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.)

Blum:
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.

Abstract

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.

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