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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."
Probably has some implications in to why we die...could understanding why cells die when they do help create ways to make us live longer?
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.'
programmed cell death With the new technamolagical advances in biology, i wonder if it would be possible to "reprogram" these cells to have an infinite life span.
Slash-for-Thought
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.
There are a number of issues in going from making a cell live forever, and making us do so.
First, you have to develop. Wouldn't want to make a 6 year old's cells live forever.
Then, you have to repair. You need to balance growth with externally induced damage (injury, sickness). If you make cells live forever, you also have to stop them from dividing... Or you'd end up quite the mess.
Many cells in the body, like skin, grow and die and that is very important to us. If the didn't die, you'd slowly erode the dead surface and end up one quivering blob of ozing red pain.
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)
"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."
I believe Horvitz actually conducted the seminal work (first discovering and characterizing genes controlling cell death) while working (along with Sulston & Brenner) as a postdoc at the MRC (in the UK).
This is to notify you that I have contacted the office of Attorney General John Ashcroft to legally prevent the ritualistic suicide of these countless cells. He, as a True Christian (tm), will not stand for these wicked acts.
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.
.
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.
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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When I heard this announced I kept confusing these guys with UCSF's Dr. Cynthia Kenyon, who was on Scientific American Frontiers not long ago talking about her work with elegans and their age-resistant genes. Anyone know what's the difference between her research and these guy's?
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.
Back in first grade, they teased him when he would play with worms during recess. He swore he'd show them, and now...
Millions of seven-year-olds were inspired today to poke at slugs and other slimy invertebrates.
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.
The big question in programmed cell death research is how does one pronounce apoptosis. Is it literally a-POP-tosis or is the second p silent, as if we were ancient greeks? I thank the Academy for the honour but the debate will still rage I fear.
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.
Cell death?
What prize do I get if I kill a cat in the name of quantum physics?
Table-ized A.I.
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
Now if we could only train bad HTML to kill itself off....
Table-ized A.I.
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.
Damn you, Cytochrome C!!!
I'll get you...you and your little friends BAX and BCL-XL, too!
-- I'd say your post was about 3 monkeys, 18 minutes.
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.
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
"...Sydney Brenner, H. Robert Horvitz, and John E. Sulston for their discovery of programmed cell death (also called apoptosis). 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." From what i know on the subject matter(I will discuss later), apoptosis was not discovered by Horvitz's lab, but was discovered in what i believe was the early 70s by Kerr, Wyllie, and Curie, three British doctors. I am not positive on the dates, or their actual specialities, but I do know for a fact that those three were the first to discover the phenomenon known as apoptosis. I know this all because despite me being only a high school student, I spent the last two years working on my Intel Science Research topic in the field of apoptosis. Unfortunately I never found a mentor and was dropped from the program, but I do have a very good understanding of the process as I would attend monthly meetings at MSKCC in NYC for an attempt to better understand.Email me if you wish to flame me or whatever.
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
> I wonder if "cell suicide" applies to human stem cells as well?
s ue s99/jan99/phenom_jan99.html
Thats the kicker: human pluripotent (aka embryonic) stem cells express telomerase, and appear to be pretty much immortal in culture.
http://www.smithsonianmag.si.edu/smithsonian/is
IOW, rather than keeping those frozen IVF embryos on liquid N until they die as the Religious Rightists demand, stem cell researchers actually want to make them immortal!
& if they do turn out to have souls, well, we can always go to the pluripotent stem cell culture & induce it to reform into a blastula...
Maybe they can explain to my why my Cingular phone cuts out in the middle of my F*ING CALLS!
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
that the key to the immortality that we seek possibly lies in the cancers that plague us?
Cancer is just a bunch of immortal cells. (ie: won't undergoe apoptosis)
Reminds me of the Hela Virus cells that were collected from Henrietta Lacks still sitting in some fridge somewhere...
Is "Sex and the Origins of Death." by William Clark. Well written, easy to read. He introduces cell death and describes necrosis as well as apoptosis. Discusses some of the ideas behind what apoptosis means (propagation of the species versus propagation of the individual) for organisms. Towards the end, goes into some possible applications for longer-life, etc. Good Book.
ummm....apoptosis doesn't have a lot to do with shortening telomeres. That is a completely different phenomenon. There is no time clock in apoptosis; there is a signal that originates either outside or inside the cell that causes the cell to die in an ordered, controlled fashion. Nothing to do with shortening of DNA chains at the ends.
There is a reason for everything. Sometimes that reason just sucks.
'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.
Wouldn't we be able to eliminate cancer then by assuring the p53 gene is properly producing proteins? Or any variation of this... Wouldn't we be able to destroy every dangerous cell by killing anything that has a mutated p53 gene? Is there a part of cancer research devoted to this p53 topic?
The problem with p53 is that cancer cells contain a mutated p53 gene.
.
Normal nonmutated p53 acts as a tumor suppressor, binding to genomic DNA and starting gene expression of p21 if the DNA copy is incorrect (as is the case with cancerous cells with genomic mutations)
p21 halts the cell division, stopping reproduction of the cancerous cell.
In a already cancerous existing cell with a p53 mutation, the cell will divide normally, because the p53 is mutated and it cannot bind DNA effectively. Therefore, the p21 will not get signalled, and the cancer will continue to multiply.
Cell phone: $99
Humongous gas guzzling SUV: $32,000
Inattentive soccer mom: free (god knows there's enough of them)
Bicycle on same roadway: $199
Video sent in to Real TV showing gruesome death: priceless.
It may look like I'm doing nothing, but I'm actively waiting for my problems to go away.
--Scott Adams