The Personal Scientist Who Knew Too Much

Seth Roberts3 Comments

The San Jose Mercury News recently ran a story by Lisa Krieger about a father (Hugh Rienhoff) who found a single-amino-acid mutation that he believes causes his daughter’s growth difficulties.

Born with small, weak muscles, long feet and curled fingers, Beatrice confounded all the experts.

No one else in her family had such a syndrome. In fact, apparently no one else in the world did either.

Rienhoff — a biotech consultant trained in math, medicine and genetics at Harvard, Johns Hopkins and the Fred Hutchinson Cancer Research Center in Seattle — launched a search.

He combed the publicly available medical literature, researching diseases, while jotting down each new clue or theory. Because her ailment is so rare, he knew no big labs or advocacy groups would be interested.

He did some of his own lab work in his San Carlos home, borrowing tools or buying them used online.

A few commercial labs, like the San Diego-based biotech Illumina, offered him help for free. And a wide array of pediatricians, geneticists and neurologists volunteered their opinions.

Over time, he zeroed in on a stretch of genes that control a growth hormone responsible for muscle cell size and number. And he knew he could further target his search — saving time and money by not sequencing Bea’s entire genome, but only the exomes, which are the genes that code for proteins.

This is not a simple upbeat story. The father is a genetic researcher and doctor. I agree, he has made considerable progress in understanding the cause of his daughter’s problem. Not addressed are two questions: 1. Why is he sure he has the right mutation? Perhaps his daughter has other mutations. I’m sure the father understands this, the journalist may not. 2. What about environmental causes? As Aaron Blaisdell’s story shows — Aaron has/had a single-gene genetic disease that vanished when he changed his diet — single-gene diseases may respond to environmental changes. Early work with bacteria emphasized this. If Rienhoff had spent equal effort in trying to find environmental changes that help, he might be further along in discovering them. An obvious place to start would be testing different diets. There is no sign he has done that. His knowledge of genetics, plus the brainwashing that doctors undergo (they are told genes are incredibly important), may have led him to waste a lot of time. Someone with less understanding of genetics may realize better than Rienhoff that knowing what genes have changed may be very little help in finding helpful environmental changes.

Thanks to Allan Jackson.

 

Big Diet and Exercise Study Fails to Find Benefit

Seth Roberts34 Comments

Persons with Type 2 diabetes have an increased risk of heart disease and stroke. They are usually overweight. A study of about 5000 persons with Type 2 diabetes who were overweight or worse asked if eating less and exercise — causing weight loss — would reduce the risk. of heart disease and stroke. The difficult treatment caused a small amount of weight loss (5%), which was enough to reduce risk factors. The study ended earlier than planned because eating less and exercise didn’t help: “11 years after the study began, researchers concluded it was futile to continue — the two groups had nearly identical rates of heart attacks, strokes and cardiovascular deaths.”

Heart disease and stroke are major causes of death and disability. Failure of such an expensive study ($20 million?) to produce a clearly helpful result is an indication that mainstream health researchers don’t understand what causes heart disease and stroke. Another indication is that the treatment being studied (eating less and exercise) was popular in the 1950s. Mainstream thinking about weight control is stuck in the 1950s. It is entirely possible that greater weight loss — which mainstream thinking is unable to achieve — would have reduced heart disease and stroke. If you understand what causes heart disease and stroke, your understanding may lead you to lines of reasoning less obvious than people with diabetes are overweight –> weight loss treatments).

One of the study organizers – Rena Wing, a Brown University professor who studies weight control — told a journalist “you do a study because you don’t know the answer.” She failed to add, I’m sure, that wise people do not give a super-expensive car to someone who can’t drive. You should learn to drive with a cheap car. Allowing ignorant researchers to do a super-expensive study was a mistake. To learn something, do the cheapest easiest study that will help. (As I have said many times.) You should not simply do “a study”. This principle was the most helpful thing I learned during my first ten years as a scientist. In this particular case, I doubt that a $20 million study was the cheapest easiest way to learn how to reduce heart disease and stroke.

I made progress on weight control, sleep, and other things partly because studying myself allowed me to learn quickly and cheaply. If researchers understood what causes major health problems, they would be able to invent treatments with big benefits. That the Nobel Prize in Physiology or Medicine is given year after year to work that makes no progress on major health problems is another sign of the lack of understanding reflected in the failure of this study. I have never seen this lack of understanding — which has great everyday consequences — pointed out by any science blogger or science columnist or science journalist, many of whom describe themselves as “skeptical” and complain about “bad science.”

 

 

Assorted Links

Seth Roberts6 Comments
  • You can major in Fermentation Science. No joke. When I was eight, I learned the concept of college major. I asked my mom, “What did you major in?” “Extracurricular activities,” she said. I failed to get the joke. She later explained she had spent more time working on the school paper than on her classes.
  • In a famous paper, the statistician Ronald Fisher accused Mendel of faking his data. Fisher wrote: “the data of most, if not all, of the experiments have been falsified so as to agree closely with Mendel’s expectations.” This is not terribly consistent with the fact that Mendel’s highly improbable conclusions were correct. It’s as if Fisher had said “Person X used false info to claim he is worth $10 billion” and (b) in fact Person X is worth $10 billion. You can see that (a) and (b) may both be literally correct but that the term “false info” (Fisher’s “falsified”) probably conveys the wrong impression. This paper (“A Statistical Model to Explain the Mendel–Fisher Controversy”) has a more plausible explanation of the pattern in the data that Fisher noticed.
  • Conflict of interest in the Nobel Prize in Literature. The conflicts of interest underlying the Nobel Prize in Physiology and Medicine — which are given out for “pure” science, thus justifying more funding — remain unnoticed by journalists.

Thanks to Bryan Castañeda.

Short-Term Effects of Fat, Protein and Carbohydrate on Cognition: Fat Best

Seth Roberts22 Comments

A German study published in 2001 measured the effect of starkly different breakfasts (all fat, all protein, or all carbohydrate) on cognition during the next hours. Participants (17 men in their 20s) ate the same packaged dinner at home and next morning came to the lab and ate different breakfasts. All of the breakfasts were “cream-like” and all contained 400 calories. The design was relatively sophisticated. Practice effects were reduced by giving considerable practice with the tests before the main measurements began. Brain tests included a simple reaction time task, a choice reaction time task, and a “combi-test” in which the subject does two things at once that provides six measures of performance. One set of tests took 15 minutes. The tests were done once/hour for 3 hours after the breakfast.

The simple reaction time test showed no difference between the breakfasts. The choice reaction time test and the combi-test did show differences: The all-fat breakfast was better. The improvement produced by the fat breakfast compared to the other two breakfasts was clearest about two hours after the breakfast.

EMG (brainwave) measurements showed no differences between the breakfasts.

These results agreed with previous work.

Cunliffe et al. (1997) reported that a pure fat meal did not increase reaction times in contrast to carbohydrate ingestion when measured hourly for 4 h after the meal. In our study, fat ingestion even improved reaction times compared with baseline. Our subjects scored best for all tasks of the combi-test after the fat meal. This finding is in line with the higher accuracy of a focused attention task after a high-fat meal compared with a low-fat meal reported by others (Smith et al. 1994).

The “fat” breakfast in this study was 25% soybean oil (high in omega-6), 25% palm oil (high in saturated fats) and 50% cream (high in saturated fats). I have not compared omega-6 to nothing but I suspect it would produce worse results, given that olive oil appears worse than nothing. So I suspect that the improvement due to fat was due to the palm oil and cream. I concluded, based on evidence that I and others collected, that butter (high in saturated fats) improves arithmetic speed. I usually ate 30 g (= 2 tablespoons = 270 calories) of butter twice/day. Close to the dosage of this experiment. The timing of the effects I saw (sharp improvement from one day to the next) is consistent with a change that happens within 2 hours.

These results, which I didn’t know about until recently, support my earlier conclusions about butter. My measurements cost almost nothing whereas this experiment must have cost thousands of dollars ($400/subject?) plus hundreds of hours of researcher time. Maybe I should compare cream and butter. Cream has advantages. Mark Frauenfelder suggested using cream to make yogurt. Superfood!

A more recent study found saturated fat consumption correlated with cognitive decline. It was a survey, however, with many differences between the groups being compared. I trust experimental evidence much more than survey evidence.

More Fermented Foods, Less Runny Nose?

Seth Roberts5 Comments

As recently as four or five years ago,and for many years before that, I often had a runny nose. I went through boxes and boxes of Kleenex. I carried a handkerchief everywhere and often used it. Not because I had a cold–I almost never got colds. It was different than that. You might say I was mildly allergic to something in the air.

Because of reading an article I will discuss in a moment, I have just noticed that my runny nose has vanished, both in Berkeley (clean air) and Beijing (dirty air). So I don’t think it’s due to the dirty air in Beijing. There was no sharp change but as best I can remember it went away during the period when I started eating lots of fermented foods. Most days I eat about three types — yogurt and two other things, such as kimchi or kombucha. It is plausible that more exposure to bacteria caused my immune system to stop overreacting.

The article, from The Scientist, describes research suggesting that not enough bacteria can cause disease — specifically, sinusitis. Sinusitis, just like ulcers, has been associated with a particular bacterium, but the researcher involved, Susan Lynch of UCSF, has a more sophisticated understanding of causality than those two bacteria-causes-ulcers scientists and the committee that gave them a Nobel Prize. Lynch points out, quite reasonably, that the bacteria associated with sinusitis “have also been detected in the sinuses of healthy individuals . . . “Just because you find these organisms, it does not mean they are driving disease.” (The bacterium that supposedly caused ulcers, C. pylori, turned out to be very common. Almost everyone infected did not have ulcers.)

Lynch and her colleagues discovered

Samples from [sinusitis] patients tended to have less diversity of bacterial species than those of healthy controls. Furthermore the relative abundance of certain species differed between patients and controls. Sinusitis patients’s noses were enriched with a skin bacteria called Corynebacterium tuberculostearicum, for example, while samples from healthy controls were enriched with Lactobacillus bacteria, including L. sakei.

Which you could obviously get from fermented food. Following up this observation, the researchers did a mouse study that found that giving mice the bad bacteria caused sinusitis-like symptoms but giving mice both bad bacteria and good bacteria did not cause the symptoms. The good bacteria were protective.

 

 

 

 

 

 

 

Doctor Logic: “Acne is Caused by Bacteria”

Seth Roberts10 Comments

Presumably Dr. Jenny Kim is a good dermatologist because the author of this NPR piece chose to quote her:

UCLA dermatologist Dr. Jenny Kim says many people don’t realize it’s bacteria that cause acne. “Some people say your face is dirty, you need to clean it more, scrub more, don’t eat chocolate, things like that. But really, it’s caused by bacteria and the oil inside the pore allows the bacteria to overpopulate,” Kim says.

If I were to ask Dr. Kim how she knows that acne is “caused by bacteria” I think she’d say “because when you kill the bacteria [with antibiotics] the acne goes away.” Suppose I then asked: “Is there evidence that the bacteria of people who get acne differ from the bacteria of people who don’t get acne (before the acne)?” What I assume Dr. Kim would answer: “I don’t know.”

There is no such evidence, I’m sure. It is quite plausible that the bacteria of the two groups (with and without acne) are exactly the same, at least before acne. If it turned out, upon investigation, that the bacteria of people who get acne is the same as the bacteria of people who don’t get acne, that would make it much harder to say that acne is caused by bacteria. As far as I can tell, Dr. Kim and apparently all influential dermatologists have not thought even this deeply about it. To do so would be seriously inconvenient, because if acne isn’t caused by bacteria, it would be harder to justify prescribing antibiotics. Which dermatologists have been doing for decades.

It isn’t just dermatologists. Many doctors believe that H. pylori causes ulcers — wasn’t a Nobel Prize given for discovering that? The evidence for that assertion consisted of: 1. H. pylori found at ulcers. 2. Doctor swallowed billions of H. pylori and didn”t get an ulcer. (Not a typo.) It was enough that he got indigestion or something. 3. Antibiotics cause ulcers to heal. That was enough for the two doctors who made the H. pylori case and the Nobel Prize committee they convinced. The doctors and the committee failed to know or understand that H. pylori infection is very common and almost no one who is infected gets an ulcer. Psychiatric causal reasoning has been even simpler and even more self-serving. We know that depression — a huge problem — is due to “a chemical imbalance”, according to many psychiatrists, because (a) antidepressants work (not very well) and (b) antidepressants change brain chemistry.

Dr. Kim’s false certainty matters because I’m sure most people with acne don’t know what causes it. I didn’t. Dr. Kim’s false certainty and similar statements from other dermatologists make it harder for them to find out. I wrote about a woman who figured out what caused her acne. It wasn’t easy or obvious.

Thanks to Bryan Castañeda.

The Fallibility of Epidemiologists: Neglect of the Immune System

Seth Roberts12 Comments

Anne Weiss recently repointed me to an interview with the epidemiologist Tom Jefferson about swine flu. Jefferson, let me stress, is a good epidemiologist. In the interview he makes a point I make on this blog, that research is heavily shaped by two questions: 1. what will make money? 2. what will be good for my career? (How curious that economists — with the exception of Veblen and Robin Hanson — spend so much more time on #1 than #2.) For example:

Interviewer Why aren’t researchers interested in [other viruses]?

Jefferson: It’s easy: They can’t make money with [them]. With rhinoviruses, RSV and the majority of the other viruses, it’s hard to make a lot of money or a career out of it. Against influenza, though, there are vaccines, and there are drugs you can sell. And that’s where the big money from the pharmaceuticals industry is. It makes sure that research on influenza is published in the good journals. And that’s why you have more attention being paid there, and the entire research field becomes interesting for ambitious scientists.

Because Jefferson is willing to tell the truth about virology, it is interesting what he doesn’t say.

The big glaring gap is that in a discussion about how to avoid getting sick he says nothing about improving immune function. Not one word. He isn’t a doctor. He doesn’t work for a drug company. There is no obvious reason he fails to discuss this. He is reflecting the blindness of his whole field, I believe. It isn’t a mystery how to improve immune function: Sleep better and eat more fermented food. I have blogged before (here, here, and here, for example) about how widely this supremely important question — how to improve immune function — is ignored.

The other gap in the interview is more subtle. Jefferson recommends hand-washing as a great way to avoid getting sick. He says:

I wash my hands very often — and it’s not all because of swine flu. That’s probably the most effective precaution there is against all respiratory viruses, and the majority of gastrointestinal viruses and germs as well.

Later he says:

One study done in Pakistan has shown that hand washing can even save children’s lives. Someone should get a Nobel Prize for that!

In contrast, I believe that touching other people (and thereby picking up their germs on your hands) is part of a self-vaccination system whose goal is to protect us against the dangerous microbes nearby by exposing us to them in small amounts. Part of the system is an enjoyment of touching others and being touched. Another part is whatever causes us to constantly touch ourselves around the mouth. A third part is the tonsils, perfectly placed to pick up a tiny fraction of the germs around our mouths.

This theory of mine, which is supported by several lines of evidence, suggests that hand washing has a serious downside: It interferes with the self-vaccination system. Jefferson says nothing about any downside of hand washing. I’m not saying that Jefferson should have known of this theory of mine, of course not. (For one thing, the interview was before I thought of it.) My point is that — for reasons having nothing to do with money or career — he is too certain about what he knows. Maybe hand washing is only helpful when persons have weak immune systems or in places with large amounts of germs, such as hospitals. With strong immune systems in normal places, maybe it does more harm than good.

I became aware of the big gap in research after I improved my sleep and stopped getting colds. Before that, I had gotten the usual number of colds. No one had said that could happen — had said there was so much room for improvement in immune function. Anne Weiss became aware of the gap in research when she visited her doctor:

[More than 10] years ago I was seeing a family medicine doc who also taught epidemiology at [Famous Canadian University]. At one of my appointments I asked her how I could strengthen my immune system. She laughed in my face and told me that just was not possible.

Weiss says she was treated “as if I had asked about the existence of fairies or unicorns.” (She added that attitudes seem to be changing and one Canadian hospital now uses probiotics to prevent and treat C. difficile infection.)

Epidemiologists could easily study environmental control of immune function. They could ask questions like how many colds do you get in a typical year?, when you get a cold, how long does it usually take before the symptoms disappear? and during the last year, how many days did your longest cold last? As far as I know, they haven’t done so.

The Reddit Protein Powder Tests

Seth Roberts2 Comments

A few months ago, a Redditer with access to a protein measurement device offered to measure the protein content of protein powders that readers sent him. He got about twenty samples, presumably from all over the United States. Most of them turned out to have reasonable amounts of protein but four had much less than expected.

The tester interpreted the results here. One of the tested brands, American Pure Whey, clearly has problems. Call it a positive control. By confirming those problems, the rest of the measurements gain credence. One company whose protein powder scored low is Gaspari. Unfortunately I cannot read their reply, which appears on my browser without text.

I look forward to more truth-in-advertising tests. It is really helpful that the data is public — in this case, via Google Docs. Jimmy Moore (of Livin’ La Vida Low Carb) has measured the effect of several supposedly low-carb-friendly products on his blood sugar. His results are here.

Thanks to Eric Meltzer.

Assorted Links

Seth Roberts3 Comments

Thanks to Anne Weiss.

One Man’s Interest in Fermented Foods

Seth RobertsLeave a comment

Julie O’Brien and Richard Climenhage run a small company in the Ballard neighborhood of Seattle called Firefly Kitchens, devoted to making fermented foods. The company was founded in 2010.

Climenhage, a former high-tech executive, became intrigued with fermented foods about 10 years ago after a nutritionist suggested he consume more fats and fermented food. It cured the chronic heart palpitations that he had endured for two years.

“Six weeks and two days after changing my eating the palpitations were gone, never to return,” Climenhage said. “So I was sold. I started making my own sauerkraut and never looked back.”