Monday, October 6, 2008

More on Terasawa

Ei Terasawa (and here) is a vivisector at the University of Wisconsin, Madison. She is a senior scientist at the NIH-funded Wisconsin National Primate Research Center. I have commented on her work and have scanned and posted on line many official documents associated with her research and her violations of the Animal Welfare Act. (Just stick her name into the search window above.)

Here, I will comment on two features of her work that I have not mentioned specifically elsewhere. The first is her stated justification for using animals and her stated justification for using rhesus macaques. The second is the large volume of blood taken from some of the monkeys she is experimenting on and veterinarians’ role in her work.

Terasawa’s justifications

For at least the last dozen years—the period of time for which we have many primary documents—she has consistently used nearly identical written justifications. This is question 11 and her responses from a 2008 approved protocol: (I've commented on her individual points and claims below. Here they are more or less whole and intact.)

11a. In straight-forward, nontechnical language that would be understandable to a layperson (aim for a high school-senior reading level), outline the specific scientific goal(s) and significance of this research. Be convincing as to why this work is important for advancement of knowledge, improving human or animal health, or for the good of society. Spell out all acronyms at first occurrence.
Puberty and adolescence occur during the transitional period between childhood and adulthood. Adolescence (behavioral maturation) usually follows puberty. Many disorders, including precocious and delayed puberty, and problems associated with these disorders, as well as polycystic ovarian syndrome, one of the most common infertility problems, originate at this developmental stage. Moreover, the onset of puberty at the normal age is very important, as any deviation from peer age can result in psychological problems in later life and the pubertal increase in steroid hormones modifies brain circuitry formation necessary for adolescent behaviors. Several neurological and psychiatric diseases, such as schizophrenia and autism start or worsen in association with puberty. For these reasons, investigation of the control mechanism of puberty, using the non-human primate as a model, is essential and would contribute to the understanding and management of problems associated with human adolescence. Because there are no direct methods for examining neurochemical changes in the human brain, the animal model is indispensable in achieving these goals.

At the onset of puberty, the luteinizing hormone-releasing hormone (LHRH) neuronal system in the brain (hypothalamus) begins to be active after a long dormant state. Previously, we have found that an increase in LHRH release is the key factor for determining the timing of puberty and the pubertal increase in LHRH release from the hypothalamus is the result of the reduction in a tonic 7-ammobutyric acid (GABA) inhibition and subsequent increase in glutamate release. However, the mechanism triggering puberty is still unclear. Therefore, the overall objective of this proposal is to determine the role of the hypothalamus in controlling puberty in the female rhesus monkey.

Recently, because an absence of or delay in puberty in patients withmutations in the gene encoding GPR54 has been reported, GPR54 and itsligand, kisspeptin-54, have been proposed to play a critical role in the mechanism of the onset of puberty. It has also been shown that LHRH neurons express GPR54 and kisspeptins stimulate luteinizing hormone (LH) and follicular stimulating hormone (FSH) release. Hypothalamic expression of KiSS-1 mRNA, increases with puberty. KiSS-1 is the gene for several kisppeptins, including kisspeptin-54. Moreover, mice lacking the GPR54 gene failed to undergo puberty and had immature gonads. These reports are consistent with the hypothesis that the GPR54 and KiSS-1 genes are responsible for the onset of puberty. However, to support this hypothesis several critical questions remain to be answered:
[three lines of text deleted] Thus, to answer these questions in this study we will investigate the role of kisspeptin in the mechanism of primate puberty.
11b. Specifically justify the use of animals for this research. Explain why it is imperative to use animals and why non-animal alternatives such as computer simulation or in vitro systems are not possible.
Because we are aware of the value of an individual animals life, we have considered alternatives to the use of animals. For this study, however, the use of non-human primates is essential, as the onset of puberty and the function of the hypothalamus are complex processes which cannot be simulated with computers or tissue cultures. In addition, in order to apply knowledge obtained from research to humans, we need to learn about these processes in non-human primates. This project is in the forefront of its research field and there are no duplications, as seen by continued support by NIH. Unlike the circuitry involved in long-term depression in the hippocampus, computer simulation is not yet available due to the complexity of the circuitry for hypothalamic neuroendocrine function in animals.
11c. Specifically justify why you chose the species cited in 9a for your work, such as the appropriateness of the species for your proposed work. Cost considerations are not justifications.
The overall objective of this research is to understand the function of the hypothalamus in the rhesus monkey, as a model for humans. Since the genes in the rhesus monkey are more than 95% homologous with those in the human, and many aspects of hypothalamic functions in the rhesus monkey are similar to those in the human, the studies done in the monkey are essential for the improvement of human health. Function of the rodent brain, which is often used for a model, differs from function of the primate brain. Lower organisms do not have comparable functions, in vivo studies collecting samples from the brain are not possible in humans. Thus, research in non-human primates is very important. Finally, the PI has a large amount of background data on puberty in female rhesus monkeys.

Terasawa has been receiving public funds to study puberty in rhesus monkeys since at least 1977 and has received millions of tax dollars.

She current has two grants listed on CRISP: "Hypothalamic Control of Puberty" (5R01HD011355-25 (that -25 at the end means that the study is in its twenty-fifth year of NIH support. "Hypothalamic Control of Puberty" is funded through 2012 (as of October 2008.) In 2008, it received $382,456. The other grant is "Hypothalamic Control of Gonadotropin Secretion" 5R01HD015433-24. That grant was awarded $358,401 in 2008.

A number of UW officials (various chairs and members of UW Animal Care and Use Committees) have signed Terasawa’s many protocols over the years, very many of which include the questions and answers above.

The US Department of Agriculture’s discovery of Terasawa’s Animal Welfare Act violations exposed the failure of the university’s legally mandated animal research oversight committees (comprised almost entirely of UW vivisectors) to fulfill the university’s legally mandated responsibilities regarding animal care and use and its oversight. In response, the committee made an example of Terasawa by suspending her animal use for two years and requiring many rewrites and revisions of her protocol.

It seems fair to assume, given that the protocol was much discussed by the committee and that she was required to submit a number of revisions, that the protocol was read carefully by at least some of the committee members, even if they had not been vigilant previously. Its eventual endorsement implies a clear understanding and approval of her claims, hypotheses, and methods by the committee members and other university officials.

She argues and concludes in 11a:

1. Puberty and adolescence occur during the transitional period between childhood and adulthood. [This is true for many mammals.]

2. Adolescence (behavioral maturation) usually follows puberty. [This too is true for many mammals.]

3. Many disorders, including precocious and delayed puberty, and problems associated with these disorders, as well as polycystic ovarian syndrome, one of the most common infertility problems, originate at this developmental stage. [These named and vague unnamed disorders and problems may or may not all originate during puberty. Polycystic ovarian syndrome is a human-specific disorder. Precocious and delayed puberty have a multitude of various causes including genetics and/or environmental variables that in turn have variable effects on various species.]

4. Moreover, the onset of puberty at the normal age is very important, as any deviation from peer age can result in psychological problems in later life and the pubertal increase in steroid hormones modifies brain circuitry formation necessary for adolescent behaviors. [This run-on sentence is unnecessarily confused but has survived close scrutiny for years. Her first point, that “any deviation from peer age [onset of puberty] can result in psychological problems in later life,” is hyperbole. Her second point seems a little confused and seems to imply that “adolescent behaviors” are necessary.]

5. Several neurological and psychiatric diseases, such as schizophrenia and autism start or worsen in association with puberty. [This is probably true.]

For these reasons, investigation of the control mechanism of puberty, using the nonhuman primate as a model, is essential and would contribute to the understanding and management of problems associated with human adolescence. [Where above did she say anything about nonhuman primates? Whether or not a better understanding of the “control mechanism of puberty” would lead to any better management of problems associated with human adolescence remains to be seen.]

Because there are no direct methods for examining neurochemical changes in the human brain, the animal model is indispensable in achieving these goals. [Her claim here seems to be more hyperbole. Studies examining neurochemical changes in the human brain are underway and published.]

11b.

1. Because we are aware of the value of an individual animal’s life, we have considered alternatives to the use of animals. [As suggested below, these considerations have included only computer models and tissue cultures. In fact, scanning technologies have been used to study neurochemical changes in the brains of children. See for instance: Benazon NR, Moore GJ, Rosenberg DR. Neurochemical analyses in pediatric obsessive-compulsive disorder in patients treated with cognitive-behavioral therapy. J Am Acad Child Adolesc Psychiatry. 2003.]

2. For this study, however, the use of non-human primates is essential, as the onset of puberty and the function of the hypothalamus are complex processes which cannot be simulated with computers or tissue cultures. [This bald claim has no bearing in fact. She has yet to prove that her research is essential, and she has said nothing the alternative method of studying humans directly with scanning technology.]

3. In addition, in order to apply knowledge obtained from research to humans, we need to learn about these processes in non-human primates. [This is a wild and controversial statement. She implies clearly that results from current research on the hypothalamus in many strains of mice, rats, sheep, mole-rats, zebra fish, cats, and dogs can’t be applied to humans, and while I agree with her, her claim that the results from non-human primates alone can is unproven. She implies without substantiation that the biochemistry of a marmoset’s, a gorilla’s, a rhesus macaque’s and a human’s hypothalamus are fundamentally the same while those of the afore named species are fundamentally different.]

4. This project is in the forefront of its research field and there are no duplications, as seen by continued support by NIH. [But NIH funds many duplicitous studies. Simply being one of thousands of NIH-funded studies implies nothing about possible duplication. Futher, one might imagine that if her research is important, or at least deemed important by others studying the biology of puberty, that others would be pursuing similar lines of study. Thus, duplicate discoveries could be made outside her laboratory, but she insists this isn’t the case.]

5. Unlike the circuitry involved in long-term depression in the hippocampus, computer simulation is not yet available due to the complexity of the circuitry for hypothalamic neuroendocrine function in animals. [Again, she seems blind to any other methodology, which suggests a low likelihood of innovation, insight, and meaningful discovery from her laboratory.]

11c.

1. The overall objective of this research is to understand the function of the hypothalamus in the rhesus monkey, as a model for humans. [Is her goal the development of a model, understanding the rhesus hypothalamus, or understanding the human hypothalamus?]

2. Since the genes in the rhesus monkey are more than 95% homologous with those in the human, and many aspects of hypothalamic functions in the rhesus monkey are similar to those in the human, the studies done in the monkey are essential for the improvement of human health. [But this assumes that Terasawa fully understands the genetics of hypothalamic function in rhesus monkeys, humans, and rats, but she doesn’t; no one does. Moreover, other researchers make the straightforward claim that knowledge gleaned from rats is applicable to humans. See for instance Pine MD, Hiney JK, Lee B, Dees WL. The pyrethroid pesticide esfenvalerate suppresses the afternoon rise of luteinizing hormone and delays puberty in female rats. Environ Health Perspect. 2008. And, Hiney JK, Srivastava VK, Pine MD, Dees WL. Insulin-like growth factor-1 activates KiSS-1 gene expression in the brain of the prepubertal female rat. Endocrinology. 2008. You have to wonder why the authors of this paper don’t cite Terasawa’s work in this area if she is, as she claims, at the leading edge. Her claim that her “studies done in the monkey are essential for the improvement of human health” is farfetched and unproven.

3. Function of the rodent brain, which is often used for a model, differs from function of the primate brain. [But, again, this implies that she understands how the differences influence the function of the hypothalamus, and clearly, given that understanding the function of the rhesus hypothalamus is her overall unrealized goal, she doesn’t yet have the knowledge needed to make such a difinitive statement, and moreover, researchers study rats' hypothalami say otherwise..

4. Lower organisms do not have comparable functions. [She must not understand modern ideas concerning evolution. There aren’t such things as “lower” or “higher” organisms. This is the old, quasi-divine and wholly discredited Great Chain of Being. Every organism alive today has an equally long evolutionary history. We are all descendents of an ancestral lineage. Striation into “higher” and “lower” forms is in the eye of the beholder and means nothing in a biological sense. This implies something about her grasp of biology generally. Moreover, many scientists, like those cited above, claim that other mammals’ brains and particularly their hypothalami, do share similar functions.]

5. In vivo studies collecting samples from the brain are not possible in humans. [But she hasn’t really explained why other methods would not be productive.]

Thus, research in non-human primates is very important. [Thus, nothing. Her arguments are illogical and peripheral. They are undermined by her wild claims and assumptions and confounded by contradictory facts. And yet, these are the whole of her justification for her decades of highly invasive experiments on monkeys. These are the arguments that convinced the oversight committees to repeatedly endorse her decades of cruel experiments

Finally, the PI has a large amount of background data on puberty in female rhesus monkeys. [That, at least, is undeniable.]

The large volume of blood

According to the AABB (previously known as the American Association of Blood Banks), a human can donate a pint of blood, about 10% of the total volume, once every 56 days. Terasawa says she is drawing an estimated 20% of the total volume per 30-day period from some of the monkeys.

She says, “Animals being bled at maximum level may require fluid replacement therapy and clinical care. A [redacted] veterinarian will be contacted for any single blood draw greater than 10% of blood volume and for animals being drawn chronically at maximal levels to asses clinically and provide supportive care and clinical monitoring. This may include fluid replacement and periodic CBCs.”

I suspect that these monkeys are chronically severely fatigued.

But the cruelty aside, I find particularly monstrous and grotesque the role of the veterinary staff in all of this. There is something uniquely distasteful and disturbing about doctors keeping vivisectors’ victims alive so that they can be experimented on further. To me, there is nothing more hideous or immoral than such behavior; it gives me nightmares.

2 comments:

Anonymous said...

"11a. In straight-forward, nontechnical language that would be understandable to a layperson (aim for a high school-senior reading level)..."

The instructions ask you explain what you do to a layperson, not to an animal right extremist who believes single cell organisms are conscious. No wonder you don't understand.

Anonymous said...

Who said anything about single-celled organisms? You are the one who clearly does not understand.