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Derek Lowe The 2002 Model

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Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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October 5, 2009

A Nobel for Telomerase

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Posted by Derek

As many had expected, a Nobel Prize has been awarded to Elizabeth Blackburn (of UCSF), Carol Greider (of Johns Hopkins), and Jack Szostak (of Harvard Medical School/Howard Hughes Inst.) for their work on telomerase. Blackburn had been studying telomeres since her postdoc days in the late 1970s, and she and Szostak worked together in the field in the early 1980s, collarborating from two different angles. Greider (then a graduate student in Blackburn's lab) discovered the telomerase enzyme in 1984. She's continued to work in the area, as well she might, since it's been an extremely interesting and important one.

Telomeres, as many readers will know, are repeating DNA stretches found on the end of chromosomes. It was realized in the 1970s that something of this kind needed to be there, since otherwise replication of the chromosomes would inevitably clip off a bit from the end each time (the enzymes involved can't go all the way to the ends of the strands). Telomeres are the disposable buffer regions, which distinguish the natural end of a chromosome from a plain double-stranded DNA break.

What became apparent, though was that the telomerase complex often didn't quite compensate for telomere shortening. This provides a mechanism for limiting the number of cell divisions - when the telomeres get below a certain length, further replication is shut down. Telomerase activity is higher in stem cells and a few other specialized lines. This means that the whole area must be a key part of both cellular aging and the biology of cancer. In a later post, I'll talk about telomerase as a drug target, a tricky endeavour that straddles both of those topics.

It's no wonder that this work has attracted the amount of attention it has, and it's no wonder either that it's the subject of a well deserved Nobel. Congratulations to the recipients!

Comments (20) + TrackBacks (0) | Category: Aging and Lifespan | Biological News | Cancer | Current Events


1. retread on October 5, 2009 10:47 AM writes...

It's unlikely that the telomerase work will have to be retracted or is incorrect. Compare this with the article in the NYTimes Sunday magazine a few weeks ago by Economics Nobelist Paul Krugman castigating several other Economics Nobelists (mostly from the Chicago school) for being flat out wrong. Why do they even give Nobel's for this stuff ? There aren't too many Nobel's in physics, chemistry or biology that are flat out wrong (the Cori's work comes to mind). Do readers know of others?

I find Krugman's assumptions of omniscience (particularly about matters noneconomic) irritating. He certainly didn't prevent Princeton's endowment from tanking last year. However Summer's brilliance didn't help Harvard's, nor did the expertise of the former treasury secretary (Rubin) prevent Citi from nearly going under. It makes me wonder how we will find a regulator, smarter than these 3 to keep us out of similar economic trouble in the future.

Sorry to be a bit off topic.

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2. Sili on October 5, 2009 11:24 AM writes...

The econ prize isn't a real Nobel, and I think the committee is increasingly realising that they made a biiiiig mistake in accepting the extra endowment.

Just look at the ridiculous whining there is again these days about there not being 'enought' Nobels.

GET. YOUR. OWN. FUCKING. PRIZE. if you're unhappy, people. Why does the Nobel Foundation have to coddle you?

If something needs to be changed, it's the limit on how many people can share the prize.

Sounds like a good choice this year.

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3. not in the know on October 5, 2009 11:38 AM writes...

What's "flat out wrong" about Coris' work? [I am not a bio/chemist so pardon the question]

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4. Jim Hu on October 5, 2009 11:47 AM writes...

Big difference between Nobel prize winners being wrong vs. the work for which they won the prize being wrong. The former is frequent.

For the latter, the example I think of is Ochoa for PNPase. The enzyme turned out to be important for later deciphering of the genetic code, but the citation suggests that the committee thought it was RNA polymerase, not a useful degradative enzyme running backwards.

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5. Curious Wavefunction on October 5, 2009 1:39 PM writes...

The economics prize has often been a sham since economics models are not scientific laws and often need to be overhauled or discarded later on. The author Nassim Taleb has advocated that it be abolished; consider that it was awarded for the development of derivatives whose fruits we may end up reaping for a hundred years. Plus in the fickle arena of human affairs models can never be as effective as they are in the hard science (and even there they can spring lots of surprises).

As for Krugman, his prize was awarded for work done in the early 80s and since then he has almost completely turned into a political spokesperson and nothing more. Sure, the Chicago School was not without flaws, but "flat out wrong"? Is Krugman confident that his economic theories, just like telomerase or ubiquitin, will be of unchanging permanence?

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6. RichardA on October 5, 2009 3:26 PM writes...

I am wondering if this was a total surprise? Was the topic of telomerase in the top 10 in the past few years? Does anyone sense a timeliness to the topic?

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7. Capek on October 5, 2009 3:42 PM writes...

Considering Nobels in Medicine for ideas that we now recognize as wrong, we might contemplate the prize given to Carleton Gajdusek in 1976 for his work on the disease Kuru in the tribespeople of New Guinea. This is an example of what we would now call a spongiform encephalopathy, or prion disease. He described the causative agent as a slow, unconventional virus, which is unlikely to be true. A second Nobel on this topic was later awarded to Stanley Prusiner, who maintains that prion diseases such as Creutzfeldt-Jakob disease are caused by proteins as infectious particles.

I once remarked to an expert in this field how unusual it was that two separate Nobels had been awarded for the study of a disease that has afflicted only a small number of human subjects. The expert responded that there was likely to be a third prize awarded eventually, to the scientist who eventually gets it right.

And speaking of flat-out wrong, of course Dr. Gajdusek's pedophilia with boys from the New Guinea tribes merits contempt.

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8. befuddled on October 5, 2009 5:01 PM writes...

@1, Retread,
I gather you're a (former?) physician, so I'm sure you're aware of the Nobel given to Moniz for the lobotomy, which seems questionable in hindsight (though perhaps not "wrong" in the sense that it does have some of the desired "pacifying" effects).

It's true that Krugman is currently doing a lot of journalism, but at a minimum he predicted the bursting of the housing bubble, which is better than Greenspan, Bernanke, and much of the Chicago school. Surely that's worth a little respect?

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9. befuddled on October 5, 2009 5:07 PM writes...

Mistakenly posted this on the wrong thread. Here it goes on the right one:

What really strikes me about this Nobel, other than the scientific importance of the discovery, is that Greider is sharing it. How often does the grad student share in the prize?

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10. Chalker on October 5, 2009 6:09 PM writes...

Elizabeth Blackburn was on the front page of the paper this morning here in Melbourne as the first Australian female to ever win a Nobel (yes I know all of the work was done in the US). Congrats!

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11. Brazillions of drugs on October 5, 2009 9:30 PM writes...

The general credibility of the Nobel Prize usually diminishes in the order Physics = Chemistry > Medicine > Literature > Economics > Peace

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12. Jose on October 5, 2009 11:31 PM writes...

Actually, I'd have to put Literature near the bottom of the list- Joyce never got it, while Pearl S. Buck, and Toni Morrison both won.

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13. retread on October 6, 2009 8:45 AM writes...

Befuddled -- Yup, I'm a retired MD. The work of Moniz appears barbaric with 20/20 hindsight, just as phlogiston in chemistry and the aether in physics are now known to be incorrect. However, you have to put yourself in their shoes. There was no effective treatment for schizophrenia back in the 30s. Moreover, it is an awful disease.

The best description I've ever read is "A Beautiful Mind", in which mathematicians with no theoretical axe to grind simply described what they saw. It really describes what I saw in clinical practice as a neurologist. The section is about 200 pages long, and a psychiatrist friend found it too depressing to read. Forget the romanticized stuff in the literature "One flew over the Cuckoo's Nest" etc. etc.

Also the Moniz work stands up. It really does produce the effects he claimed. The fact that it was overused and misapplied doesn't count. Even if you throw out his frontal leukotomy work, Moniz still deserves the Nobel for his development of cerebral angiography.

Shiller at Yale also called the housing bubble, with negligible effect on Yale's endowment, which tanked just like Princeton and Harvard's.

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14. chemist on October 6, 2009 9:55 AM writes...

I want to put in a plug for Alexey M. Olovnikov.

From WikiPedia: "He was the first who recognized the problem of telomere shortening, predicted the existence of Telomerase and suggested the Telomere hypothesis of aging and the Telomere relations to cancer." The story of his epiphany while standing on a subway platform is kind of like Kekule's Dream, except real. See: Experimental Gerontology, 1996, 31(4), 443-448, doi:10.1016/0531-5565(96)00005-8 for an autobiographical account.

His early publications (1971+) were all in Russian and mostly went unnoticed and uncited. In addition, political circumstances in the USSR prevented him from advancing his experimental research.

I'm not saying he should have shared this Nobel, just that he should be acknowledged.

PS. I'm still hoping that Fujishima - Honda get the chemistry Nobel.

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15. Morten G on October 6, 2009 10:28 AM writes...

Krugman might be using his Nobel as a political platform but no more than Friedman did. And Friedman used his to promote a political agenda concealed as science.

That said the Chicago school and Krugman will always be opposed since what Krugman got his award for goes a long way to explain the problems with unimpeded capitalism.

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16. JIm Hu on October 6, 2009 10:40 AM writes...

befuddled: I agree. Greider is certainly a major player in the field, but the press release focused on the work she did in Blackburn's lab. There was a mention of later work showing that loss of telomerase led to shortening of telomeres and senescence, but I don't remember if she was central to that. I thought there were a lot of groups testing that idea once there was a way to go after telomerase via the identification of telomerase RNA and TERT.

Speaking of TERT, one could make an argument for Cech. But I think the selection is largely fine. It will be interesting to hear what my telomerase colleague thinks. I'm not seeing the reaction we saw the past few years about other candidates being dissed: Gallo for HIV, and the plant RNA interference folks before that.

I think of Szostak mainly for his work on RNA aptamers, and his earlier work on recombination. Odd that he gets his prize for something where he's published only a handful of papers. Shows the importance of quality over quantity!

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17. Sili on October 6, 2009 12:17 PM writes...

And speaking of flat-out wrong, of course Dr. Gajdusek's pedophilia with boys from the New Guinea tribes merits contempt.
That does raise an interesting question. Should Haber not have been given his prize, then? Mother Teresa got a Peace prize, and you'd have to look long and hard for a more despicable old hag.

Did André Bloch's notoriety take away from his theorem. Should the entries in the OED submitted by the auto-penisectomiser be deleted? What if a quantum theory of gravity is founded by serial rapist? Should he then not be given the Nobel Prize in Physics?

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18. ex-Pfizerite on October 6, 2009 5:52 PM writes...

Which piece of work by Fritz Haber, nitrogen fixation, preventing Germany from running out of smokeless powder and high explosives in 1915 or chemical warfare?

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19. Anonymous Big Pharma Researcher on October 7, 2009 9:02 AM writes...

I don't think calling the housing bubble constitutes a qualification for an Economics Nobel because by that criterion I myself would qualify and I'm hardly an economist!

I've taken three econ courses (one in High School and two in college), all before 1980. I got worried about a housing bubble when I noticed how many books at local chain bookstores were "Make Money Fast By Flipping Houses." Calling this bubble didn't require advanced econometric models, it simply required common sense. Of course as Ben Franklin said, the trouble with common sense is that it's not sufficiently common!

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20. retread on October 12, 2009 10:21 AM writes...

The current post on Chemiotics II expands considerably on why anyone interested in schizophrenia should read "A Beautiful Mind".

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