02A0132 - Alterations in Cellular Functions in Stress Response - Tsonwin Hai - Pain Code=3E

Beginning in 1990, over the past twelve years, and 6,000 plus animals, this project has been seeking to understand the cellular changes that stress signals play in leading to liver dysfunction, heart attack and diabetes.

The records we have begin in 1996, when Dr. Hai writes in the Pain or Distress section of his protocol:
"We will not take measures to alleviate the distress. ... The animals will be recognized to be under distress when they become 'stoned', not moving, drinking or eating."

At this time Dr. Hai is using alcohol, acetaminophen, and a combination of the two, to induce stress responses. The protocol was approved October 1996. In January 1997, the issue of distress comes up again before ILACUC. Dr. Hai writes that, "If we notice that the animals are experiencing significant weight loss or displaying obvious sickness (due to infection or other non-experimental condition'), we will euthanize the animals."

We do have any other amendments until November 2000, when it becomes obvious to us that the protocol has been slowly changing from our original understanding of it's nature.. It now seems that transgenics is playing a large part in this project and the researchers have been having some problems with the mice.

The 3rd year approval (Nov. 99 - which we did not request) added an additional 1,680 mice. One year later Dr. Hai is requesting an additional 3,000 mice. "We have already used up all the mice, because the transgenic mice we generated have an unexpected phenotype: They die perinatally." ILACUC requested further information. The response from Dr. Hai:

The genetically altered mice have peri-natal lethality. Research suggests that they have liver and pancreas dysfunction and are unable to maintain their glucose homeostasis. However, the precise cause of death is not clear. (The PI had this statement bold.)
Many newborn mice died before we had an opportunity to analyze them. Estimate lost 800 mice between post-natal day 1 to post-natal day 8. This is because we can not predict whether the female mice would attack and eat the newborn mice, or whether the newborn mice would die on their own. The females ate their newborns, presumably because the newborns are unhealthy.

The additional 3,000 mice were approved for use.

Protocols are in effect for six years, so in October 2002, the protocol received a new id number - 02A0132.

The stress agents are:

Some of the pregnant females will now be decapitated to "avoid any effects from anesthetic drugs on the embryos which will be analyzed following the sacrifice of the females."

When ask about death as an end point Dr. Hai responds: (My feeling is it's a smart ass answer but the committee approved the protocol to begin year thirteen.)

In order to understand how stress signals affect cellular functions, we need to collect the tissues after the animals are treated. ... In order to collect their tissues, we need to sacrifice the animals. Therefore, sacrificing the animals is not the 'endpoint' of the experiments; the functional assays of their tissues are the endpoints.

Of course, the animals are just the holders of tissue, no feeling, no reason to be concerning with them except that they deliver tissue. Over the years, Dr. Yonushonis, director of Lab Animal Resources, has repeated to the media that animal researchers have "the highest respect and regard" for their subjects. Somehow, I don't see that respect in Dr. Hai's response.