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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?
could understanding why cells die when they do help create ways to make us live longer?
Certainly. For example, there is a theory that free radicals (oxygen atoms sometimes released during the fuel generation accomplished by our mitochondria) cause damage to the DNA of a cell. There are "sweepers" in our cells that are supposed to suck up these free radicals, but som get away and damage our cells.
Studies have shown in laboratory animals that high-antioxidant diets extend the lifetime of animals. In one particular test, a very simple worm's life was DOUBLED compared ot the control population when a special, synthetic anti-oxidant was fed to it.
I don't know how related, if at all, programmed cell death is to free radicals and antioxidants, but as you suggested, once you figure out an effect, you can try to figure out a way to prevent or reverse the effect.
What was it G.I. Joe said? Knowng is half the battle
I didn't know people were dying from using cellular phones... No, not that kind of cell death.
Sure. It happens naturally.
Usually, we call it cancer.
~Idarubicin
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.
Please select mode of death:
1. Quick and painless
2. Slow and painful
3. It doesn't matter, you're genetically predisposed to die a horrible, horrible death. (Sorry, no refunds)
Sure. It happens naturally. Usually, we call it cancer.
So, at the cellular level, what is it that makes us age?
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.
I must urge the free people of the world to root out these cells, and prevent their evil ways from spoiling our way of life. We must support a preemptive strike! We must initiate a regime change! How many more Americans must die because of these suicidal cells. It's biological terrorism and we must put a stop to it, or watch our children suffer.
After working for several years at an Immunology lab at Harvard, It's very nice to see people finally get credit for discovering apoptosis. I use it in the lab as a core immunosuppressive therapy, only in mice and monkeys as of yet -- and by harnessing the power of apoptosis (PCD) we have so far created a treatment which acts like a powerful immunosuppressant to transplanted allografcts, without all the harmful side effects.
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While it may sound pretty violent or harmful, Apoptosis is not only a natural process, but it has also opened up new gateways into research in many different fields.
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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Isn't cancer caused by cells multiplying too rapidly? Is an issue of exponential growth, where they just keep multiplying and old ones don't die off? If we could make periodic adjustments to the way cells replicate perhaps this would work? I assume that at some point all the cells start slowing down the split process. If we could periodically change that point to equalize between cancer and failure, might we live longer?
I've also heard that hair/nails can still grow for some time after death? I suppose those cells keep on going. Creepy
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.
So life is based on certain cells being able to die and be replaced, and others lasting somewhat of a longer time. Is the problem that the long-living cells eventually die off, or that other cells stop/slow their multiplication process or both.
I suppose in the cases of people who don't die of outside caused, death would generally be caused by heart failure? Interestingly enough, I've not heard of tumours growing in hearts, or of people having dying of heart cancer, but perhaps it happens and I just haven't heard of it. The heart would probably be a good place to start though, trying to keep it from degenerating too much in later years.
In an additional note, it might be noted that many of the creatures that live the longest are also not overly prolific. If we were to mess with our genes so we lived longer, we might disable the human ability as far as bearing many offspring.
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.
People have asked and speculated as to the usefullness as to preventing or inducing apoptosis.
Cancer is caused by mutation on a single cell level. In order to divide, grow, resist the immune system, spread locally, develop a blood supply, and finally spread to distant sites a cell needs to mutate.
The list of mutations literally reads as check list of to-do's... Some of the first level requirements involve turning on the growth cycle, and turning off the mechanism of automatic cell death. Many cancers are 'immortal' cells. It is litterally one cell that grows and divides. Cloning itself over and over...
If you could force the cells to apoptose, (or disable their overide of the natural apoptotic cycle) you could defeat a great many cancers...
That is of course an over simplification, most cancers do the same thing but the method they use is very different (thus there is no magic bullet on the horizon)
How do I know? check the name djmd
DJMD - The fourth man - Planetary
Cell phone.
Humongous gas guzzling SUV.
Inattentive soccer mom.
Unlighted bicycle on same roadway.
That's what came to mind skimming the headline, cell phone death. I gotta sell my bike, it's making me paranoid.
I'm half-expecting Waterston to also get the Nobel sometime in the near future, once the entire public human genomic sequencing effort has yielded all of its results. The processes and data gained have been valuable to the entire community to a whole, and he's been instrumental in bringing everything together.
Someone posted a link to an opinion opposing his own on slashdot? This is SLASHDOT! We don't tell both sides of the story here, my good man.
- None can love freedom heartily, but good men; the rest love not freedom, but license. -- John Milton
In the example he gave:
Say a cell is infected by a virus, it will present pieces of the virus on the cell surface.
A T-Cell comes along, checks out this virus piece, and sends a signal saying
"Hey, that's a virus! You're infected! It would be better for all of us if you just commit suicide."
After getting this signal, the infected cell turns on its apoptosis genes and kills itself in a sensible, precisely controlled manner.
This is just one example of apoptosis, but you can see how the controlled suicide of a few cells is beneficial to an organism.
This is rather interesting because a couple of weeks ago I was discussing with some friends how Brenner got cheated out of a Nobel for his work in discovering apoptosis -- so finally he gets one. I guess he just had to live long enough for the idea to become trendy.
You need to realise that an animal model doesn't necessarily fit with the human one e.g. leptin. Moral of the story: Don't get your hopes up!
Am I the only one whose first thought was that it was referring to deaths caused by cell phones?
To make laws that man cannot, and will not obey, serves to bring all law into contempt.
--E.C. Stanton
Uhh, AFAIK, the programmed cell death = why we age theory has nothing do do with the various free radical charlatans.
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Rather, programmed cell death in the context of aging has to do with the loss of telomeric DNA, (non-coding 'tags' on the end of DNA molecules that form a place for DNA polymerase to bind when copying the DNA).
The part of the telomere where the DNA poly first binds doesn't get copied & eventually (after reaching a number of divisions known as the 'Hayflick limit') the cell has no more telomeres & so can't divide anymore, at which point it undergoes programmed cell death.
There are other signals that activate PGD, such as viral infections and early stages of cancer (where the sad association with vitamen C overdosing came in: if the cell was damaged by 'free radicals', it should undergo apoptosis, but this would be a symptom not a cause), but the type of PGD usually referred to in aging studies is this 'molecular clock' that keeps count of how many times the cell has divided in aging (of some tissues) is then caused by many cells of that tissue reaching the hayflick limit and self destructing.
This theory of aging doesn't seem to completely cover the issue, but it does have alot more backing in scientific research than the free radical stuff. More:
http://www.nature.com/nsu/020819/020819-13
Interestingly, many "Lower" animals, along with germ (sperm & egg progenitors) cells & cancer cells make an enzyme called telomerase which rebuilds the telomere, making these cells essentially immortal.
On the subject of aging, Geron is trying to find ways to reverse some effects of aging (at least those caused by PCD due to shortened telomeres) using telomerase:
http://www.geron.com/02.01_telomeras
How then do you explain so-called reperfusion injury, which is definitely a real phenomenon on the gross level? Current molecular explanations revolve around either the idea that once apoptosis is initiated, it is irreversible, or the idea that the restoration of blood flow and hence oxygen supply actually adds fuel to the flames by creating even more free radicals AKA reactive oxygen species. Most likely, it is some combination of both, and even though control of apoptosis will not completely stop such injuries, it could at least reduce it and thereby change the outcomes of patients who have strokes or heart attacks.
Like anything Evolutionary (Sociology, Politics etc etc) arena except Biology there is one uniting factor in the application of Evolution theory to another area. It doesn't make sense, and is founded on the standard lack of understanding of science found throughout the fluffy subjects, as Rutherford said
"All research in the social sciences can be summed up by the phrase 'some do, some don't'.
To mention on the same page as Noble Prize winners a bunch of mumbo-jumbo just shows what an unscientific world we live in.
An Eye for an Eye will make the whole world blind - Gandhi
Most people pronounce it that way, but it's wrong. It's actually pronounced "ape-oh-toe-sis". The second p is silent and both o's are long.
"I may not have morals, but I have standards."
Just don't tell the Vorlons what you're up to. "You are not ready for immortality." - Kosh
A steaming cup of soykaf would be real wiz right now.
'Bout damn time. After so many episodes of Goku, Gohan, Vegeta, and Piccolo powering up, all interrupted by flashbacks of past seasons and the original series, I didn't think they'd ever get around to Cell's Death.
Good judgment comes from experience.
Experience comes from bad judgment.