Ernst Wynder on the Nurses’ Health Study

It says a lot about the Nobel Prize in Medicine that Ernst Wynder, co-discoverer that smoking causes cancer, never got one. Wynder was also one of the founders of modern epidemiology. Here’s what he believed about the Nurses’ Health Study:

He had a strong skepticism about methods of dietary assessment, and always felt that the failure of analytic studies such as the Nurses’ Health Study to report associations between cancer and diet were due to a combination of random misclassification related to the imprecision of food frequency questionnaires and the narrow range of nutrient intake within a given population. I feel certain that he would have criticized the recent negative findings from the Women’s Health Study on dietary fat and breast and colon cancer on similar grounds. This was one area where he felt that international comparisons at the ecological [country-by-country] level provided better etiologic support than [more] analytic studies, and he published many studies over a period of decades to make just that point.

For example,

He developed a friendship with Kunio Aoki at the Aichi Cancer Research Institute in Nagoya, Japan, which resulted in our study which found that Japanese men with smoking habits similar to American men had considerably lower lung cancer risks.

I didn’t know that. It suggests that either Americans eat something that promotes cancer or the Japanese eat something that protects against it. I suspect it’s the latter — specifically, the big consumption of fermented food in Japan and not in America. I’m sure the food-frequency questionnaires Wynder criticizes, written by Americans, are tone-deaf to fermented food. I doubt they ask about kimchi or kefir or miso consumption, or distinguish between pickles aged for a day and pickles aged for a year. In Japan, people eat fermented food in many forms: vinegar drinks, yogurt, other fermented milk drinks, and alcoholic beverages. Above all, they eat miso and long-fermented pickles daily. They also have the longest life expectancy in the world.

The Foxconn Suicides

Foxconn, located on the coast of China, is the largest electronics manufacturer in the world. They make iPhones, Wiis, and many other famous products. You may have read about the epidemic of suicide that has broken out among its employees. There were two in the last few days, for example. The count now stands at something like a dozen suicides in about a month. The factory complex involved is gigantic, with perhaps 300,000 workers, but no question this is a terrible thing. The victims are all or mostly men in their early twenties. The median length of employment at Foxconn might be about a year.

Foxconn has appealed to my university (Tsinghua) and in particular my department (Psychology) for help. I’m told their assembly line was designed at Tsinghua. In any case, several people from my department (faculty and graduate students) have gone to the factory and tried to do something.

At a department meeting we discussed our department’s involvement. I said it’s really hard to make progress on such problems for reasons that might not be obvious. When I had trouble waking up too early, I started to study the problem via self-experimentation. All I cared about was solving the problem. Any answer was acceptable. I would spend as long as it took to find it. It took me 10 years to make visible progress. The first thing I figured out was that the problem was partly due to eating breakfast — which sleep researchers had failed to discover.
Consider the Foxconn suicides. It would be incredibly helpful to figure out what’s causing them. But few professors want to study a problem that they have no idea if they can solve nor how long it will take. They don’t want to wait ten years to write a paper. By then their funding will have run out. If funding is assured regardless of progress, then how does the funder ensure they are actually doing something? And few professors have total academic freedom. Their graduate school advisor, their academic friends, the people who control their career have certain beliefs. About which theories are good and which are bad. About which methods are “correct”. If their results contradict these beliefs, if they use a “wrong” method, they will suffer, just as all heretics suffer. So there is pressure to come up with an acceptable answer using proper methods. This gets in the way of coming up with the actual answer.

This doesn’t mean academic research is useless, but it does mean that professors work in shackles that outsiders are, in my experience, unaware of. I wrote about this in my Medical Hypotheses paper. It is a big reason my self-experimentation found new and surprising answers to old questions: I had total freedom. All I cared about was finding the answer. I didn’t care about publications. I didn’t worry about funding. I had as much time as it took.

Resveratrol Revisited: The Plural of Data is Not Data

In 2007 I got an email from Preston Estep, a gerontologist and former Chief Scientific Officer of Longenity, Inc., offering me a place in an informal trial of the benefits of resveratrol that he was organizing. Recently I wrote him to find out what happened. Here’s his reply:

We got a few people to volunteer but not enough for an organized trial to be worth the effort, partly because initial reported benefits evaporated under scrutiny and we couldn’t decide what variables/bio-markers to test. There are a couple of efforts that have taken off since then to try to collect data on therapeutic modalities, including resveratrol. The largest-scale effort I know of is CureTogether but it isn’t very useful because the vast majority of reports appear to be subjective and unreliable (e.g. “I feel that resveratrol has slowed my aging …” and so forth). Such a web-based approach would be much more useful if objective tests like those you have done could be implemented but I’m skeptical you could get many people to produce and report data in an unbiased fashion. I have found that the desire to believe whatever you’re doing is good is incredibly strong and can be rationalized ad infinitum.

Interestingly, it looks like professional scientists and even big pharma might have gotten caught up in that mindset. Many of the reported benefits of resveratrol have been controversial from the beginning and recent reports suggest that neither scientists nor pharma can reproduce key results. Matt Kaeberlen, one of the first discoverers that sirtuin overexpression extends lifespan and co-founder of a biotech company with me in the early 2000s, returned to academia and has raised some red flags about the resveratrol research. He showed that the key assay used to discover resveratrol in a drug screen seems to depend on a biochemical artifact. Sirtris, a biotech company specializing in sirtuin research and that was bought by Glaxo for $720M, developed some resveratrol analogs that were reported to have multiple benefits, including control of type 2 diabetes. But recently Pfizer and Amgen have published studies saying they cannot reproduce Sirtris’s results. You can read many reports of this mess on the web but here are good, recent accounts of the controversy:

In a recent New Yorker article about cancer chemotherapy Malcolm Gladwell told a similar story: High hopes for a cancer drug disappeared when more data came in. I am more positive than Estrup about the CureTogether study of resveratrol. If the collected data suggest benefits, it supports more work; if the data do not suggest benefits, it argues against more work. Above all, the CureTogether data will others decide whether to try resveratrol.