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Cell Death Nets 2002 Nobel Prize in Medicine
An anonymous reader writes "The recent press release at the Nobel website details the first of the 2002 Nobel Prizes. This year the Medicine prize goes to Sydney Brenner, H. Robert Horvitz, and John E. Sulston for their discovery of programmed cell death (also called apoptosis). Their seminal work in the model organism C. elegans established the foundation of cell suicide as a normal physiologic process. The implications are wide ranging including understanding organ development and cancer."
by eating the yummy, healthy brain of a living.
See here.
Mmmm... braaaaiiinnnss...
A message from the system administrator: 'I've upped my priority. Now up yours.'
To be precise, the Horvitz lab at MIT discovered apoptosis. Brenner and Sulston were honored for their roles in establishing C. elegans as an experimental system.
Why study a nematode, you ask? They're small, transparent (so they don't need to be dissected) and are self-fertilizing. Most interestingly, they have a precise number of cells that arise from an entirely predictable series of divisions and deaths, making it easy to pick out genes that affect that process.
What I'm listening to now on Pandora...
NPR has a pretty good link to an explanation. At the top of the article, there's an real audio recording of the actual report that I listened to this morning. I thought it was fairly accurate, and should give some explanations.
To be precise about it, these fellows did not "discover" apoptosis, they have done a lot of very good work defining the genes and methods responsible for triggering it. From what I've read, though, they certainly deserve the prize.
hmmmm?
I didn't know people were dying from using cellular phones... No, not that kind of cell death.
Or more precisely, it's a likely side effect of using C#.
i think it's inhumane to let your cells get to the point where they have to commit suicice. i euthanize my weak cells with jack daniels on a periodic basis.
Yes, but not in the way you think. We can use apoptosis to kill harmful cells, like cancer cells. This is a "natural purpose" of apoptosis, and drugs are under development to "encourage" cancer cells (and virally infected cells) to die by this mechanism.
The theory that apoptosis plays a central role in human aging is part-and-parcel of the "free radical" theory of aging, which I think is bullshit.
The basic idea is that reactive oxygen species - these are chemicals that want to take electrons away from biological molecules and can do in such a fashion that the biological molecule is damaged - damage your mitochondria in such a fashion that the mitochondria signal the cell to die. This definitely CAN happen - however, I don't believe that it actually does, or that any of the pathologies we observe in human aging actually depend on this pathway. Btw, I'm a bioinformatician (grad student); when I worked with my Dad, I studied oxidative stress - he still does but he does not think it plays a role in normal aging. Certain conditions - being a chain smoker, being on hemodialysis, whatever - may actually put enough of these reactive oxygen species into your system that this could happen, but I doubt it.
FYI: some people try to sell you antioxidant dietary supplements (or other treatments.) I cannot emphasise enough - these products are snake oil. Even if reactive oxygen species do play a significant role in aging (which I doubt,) taking spills to scavenge them or soak them up is utter malarky.
The opinion of someone with whom I disagree almost completely. More of the same - the summary is fairly accesible.
To sum up - I can't say conclusively that there is no aging-related process that depends on apoptosis, but I don't find the evidence at all convincing. The one that people are fond of at the moment, which is oxidative stress-come-apoptosis, is hogwash.
Aptoptosis serves two functions:
1) Developmental. Developmental Aptoptosis is necesarry to "carve out" your body. For example, when your fingers form, the tissue between what will become the fingers goes aptoptotic and dies. There is no real evidence that this is what happens when you get old.
2) Defensive. Cells which are pre-cancerous, or which have been infected with viruses, can become apoptotic. Certain conditions that some old people get - autoimmune disorders, for example - depend on apoptosis to do harm. However, this is not a part of normal aging.
P.S. Most scientists pronounce it "apo-tosis," the p is silent (like pterodactyl.) On the other hand, by this reasoning, helicopter (which comes from the same root as pterodactyl) would be "heli-coter", so say the p if you want.
The good and new comes from no quarter where it is looked for, and is always something different from what is expected.
If you can answer that question, you'll be getting the next Nobel Prize in Medicine or Physiology. "What makes us age?" is one of those deceptively simple questions in biology, like "How do proteins fold?" that seems like it should be simple to answer but turns out to be fractal in its complexity -- the closer you look, the more details emerge, and the closer you look at those details ... etc.
The correlation between ignorance of statistics and using "correlation is not causation" as an argument is close to 1.
The next step is to quantify the signals (chemicals) responsible for triggering the series of events that are called apoptosis and to elucidate just how transcription switches work. All 'switches' in the body are based off the concentration of various molecules, be they enzymes, cofactors, structural proteins, minerals (Na+, K+, Ca+), etc. The most interesting exploration would entail studying how a concentration of a signal yields a binary switch, that an event either be triggered or not.
The cell widely uses feedback loops, both positive and negative, to exponentially increase and decrease the amount of signal that is being produced at any one time. This signal may interact with other signal-producers to give a multi-signal, multi-enzyme response system that, through the non-linear dynamics of the system, yields a definitive high and low concentration of signal that determines whether an event is to be triggered or not.
To fully understand the mind-boggling complexity of a single cell, imagine a system composed of 5000 enzymes (or more) all interacting with 10,000 molecules (or more) with thousands of possible reactions. Now try to simulate this all at the same time, using non-linear kinetics, and predict the outcome of an initial state.
A lot of crazy things happen, including shifts in entire groups of genes (responsible for protein & sRNA synthesis) caused by very tiny disturbances. The non-linear dynamics of the cell are set up so perfectly that its self-regulation is simply amazing.
My Two Cents...not meant to be a full explanation of why apoptosis is so cool or where the research is going from there.
Salis
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Evolutionary psychology has pointed out that it is possible for suicide to be evolutionarily advantageous. If my existance makes it less likely that my genes will be replicated, then it would be evolutionarily advantageous for me to kill myself.
For example, if I am a large drain on my family, and I'll never be able to have children, and I'll just make it harder for my siblings to get by, then my existence will make it harder for my (siblings) genes to be replicated.
Of course, this is almost never actually the case. But it makes sense that perhaps it used to be, when we didn't have such a easy time surviving. Now those same urges, that may have made sense when most people died by the time they were 30, are completely out of place.
Same basic concept.
There are no trails. There are no trees out here.
It is vital to development of many tissues, such as nervous tissue in the spinal cord or the brain. Death of a human is not massive PCD.
Programmed cell death / apoptosis is caused by intercellular communication.
Apoptosis can be stimulated in a cell through a variety of ways, for example in an antigen-presenting immunoreactive T-Cell which binds through a Fas / FasLigand compliment, the t cell will undergo apoptosis and kill itself so that it cant kill the other cell.
So in reality, no, it has nothing to do with human death, just regular cell death.
Sorry abut the raw-HTML post above. I forgot to switch from code mode. Here is the correct version:
Because it is an interesting and often misunderstood subject, here is a small primer on the topic of apoptosis (Programmed Cell Death).
FYI I work in an immuno lab which uses apoptosis as a main treatment for transplant tolerance.
Death by suicide
Cells that are induced to commit suicide:
The pattern of events in death by suicide is so orderly that the process is often called programmed cell death or PCD. The cellular machinery of programmed cell death turns out to be as intrinsic to the cell as, say, mitosis.
Why should a cell commit suicide?
There are two different reasons.
1. Programmed cell death is as needed for proper development as mitosis is.
2. Programmed cell death is needed to destroy cells that represent a threat to the integrity of the organism.
It's a little bit of both. Cancer is the result of uncontrolled cellular replication due to genetic damage to cellular regulatory machinery. Apoptosis is supposed to kill off cells that have problems with their internal structure (for example, a genetic error causing a fault in the systems that regulate growth and proliferation) as well as cells at the end of their useful lifespan.
If we could make periodic adjustments to the way cells replicate perhaps this would work?
And you've just hit on the holy grail of oncology. Unfortunately, we can't just tell all the body's cells to commit suicide. Cures cancer--but results in unsatisfied customers. And some quickly replicating cells are supposed to be that way (bone marrow, gut lining, hair, etc.) so we can't even just mow down fast-growing cells. Actually, that's sort of what chemo and radiation therapies do in a very ham-fisted way--toast all the fast-growing cells, and hope that the cancer dies faster than the rest of the body. It's why chemo makes your hair fall out, and causes anemia and nausea.
Rest assured, however, that your tax dollars are hard at work on a solution.
I've also heard that hair/nails can still grow for some time after death? I suppose those cells keep on going. Creepy
This one is mostly an urban legend. Mostly, it's due to the slight dessication/dehydration the body underdoes after death. There's a bit of evaporation, and shrinkage. Contraction of surrounding tissue can force hair and nails to protrude further than before death, giving a perception of growth. Also, there were cases up until the last century or so that involved patients in deep coma states--still alive, but apparently dead. Yes, hair and nails grew on those 'dead' people. And they got pissed off when they got buried.
~Idarubicin