Seymour Benzer (crippling medical school research)

In an interview, Seymour Benzer, the great Caltech biologist, told a story that I think explains a lot about medical-school research, including UCLA medical school professor John Ford’s complaint about The Shangri-La Diet:

Harold Brown [president of Caltech 1969-1977] made himself quite conspicuous by . . . trying to develop a medical school relationship. . . . His idea was for Caltech to pair up with UCLA to make a medical school. We would do the first two years of basic education of the medical students, and afterwards they would be guaranteed two more years of clinical experience at UCLA. And then they could be doctors. . . . In the Biology Division, it went over like a lead balloon: Why should we be knocking ourselves out teaching these guys, and then they go away elsewhere and don’t even do research — they become doctors? What’s in it for us?

Some things are hard to learn by reading. Saul Sternberg, now a professor of psychology at Penn, once spent a quarter at Berkeley and was around when Stanford grad students and faculty in cognitive psychology came up to Berkeley to present their research. One of the grad students told Sternberg about a reaction-time experiment she had done about mental something or other (mental rotation?) in which the conditions compared varied in what the subject saw. Sternberg pointed out that it would be better to keep constant what the subject sees. This is the beginning of wisdom in the design of cognitive psychology experiments, but you won’t find it written down anywhere.

Four Great Modern Books (part 1: description)

Last week I read Send In The Idiots by Kamran Nazeer. It was so good — so fresh, clear, and moving — it made me wonder how it came to be. In other words, where do great books come from? Asking what several great books have in common should suggest answers to this question.

Among books published in the last 40-odd years these are the best I have read:

The Economy of Cities
(1969) by Jane Jacobs. Why and how cities grow or fail to grow. How new goods and services arise. They almost always begin in cities — the book starts with a discussion of how agriculture began. Cities and the Wealth of Nations (1984) by Jacobs is also great but too similar to Economy to be worth separate discussion.

Totto-Chan (1981) by Tetsuko Kuroyanagi. A memoir of the author’s primary school days at a progressive Tokyo private school. (Mentioned in The Shangri-La Diet.)

The Man Who Would Be Queen (2003) by J. Michael Bailey. What scientists, especially Bailey (a psychology professor at Northwestern University), have learned about the causes and effects of male homosexuality. One chapter is about male transsexuals, who are not always homosexual.

Send In The Idiots (2006) by Kamran Nazeer. The beautiful subtitle is Stories From the Other Side of Autism. When he was a child, Nazeer attended a school for autistic children. This book is about the adult lives of several of his classmates.

In later posts I will explain why I like these books so much and try to ferret out the secrets of their greatness.

How Well Does the Shangri-La Diet Work? (part 1: breakdown by starting weight)

The most basic question about the Shangri-La Diet is how well it works. As the host of The Amazing Race might say, there are many ways to answer this question, each with their own pros and cons. Thanks to Rey Arbolay, we can answer this question in a new way: by looking at the data in the Post Your Tracking Data Here section of the Shangri-La Diet forums, where more than 80 people have posted.

The goal of SLD, of course, is weight loss. The problem with just plotting pounds lost as a function of time on SLD is that a loss of 10 pounds is quite different to someone who starts at 120 pounds and someone who starts at 300 pounds. To deal with this I have divided the results by starting weight. In the graphs below, the ranges of weights were chosen so that there would be roughly the same number of people in each graph.

Starting weight makes a big difference — at least, between the two extremes. Many of the people who aren’t losing very fast are in the lowest quartile. There are still a few outliers — people at the higher starting weights who are losing slowly if at all — but not many.

The next step is to do an analysis that estimates the effect of starting weight and somehow removes it. It might be better to divide people by BMI rather than starting weight, and maybe the y axis can be improved.

Seymour Benzer (crippling the Salk Institute)

One of the most fascinating stories in Benzer’s oral history interview is about construction of the Salk Institute in La Jolla, California:

Benzer: Louis Kahn [the architect] asked Salk, “How much money have you got to put into the building?” And Salk said, “Ten million for endowment” — this was all from the commitment from the March of Dimes — “and a million dollars a year for operating expenses in perpetuity.” So Kahn went home and designed a building for $20 million. In fact, he bragged about this at some dinner he had in La Jolla. He talked about other buildings he had designed and he said it was always his policy to make the building for twice as much as the money available, because you could always count on the fact that people scurry around to find the extra money.

Salk went for that idea on the argument that later on it would cost much more to build it. That was absolutely true. But at the time it had the effect of liquidating the endowment. And everything suffered from then on. The institute . . . was always worrying about where the next buck was coming from.
. . .
Interviewer: So they liquidated their entire endowment to construct a more expensive building?

Benzer: Yes.

Kahn knew a general principal about human nature that I do not. Why do backers reliably “scurry around to find the extra money”? Something powerful is at work here.

Seymour Benzer (part 1)

I found a long interview with Seymour Benzer, a biologist at Caltech, who is one of my favorite scientists — lots of creative and important work. I was pleased to learn he is a foodie. During a 1956 trip to Japan he had sushi for the first time. “One of the greatest things about the trip,” he said in 1990 (when the interview took place), presaging a future in which every upscale American supermarket sells sushi. (For dinner tonight I made salmon tartare.) When I was a student at Caltech I knew the other students liked him, but I never met him.

Benzer began the use of fruit flies to study behavior. At Woods Hole I took a course called Neural Systems and Behavior with a fruit-fly segment taught by Laurie Tompkins. She had met Benzer at a party. When she told him she studied fruit-fly mating, Benzer asked if they have orgasms. Very early in his work on behavior, he gave a talk to Roger Sperry’s lab about his plans. After his talk there was a lot of debate about it. Some people thought it was very promising; others thought it was nonsense.

Interviewer: Why were people so skeptical?

Benzer: Why? A lack of imagination.

Excellent answer. I would have said: People are always skeptical.

Brain Food (part 9: supporting data, and a problem)

I reduced the amount of omega-3 in my diet. I stopped taking flax-seed oil capsules (I had been taking 10 1000-mg capsules/day) and started drinking extra light olive oil (2 tablespoons/day) instead of walnut oil. I made the change at midnight: Tuesday high, Wednesday low. The graph below shows measurements of my balance.

From Saturday through Tuesday, and preceding days, my intake of omega-3 was high; on Wednesday and Thursday it was low.

My balance was worse Wednesday morning than expected by extrapolation, which supports the idea I started with: omega-3 affects my balance. The time course of the change (the impairment was clear in hours) resembles the original observation: I could put on my shoes while standing much more easily the morning after the day I increased my omega-3 consumption.

But, as you can see, there was a problem: My balance rapidly improved during the low omega-3 condition. Although the results support my original idea, they don’t support it as strongly as they might. A comment on a previous post was “Aren’t you worried that your expectation of worse balance will skew the results?” No, I’m not I thought when I read it. I had several reasons for not worrying about the effect of expectations, and now another has come along: Surprising results, which imply that expectations have little effect. I did not expect significant improvement from practice. I had believed that because I balance everyday for hours while standing and walking, there would not be a large practice effect. I was wrong.

Psychologists don’t know much about motor learning. There are few well-established empirical generalizations about what makes motor learning faster or slower. Another gap in our knowledge is about the nature of the underlying change. When you get better with practice, how does your brain change?

After I shifted to low omega-3, I was surprised not only by how much I improved but also by how quickly. Was my improvement due simply to more tests? I plotted my scores versus test number:

This graph suggests that I improved more per test (greater slope) during the low-omega-3 condition than during the high-omega-3 condition. I think it is a spacing effect: During the low-omega-3 condition, I tested more often. During the high-omega-3 condition, I did 14 tests in 3.5 days — 4.0/day. During the low-omega-3 condition, I did 11 tests in 1.2 days — 9.1/day. I tested more often because I wanted to track the decrease. I think this difference in test rate is the reason for the slope difference. This effect is the opposite of the usual spacing effect in learning experiments, in which close-together (”massed”) practice is less effective than widely-spaced practice.

Relevant to the theme of inspiration via self-experiment, these results and my experience gave me several new (at least to me) ideas about motor learning. One was the existence of this spacing effect. Another was that practice changes the brain by increasing how much of the brain is devoted to the task. (The areas used for other tasks shrink.) Practice increases accuracy because more neurons become involved. The output, the action, is an average from a larger sample. One reason I thought of this is that after lots of practice, and I became quite accurate, the circular area on which I was balancing seemed larger. The notion that the brain area used by the task gets larger helps explain the spacing effect. Spacing is important because the brain doesn’t care how often you have done something in the distant past; what matters is how often you are doing it now. Thus the spacing effect helps make efficient use of scarce resources (neurons). The spacing effect occurs because neural activity causes an increase in something (call it X) that slowly fades away. If later activity happens while X is above a threshold, neural rewiring occurs.

The big practice effects and the idea that practice is more powerful when more frequent should interest anyone who wants to improve their balance (and probably other motor skills), from athletes to the elderly. In a simple cheap easy safe way I got better quickly–too quickly, actually. What happened reminds me of Little League: My batting got much better when I started swinging a bat in my backyard.

The lesson for my experimental design is that I should reduce and keep more constant how often I test.

Brain Food (part 8: a little more baseline)

As I mentioned earlier, while measuring my balance I’ve been listening to a book called Cod: The Fish that Changed the World. Around Hour 4 of the book I realized it was related to what I was doing: fish, brain food. Duh!

Each test of balance consists of 5 warmup trials followed by 15 regular trials. Each trial generates one number, a duration: how long I stand on one foot before the other foot touches the floor. It’s is a bit like surfing–balance, balance, balance, balance, balance, wipe out. (Surfers, skateboarders, skiers, snowboarders, gymnasts . . . this may interest you.) I enter the stopwatch times directly into my laptop. Each test lasts about 12 minutes. Because of the book, they’re pleasant.

I made several more baseline measurements of my balance with two changes:

1. To reduce fluctuations in the concentration of omega-3 in my brain, I did my best to take the flaxseed oil capsules as evenly spaced as possible. The general rule was to take 1 every 2.4 hours (= 10 per day). I didn’t take the capsules with me when I left home but I did follow that rule when I was home (not waking up to take them, however).

2. To make the distribution of (log) balance times more Gaussian (normal), I raised the maximum possible time from 30 seconds to 60 seconds. Previously I had stopped the test at 30 seconds; now the cutoff was 60 seconds. The problem was 30 seconds was too common — my balance was too good. Before the change, 3% of baseline measurements (6 out of 210) were 30 seconds. After the change, 12% of measurements (25 out of 210) were between 30 and 60 seconds and <1% (1 out of 210) were 60 seconds.

The graph below shows results (mean & standard error) for 28 sessions.

The early problem (first 10 tests), discussed in my previous post, was that the means were fluctuating too much. A one-way ANOVA, with each test a different level, gave F (9, 140) = 2.6, p = 0.008. This is why I started trying to evenly distribute the flax capsules over the day. This seemed to work. For the last 18 tests, F (17, 252) = 1.0, p = 0.4. Unfortunately there is obviously an upward trend but that is okay because the change I am going to make — much less omega-3 — should if anything impair balance.

Brain Food (part 7: looking for a steady baseline)

Thanks a lot to those who commented on my previous post, very helpful comments. Barleyblair said that after greatly increasing her omega-3 intake she too found her balance greatly improved — not only could she put her socks on while standing she could put her shoes on while standing, which she hadn’t even dreamed of being able to do. Bekel said her sleep is deep and restful because of flaxseed oil. Pauls referred me to a Real-Age test of balance where you stand on one foot with your eyes closed. I tried it. It was way too easy: After two minute I opened my eyes and stopped the test. The table that tells you what the results means only goes up to 28 seconds. If the table is not completely bogus, then my balance is much better than average. Which is consistent with my working hypotheses that (a) the average American gets far too little omega-3 and (b) my brain function — indexed by my ability to balance — greatly improved when I increased my omega-3 intake. Keep in mind that according to conventional recommendations I ate plenty of fish (several servings per week) before increasing my omega-3 intake.

Before doing a simple test of the effects of omega-3 on my balance, I would like to establish a steady baseline and get an idea of what normal variation is. If possible, I would like to reduce normal variation — reduce background noise, in other words. With this goal I have measured my balance 13 times under roughly the same conditions: barefoot, listening to a book (a fascinating book, by the way: Cod: A Biography of the Fish that Changed the World by Mark Kurlansky) while doing the test, 20 trials per test. Each trial consists of standing on one foot on the cutting board on the 0.5-inch platform (see equipment here) and measuring how long until my other foot touches the ground. Each test takes about 10 minutes. I like the book so I enjoy the tests.
Below are the results from all 13 tests as a function of trial number. They show that there is a warmup period lasting 5 trials.

That just refines warmup measurements I posted previously. This is completely new:

The x axis shows when the test was done; points that are close together on the x axis were done close together in time — e.g., an hour apart. I hoped for a steady baseline so that I could go on to more interesting stuff. That is not what I found. I did a one-factor F test to see if there was significant heterogeniety. I used only the last 15 trials of each test, dropping the first 5 “warmup” trials. There were 13 levels (the 13 tests) of one factor. There was a highly reliable (p = .003) effect of test, meaning the variation from one test to the next was too large to be sampling error. And this test did not take into account the obvious clustering — tests close in time had similar results. The clustering makes it even more likely there were real differences in balancing ability from one test (or rather cluster of tests) to the next.

Apparently my balancing ability can change substantially in several hours! (For example, the time between the last test and the next-to-last test, the last in a cluster of three, was 7 hours.) And my test is sensitive enough to detect this! Forgive the exclamation marks. Nothing in my knowledge of psychology makes it obvious or even likely that this would be true — that a measure of quality of brain function would vary so much in hours that it could be detected by single measurements. Or that single measurements would be precise enough to detect such a change. Of course brain function (e.g., alertness) may get worse as you get sleepy but in this case my balance was much better in the evening than in the morning. The differences in my scores had no correlate that I could notice — I didn’t feel noticeably different when I did worse than when I did better.

What might be causing the differences? Body temperature or other circadian rhythm: Unlikely, because one would expect best performance when body temperature is highest, around 4 pm, which does not fit the results very well. More plausible: blood concentration of omega-3. It will be relatively low in the morning because while I was asleep I took no flaxseed oil or walnut oil. It will rise during the day as I consume these. This is consistent with the high measurements in the early evening.

Whatever the cause, these data suggest that something in ordinary life (which includes omega-3 consumption) can improve brain function within hours. If you, dear reader, know of other data that suggests this conclusion please let me know. Drugs and alcohol can quickly change brain function but they are not involved here. Nor am I listening to music, also believed to improve brain function (slightly). I am going to try to reduce fluctuations in omega-3 blood levels and see if I get more uniform measurements. I had a cup of tea with caffeine this afternoon; caffeine consumption is something else I will better control (by eliminating it).

Brain Food (part 6: a little more progress)

I did two balance experiments with a warmup of 8 trials. In one, the order of feet (which foot I stood on) was left, then right; in the other, right, then left. In both experiments I did much better (i.e., balanced longer) on my right foot than my left foot, p s < 0.001. This surprised me; I had never heard of such an asymmetry. The difference was so large that the platform size (0.75 inch) good for the left foot was too easy for the right foot.

To make things as simple and easy as possible I decided to stop testing both feet and to only measure balancing on my right foot (and to use a 0.5-inch platform to make it more difficult and avoid a ceiling effect). I tested my balance (a) in silence and (b) listening to a book. The results were similar so I decided the standard condition will be listening to something. I want to make my balance test fast and pleasant.
I came across several promising related facts:

1. On the Shangri-La Diet (SLD) forums, spacehoppa said she felt “solid on [her] feet” — which may mean her balance has improved. If so, the improved balance that I noticed may be widely true. She also said “my mind feels clearer,” another effect I noticed from omega-3’s, and more reason to think omega-3 improve brain function.

2. On the SLD forums, porkypine wrote, “I have a very strong reaction to the 1500 mg of OmegaBrite that I have begun taking in the morning. . . . During the day, I am not just happier, but actually chipper, which is not a normal state for me. I have wondered if I am getting too much Omega-3.” This supports one of the assumptions behind my upcoming tests of the effects of omega-3 on balance: the effects of omega-3 on the brain happen quickly. It also highlights an advantage of measuring balance rather than something else, such as mood — namely, it is reasonable to assume that the better your balance, the better your brain is working. As this quote shows, the mapping between mood and goodness of functioning is not so clear.

3. In a book about neurology (Defending the Cavewoman by Harold Klawans), including Creutzfeldt-Jacob disease, I read: “A [Fore] woman in late pregnancy who was unable to walk easily across a narrow tree trunk bridging a gorge knew from that change in her balance that she had kuru and that she would die of it. The physicians examined her and thought she was normal, but in less than one year, she was dead.” This shows that balance is an especially sensitive measure of brain function, at least under demanding conditions. It’s relatively easy to notice worse balance.

Balance is also much easier to quantify than many other measures of brain function, such as mental clarity.

Brain Food (part 5: a little progress)

I’ve been doing small experiments on my balance to learn what affects it. Most research using new tools follows a progression. Step 1: you learn what people already knew. Step 2: you find new information that isn’t very interesting. Step 3: you find interesting new information. Earlier I found that I could balance on one foot longer on a wider platform — Step 1.

Now Step 2. I’ve done a few experiments comparing different footwear (sandals, shoes, barefoot). In each experiment I ran several conditions, each consisting of 12 trials standing on my left foot followed by 12 trials standing on my right foot. These trials had gaps of seconds between them. Different conditions (different footwear) were separated by at least 10 minutes and usually more.

The right-foot average was always more than the left-foot average. You can see examples of this in my earlier results. I doubt that the right foot/leg is actually better than the left so this suggests there is a substantial warmup effect, as there is in most tasks.

To make measurements more precise, it would help to have a warmup period before collecting the main, more stable data. How long should it be? The graph below shows data from many of the conditions I have run arranged by trial number, with a lowess summary line.

The y axis is in log seconds, not seconds; I used a log transform to make the distribution of the data more symmetrical. The maximum time was 30 seconds. (Log(30) = 3.4.) If I kept my balance for 30 seconds, I stopped, and recorded the result as 30 seconds.

The graph shows an early warmup period that lasts 6-8 trials long, followed by a slow improvement that lasts at least 24 trials. Here is something new and not very interesting: details about the warmup effect.