The Truth in Small Doses: Interview with Clifton Leaf (Part 2 of 2)

Part 1 of this interview about Leaf’s book The Truth in Small Doses: Why We’re Losing the War on Cancer — and How to Win It was posted yesterday.

SR You say we should “let scientists learn as they go”. For example, reduce the need for grant proposals to require tests of hypotheses. I agree. I think most scientists know very little about how to generate plausible ideas. If they were allowed to try to do this, as you propose, they would learn how to do it. However, I failed to find evidence in your book that a “let scientists learn as they go” strategy works better (leaving aside Burkitt). Did I miss something?

CL Honestly, I don’t think we know yet that such a strategy would work. What we have in the way of evidence is a historical control (to some extent, we did try this approach in pediatric cancers in the 1940s through the 1960s) and a comparator arm (the current system) that so far has been shown to be ineffective.

As I tried to show in the book, the process now isn’t working. And much of what doesn’t work is what we’ve added in the way of bad management. Start with a lengthy, arduous, grants applications process that squelches innovative ideas, that funds barely 10 percent of a highly trained corps of academic scientists and demoralizes the rest, and that rewards the same applicants (and types of proposals) over and over despite little success or accountability. This isn’t the natural state of science. We BUILT that. We created it through bad management and lousy systems.
Same for where we are in drug development. We’ve set up clinical trials rules that force developers to spend years ramping up expensive human studies to test for statistical significance, even when the vast majority of the time, the question being asked is of little clinical significance. The human cost of this is enormous, as so many have acknowledged.

With regard to basic research, one has only to talk to young researchers (and examine the funding data) to see how badly skewed the grants process has become. As difficult (and sometimes inhospitable) as science has always been, it has never been THIS hard for a young scientist to follow up on questions that he or she thinks are important. In 1980, more than 40 percent of major research grants went to investigators under 40; today it’s less than 10 percent. For anyone asking provocative, novel questions (those that the study section doesn’t “already know the answer to,” as the saying goes), the odds of funding are even worse.

So, while I can’t say for sure that an alternative system would be better, I believe that given the current state of affairs, taking a leap into the unknown might be worth it.

SR I came across nothing about how it was discovered that smoking causes lung cancer. Why not? I would have thought we can learn a lot from how this discovery was made.

CL I wish I had spent more time on smoking. I mention it a few times in the book. In discussing Hoffman (pg. 34, and footnote, pg. 317), I say:

He also found more evidence to support the connection of “chronic irritation” from smoking with the rise in cancers of the mouth and throat. “The relation of smoking to cancer of the buccal [oral] cavity,” he wrote, “is apparently so well established as not to admit of even a question of doubt.” (By 1931, he would draw an unequivocal link between smoking and lung cancer—a connection it would take the surgeon general an additional three decades to accept.)

And I make a few other brief allusions to smoking throughout the book. But you’re right, I gave this preventable scourge short shrift. Part of why I didn’t spend more time on smoking was that I felt its role in cancer was well known, and by now, well accepted. Another reason (though I won’t claim it’s an excusable one) is that Robert Weinberg did such a masterful job of talking about this discovery in “Racing to the Beginning of the Road,” which I consider to be the single best book on cancer.

I do talk about Weinberg’s book in my own, but I should have singled out his chapter on the discovery of this link (titled “Smoke and Mirrors”), which is as much a story of science as it is a story of scientific culture.

SR Overall you say little about epidemiology. You write about Burkitt but the value of his epidemiology is unclear. Epidemiology has found many times that there are big differences in cancer rates between different places (with different lifestyles). This suggests that something about lifestyle has a big effect on cancer rates. This seems to me a very useful clue about how to prevent cancer. Why do you say nothing about this line of research (lifestyle epidemiology)?

CL Seth, again, I agree. I don’t spend enough time discussing the role that good epidemiology can play in cancer prevention. In truth, I had an additional chapter on the subject, which began by discussing decades of epidemiological work linking the herbicide 2-4-D with various cancers, particularly with prostate cancer in the wheat-growing states of the American west (Montana, the Dakotas and Minnesota). I ended up cutting the chapter in an effort to make the book a bit shorter (and perhaps faster). But maybe that was a mistake.

For what’s it worth, I do believe that epidemiology is an extremely valuable tool for cancer prevention.

[End of Part 2 of 2]