The Future of Dentistry and Experimental Psychology?

Rereading an old post, I found this:

Today I had my teeth cleaned and was told my gums were in excellent shape, better than ever before [due to flaxseed oil]. They were less inflamed than usual. “What causes inflammation?” I asked. “Tartar,” I was told.

I believe that reddish gums are a great sign (so easy to see) that overall your body has too much inflammation, putting you at higher risk for many common diseases. (Perhaps due to too little omega-3, which the body uses to make an anti-inflammation hormone.) Every day my dentist measured, or at least saw, a great correlate of health (the redness of his patients’ gums) and failed to notice. It’s like failing to notice an oil field under your property. If dentists became experts in measuring gum redness and helped their patients lower overall inflammation, the public health contribution would be great. (Writing this makes me wonder why I haven’t become skilled at measuring the redness of my gums.)
Experimental psychologists are in a similar position. I believe brain health is closely correlated with health of the rest of the body. In other words, the foods that make the brain work better make the rest of the body work better. I discovered the anti-inflammatory effects of flaxseed oil because it improved my balance. The brain is much easier to study (via behavior) than the rest of the body — it’s a model system for the rest of the body. Experimental psychologists are as unaware of their good fortune as dentists. By using their skills to figure out how to have the healthiest possible brain, they could make a great contribution to human welfare.

Ad Hominem Attack on The Rational Optimist

I have yet to see Matt Ridley’s new book The Rational Optimist, which is related to stuff I’ve said about human evolution. But George Monbiot seems to consider it damning that Ridley was chairman of the bank Northern Rock when it failed. Bailout of Northern Rock was an example of government intervention — which The Rational Optimist is against, Monbiot says. Hey, why not attack Ridley for drinking government-supplied water from the tap in his kitchen? What a hypocrite!

Nassim Taleb Interview

Nassim Taleb has honed his replies to common questions:

Why did economists get the crisis so wrong?
That’s like asking why fortune-tellers don’t get things right. Their tools don’t work, but they continue to use them. And the Nobel committee gives prizes to people who aren’t scientists.

Which is what I’m saying about geneticists — their tools don’t work (also here) and the Nobel committee fails to notice (e.g., the recent award for teleomere research, which hasn’t yet had practical value).

You have a great phrase in The Black Swan: “Don’t drive a school bus blindfolded.” Is that still happening?
Worse. I was talking about Bernanke – they’ve given him a bigger bus.

Thanks to Dave Lull.

Omega-3 Correlations in Eskimos Support Anti-Inflammation Effect

A problem with much nutritional epidemiology, as I blogged earlier, is “the narrow range of intakes within a given population”. For this reason Ernst Wynder thought it better to make between-country comparisons. Of course different countries differ in many ways other than the ones you care about. A solution to both problems is to study an unusual country — a country with a wide range of intakes of the nutrient you care about — in depth.

This is what a new paper about omega-3 has done. The researchers measured the blood of about 400 Eskimos, who had a much larger range of omega-3 levels in their blood than Americans or Europeans. The results aren’t easy to sum up because there were plenty of non-linear associations. Here’s what I think is their most interesting result:

Associations of EPA and DHA with C-reactive protein were inverse and nonlinear: for EPA, the association appeared stronger at concentrations >3% of total fatty acids; for DHA, it was observed only at concentrations >7% of total fatty acids.

C-reactive protein is a marker of inflammation. Notice that, due to the details, the combination of (a) high intakes and (b) a wide range of intakes makes this correlation much easier to see. This result suggests that EPA and DHA (or something correlated with them) indeed reduce inflammation, as is often proposed. Perfectly consistent with my dentist’s observation that my gums looked a lot better (less inflamed) right after I started drinking 4 T/day flaxseed oil. Plus a reader’s observation that his sports injuries healed much faster after he started drinking 4 T/day flaxseed oil. (And here.)

Previous epidemiology had had a hard time detecting the anti-inflammatory correlation of omega-3s. My self-experimentation plus other people’s observations made it obvious there was something to it (and provided experimental evidence for causality: more omega-3, less inflammation). Better epidemiology has now supported this.

Thanks to Dave Lull.

Assorted Links

Thanks to JR Minkel.

Bruce Charlton on the Trouble With RCTs

In response to my post about the trouble with randomized controlled trials (RCTs), Bruce Charlton, the editor of Medical Hypotheses, wrote me:

The golden age of medical discovery came before the widespread usage of RCTs. This golden age was all but over by the end of the 1960s; since then the rate of progress has declined (see refs such as Horrobin, Le Fanu and Wurtman in https://www.hedweb.com/bgcharlton/funding.html).

The earliest big and influential RCT in psychiatry was in the mid 1960s, and it was – in retrospect – misleading wrt MAOIs due to too low a dosage. Now that RCTs are regarded as indispensible, medical research is captive to Big Pharma

https://www.guardian.co.uk/commentisfree/2009/aug/08/seroxat-pharmaceutical-birth-defect

Another area of medicine [in addition to obstetrics] that has made big progress without being RCT-led is anesthetics. Dentistry is a third. These specialties are instead technology-led.

He also pointed me to an article by David Horrobin, the founder of Medical Hypotheses, titled “Are large clinical trials in rapidly lethal diseases usually unethical?” His answer was that some of their aspects are unethical: Prospective subjects (sick persons) are not told the low chance of benefit, the high chance of bad side effects, and the great financial benefit of such trials to the institutions that run them.

Horrobin’s article also made the point I made: The emphasis on RCTs suppresses innovation because only big well-established companies can afford them:

50 years ago, good scientific evidence of a potential therapeutic effect would quickly have generated a small clinical trial in one or two centers with perhaps 30 or 40 patients. Such a trial would have cost almost nothing. It would certainly have missed small or marginal effects, but it would not have missed the sort of large effect that most patients want. Unfortunately, now, such an approach has become impossible. . . . The escalation of costs has therefore drastically reduced the range of compounds from which new treatments can be drawn.

My reading of history is that suppression of innovation can last a long time but eventually change comes from the outside and the system collapses. Detroit, for example, has collapsed. General Motors was once as dominant as big drug companies are now.

The Trouble With RCTs

In an email to a friend, I compared the obsession of med school professors with methodological purity (e.g., efficacy must be demonstrated with an RCT, randomized controlled trial) to religious ritual. More concern with appearances (ritual), I said, is linked to less understanding of substance. My friend replied:

I am actually a believer in this particular religion (The Cult of RCT)! Seriously: I think the medical world is quite right to put a huge premium on RCTs, because RCTs so often prove that things they are doing don’t work. While sometimes the RCT may provide a negative verdict on something that does work, this seems to me an unusual case, and generally avoidable if one considers statistical power, possible subgroup responses, etc and avoids overgeneralizing the conclusions.

I replied:

Are RCTs better than what prevailed before? Probably. But I would say the same about religion, which has its benefits.

I think the medical world has turned off a large fraction of its brain via insistence on RCTs and failure to understand their weaknesses and the strengths of alternatives. It isn’t just that “RCTs may return a negative verdict on something that works,” it’s also that such a requirement for very expensive research suppresses innovation — testing things via cheaper ways. Atul Gawande wrote about how obstetricians made a lot of progress by ignoring this requirement:

https://www.newyorker.com/archive/2006/10/09/061009fa_fact

Other areas of medicine, which followed the RCT requirement, made less progress during the same period, it can be argued.

Let’s say I told you that the only way you can travel to work is via an armed escort — you would be appalled, even though it’s true you would be safer. An insistence on RCTs is overreaction. Given the lack of innovation in medicine/health care, for which I believe they (or at least the lack of understanding they embody) are partly responsible, very expensive overreaction.

The best way to learn is to do. The best way to learn about health is to do as many experiments as possible. Not slow, expensive RCTs. Not slow, expensive surveys, which don’t involving “doing” to the extent that an experiment does. This is a big reason my self-experiments taught me a lot — because I could do so many of them.

More Fermentation, More Anti-Cancer Effect

Doenjang is a fermented soybean paste often served in Korean restaurants — as a vegetable dip, for example. This study found that the longer it’s fermented, the more powerful its anti-cancer action:

Doenjang fermented for 24 mo exhibited a two- to three-fold increase in antitumor effects on sarcoma-180-injected mice and antimetastatic effects in colon 26-M 3.1 cells in mice compared with the 3- or 6-mo fermented doenjang. The 24-mo fermentation was the most effective in preventing cancer by decreasing tumor formation and increasing natural killer cell activity in spleens and glutathione S-transferase activity in livers of mice.

Many things about doenjang stay roughly the same during fermentation. This study shows that what’s increasing (bacteria, etc.) is responsible for the anti-cancer effect, which supports my umami hypothesis (that we need fermented foods or something similar to be healthy).

I make yogurt rather than buy it so that I can ferment it a long time (e.g., 24 hours in a yogurt machine). The yogurt I make is much sourer than commercial yogurt.

Assorted Links

Thanks to Michael Bowerman.

The Dreams of Geneticists

In a wiser world, we would see genetics research as we see astronomy: worth supporting, but without expecting practical benefit. In this world, however, genetics research is far better funded than astronomy and is expected to have practical benefits.

Unfortunately, the benefits have been slight. A New York Times article by Nicholas Wade makes this clear:

The primary goal of the $3 billion Human Genome Project — to ferret out the genetic roots of common diseases like cancer and Alzheimer’s and then generate treatments — remains largely elusive. Indeed, after 10 years of effort, geneticists are almost back to square one in knowing where to look for the roots of common disease.

“Largely” elusive? Completely elusive is more accurate, as far as I know. Not one treatment has come from this work.

In spite of ten years of failure, geneticists appear no wiser than before:

With most diseases, the common variants have turned out to explain just a fraction of the genetic risk. It now seems more likely [to prominent geneticists] that each common disease is mostly caused by large numbers of rare variants.

I know of no examples where a common (or any) disease has been shown to be caused by “large numbers of rare variants.” Perhaps these estimates of “genetic risk” are as misleading as asking what percentage of the area of a rectangle is determined by its width.

History repeats. Ten years ago, geneticists had zero examples of how mapping the human genome would help anyone with a common disease. Absence of any examples didn’t prevent such vast claims as human genome mapping will ““revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases”. From zero, they extrapolated to “most”.

It’s a sad comment on science journalism that, at the time, no one pointed out the absence of examples, as far as I know, and a sad comment on Wade, holder of a powerful and prestigious job, that he has not pointed it out now. He simply repeats a claim. At least he has noticed a gigantic failure after it happens, even if he inaccurately describes it (“largely” rather than “completely”).

Lack of examples of the practical value of genetic mapping didn’t keep a huge amount of money from being spent.

With the catalog [of common genetic variants] in hand, the second stage was to see if any of the variants were more common in the patients with a given disease than in healthy people. These studies required large numbers of patients and cost several million dollars apiece. Nearly 400 of them had been completed by 2009.

Ten failures would have been plenty; 400 failures shows the resistant-to-evidence nature of the whole enterprise. It’s an example of how a little biochemical-mechanism research goes a long way; a lot of biochemical-mechanism research goes a little way.

For geneticists, to acknowledge the lack of examples is scary. Their funding might be cut! So they don’t. But nothing prevents journalists from thinking for themselves and asking a supposedly “tough” question (“what’s an example?”) — although asking for examples is the most basic question there is.

Thanks to Alex Chernavsky. More about the cargo-cult nature of modern biology. If you don’t believe me, read this: “Of the roughly 50 companies at the conference, not one is focused on approaches related to tracking down new genes. . . . The one corner of the genome-focused biotech industry that’s thriving is the one churning out equipment and services to support researchers in their endless hunt for gene links.”