained through using them.

All in all, it is difficult to find any evidence that regulations governing research using animals have more than a superficial similarity to the regulations governing research using humans.

It is difficult to find evidence that researchers using animals engage in formal discussions of the ethical issues associated with animal use or that there has ever been discussion and deliberation similar to that underpinning the regulation of human use.

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