Linus Pauling reconsidered.

Stochastic, the Seed Blog has an interesting post this morning about Linus Pauling's "golden years" as a scientist. It's a good read, to which I only have a few thoughts to add.

First, to bring you up to speed on the story, here's an excerpt from the Stochastic post:

[Pauling] proposed that "megadoses" of vitamin C could effectively treat several illnesses, most notably cancer and the common cold, and published a few books to popularize these ideas. In 1973, he formed the Linus Pauling Institute of Medicine, where he performed multiple experiments to verify his claims.

The real trouble started when other researchers tried--and failed--to replicate his results. Despite exhaustive examination, today the efficacy of vitamin C as a cold and flu treatment remains questionable. Three successive studies by the prestigious Mayo Clinic testing orally administered vitamin C demonstrated no significant cancer-fighting effects. Additionally, it was revealed that Hoffman-La Roche, a company that at the time produced most of the world's vitamin C supplements, extensively funded Pauling's Institute. Naturally, all this damaged his credibility and he was relegated to the fringes of science in the twilight of his life.

Fortunately for poor old Pauling, this story might yet have a happy ending. Two papers published in the last year are forcing a re-appraisal of vitamin C's effects on cancer. The first, from the September 20th, 2005 Proceedings of the National Academy of Sciences, found that vitamin C selectively killed various cancer cell types, leaving normal cells unharmed, but only when in serum concentrations achievable solely via intravenous administration.

The second study, published in the March 28th, 2006 Canadian Medical Association Journal, presented 3 well-documented cases where intravenous injections of very high doses of vitamin C had apparently extended the lives of advanced cancer patients. An accompanying commentary should temper any pro-Pauling optimism with its discussion of spontaneous remission rates and unknown sample sizes, but it leaves the question open and the door cracked for further inquiry.

It's curious - if Pauling's original experiment demonstrating vitamin C's anti-cancer effects was based on both oral and intravenous vitamin C supplementation, why did the subsequent studies attempting to "replicate" his findings forego testing both routes? When they couldn't replicate Pauling's results, why wasn't their methodology challenged? It seems increasingly plausible that if anyone had bothered to notice and correct these fundamental oversights, Pauling's reputation would have been redeemed and a potentially valuable cancer therapy might have gained mainstream acceptance much sooner.

If you didn't know anything at all about the players, you might look at these facts and ask, why did these researchers who were purportedly "replicating" Pauling's experiments, not replicate the methodology? Were they sloppy, or did they have it in for the old guy? (Or, did they think the delivery method of the vitamin C was irrelevant to any expected effect?)

My guess is that this was less a case of other researchers having it in for Pauling than looking at a distinguished scientist getting on in years and expecting that he had entered his period of crackpottery. Seriously, the man had won a Nobel Prize in chemistry, and later a Nobel Peace Prize; if anyone has earned the freedom to dance around the fringes, he had. Those books he published to popularize the idea that vitamin C might have curative powers? Popular books -- fine for the masses, but not Solid Science. Probably no one expected the crazy ideas of Pauling's dotage to pan out, so no one looked too critically at the methodology of the research that contradicted Pauling's.

The late-career turn to the crackpot is a well-known phenomenon, which is to say, it's the kind of thing that is pointed out to graduate students, in hushed tones, before department seminars. Sometimes the well-established scientist will start writing poetry or plays (not technically crackpottery, but certainly the kind of behavior that might be looked upon as dangerous from a less-well-established scientist). Sometimes, after a career of scientific achievement, he will start dabbling in the philosophy of science (which, many such scientists will assure you, requires no specialized training).

But sometimes, the turn to the weird will be in the sciences. If that turn is in an area of science sufficiently distant from the area in which one established one's scientific reputation, it's easy enough to dismiss it as the puttering of a mind that is still active but is no longer at the top of its game.

In some sense, the fact that scientific fields have stars -- Nobel Prize winners like Pauling, for example -- is in tension with the idealized view of science that what matters are the theories and the empirical facts, not so much the individual characteristics of the people who put them forward. That the speculative theory that vitamin C might cure cancer got as much attention as it did (especially from the public at large, but also in the research Pauling and others conducted) is probably due in large part to Pauling's record of scientific achievement. But at the same time, the theory was taken less seriously than it might be because it came from a scientist who was getting on in years and had, perhaps, stretched past the proper tether of his expertise.

Either way, salient facts about the person behind the ideas may end up playing a role in what kind of close scientific examination those ideas are given before they're annointed "Worth Paying Attention To" or "The Regrettable Result of the Ravages of Age".