When our knowledge of genetics brings us to the day when we can understand and control cancer, we're not far away from longevity. It's all about cell division and telomeres...
Multicellular organisms replace worn-out cells through cell division. In some animals, however, cell division eventually halts. In humans this occurs on average, after 52 divisions, known as the Hayflick limit. The cell is then referred to as senescent. Senescent cells deteriorate and die, causing the body to age. Cells stop dividing because the telomeres, protective bits of DNA on the end of a chromosome, become shorter with each division and eventually can no longer protect the chromosome. Cancer cells, on the other hand, are "immortal." An enzyme called telomerase, present in large quantites in cancerous cells, rebuilds the telomeres, allowing division to continue indefinitely.
Big Pharma knows this, and they must know that they'll be making trillions if they can ever bring longevity meds to the market. I hope that pushes them to get safe drugs to market in the next 30 years.
Thanks for the vid, I'll have to watch it at some point. This is part of the reason I investigated a masters degree in bioinformatics and computational genetics a while back.
Bear in mind that one of the reasons for limiting the number of cell divisions is that DNA polymerase isn't perfect. Divide too often and there's a reasonably good chance that you'll end up with malfunctioning cells anyway. Telomerase may well be an important part of life extension, but it's not a magic bullet.
Understood and agreed. The telomare restriction is there for a reason, likely for the long term survival of the genes themselves.
Also agreed with your post below, we're still missing several pieces of the puzzle before this isn't laughed out of the room. It's worthy of research, and it's possible the P.T. Barnum aspect of this will get it more funding than other projects.
(Many of my own ideas are crazy enough to get laughed out of the room, so I'll take my first post and the valid criticism of it in stride... :)
Death is a survival mechanism that protects us from cancer. Its about that simple.
Okay, that was a bit pat. To expand a it - evidence seems to support the idea that without pre-programmed cellular death cancers would arise rapidly. Supposedly so quickly that getting to the point where you could reproduce would take a miracle. Now, if you can control and eliminate cancer then maybe you can start mucking about with the other stuff. There is only one problem - there isn't just one type of cancer. There are *many* different types of cancer each one of which presents itself in different ways and has different origins and vulnerbilities. A treatment that wil lwork for one cancer will end up being completely effective against another. Unless you can uncover a single common vulnerability that all cancers share there will never be a 'cure for cancer'. There maybe be 'cures for cancers' but the likelihood of one treatment that fixes all types is very remote.
"A treatment that wil lwork for one cancer will end up being completely effective against another."
You should probably sleep more.
To put it in modern terms, cellular aging is a survival mechanism for our genes to reach the age of reproduction.
Bloody selfish genes, thinking they're more important than we are... ;)
Yeah... you know what happens when you take out the telomere restriction?
Cancer. Cancer of the everything. I wish I could remember a real citation for you, but I know that I learned this from Nick Cozzarelli in my intro-grad molecular biology class my first year at Cal. So I'm pretty sure it's been tested.
What this means is that it's a little more complicated than just turning off the apoptosis (programmed cell-death) protocols.
Even cancer of the feelings?
So, cancer's just the bio equivalent of a buffer overflow or smashed stack, right? A common symptom reachable from a zillion different kinds of failure. Like how nobody really dies of "heart failure", that just happens to be the last square on the board. I think we'll know that real progress is being made when we stop hearing the word "cancer" because it has been chased upstream.
Cancer is a failure of the normal cell division regulation. There's various points at which this can happen and a myriad of ways that each of them can be affected. It might be due to chemical DNA damage. It might be due to environmental DNA damage. It might be due to a retrovirus inserting itself into your DNA in an especially unfortunate place. It might be due to being especially unlucky with some transposable element. It might be an accumulation of errors from transcription errors. It might be due to having inherited fucked genes that mean some of your repair or regulation mechanisms don't work properly. At the end of the day, it doesn't really matter - your cells are fucked.
The problem is that fixing some of these would basically require reengineering your cells. But while there's a large number of initial causes, the range of final symptoms is much smaller. Cancer cells are pretty obviously different to the surrounding ones, especially once a tumour heads towards malignancy. As a result, we can target them. As therapies improve, it's likely that most cancer will move more towards being an inconvenience rather than anything else.
I guess an analogy is that it's easier to implement non-executable stacks than it is to find every single piece of crap C and fix it. Future technology might make that possible, but right now it's easier to try to reduce the damage as much as possible.
Considering that the human body has on the order of 10^14 cells, that's a lot of stacks.
I don't doubt that virtual immortality isn't possible for human cells in a petri dish. The actual mechanism of repairing all the cells in the human body is a monumental task on the verge of being science fiction.
I'm not losing my initial optimism though, I think there's a non-zero probability of seeing such a technique in my lifetime.
Mostly. I'm no expert in cancer biology, but my understanding is that it is an endemic failure mode. That is, cellular systems are particularly given to "crashing" this way. I don't know a lot about computer innards, but the analogy that comes to mind is the infinite loop. You can get to it in any number of ways, but once you get there, the effect is the same and the program just keeps running, sucking up whatever resources it can get its hands on.
I agree with this analogy.
Re-read the first sentence of my original post. I think we're talking about the same thing here. :)
Cancer and longevity aren't just opposite sides of the coin, they are the same coin.
By "understanding and control cancer", I mean "having total understanding and control over the process of cell division in cells, both cancerous and normal", rather than "keeping cancer in check by application of known medicine or something just around the corner". A true "cure" for cancer is an almost unimaginably complex task, a solution for longevity only slightly moreso. I'd be highly pessimistic of seeing either in my lifetime if it weren't for the massive piles of cash being thrown into biochemical research.
Caveat: I am not a geneticist but rather a lowly computer programmer, so my posts on this subject are about as authoritative as "The Beverly Hillbillies Guide to Fine Dining and Etiquette." :)
I was wondering... cancer cells are essentially immortal. Do they have very long teleomeres?
According to another part of this discussion which references Wikipedia, they have an enzyme called telomerase that extends the telomeres. My mol-bio/cell-bio is fading, but that assertion sounds right.
I do recall that telomerase is normally only present in germ-line cells, which is necessary if the next generation is to have telomeres of the appropriate length. Failure of this process is, essentially, what messed up Dolly The Sheep and her cloned kin.
Right now? It's snake oil. Standing up and talking about how we're going to live forever as long as these minor technological inconveniences can be surmounted isn't insightful or visionary. It's overselling science to credulous people with large piles of money who are terrified of dying and have grown up to believe that technology can fix everything. Is it possible in theory? Yes, just like nuclear fusion as a viable source of power is - we just need to deal with the issues like
and so on.
If you assume sufficiently large technological advances, many things are possible. That doesn't make it ethical to lecture people on how there's a good chance that they'll live to be a thousand if they'll just provide some more money for this research. When Aubrey presented a talk awfully similar to this one at the genetics department in Cambridge (where he was working at the time, but as a programmer rather than a biology researcher) he was basically laughed out of the place. This simply isn't legitimate biology yet.
Yeah, de Grey is a charlatan. Molecular biology is right now is where computer technology was in the 40s: developed enough to support an engineering discipline, but far, far away from being what it is today. De Grey is the equivalent of dropping Ray Kurzweil into Bletchley Park: maybe a vision of the future, but one that's neither inspired nor useful.
Oh thank god someone else made the Kruzweil/de Gey analogy. I suddenly feel like I'm no longer alone in this great big crazy world.
You may also want to watch his presentation at TED. You can download the video from the TED website.
Also, what's with the people who introduce talks at Google? The one who introduced the woman from the OED was similarly bad, though bad for longer.
But a couple of things I wanted to add to the conversation:
Telomerase is in all cells (except RBCs of course). It both shortens and lenghtens telomeres. Recently it was discovered that telomeres shorten and lenghten throughout subsequent divisions. Although cells to become senescent without telomeres, it is not a countdown timer.
Cancer happens when the genes that encode proteins that act as regulators of cell division or apoptosis become defective. Some of these proteins stop the cell from dividing, some check for errors, some act as signals to start division. There are tons of these regulators.
Gene mutations occur constantly, cells fail due to them constantly. Usually it's something that deals with it's function, metabolism, etc. so only that cell is affected. When it involves it's division regulation, then (in some instances) it becomes cancer.
In any event, throwing money at biotech will give answers because there are way more avenues open for exploration than can be taken currently, but unlike engineering problems: answers != solutions.
Bioengineering is not a valid descipline yet. We are not at where computer engineering was in the 1940's. We are at where electrical engineers were at in the 1900-1910's.