Thursday, February 15, 2007

On the Endangered Lab Chimp

The January 26, 2007 issue of Science includes an article written by Jon Cohen titled “The Endangered Lab Chimp.” [Vol. 315. no. 5811, pp. 450 – 452.]

Mr. Cohen’s article begins with the headline: “A decline in the number of chimpanzees available for biomedical research in the U.S. has sparked a growing debate on the opportunities and costs of studies with our closest relatives.”

I don’t know whether these are Cohen’s words or an editor’s, but they are indicative of the ivory tower or head-in-the-sand mentality so often expressed in Science and similar journals. Who could be so out of touch as to claim that the debate over our use of chimpanzees is a new phenomenon sparked by the decline in their availability? Have Cohen and the editors of Science never heard of Jane Goodall?

Before bloodying my hands with a dissection of Cohen’s article, let me first say a bit about the author and the journal’s decision to have Cohen write about this issue. Cohen is the author of Shots in the Dark: The Wayward Search for an AIDS Vaccine (W. W. Norton & Company; December 2001.)

Cohen believes that the way to an HIV vaccine is a “March of Dollars,” a modern day March of Dimes, that he calls a “grand experiment” that would “possibly use more moneys than are currently available for research.” (p 329.) In the chapter notes he clarifies his estimate to a mere 1000 monkeys. Cohen seems unmoved by the fact that using monkeys in AIDS research has resulted in dozens of vaccines – all successful in monkeys, all failures in humans. Cohen has a hard time understanding that HIV is uniquely a human disease.

In Shots, Cohen urges us to keep doing something that has proven ineffective, like sending more troops to Iraq.

Who better to write about the use of chimpanzees in biomedical research and the debate that’s just been sparked by “a decline in the number of chimpanzees available for biomedical research”?

Cohen begins his article by twisting the facts into a scenario that he presumably finds worrying and apparently hopes will worry the biomedical community as well. He writes:
As a result, [of the 2000 CHiMP Act, and animals being moved into a quasi-sanctuary] the population has dropped from 1500 in 1996 to 1133 in October 2006. Now, many researchers who conduct biomedical research on chimpanzees are worried that the number of breeding animals is declining so rapidly that there will soon not be enough left to sustain the population. “The population is heading for a cliff,” says Todd Preuss, a neuroscientist at Yerkes National Primate Research Center in Atlanta, Georgia, which has the country’s oldest colony of research chimpanzees. “If we don’t start breeding these chimpanzees soon, they’re going to go away, and they’re going to be gone for good.”
First, there aren’t “many researchers who conduct biomedical research on chimpanzees.” In fact, in 2004, there were a total of 25 principal investigators (the scientist whose name is on the grant) using chimpanzees. About the only biomedical research niche found for chimpanzees is in hepatitis research. In 2004, there were 21 funded studies underway by 17 principal investigators studying hepatitis. Most of these studies were on-going and using the same chimpanzees year after year. Chimpanzees can remain in a hepatitis protocol for many years and be subjected to many painful and debilitating liver biopsies. In 2004, there were over 1000 studies underway using monkeys, and many thousands of studies using mice. Cohen’s claim is hyperbole.

Cohen writes: “The push to breed more chimpanzees is forcing a reexamination of questions that have long surrounded research with our closest relatives, an endangered species that is rapidly disappearing in the wild.”

Given the fact that so few chimpanzees are being used in so few studies, just what push is Cohen referring to? Most of the 1100 chimpanzees being held at federally funded laboratories are being warehoused. The lack of demand for chimpanzees is exactly what led to the NIH supporting the passage of the Chimpanzees Health Improvement, Maintenance, and Protection (CHIMP) Act of December 2000.

Still other researchers caution against making a blanket proclamation that invasive experiments with chimpanzees are unethical. “To draw a hypothetical line in the air I don’t think does justice to the subtlety of these questions,” says Norman Letvin, an immunologist at the Beth Israel Deaconess Medical Center in Boston, who has done AIDS vaccine experiments in chimpanzees and monkeys. “These kinds of discussions need to be focused on very specific questions about a particular study.” Letvin no longer experiments on chimps and says he can’t see any compelling reason today to use large numbers of them for biomedical research. But he stresses, as do many other investigators, that this animal model has led to “enormously valuable” medical advances in the past and may well in the future.
Letvin’s research and his judgment are proven failures. In 1987 he declared:
Substantial advances have already been made in the understanding of acquired immunodeficiency syndrome (AIDS). The major issues for AIDS research during the next few years must be practical ones: the development of a safe, effective vaccine for individuals not yet infected with the causative virus and the development of drug therapies for those already infected. Suitable animal models will be needed for studies designed to achieve these goals. Areas of investigation in animal models can be divided into four categories on the basis of increasing direct relevance to AIDS in humans: retroviruses that have no obvious, close relation to human immunodeficiency virus (HIV) but can induce chronic diseases with manifestations that include immunologic abnormalities; ungulate lentiviruses; HIV-related viruses of Old World primates; and HIV infection of chimpanzees. It is hoped that important research developments in experimental models can be quickly extrapolated to human AIDS. Desrosiers RC, Letvin NL. Animal models for acquired immunodeficiency syndrome. Rev Infect Dis. 1987 May-Jun;9(3):438-46. Review.
(Ron Desrosiers, Director of the New England National Primate Research Center may hold the record for announcements that he has found a vaccine for HIV.)

Chimpanzees, the animal model with the most direct relevance to AIDS in humans, according to Letvin, have been abandoned as HIV models. How could Letvin’s opinion on this issue have any weight whatsoever? His claim that this animal model has led to “enormously valuable” medical advances in the past is just more hyperbole. The single medical advance that could conceivably be attributed to some use of chimpanzees is the development of the hepatitis B vaccine, but even this claim has been challenged.

Undoubtedly, Cohen went to Letvin for a statement because Letvin has built his career on plowing ahead with ever more NIH-funded SIV experiments on monkeys, Cohen’s version of the AIDS Grail.

Cohen seems to almost understand that biomedical research with chimpanzees has been a bust:
As many proponents of this animal model note, such research played a crucial role in the development of the vaccine for hepatitis B, a sometimes lethal virus that has infected 2 billion people. But scientists around the world have also performed studies that are now considered bizarre or brutal. The U.S. Air Force’s chimponaut program shot them into space. Other researchers harvested their organs for human transplants, implanted electrodes into their brains to study sleep, and used them to gauge the effects of alcohol and marijuana. And a Soviet scientist attempted to inseminate them with human sperm to make a “humanzee.”
He follows up by noting that: “the chimpanzee AIDS model had problems from the get-go.”

Cohen finally gets to his claim about what "sparked" the "recent debate."
With the publication of the first draft of the chimpanzee genome in September 2005, calls mounted for NCRR to lift the moratorium. In a commentary in that same issue of Nature, the heads of the U.S. primate centers again extolled the benefits of maintaining this “unique resource” and warned that if the moratorium were not lifted, the population would sharply decline within 5 years.

Since then, one of the co-authors, John VandeBerg, director of Southwest National Primate Research Center, has performed a more detailed analysis of the age and health status of the chimps housed at all six facilities. At a chimp meeting at Yerkes in October 2006, Vande-Berg said that of the 1133 animals then available, just 200 females were potential breeders. If the breeding moratorium were not lifted, he added, there will be no research chimps left by 2037 when all of these chimpanzees will have died.
Cohen spins the facts. The commentary he refers to in Nature was not written by “the heads of the U.S. primate centers.” (VandeBerg JL, Zola SM. A unique biomedical resource at risk. Nature. 2005 Sep 1.) The term “U.S. primate centers” is invariably used to refer to the eight NIH National Primate Research Centers.

Not surprisingly, the commentary was written by John VandeBerg, director of Southwest National Primate Research Center, and Stuart Zola, director of Yerkes National Primate Research Center, which just happen to be the only two of the eight National Primate Research Centers that have chimpanzees. To Southwest and Yerkes, these animals are not chimpanzees, they are cash cows.

Co-authors included Jo Fritz, Primate Foundation of Arizona, Mesa; D. Rick Lee, Alamogordo Primate Facility, New Mexico; Thomas J. Rowell, University of Louisiana at Lafayette, Louisiana; and William C. Satterfield, M. D. Anderson Cancer Center, Bastrop, Texas. These are the only facilities in the U.S. holding chimpanzees for research.

I wonder what the buggy whip manufactures had to say about the importance of buggy whips as their industry failed?

From Table 1: Five-year projection of the number of chimpanzees available for research in the absence of breeding. (VandeBerg JL, Zola SM. A unique biomedical resource at risk. Nature. 2005 Sep 1.)

Cohen claims that VandeBerg report at a “chimp meeting” that current trends suggest that the US chimpanzee population will be too old to breed in a few years “startled many at the meeting…. Others noted that the aging of the population is already limiting brain and behavioral research that depends on younger animals.”

Given the tiny number of studies recently published or underway using chimpanzees in brain and behavioral research, this claim should be understood to be hyperbole as well. It also begs the question as to whether any of these very few studies have any merit in the first place.

Cohen goes on to cite other nations and private institutions that have halted their use of chimpanzees. He quotes a few scientists who argue from an ethical perspective that chimpanzees should no longer be used in research.

To counter this nod to apparent balance, Cohen again relies on vested parties:
In their 2005 Nature commentary, VandeBerg and co-authors argued that chimpanzees should remain available for disease research and for testing drugs and vaccines. VandeBerg notes that some proprietary experiments with monoclonal antibodies done for commercial companies have led to illness or even death of chimps—preventing harmful drugs from entering human trials. “It’s unethical from a human standpoint to not do this research,” he says.
This is a pretty clear example of the spin and fear mongering used by primate vivisectors everywhere. There is no reason to assume that a drug or disease that negatively affects a chimpanzee will have a similar effect in a human or visa versa. The most glaring and ironic example given Cohen’s biases is HIV: deadly in humans, a brief sniffle in chimpanzees. VandeBerg has a weak grasp on ethics.

And of course, Cohen gives the last word to Letvin:
… others say the U.S. government should simply support a core breeding group of chimpanzees for biomedical research as an insurance policy for future emergencies. Beth Israel’s Letvin agrees with this minimalist strategy. “If we’ve learned anything over the years, it’s that we don’t know what the next epidemic will be and what the next major health crisis is going to be,” says Letvin. “It would be foolhardy to take any potential animal model off the table.”
Letvin’s predictions and research have so far missed the target altogether. Cohen cheers him on.

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