The Disturbing Case of Dr. Ei Terasawa
An increase in in vivo release of LHRH and precocious puberty by posterior hypothalamic lesions in female rhesus monkeys (Macaca mulatta).
We have previously shown that a decrease in gamma-aminobutyric acid (GABA) tone and a subsequent increase in glutamatergic tone occur in association with the pubertal increase in luteinizing hormone releasing hormone (LHRH) release in primates. To further determine the causal relationship between developmental changes in GABA and glutamate levels and the pubertal increase in LHRH release, we examined monkeys with precocious puberty induced by lesions in the posterior hypothalamus (PH). Six prepubertal female rhesus monkeys (17.4 +/- 0.1 mo of age) received lesions in the PH, three prepubertal females (17.5 +/- 0.1 mo) received sham lesions, and two females received no treatments. LHRH, GABA, and glutamate levels in the stalk-median eminence before and after lesions were assessed over two 6-h periods (0600-1200 and 1800-2400) using push-pull perfusion. Monkeys with PH lesions exhibited external signs of precocious puberty, including significantly earlier menarche in PH lesion animals (18.8 +/- 0.2 mo) than in sham/controls (25.5 +/- 0.9 mo, P < 0.001). Moreover, PH lesion animals had elevated LHRH levels and higher evening glutamate levels after lesions, whereas LHRH changes did not occur in sham/controls until later. Changes in GABA release were not discernible, since evening GABA levels already deceased at 18-20 mo of age in both groups and morning levels remained at the prepubertal levels. The age of first ovulation in both groups did not differ. Collectively, PH lesions may not be a good tool to investigate the mechanism of puberty, and, taking into account the recent findings on the role of kisspeptins, the mechanism of the puberty onset in primates is more complex than we initially anticipated.
I don't remember when we first learned that the university had long been ignoring the problems in Dr. Terasawa's lab. It might have been the minutes from the UW-Madison Graduate School Institutional Animal Care and Use Committee (IACUC) that we got through an open records fishing expedition.
The story broke in August, 2006:
Since that time, we've been trying to put the pieces together in order to better understand the day-to-day ordeals the monkeys are forced to endure in the labs at the University of Wisconsin-Madison, and – based on UW Primate Center Director Joseph Kemnitz's assertion that all the primate labs operate in the same way – in all the monkey labs here in the US and abroad. In the process, we've also learned something about the UW's oversight, such as it is.
We have collected a number of primary documents that were not available to us or to the media during our early efforts to investigate the Terasawa oversight situation.
As you review the following documents and comments, keep in mind the 2007 abstract at the beginning of this essay. Dr. Terasawa is still using the push-pull perfusion procedure in her studies, which means that the UW approves of her methods.
Here is the May 25, 2003, USDA inspection report that forced the university to take action.
And, here is Dr. Terasawa's response, dated May 7, 2003. It's clear that she's responding to the USDA inspector's discovery. I don't know why her letter is dated over two weeks prior to the date of the inspection; I attribute it to messy record keeping by the USDA inspector. What is clear is that she's full of excuses for having killed this 31 year-old monkey without the blessing of the IACUC.
Dr. Eric Sandgren's May 13, 2003, response to Terasawa.
Next, comes a report dated July 1, 2003, addressed to Christine Parks (who at the time was apparently the director of the UW Research Animal Resource Center) from Terasawa. It was prepared by an unknown author and Bret M. Windsor-Engnell, the “Bret” named in the document. Although both names are redacted here, Bret's name is clear in other documents. Bret is listed as a coauthor of many of Terasawa's papers like the one at the top of this essay.
Parks then prepared a report and recommended a very mild rebuke based on the report she received from Terasawa and her and Crumbaugh's review of clinical histories of the monkeys used in Terasawa's lab. It is dated July 10, 2003. The Parks July 10 report has been incomplete until now. The last two pages were not available to the press at the time the story was publicized. The full report gives a good idea of what the monkeys in Terasawa's studies were being put through, and have been subjected to for at least two decades. The name redacted on page two is Amanda Crumbaugh, a primate center staff member.
The Parks report resulted in a letter from the university dated September 22, 2003, to the National Institutes of Health's Office of Laboratory Animal Welfare (OLAW), a regulatory requirement whenever a significant violation of the Animal Welfare Act is committed, and to Dr. Goldentyre, the USDA inspector who discovered the situation. The letter shows that even with the profound suffering, the lack of experiment supervision, and the ridiculously flawed lab notes, the university came to the conclusion that closer monitoring would be sufficient to handle the situation.
Goldentyre responded with a perfunctory, “Sounds good!”
OLAW's response was a little more probing. It also notes (in the first redacted part) that there were three instances of non-compliance with the Public Health Service's animal care policy. The second and third instance, hidden in the large redaction, may refer to a second and third monkey left unmonitored while strapped into the chair while the their brains were perfused.
R. Timothy Mulcahy, Chair of the UW All Campus IACUC and Christine Parks responded to OLAW's questions on December 2, 2003.
OLAW responded two days later. It's worth noting that up until this point, in spite of all the problems, Terasawa had received only a temporary suspension as the investigation proceeded and was reinstated once the IACUC had detailed the many problems and suffering.
Further, OLAW said that the UW should notify the journals that published Terasawa's papers because of most journals' stated ethical guidelines regarding adherence to animal care regulations. It appears that the only one who contacted any of these scientific journals was PeTA. For the record, since 1999, Terasawa's research, specifically papers in which the push-pull procedure was employed, included Endocrinology, the Journal of Endocrinology, the Journal of Clinical Endocrinology & Metabolism, and the American Journal of Physiology – Endocrinology Metabolism. No journal pulled her papers; there is no record that the university took the time to contact any of them. What a surprise.
This next document, from the Primate Center Attending Veterinarian (at the time), Iris Bolton, may be the most enlightening document in this collection. It suggests just what has been going on in Terasawa's lab for the past two decades. Taken with the Parks report, the suffering is difficult to overstate. Note that the bungling and the suffering are not what eventually lead to Terasawa's short suspension but rather her interpersonal style.
This memo is probably the best estimation of the actual work going on in Terasawa's lab; it probably represents the work that has been going on for two decades; and it probably well represents the on-going research activities as well.
Hearing that all her grants might be suspended, Terasawa freaked out. In 2003, her publicly-funded grants were worth almost exactly a half-a-million dollars. There was a lot at stake, so she groveled, which turned out to be exactly the right tact to take.
Mulcahy responded that that IACUC had found her appropriately contrite, but that as a reminder to always kiss ass, she would not be allowed to be near animals for two years.
In case you imagine that the details of the Terasawa story are exceptional (other than the fact that the USDA actually caught the university failing to fulfill any meaningful oversight of on-going research) and that other researchers would find something troubling concerning the care and use of the monkeys in her lab, consider UW primate vivisector Göran Hellekant 's outrage:
At the end of the day, Terasawa continues to strap monkeys into restraint chairs and attaches a pump to a tube forced into their brain. They remain restrained for hours on end while chemicals are pumped into and out of their brains.
Dr. Eric Sandgren, mouse vivisector and the current chair of the UW All Campus Animal Care and Use Committee, the current chair of the Graduate School Animal Care and Use Committee, and the current acting-director of the Research Animal Resource Center says that the Terasawa affair is evidence that the UW oversight system is working.