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.

Sunday, November 21, 2010

Marolt to Streiffer on Housing

Below is another post from Rick Marolt. I supplied the title. The 'Housing' bit is simply to tag it with a term that will distinguish it from other possible future related posts.



I have asked Rick Bogle to elevate this comment to a main post because 1) some issues raised in the discussion merit more visibility and 2) I want to encourage other people to participate in the discussion. Many people read this blog. What do you think of these issues? See the original post and comments here.

Rob Streiffer:
Second, I asked whether IACUCs have the authority to address ethics questions. I argued that they do and fail to understand your basis for saying that IACUCs "are constituted by law not to make ethical decisions." To which federal regulation are you referring? At any rate, it is misleading to say I made this claim "without providing evidence," as I cited examples of rules from the U.S. Government Principles which require IACUCs to frequently make ethical determinations about animal housing and about whether the value of the research justifies the harm to the animals. Perhaps you disagree with my argument here, but I did make one.

I cannot tell what statement of mine you think is misleading. I wrote: "The committee claimed, without providing evidence, that they make ethical decisions all the time." I think that statement is true. I see no such evidence in your statement or Sandgren's statement and I do not recall hearing such evidence at the committee meeting. Citing rules that require the ACUCs to do something, which you have done, is not evidence that they actually do it. Saying that the ACUCs do something, which Sandgren has done, is not evidence that they actually do it.

After the ACUC meeting last January, I asked Sandgren for evidence: minutes of meetings where specific experiments were approved, documentation of decisions not to approve an experiment because the benefits were not projected to exceed the costs, and evidence that benefits of completed experiments exceeded their costs. Sandgren was not able to provide such evidence.

Rick Bogle has responded to the point about ACUCs and ethics. Note also that the Animal Welfare Act, which contains the requirement of research organizations to have ACUCs, says: "Such members shall possess sufficient ability to assess animal care, treatment, and practices in experimental research ..." and the responsibilities listed have to do with assessing animal care, treatment, and practices. Members are not required to have expertise in ethics. The words "ethics" and "ethical" do not appear in the AWA. The AWA says nothing about larger ethical decisions such as whether or not experimenting on a given species is ethical, and those are the decisions that I am talking about.

ACUCs exist to ensure compliance with federal regulations concerning the treatment of non-human animals. They operate within a system that assumes that keeping monkeys in cages for their whole lives, giving them diseases, birth defects, and brain damage, and killing them are acceptable actions. (You might say that the ACUCs decide case-by-case when these things are ethical and when they are not. But the ACUCs have approved very many experiments of these kinds, and I am aware of no evidence that the ACUCs ever find such experiments unacceptable or unethical.) There is a deep, underlying assumption that treating monkeys in a certain way -- much differently from how we treat people -- is acceptable. The ACUCs do not question that assumption.

Let's imagine that UW-Madison keeps people in small cages their whole lives and conducts injurious and fatal experiments on them. I question the ethics of experimenting on people. You say "We make ethical decisions all the time about how to house the people and we approve experiments only when we think that the value of the research justifies the harm to the people." Most reasonable people would say that you missed the point. And you're missing the point about monkeys.

I did not mean to say that the ACUCs cannot or should not (or even do not) make ethical decisions, only that ACUCs are constituted primarily to make other decisions. My wording probably could have been better. And, yes, decisions about housing can have an ethical component. But what about a bigger question such as whether or not experimenting on a given species is ethical? That's the question that matters most. And you have argued that the ACUC should not even try to answer it. So all this talk about the ACUCs making ethical decisions is pretty minor quibbling and not very relevant to the bigger issues.

Except ... your statement includes this excellent paragraph:
IACUCs are required by law to prohibit any research that is not in compliance with what are referred to as the U.S. Government Principles. Principle VII requires that “the living conditions of animals should be appropriate for their species and contribute to their health and comfort.” It would thus be within the IACUC’s jurisdiction to prohibit research with a species if they concluded that appropriate housing conditions on campus could not be secured. (Imagine a researcher trying to bring chimpanzees onto a campus that can only secure funding for cages of the size typically used for macaques.) A decision about the appropriateness of housing conditions, which falls squarely within the jurisdiction of an IACUC, can amount to a prohibition on a certain kind of research. An even clearer, second, example comes from Principle II, which requires that “procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society.” So if an IACUC finds that procedures involving animals do not produce sufficiently important knowledge, then it is within the IACUC’s legitimate authority to prohibit that research.
So let's ignore the bigger issues for a moment and just focus on housing, since you have brought it up. Both you and Sandgren have cited the U.S. Government Principles. Now, there is much evidence that monkeys suffer in their little cages, that they get chronic diarrhea, and that they mutilate themselves out of boredom and isolation. Some people say that the monkeys become neurotic or even go insane. A former UW-Madison veterinarian has written:
Each monkey was kept alone, in a cage that was so small that he/she could not take a few steps in one direction, let alone jump or run in monkey fashion. There was no companion to huddle, groom or play with.

It should be remembered that macaques are primates - just like us - who have an intensive need for social contact and social interaction. Solitary living conditions are similarly unbearable for them as it would be for us.

Most cages were completely barren, offering not even a perch that would have allowed the animals to make use of the arboreal dimension. In the wild, macaques spend most of the day in elevated sites - away from ground predators - and seek the refuge of trees at night.

When kept in cages without a high perch, the animals have no way of retreating to a "safe" place during alarming events, such as when a staff member approaches them. Being cornered in this manner must, indeed, be a very distressing experience for a helpless monkey who associates people with painful and distressing handling procedures.

In order to accommodate as many monkeys in one room as possible, cages were arranged in double-tiers with one row stacked on top of the other. This condemned half of the animals to confinement in a permanently shady, cave-like environment. Needless to say, this was not a living quarter that was suitable for diurnal animals.

The conditions I witnessed were so depressing that most monkeys had developed stereotypic behaviors such as pacing, rocking, bouncing, somersaulting, swaying from side to side, biting parts of their own bodies, pulling their ears, tossing their heads back and forth, or smearing feces on the cage walls. (Viktor Reinhardt, "The Impossible Housing and Handling Conditions of Monkeys in Research Laboratories")
It's impossible to argue that the monkeys' housing is "appropriate for their species and contribute[s] to their health and comfort". (Please don't tell me that the little enrichment that the monkeys receive makes their housing appropriate for their species and contributes much to their health and comfort.) If the ACUCs make ethical decisions all the time about things like housing, when are they going to correct this situation? And if they cannot correct it, isn't it time for a "decision about the appropriateness of housing conditions" that "can amount to a prohibition on a certain kind of research"?

If your argument means anything, this topic will be on an upcoming ACUC meeting agenda and the committee will consult with experts before making a decision.

Let's talk about Principle II, which you brought up. If a utilitarian standard is used, only actual benefits matter, not just knowledge (unless you're going to argue that the satisfaction that a few people get from gaining and having knowledge justifies the suffering and deaths of monkeys). So I would revise your sentence: "If an IACUC finds that procedures involving animals do not produce sufficient benefits, then it is within the IACUC’s legitimate authority to prohibit that research."

Paul Kaufman and Eric Sandgren have said that there is a "low hit ratio" in translating basic science into health benefits, and one survey of 25,000 articles concluded that that hit ratio is just about 0% (W. F. Crowley, Jr., Am J Med 114, 503 - Apr 15, 2003), so there must be a lot of research that should be prohibited.

If your argument means anything, then the ACUCs will identify research that does not produce substantial benefits and prohibit it.

While I'm critiquing the ACUCs, I must note also that they are required to "represent society's concerns regarding the welfare of animal subjects". Evidence that many people and organizations in Madison have deep concerns about experimenting on monkeys became clear during discussion of Resolution 35 on the Dane County Board of Supervisors last summer. But UW-Madison declined, with the help of your statement, to study the ethical issue and it fought hard against Resolution 35. How and when do the ACUCs at UW-Madison represent society's concerns regarding the welfare of animal subjects? (If you, like I, distinguish the main ethical question from welfare issues, note that the scope of Resolution 35 included treatment of monkeys.) Please don't tell me that just having one or two ACUC members come from outside the UW takes care of this responsibility of the ACUCs.

Third, I asked whether UW was obliged to comply with your request. I argued that it was not. Not because I ignored "all the scientific and morally significant findings about monkeys that raise the ethical question," as you mistakenly say I did. To the contrary, I explicitly acknowledged them.
You did indeed mention some scientific and morally significant findings about monkeys. The committee then ignored the implications of those findings when it chose not to study the ethical issues.

The validity of most or all of your other points is clear and I have no disagreement with them. But they are not very relevant to the main issue.

Friday, November 12, 2010

Let's set the record straight

A guest post from Rick Marolt:

Eric Sandgren, who frequently serves as UW-Madison's spokesman for animal research, said in a public forum recently that local critics of experiments on animals are wrong when they claim that UW-Madison did not take up the ethical issue of experimenting on monkeys. In that public forum, Sandgren said more than once that people cannot believe what they hear because critics of experiments on animals make inaccurate statements.

So let's set the record straight.

In August 2009, I proposed to UW's top research oversight committee that the UW conduct a study to determine if experimenting on monkeys is ethical, and I requested a response to my proposal by a certain date.

That date came and went without any news, so I asked the chairman of the committee for an update. He told me that the committee had decided against my proposal. I asked him when the committee had made that decision. He said that the committee had discussed my proposal during the meeting that I attended, when I was out of the room. That was a lie. (And the committee probably violated the state's open meetings law by deliberating outside the meeting -- if they bothered to deliberate at all.) In any case, the committee declined to deal with the fundamental ethical question.

I shared this news with UW-Madison chancellor Biddy Martin because Martin had insisted that this committee was the appropriate body for answering the ethical question. Martin then instructed the committee to discuss my proposal formally and to give me a formal written response.

So that committee met again on January 8, 2010. The bio-ethicist on the committee presented a statement that concluded with a motion: "I move that the committee endorse the position that existing standards of veterinary care and applicable animal welfare laws, regulations, and policies provide a suitable and appropriate basis for determining when the use of nonhuman primates in research, teaching, or outreach at the University of Wisconsin-Madison is ethical."

Note that this motion does not respond meaningfully to my proposal and does not try in any way to answer my question. It says only that a basis for answering the question (or at least a similar question) exists. But the motion seems to assume that experimenting on monkeys, as it is done at UW-Madison, is at least sometimes ethical. I had asked the UW to question that assumption, not just to re-state it.

Sandgren presented his own written statement that the oversight processes ensure that experiments on monkeys meet a utilitarian ethical standard. But this statement only begs the main question and prompts a few more. Why should a utilitarian standard be applied to experiments on monkeys but not to experiments on people? (Sandgren has said elsewhere that "Utilitarianism trumps rights", which actually makes some sense to a principled utilitarian, which he is not, but still fails to explain why utilitarianism trumps the rights of monkeys but not the rights of people. And a deontologist would say that "rights trump utility".) What are the costs? What are the actual benefits to people? Where are the numbers, the evidence that a utilitarian standard is met? Why is it ethical for a powerful majority to exploit a powerless minority in pursuit of its self-interest? How do we know not only that the benefits of experimenting on monkeys exceed the costs but that experimenting on monkeys is the research approach with the greatest ratio of benefits to costs? How could it be if, as Sandgren himself has said in public, that there is a low "hit ratio" in translating experimental results into human benefits?

There was no study, no deliberation, no public input, and no testimony from experts, just statements that said, in effect: the status quo is fine. I wrote in a guest column in the Wisconsin State Journal after that:
The top animal research oversight committee at UW-Madison concluded recently that experimenting on monkeys is ethical. Here's what happened: a group of insiders who are constituted by law not to make ethical decisions but to ensure that the care of animals in labs meets a minimum standard, decided that the work that pays their salaries, funds their labs, and gives them a basis for tenure and promotion is ethical.

It was as if the Mississippi Slave Owners Association was asked in 1850 to determine whether or not slavery was ethical.

The committee ignored all the scientific and morally significant findings about monkeys that raise the ethical question: their advanced mental abilities, their strong emotions, their complex social relationships, and their profound similarity to you and me.

The committee confused the question about the ethics of experimenting on monkeys with the question of the treatment of the animals. They made the absurd claim that meeting a legal minimum standard of care ensures that the experiments are ethical. But if experimenting on monkeys is not ethical, then no standard of care can make it so.

The committee claimed, without providing evidence, that they make ethical decisions all the time. But years ago, when I heard someone ask one member [Sandgren] how ethical decisions were made, his only answer was "I will have to get back to you on that." And someone who has attended about fifty committee meetings tells me that she has heard committees discuss ethics only three or four times — and only because they seemed to be making a show of it.

Instead of wrestling with the ethical issue, the committee simply endorsed an answer that they like. I know from my interaction with some committee members that some of them do not even understand the issue. And the few who do understand it are afraid to speak openly.
So, did the UW take up the ethical question in any meaningful way? No. Sandgren should stop accusing concerned citizens of misleading the public.

By the way, I am still waiting for the formal written response to my proposal.

Thursday, November 11, 2010

Harlow, Responsibilty, and HIV

Meaningful discussion requires an attempt at honesty. We all make mistakes of course, and can unknowingly make false claims and hold unfounded opinions, but making things up, trying to mislead, and refusing to acknowledge plain facts is something altogether different.

Animals in Research and Testing seems like an effort to hoodwink the uninformed and unwary (or maybe just UW employees).

There are many silly claims on the site. Consider the statement below regarding the work of Harry Harlow on a page titled: “UW Animal Research Achievements. The Tangible Benefits of Animal Research.” This is matter-of-factly wrong.

In the forum I linked to at the bottom of the previous essay, you can hear Eric Sandgren saying that people should look up the facts themselves. Indeed, but people trying to do so have a reasonable expectation that information presented on a UW-Madison website is accurate, and they have an even stronger expectation that the information on the website is believed to be true by the authors. The public rightly expects that the state university will not knowingly mislead them. The problem is significantly compounded when publishing the false information is intended to benefit the institution itself. This is, I believe, an abuse of authority.
The importance of mom

Monkey research by Wisconsin’s Harry Harlow proved the importance of mother-child attachment to human development during the 1950s, when many psychologists discounted the relationship. In studies with a few animals, Harlow showed that food, water and medical care were not enough: young primates cannot grow into normal, healthy adults without contact with their mother. Harlow’s discoveries are widely applied in such settings as neonatal intensive care units.
This claim might not be recognizable as a lie if the actual historic facts had not been pointed out to the “author” of the “blog" associated with the university website, Eric Sandgren. But they have been, very clearly, and yet he – and by extension his employer – continues to make matter-of-fact false claims about Harlow’s work.

It is one thing to defend honestly one’s opinion that animals’ experiences and lives don’t matter very much, that scientists or ranchers or dog fighters should be able to kill them or hurt them in any way they choose, but it is an altogether different matter to present straightforward falsehoods as facts, and this seems to be a common tactic used on this University of Wisconsin-Madison website. Everyone acting as a university agent – everyone who produces copy for the site – has a higher than ordinary duty of honesty to the state’s citizens and Internet users everywhere.

Rather than repeat what I have written before regarding the actual facts surrounding Harlow’s work, I refer the reader to my essays: “Harry Harlow's Dark Shadow,” September 18, 2008, and “Monsters: Harry Harlow and Stephen Suomi,” web posted: August 29, 2010.

Repeating the Harlow myth isn’t the half of it. It’s not the tenth of it. Half-truths abound.
This university accepts responsibility for the stewardship of all animals under its care.
How would one go about judging the veracity or even determining the meaning of a statement like that? One way might be to look at how the university responds to citations for its violations of the Animal Welfare Act. If one took responsibility and acted responsibly, one wouldn't let things deteriorate to the point that a team of inspectors would be called in, or at least act responsibly and fix the problems pointed out to you.

USDA inspectors returned recently to the university and discovered that major violations like the university approving experiments even though researchers have not demonstrated that they have looked for alternatives to painful procedures, have gone uncorrected.
Because animal models are used only to answer questions that cannot be answered in any other way, experiments are not approved unless the lead investigator can show that no effective alternatives exist.
This is a half-truth because the animal models are themselves demonstrably ineffective.

Here’s a really misleading statement:
Nobel Prizes for Medicine or Physiology routinely recognize research that relied on animal models. The 2008 prize was awarded for discovering the human immunodeficiency virus, based on work with monkeys, chimpanzees and mice.
Like the false claim about the importance of Harry Harlow’s work, I believe the university’s claim that the discovery of the human immunodeficiency virus (HIV) was based on work with monkeys, chimpanzees and mice is factually incorrect.

The isolation of HIV was first reported and published in 1983, as explained below by Françoise Barré-Sinoussi in her Nobel acceptance speech.

UW-Madison professor and author Deborah Blum tells the story of the discovery of simian immunodeficiency virus (SIV) in “Not a Nice Death,” Chapter 9 of her 1994, The Monkey Wars, (which are still raging.)

She tells us that in 1976, a fatal epidemic swept through the stumptail macaque colony at the California Regional Primate Research Center at the University of California-Davis (now the California National Primate Research Center.) It turned out to be SIV, but at the time the cause of the disease was unknown. She quotes California primate center veterinarian Roy Henrickson: “They were suddenly dying, and whatever it was, it was a terrible death, a cascade of infections, cramming one on top of another, wearing the little monkeys out.”

In 1980, another wave of the same disease swept through the rhesus colony. A disease with the same symptoms broke out at the New England Regional Primate Research Center at Harvard University at about the same time. (The facility is in Southboro, a few miles from Boston.)

And this time, there was something similar spreading into the human population. A troubling illness was emerging, a disease that caused a lethal collapse of the immune system, crippling the body’s ability to fight off infection. The human disease was AIDS, Acquired Immune Deficiency Syndrome.

The New England scientists realized, and then the California researchers, that the monkey disease was almost a mirror of the human one....
The discovery of the human immunodeficiency virus, was not based on work with monkeys, chimpanzees or mice.

The opposite is true. The discovery of the simian immunodeficiency virus was based on work with humans. HIV was first described in 1983.

SIV was first described in 1985. See: Isolation of T-cell tropic HTLV-III-like retrovirus from macaques. Daniel MD, et al. Science.

Consider the beginning of Françoise Barré-Sinoussi’s Nobel acceptance speech.

Does this sound like monkeys, chimpanzees, and mice were used?
The Early Days

The story begins more than 25 years ago, when the initial clinical observations of a new alarming epidemic were made. In June 1981, clinicians in the United States first reported a number of cases of Pneumocystis carinii in homosexual men. Subsequently, the first cases of what would later be known as AIDS were observed in France. At the time, I was working at the Institut Pasteur with Luc Montagnier and Jean-Claude Chermann. In December 1982, we were contacted by clinicians in France who provided us with a biopsy of a lymph node from an AIDS patient, with the aim of isolating the etiological agent causing the disease.

The hypothesis at the time was that a retrovirus might be the etiological agent responsible for AIDS. The only human retrovirus known at that time was the human T-lymphotropic virus (HTLV), known to cause transformation of T cells, and arguably it would have been possible to culture the cells from the lymph node biopsy and simply observe for T-cell transformation. Luckily, we did not assume that HTLV was necessarily the cause of the disease, and we decided to sample the culture supernatant every three to four days to detect for reverse transcriptase activity. Indeed, we started to observe a reverse transcriptase activity, which decreased shortly after, in correlation with cell death. Initially we were concerned about possible toxicity related to tissue culture components, but following the addition of fresh lymphocytes and fresh components to the culture, the same cell-death phenomenon was observed, in correlation with the detection of reverse transcriptase activity. We thus realised that the virus itself was responsible for this phenomenon.

The isolation of this new human retrovirus (at the time known as LAV, lymphoadenopathy-associated virus) was first reported and published in May 1983. In this first report we described that LAV could be propagated on peripheral blood mononuclear cells and on cord blood lymphocytes. We also described the viral protein p25, and importantly we determined that there was no, or weak, cross-reactivity with HTLV-1 proteins, indicating that we were dealing with a new human virus. In the same report we demonstrated the presence of antibodies against LAV in a second patient affected by AIDS. The report of the virus was, however, just the beginning.

The isolation of the virus was not sufficient, however, to convince the scientific community of the implication of the virus in AIDS. It was, therefore, essential to further characterize the virus and establish a clear link between the virus and the disease to persuade the scientific community and the relevant authorities that the newly isolated virus was the etiological agent responsible for the emerging epidemic. In 1983, we decided to immediately halt all other research projects which were ongoing in the laboratory (including determining whether MMTV sequences could be associated with breast cancer—a hypothesis still valid today) and to mobilize a network of efficient collaborations with clinicians, immunologists, and molecular biologists. In order to determine whether this newly isolated virus was truly responsible for the disease affecting AIDS patients, we quickly developed a serological test to perform sero-epidemiological studies. Crucially this same test was subsequently used as a diagnostic tool for blood testing. The development of the diagnostic test was made possible by a strong and efficient partnership with the private sector, namely Sanofi Pasteur.
And the date of this paper also from Barré-Sinoussi:
Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Barré-Sinoussi F, et al. Science. 1983.


A retrovirus belonging to the family of recently discovered human T-cell leukemia viruses (HTLV), but clearly distinct from each previous isolate, has been isolated from a Caucasian patient with signs and symptoms that often precede the acquired immune deficiency syndrome (AIDS). This virus is a typical type-C RNA tumor virus, buds from the cell membrane, prefers magnesium for reverse transcriptase activity, and has an internal antigen (p25) similar to HTLV p24. Antibodies from serum of this patient react with proteins from viruses of the HTLV-I subgroup, but type-specific antisera to HTLV-I do not precipitate proteins of the new isolate. The virus from this patient has been transmitted into cord blood lymphocytes, and the virus produced by these cells is similar to the original isolate. From these studies it is concluded that this virus as well as the previous HTLV isolates belong to a general family of T-lymphotropic retroviruses that are horizontally transmitted in humans and may be involved in several pathological syndromes, including AIDS.
Maybe the university’s writer is correct, maybe the discovery of HIV was dependent on experiments on chimpanzees, monkeys, and mice, but dates and statements from people who were there at the time strongly suggest otherwise.

I challenge them to provide clear relevant references for their claims. I don’t believe they can; I don’t believe they exist.

Wednesday, November 10, 2010

Symposium Addresses Ethics

Symposium Addresses Ethics, Standards, Beneficiaries of Research

Madison, Wisconsin - Drawing on issues raised by this year's Go Big Read selection, a fall symposium at the University of Wisconsin-Madison will address responsible conduct and ethical decision-making in research.

The Integrating Research Ethics and Scholarship (IRES) is an initiative, sponsored by the Graduate School, that offers both novice and seasoned researchers and scholars educational opportunities and resources that reflect best practices in ethics education and scholarly integrity.


A public evening session, "Who Decides and Who Profits: Research at UW-Madison," will feature a panel discussion about the decision-making and administrative processes behind campus research. The panel will include a mix of researchers, research administrators and deans.

"We are hoping to put an open, public face on how we, as an institution and as individuals, go about the process of research," says William Mellon, professor of pharmacy and associate dean for research policy, who will moderate the discussion. "In general, researchers are interested in producing results that will benefit people. Most researchers are motivated by making a difference."

Discussion topics will include the costs and benefits of research, research oversight and infrastructure at UW-Madison, how the public can influence the research agenda, how federal and state money is spent and why basic science research is done.

"To the general public, the nature of how research gets done - the organization and administration - is not transparent and so complex. There are many misconceptions," says horticulture professor Irwin Goldman, one of the panel members.

I attended the evening panel discussion held on November 4, 2010. The event was video-recorded; when it becomes available, I’ll link to it here.

The moderator was William Mellon, the Associate Dean for Research Policy. The participants were Susan Ellis Weismer, Associate Dean in the College of Letters and Science, Professor, Communicative Disorders; Sharon Dunwoody, Interim Associate Dean for Graduate Education, Evjue-Bascom Professor of Journalism and Mass Communication; Eric Sandgren, Director, Research Animal Resources Center, Associate Professor, Experimental Pathology; Nichelle Cobb, Director of the Health Sciences Institutional Review Board; Richard Moss, Senior Associate Dean for Basic Research, Biotechnology, and Graduate Studies, School of Medicine and Public Health, Professor of Physiology; Irwin Goldman, Professor of Horticulture; and Jill Sakai, University Communications.

The event was interesting in a geeky sort of way though it did not answer the questions posed in the advertising. I enjoyed it and came away with some new insight. One thing that struck me was the gigantic chasm between oversight of human-based research and animal-based research.

The event grew out of the university’s Go Big Read campus-wide book circle’s first selection (a play on the university’s Go Big Red athletic slogan): The Immortal Life of Henrietta Lacks, by Rebecca Skloot.

Before, via email, and during the panel discussion, the audience was invited to submit questions. These were vetted and edited by Associate Dean Mellon, and no follow-up was allowed.

Nichelle Cobb, Director of the Health Sciences Institutional Review Board, the committee responsible for oversight of human-based experiments answered questions read by Mellon concerning human experimentation. She said that even the use of tissue left over from surgery is highly regulated, and that informed consent is expected and required in certain cases.

It is apparently common and accepted practice in hospital admissions to include a generic approval clause in the fine print granting permission for the use of incidental tissue residues. These tissues are apparently not associated with a patient’s identity and apparently may be used generically in research. On the other hand, if a researcher has a specific desire for certain types of tissues from certain patients, then informed consent is required, and if there is a profit motive behind the collection of specific tissues, then the request, according to Cobb, would be almost certainly denied.

This sensitivity to the use of leftovers from surgery on humans is at distinct odds with the de facto rubber-stamping of nearly any requested use of whole live animals. Yet we hear repeatedly by industry spokespersons and other vested parties that the oversight of experiments on animals is more stringent than oversight of experiments on humans. For instance:

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
I had not previously looked into these claims and had merely assumed that they were false, but as a result of the panel discussion, I did a little research. I can say now, and support it with evidence, that such a claim – that animal-based research is more highly regulated than human-based research is absolutely ludicrous. I imagine that those who make such claims are either repeating falsehoods they’ve heard or else are making them up themselves.

I submitted two questions to the panel, neither of which was asked fairly by Mellon.

The first one had to do with the ever-growing body of research demonstrating through meta-analyses and retrospective reviews that clinical care of human patients is not being appreciatively improved as a result of basic biomedical research using animals.

When a protocol comes before an Animal Care and Use Committee for approval, there is a near certainty that the research results will provide no new knowledge that will lead to an improvement of human patient care. [See for example, Lindl T, Völkel M & Kolar R. 2005 and 2006.] Yet the public is told that the oversight committees weight the costs to the animals against the potential benefits to humans. But the costs to the animals are a lifetime of being caged in bleak tight confinement, often-serious discomfort, stress, and almost always death, and the benefits to humans are nil.

Thus, in every approved project, and generally all projects are approved, the ethical weighing that occurs is this: no likely benefit to humans vs. certain suffering and death to the animal = an approved project.

How could an informed honest person argue that this system is ethical?

One of the panelists, Irwin Goldman, Professor of Horticulture, was a spokesperson in the university’s strong efforts to host the Department of Homeland Security and USDA jointly sponsored BSL-4 laboratory, the National Bio and Agro-Defense Facility (NBAF).

The university argued vigorously that the NBAF would be perfectly safe and should be built in the Town of Dunn, a few miles from Madison, and successfully cajoled some local politicians to get behind their effort. [See my essays: "regrettable consequences" July 30, 2009; UW Experts Dead Wrong, again. July 28, 2009; Are UW Vivisectors Anti-Knowledge? June 8, 2007. NBAF Fiasco Reveals Idiocy of UW Decision-Makers. May 10, 2007; Wanna buy a bridge? March 12, 2007.]

But the Government Accounting Office reported in 2009 that the lab would pose unnecessary risks if it were built anywhere on the mainland. The GAO reported that the Department of Homeland Security’s analysis of the risks was flawed in a multitude of ways. See: Observations on DHS’s Analyses Concerning Whether FMD Research Can Be Done as Safely on the Mainland as on Plum Island. United States Government Accountability Office. Report to Congressional Committees. 2009.

So I asked whether it was ethical for the university to ask the Department of Homeland Security to build the facility here and to tell the public that there was no appreciable risk, without first seeking an analysis of the risks from experts at the university?

Apparently the university had conducted no independent analysis of the risks; instead, they merely argued that the facility would be an economic boon to the community and that any concern over safety was mere hand wringing by uniformed or misinformed Luddites. Mellon twisted this question, like my question about the ethical weighing of costs and benefits of experiments on animals, into something nearly unrecognizable.

There was no discussion with the audience. There were no follow up questions.

A couple interesting tidbits:

Associate Dean Mellon started out by saying that the panel, or maybe IRES, was: “[O]ur initial foray into this area.” Public discussion about ethics is apparently a new idea at the university.

Mellon “read” a question that asked what the university was doing to counter the negative press about its use of animals. There was much hemming and hawing, but Jill Sakai of University Communications said she was aware that a recent telephone opinion poll by a group named CURES or C.U.R.E.S. or something like that, there was no opportunity for follow-up questions, had found great support for university research.

As far as I can tell, there isn’t an organization by this name. I contacted Ms. Sakai (twice) and asked her for a reference or a link, or any information whatsoever she might have about this survey, but she said she knew nothing, had nothing, and could point to nothing about it. This seems odd to me given her significant “knowledge” of it at the panel.

Associate Dean Mellon had told me in an email that the panel would not address animal research, but of course, with two vivisectors (Moss and Sandgren) on the panel, it did. Mellon also told the audience that the university is planning a series of “forums” specifically addressing the use of animals. The “forums” were proposed by the university as part of their successful efforts to defeat Dane County Resolution 35, though Mellon didn’t mention that. As of this writing, as far as I am aware, the “forums” planning committee has met only once. If the IRES symposium can be used as a indication of the substance and value of these promised “forums,” they may be more form than substance.

P.S. and a little aside: I recently participated in a genuine forum with actual discussion with the audience at the First Unitarian Society of Madison, Wisconsin. One of the other two panelists was Eric Sandgren. You can watch it here. Sandgren told the audience [beginning at about 16:08 and then again at 1:10;15] that he had opposed Resolution 35 because it had a fatal flaw, the committee proposed by the Resolution created would decide for the County whether experiments on monkeys are ethical. The actual text reads:
BE IT FURTHER RESOLVED that the Panel’s “Final Report” will include a recommendation to the Dane County Board of Supervisors either to officially endorse or officially oppose experimenting on monkeys in Dane County.
Eric may need some reading remediation. He should look up the meaning of recommendation.

Sunday, November 7, 2010

"Animal Research: Groupthink in Both Camps"

You might think that in a dispute when one party asks the other to meet it 0.1 percent of the way, a mutually agreeable resolution could be readily reached. But no, researchers will not renounce vivisection of monkeys, dogs, or cats.
--- Lawrence A. Hansen, M.D., professor of neuroscience and pathology at the University of California at San Diego, where he also leads the neuropathology core of the Shiley-Marcos Alzheimer's Disease Research Center.

From: Animal Research: Groupthink in Both Camps. The Chronicle of Higher Education. November 7, 2010.