Category: personal science

How Useful is Personal Genomics? A Case Study

Seth Roberts12 Comments

How much can you help yourself by getting your genome sequenced? A lot, a little, not at all? Scenario 1 (big help): You discover you have a greatly elevated risk of Disease X. You do various things to reduce that risk that actually reduce it. Scenario 2: (a little help): You discover you have a greatly elevated risk of Rare Disease X. You do various things to reduce that risk but they don’t help. At least, when Disease X starts, you will be less upset. Scenario 3 (no help): You discover that you have a greatly elevated risk for a common easily-noticed disease (such as obesity). You already watched your weight, this changes nothing. Scenario 4 (harm): You discover that you have a greatly elevated risk of Scary Disease X (e.g., bipolar disorder). It is depressing news. Later studies show that the gene/disease association was a mistake. (Many gene/disease associations have failed to replicate.)

A recent Wired article tries to answer this question for one person: Raymond McCauley, a bioinformatics scientist who had his genome sequenced four years ago and learned he was “four or five times more likely than most people to develop age-related macular degeneration (AMD)”. The article says “of all the ailments described in the 23andme profile, AMD has one of the strongest genetic associations”. If I found this in my genetic profile, I would want to know the confidence interval of the increased risk. Is it a factor of 4.5 plus or minus 1? Or 4.5 plus or minus 8? This isn’t easy to figure out. In addition to the question of variability, there can easily be bias (= estimate is too high). Let’s say I do 100 gene/disease association studies. Then I scan these studies to pick the one with the strongest gene/disease association. It should be obvious that this particular association is likely to be too high and, depending on the details, could plausibly be pure chance (i.e., true association is zero). I have been unable to find out how replicable the gene/AMD association is. According to Wikipedia, “the lifetime risk of developing late-stage macular degeneration is 50% for people that have a relative with macular degeneration, versus 12% for people that do not have relatives with macular degeneration.” (Until it was eliminated via better diet, pellagra also ran in families.) The Wired article does not say whether any of McCauley’s relatives have/had AMD — a huge omission, given the uncertainty of gene/disease associations.

It wasn’t obvious what McCauley should do, according to the article:

McCauley read that there were a few preventative measures he could take to reduce the chances of AMD one day rendering him blind: don’t smoke and avoid ultraviolet light, for instance. Also, it seemed, he could try taking a special combination of vitamins, including B12 and lutein. But when he consulted the research, he could find little evidence to support the effectiveness of the regime, based on his genotype.

The article says nothing about quitting smoking but he does wear glasses that reduce ultraviolet light and takes certain vitamins. It is very hard for him to determine whether they help.

Here is a study that found greater omega-3 consumption associated with lower risk of AMD. Here is a study that found AMD associated with inflammation (too little omega-3 increases inflammation). Here is a study that found no association between vitamin and mineral intake and AMD. Based on this, if 23andme told me I had an increased risk of AMD, I would make sure to optimize my intake of flaxseed oil (or other omega-3 source) using some sort of brain test. I have documented in other posts that brain function is sensitive to omega-3 intake and (probably) most people don’t get enough. Of course, just as it is foolish to smoke (a lot) regardless of whether you have genetic risk of AMD, it is foolish to not optimize one’s omega-3 intake, whether or not you have genetic risk of AMD. In other words: everyone should optimize their omega-3 intake. If the 23andme results cause McCauley to do something wise like this that he would otherwise not have done, they have helped him.

The omega-3 study appeared after the Wired article so I don’t know how McCauley reacted to it. A puzzle about the story is that it isn’t even clear that the gene/AMD associations are true. Consider McCauley’s older relatives: parents, grandparents. Did/do any of them have AMD? If not, it is more plausible that all of them were at 12% risk of the disease than at 50% risk. Suppose all of them had, according to 23andme, the same increased risk as McCauley (at least some of them have the risk-bearing genes). Now it becomes more plausible that something is wrong with the 23andme risk estimate. If some of McCauley’s older relatives do have AMD, it is not clear why the 23andme results would make much difference. He should have already have known he was at increased risk of AMD.

The upshot is that in this particular case, I cannot even rule out Scenario 4 (does harm). All four scenarios strike me as plausible. Based on this article, we are a long way from learning the value of personal genomics.

Previously I used the example of Aaron Blaisdell to make the possibly counter-intuitive point that if you have a genetic disease something is wrong with your environment. Well, I do not have any obvious genetic disease. But I discovered, via self-experimentation, that my environment was terrible — meaning it could be improved in all sorts of ways: stop eating breakfast, drink flaxseed oil, eat butter, look at faces in the morning, take Vitamin D in the morning, and so on, not to mention eat fermented foods (which I figured out via psychology, not self-experimentation). My findings about what is optimal are so different than the way anyone now lives (except people who read this blog) that I believe everyone‘s environment can be vastly improved. If so, the value of discovering you have a genetically elevated risk of this or that is not obvious — you should already be trying to improve your environment. At least that is what my data has taught me. On the other hand, maybe genetic info (even wrong genetic info!) will give you a kick in the pants. Maybe that has happened with McCauley.

 

The Glacially-Slow Conquest of Scurvy And Its Relevance to Modern Life

Seth Roberts9 Comments

Scurvy is a disease of civilization because you need civilization to make long ocean voyages. It is the first disease of civilization to be understood and eliminated. In a paper called “Innovation and Evaluation” (gated), Frederick Mosteller, a professor of statistics at Harvard, noted how long it took. In 1601, James Lancaster, a sea captain, did an experiment involving four ships on a long voyage. Men on one ship got lemon juice, men on the other three ships did not. The men given lemon juice were far less likely to get scurvy. In 1747, James Lind, a doctor, compared six purported cures for scurvy. Lemons and oranges (one cure) were much better than the other five (as Lind expected). In 1795 the British Navy started using citrus juice regularly and wiped out scurvy on their ships. In 1865, the British Board of Trade recommended citrus juice for commercial ships. It took more than 200 years for a simple and effective remedy — discovered before Lancaster — to spread widely.

The sailors at risk of scurvy did not control what they ate. The people who controlled what they ate never got scurvy. Sure, the people who controlled what sailors ate did not want them to get scurvy (high rates of scurvy were a big problem) but they also had other concerns. The lesson I draw from this story is do not let anyone else (doctor, expert, etc.) solve your health problems for you. Sure, other people, as part of their job, will sell you something, provide advice, write a prescription, provide therapy, do surgery, whatever. It might work. They want to help you — the more they help you, the better they look, the more business they attract. But it is entirely possible, this bit of history teaches, that they are slow on the uptake or have conflicts of interest and a much better solution is available.

Thanks to Steve Hansen.

Personal Science is to Professional Science as Professional Science is to Engineering

Seth Roberts3 Comments

A few days ago I gave a talk at Microsoft Beijing titled “The Rise of Personal Science: Discoveries about Acne, Blood Sugar, Mood, Weight Loss, Sleep, and Brain Function.” (Thanks to Richard Sprague, who invited me.) The audience was engineers.

In response to a question, I said that the relationship between personal science and professional science resembled the relationship between professional science and engineering. Cause-effect statements (X causes Y) vary in their degree of plausibility anywhere from zero (can’t possibly be true) to one (absolute certainty). Engineers, professional scientists, and personal scientists tend to work at different places along this scale:

Engineers work with cause-effect relationships at the top of the scale, that are well-established. (For example, Newton’s Laws.) Relationships in which we have total confidence.

Professional scientists like to study cause-effect relationships that are in the middle of the scale of degree of belief: true and false are equally plausible. When both true and false are plausible, you can publish the results no matter what you find. If everyone already agrees that X causes Y, further evidence isn’t publishable — too obvious. If it is highly implausible that X causes Y, professional scientists cannot study the question because a test of whether X causes Y is too unlikely to pay off. If you find that X does cause Y you can publish it but that’s too unlikely. Finding that X does not cause Y is unpublishable (“we already knew that”).

Personal scientists can easily test ideas with low plausibility. First, because personal science is cheap. Many tests cost nothing. Second, because what other people think is irrelevant. (A professional scientist who takes seriously an idea that “everyone knows is nonsense” risks loss of reputation.) Third, because there is no pressure to produce a steady stream of publications. An example of a personal scientist testing an idea with low plausibility is when I tested the idea that standing causes weight loss. I thought it was unlikely (and, indeed, I didn’t lose weight when I stood much more than usual). But I could easily test it. It led me to discover that standing a lot improves my sleep.

Plainly we need all three (engineers, professional scientists, personal scientists). Has anyone reading this heard someone besides me make this point?

I have been shocked — I sort of continue to be shocked — how much I have been able to discover via personal science. But a high rate of discovery makes sense if personal science supplies a necessary ingredient — ability to test low-plausibility ideas — that has been missing.

Surprising Predictions From Self-Measurement

Seth Roberts2 Comments

Patrick Tucker, an editor at The Futurist, posted a request on the Quantified Self Forums for “astounding” predictions based on self-quantification. He is writing a book about using data to make predictions.

Here are examples from my self-measurement:

1. Drinking sugar water causes weight loss. The self-quantification was measuring my weight. It began when I found a new way to lose weight, which pushed me to try to explain why it worked. The explanation I came up with — a new theory of weight control — made two predictions that via self-experimentation I found to be true. That gave me faith in the theory. Then the theory suggested a really surprising conclusion, that loss of appetite during a trip to Paris was due to the sugar-sweetened soft drinks I had been drinking. If so, drinking sugar water should cause weight loss. (The nearly-universal belief is that sugar causes weight gain, of course.) I tested this prediction and it was true. More.

2. Seeing faces in the morning improves mood the next day (but not the same day). This is so surprising I’ll spell it out: Seeing faces Monday morning improves my mood on Tuesday but not Monday. For years I measured my sleep trying to reduce early awakening. Finally I figured out that not eating breakfast helped. There was no breakfast during the Stone Age; this led me to take seriously the idea that other non-Stone-Age aspects of my life were also hurting my sleep. That was one reason I decided to watch to watch a certain TV show one morning. It had no immediate effect. However, the next morning I woke up feeling great. Via self-measurement of mood, I determined it was the faces on TV that produced the effect, confirmed the effect many times, and learned what details of the situation (e.g., face size) controlled the effect. More.

3. One-legged standing improves sleep. Via self-measurement I determined that how much I stood during a day controlled how well I slept. If I stood a long time, I slept better. Ten years later I woke one day after having slept much better than usual. The previous day had been unusual in many ways. One of them was so tiny that at first I overlooked it: I had stood on one leg a few times. Just for a few minutes. Yet it turned out that it was the one-legged standing that had improved my sleep. Without the previous work on ordinary standing I would have ignored the one-legged standing — it seemed trivial.

4. Butter is healthy. I found that butter improved how fast I can do arithmetic problems. No doubt it improves brain function measured in other ways. Because the optimum nutrition for the brain will be close to the optimum nutrition for the rest of the body — at least, this is what I believe — I predict that butter will turn out to be healthy for my whole body, not just my brain.

5. Mainstream Vitamin D research is all messed up. Via self-measurement I confirmed Tara Grant’s conclusion that taking Vitamin D3 in the morning (rather than later) improved her sleep. It improved my sleep, too. When I had taken it at other times of day I had noticed nothing. Apparently the timing of Vitamin D — the time of day that you take it — matters enormously. Take it at the right time in the morning: obvious good effect. Take it late in the evening: obvious bad effect. Vitamin D researchers haven’t realized this. They have neither controlled when Vitamin D is taken (in experiments) nor measured when it is taken (in surveys). Because timing matters so much it is as if they have done their research failing to control or measure dose. If you fail to control/measure dose, whatever conclusion you reach (good/no effect/bad) depends entirely on what dose your subjects happened to take. And you have no idea what dose that is.

Effect of Vitamin D3 on My Sleep

Seth Roberts23 Comments

I have blogged many times about biohacker Tara Grant’s discovery that she slept much better if she took Vitamin D3 in the morning rather than later. Many people reported similar experiences, with a few exceptions. Lots of professional research has studied Vitamin D3 but the researchers appear to have no idea of this effect. They don’t control the time of day that subjects take D3 and don’t measure sleep. If the time of day of Vitamin D3 makes a big difference, measuring Vitamin D3 status via blood levels makes no sense. Quite likely other benefits of Vitamin D3 require taking it at the right time of day. Taking Vitamin D3 at a bad time of day could easily produce the same blood level as taking it at a good time of day.

I too had no idea of the effect that Grant discovered. I had taken Vitamin D3 several times — never in the morning — but after noticing no change stopped. I tested Grant’s discovery by taking Vitamin D3 at 8 or 9 am. First, taking it at 8 am, I gradually increased the dose from 2000 IU to 8000 IU. Then I shifted the time to 9 am. The experiment ended earlier than I would have liked because I had to fly to San Francisco.

When I woke up in the morning I rated how rested I felt on a 0-100 scale, where 0 = not rested at all and 100 = completely rested. I’d been using this scale for years. Here are the results (means and standard errors):

Vitamin D3 had a clear effect, but the necessary dose was more than 2000 IU. If Vitamin D3 acts like sunlight, you might think that taking it in the morning would make me wake up earlier. Here are the results for the time I woke up:

There was no clear effect of dosage on when I got up. Shifting the time from 8 am to 9 am may have had an effect (I wish I had 3 more days at 9 am).

Many people have reported that taking Vitamin D3 in the morning gave them more energy during the day. I usually take a nap in the early afternoon so I measured its effect on the length of those naps:

Maybe my naps were shorter with 6000 and 8000 IU at 8 am. It’s interesting that 4000 IU seemed to be enough to improve how rested how I felt but not enough to shorten my naps.

What do these results add to what we already know? First, the large-enough dose was more than 2000 IU. (A $22 million study of Vitamin D3 is using a dose of 2000 IU.) The dose needed to get more afternoon energy may be more than 4000 IU. Second, careful experimentation and records helped, even though many people found the effect so large it was easy to notice without doing anything special. For example, these results suggest the minimum dose you need to get the effect. Three, these support the value of supplements. Many people say it is better to get necessary nutrients from food rather than supplements. However, supplements allow much better control of dosage and timing and these results suggest that small changes in both can matter. I cannot imagine this effect being discovered with Vitamin D3 in food.

Assorted Links

Seth Roberts2 Comments
  • The corruption of science by research grants. This reminds me of a BBC documentary called something like Science Under Attack. It was hosted by a Nobel Prize winner (Biology) named Paul Nurse. Part of it was about “climate change denialism”. If you don’t believe that humans are dangerously warming the planet, Nurse implied, you are somehow attacking science. When people who win Nobel Prizes cannot see that AGW is a crock, something curious has happened.
  • Edward Jay Epstein interviews DSK. “”Thank you so much for your interest in this case,” he says.”
  • Researcher discovers new treatment for her own vertigo. ” A University of Colorado School of Medicine researcher who suffers from benign paroxysmal positional vertigo (BPPV) and had to “fix it” before she could go to work one day was using a maneuver to treat herself [the usual treatment] that only made her sicker. “So I sat down and thought about it and figured out an alternate way to do it. Then I fixed myself and went in to work” and [thereby] discovered a new treatment for this type of vertigo.”

Thanks to Melissa Francis.

What Motivates Scientists? Evidence From Cancer Research

Seth Roberts4 Comments

A friend of mine who worked in a biology lab said the grad students and post-docs joked about the clinical-relevance statements included at the end of papers and grant proposals: how the research would help cure cancer, retard aging, and so on. It was nonsense, they knew, but had to be included to help funding agencies justify their spending.

Principal investigators never say such things. Are they wiser than grad students and post-docs? Fortunately for the rest of us, actions speak louder than words. An action — actually, a lack of action — that suggests that P.I.’s know their research has little connection to curing cancer, etc., is 50 years of widespread indifference by cancer researchers to the possibility that their research uses a mislabeled cell line. For example, you think you are studying breast cancer cells but you are actually studying melanoma cells. A recent WSJ article says that the problem was brought to the attention of cancer researchers in 1966 but they have been “slow” to do anything about it:

University of Washington scientist Stanley Gartler warned about the practice [of using mislabelled cells] in 1966. He had developed a pioneering technique using genetic markers that would distinguish one person’s cells from another. Using the process, he tested 20 of the most widely used cancer cell lines of the era. He found 18 of the lines weren’t unique: They were Ms. Lacks’ cervical cancer. . . . A decade after publication of his findings Gartler attended a conference and introduced himself to a scientist. Dr. Gartler recalled the man told him, “‘I heard your talk on contamination. I didn’t believe what you said then and I don’t believe what you said now.’ “

What he meant was: I ignored what you said. Yet it costs only $200 to check your cell line. Fifty-plus years later, mislabeled cell lines remain a big problem. “Cell repositories in the U.S., U.K., Germany and Japan have estimated that 18% to 36% of cancer cell lines are incorrectly identified,” says the article. This indicates considerable indifference to the possibility of mislabeling.

If you truly wanted to cure breast cancer, would you spend $200 (out of a grant that might be $100,000/year) to make sure you were using a relevant cell line? Of course. If you were trying to cure your daughter’s breast cancer or your mother’s melanoma, would you make absolutely sure you were using the most relevant cell line? Of course. I conclude that a large fraction of cancer researchers care little about the practical value of their research.

I believe that one reason my personal science found new solutions to common problems (obesity, insomnia, etc.) is that my overwhelming goal was to find something of practical value. I wasn’t trying to publish papers, impress my colleagues, renew a grant, win awards, and so on. No doubt many cancer researchers want to cure cancer. But this 50-year-and-not-over chapter in the history of their field suggests that many of them have other more powerful motivations that conflict with curing cancer.

Thanks to Hal Pashler. Hal’s work on “ voodoo neuroscience” is another instance where the guilty parties, I believe, knew they might be doing something wrong but didn’t care.

Assorted Links

Seth Roberts1 Comment

Thanks to Peter Spero and Hal Pashler.

Paging Dr. Google: Magnesium, Constipation, and Subarachnoid Hemorrhages

Seth Roberts7 Comments

Did you know that magnesium can reduce constipation? I didn’t. Did you know that constipation can cause bleeding under your skull (subarachnoid hemorrhages), which are earth-shatteringly painful? Apparently a lot of doctors who treat subarachnoid hemorrhages don’t know this. Here is a story from Metafilter:

A year after [cancer] chemo ended I had . . . 4 aneurysms (subarachnoid bleeds) in 12 days. These aneurysms (subarachnoid hemorrhages) were serious agony, the most pain I’ve ever experienced. . . . It’s like the World Trade Center falling down in one’s head, involuntary non-stop screaming, passing out from the pain kind of thing. . . . None of the docs could figure out what these aneurysms were from. They all seemed totally mystified. They gave me a very risky test, brain surgery basically, a brain endoscopy that meant putting a probe into my brain. I had to sign papers that it wasn’t their fault I came out a vegetable.

Several lumbar punctures. 2 CT scans then an MRI. Then my neurologist wanted me to do a really risky test, that involved stopping my heart momentarily. . . . The chances of surviving just one of these aneurysms isn’t good: “An estimated 10-15% of patients die before reaching the hospital. Moreover, mortality rate reaches as high as 40% within the first week, and about 50% die in the first 6 months.” So I felt forced to take this dangerous test. . . .

[I] looked at when the aneurysms happened and the relief I experienced in the Emergency Ward when I’d been injected with magnesium. I googled magnesium and realized its help in treating constipation. I’d been constipated for over a year from the chemo and pain meds for the chemo pain. I realized I had these aneurysms after trying to go to the toilet, from straining. The neurologist didn’t want to hear about constipation . . . . None of the docs asked me about constipation. . . .

I self medicated with magnesium citrate, which relieves constipation in a different way than laxatives, it brings water into the colon, which helps the evacuation process a lot. Calcium and magnesium citrates combined, to be exact. And that did the trick, instantly. No more aneurysms. No more dangerous tests. No more brain surgeries.

I wonder if blood tests showed she was magnesium deficient. I also suspect fermented foods would have helped. Chemo causes constipation, I’m guessing, because it kills intestinal microbes, which fermented foods replace.

If you are nickyskye (the author of this) I hope you will contact me, I would like to write more about it and I have some questions.

Thanks to Melissa McEwen.

Assorted Links

Seth Roberts4 Comments

Thanks to David Cramer and Nadalal.