Paul Jorgensen and frogs

Paul Jorgensen from Marc Kirchner's lab took me on a little tour of the frog lab.

Xenopus Laevis look inflated; like you stuck a straw in their, um, sides and blew in lots of air. They float around in their water tanks, hugging each other in futile mating grips or perhaps simple gestures of closeness. The males have textured skin on their forelegs called nuptial pads, with which they grab on to the female to squeeze out her eggs, all the while spreading their sperm on the copious ovarian output. To get the eggs manually, the researchers mimic this squeezing technique, milking the females for their unfertilized young. I wonder how they feel while doing this.

Up in the corner of the room is a tank fool of kermit-like albinos. Creepy and compelling, they seem to know more then they let on.

A personal connection: the species is originally from South Africa, like me (Port Elizabeth, 1968).

Peter Sorger and cell suicide

Complexity, complexity and more overwhelming complexity. Peter is from MIT, and, like Mike Laub from the last entry, is studying signal pathways. Peter, however, is focusing on apoptosis, or cell suicide. This is a way for damaged cells to destroy themselves rather than do damage to the larger body. And apoptosis is no quiet death; the cells explode in beautiful eruptions. Interestingly, apoptosis is also a way to guide structural growth. When our hands and feet first develop, the bones are contained in one big web. Groups of cells die so that our fingers and toes can separate. When this doesn't work as planned, you get syndactyly.

The pathway here is complex, with many components that reinforce each other positively and negatively. To understand what a particular component is doing, Peter might turn that component off and watch the resulting cell. By repeating this many times with different combinations of pathway components, he can build a theoretical model of what is happening.

It's like trying to understand a computer program by looking at and manipulating the contents of the computer memory (registers, stack, and heap). The metaphor I've heard a few times here is that understanding the body is like trying to reverse engineer a 747 with no previous knowledge.

So Peter and his lab found that the pathway to apoptosis has four components, and here's the interesting part: some encourage death while others discourage it. It's as if the cell is saying, "I want to die. Am I sure I want to die? Yeah, I'm pretty sure. Wait, am I really, really sure?" If the signals pass through all these stages in the 'correct' way, the cell switches to what's ominously called a death response.

Another interesting thing is that this switch to a death response is fast and complete. As Peter said, "States of partial cell death do not exist." The cell is either alive and functioning normally, or has decided to kill itself and is in the process of doing so. This is different from humans, where states of partial death surround us. Depression, anxiety, neurosis. I've been reading Jeanette Winterson's Art & Lies, a beautifully written book whose three protagonists berate the passionless existence of modern man. The three of them aim for something else. Art, passion, release, fulfillment.

Back to Peter. Some of the chemicals sent along the apoptosis, or suicide, pathway are 'extracellular', meaning they are emitted by the cell to the outside environment where other parts of the cell pick them up and the continue the pathway. This means that nearby cells are affected. The cells are communicating their suicide desire (need? aptitude?) to their neighbors, and this affects their neighbors' desire. This might be why, in a group of similar cells exposed to the exact same damage, some die and others live. Many metaphors here.

Beautiful words/phrases
hetero-oligomeric
ubiquitination
vesiculated