How much disease do genes cause? Sure, they cause some rare diseases that affect very few people but what about major health problems, such as depression, that affect everyone? The notion that genes make a big difference to human health — that some people are healthy and others sick because of genetic differences — was much of the rationale for funding the human genome sequencing project, which cost billions. The founders of the company 23andme (23 = 23 human chromosomes) often say genes matter, most recently in The New Yorker:
“It’s very useful if you know that you’re at increased risk for deep-vein thrombosis and you’re on a plane,” she continued. “You might want to stay vigilant about moving around.” Instead of finding out the hard way that their children are allergic to peanuts, parents may someday be able to test their DNA. Even small inherited traits, Avey added, can serve as health clues: “There is some correlation between your ability to metabolize caffeine and your risk for a heart attack.”
There is something breathtaking in the fact that someone who believes you can learn about allergies by studying DNA is taken seriously in The New Yorker.
Some rare non-hype on this issue has recently come from Dr. David Goldstein:
But David B. Goldstein of Duke University, a leading young population geneticist known partly for his research into the genetic roots of Jewish ancestry, says the effort to nail down the genetics of most common diseases is not working. “There is absolutely no question,” he said, “that for the whole hope of personalized medicine [where people with different genes are treated differently], the news has been just about as bleak as it could be.”
The researchers have been unable to find genes that make much difference.
If they had found such genes, I would have been stunned. My self-experimentation has led me to believe that our environments are far from ideal — in non-obvious ways. I believe that people don’t get sick because of their genes, or gene-by-environment interactions, they get sick because of their environments, which lack something essential or include something bad. Animal experiments have given us a decent understanding of nutrition; maybe we know half or more than half of the basic requirements. When it comes to subjects that don’t lend themselves to animal experiments, little is known — about what causes depression, for example. My self-experimentation took over where animal experiments left off; it provided a way to do experiments that generate ideas. (Which is crucial for knowledge advancement, as opposed to career advancement.) I have been able to find one big self-experimental effect after another (most recently, about omega-3s and sleep) related to common health problems only because (a) so little was known and (b) I accidentally picked up an effective tool (self-experimentation) that no one else had used this way (to find new experimental effects).
More More from the other side of the debate: 1. Elderly genetics. 2. Google co-founder has Parkinson’s gene. It is hard to find support for my side of the debate in print. It isn’t easy to notice when you don’t get sick (because of advances in the study of nutrition, for example) so it isn’t easy to notice how study of the environment has paid off in concrete ways. I’m in an unusual position: I can easily notice how my life has improved via self-experimentation.
Even more Dean Ornish agrees with me. Thanks to Carl Willat.
seth, have you ever tried to control for placebo effects in your self-experiments? based on something you wrote recently i suspect you think its too difficult. Here’s one method i’ve thought of:
you could make identical (gelatin?) capsules containing a dose of flaxseed oil, a placebo (e.g. water) and olive oil. Store them on identical plates (one plate for each) so that they are indistinguishable from each other by touch alone and then blindfold yourself as you reach down to take one randomly – use a webcam to record which one you’re taking.
The only problem here is that you know there’s a chance of placebo, and as i remember from my health psychology lectures this has been shown to have an effect (infact, some studies indicate that even the doctor knowing they are prescribing a placebo has an effect on the patient – i can probably dig up the reference for this if you want..)
“Have you ever tried to control for placebo effects”? Yes, by varying the dose. I like to think that’s the sophisticated way to control for expectancy effects. Of course, most experiments use a placebo pill, which generally varies in 20 ways from the treatment. All these differences allow subjects to figure out what group they are in. If subjects figure out what group they are in, the “placebo control” stops controlling for expectancy effects because expectancies are no longer equal.
I have read that dietary intake of LA downregulates the conversion of ALA to DHA+EPA. If this be true, then consuming large amounts of ALA might be necessary since the body is going to convert only a small amount to DHA+EPA and burn the rest of ALA?.
Gyan, yeah, maybe. Because I was able to measure the effects of ALA (in flaxseed oil) I could adjust the amount of ALA I consumed until I got the biggest possible effect.
Your questioning of the merit of genetic testing is less commonly heard and useful to highlight, but there are good ways to use information about genetic predispositions as well.
If genetic sequencing of test subjects in experiments were mandatory in the FDA approval process it might be possible to link the efficacy of drugs to certain genotypes, and in the process use drugs that are clinically effective and safe for those populations, and/or not use drugs that seem statistically unsafe for others. There are effective drugs which aren’t used because they are lethal or unhealthy to small numbers of people, so they are banned, but the source of that lethality may be related to a genetic factor.
Similarly some approved drugs could be used more appropriately. A friend of mine had her life destroyed taking Accutane for a mild case of acne, as prescribed by a dermatologist, became severely ill, and has not recovered after five years. This drug is allowed despite such known problems because they are rare. It would be nice to protect people for whom such events are more likely.
This is all based on probability, and doesn’t account for all other relevant factors, but is still worthwhile.
Exercise overriding the FTO “obesity gene”:
Physical Activity and the Association of Common FTO Gene Variants With Body Mass Index and Obesity
Evadnie Rampersaud, MSPH, PhD; Braxton D. Mitchell, PhD; Toni I. Pollin, PhD; Mao Fu, PhD; Haiqing Shen, PhD; Jeffery R. O’Connell, PhD; Julie L. Ducharme, MD; Scott Hines, MD; Paul Sack, MD; Rosalie Naglieri, MD; Alan R. Shuldiner, MD; Soren Snitker, MD, PhD
Arch Intern Med. 2008;168(16):1791-1797.
Background Common FTO (fat mass and obesity associated) gene variants have recently been associated with body mass index (BMI) and obesity in several large studies. The role of lifestyle factors (such as physical activity) in those with an underlying FTO genetic predisposition is unknown.
Methods To determine if FTO variants are associated with BMI in Old Order Amish (OOA) individuals, and to further determine whether the detrimental associations of FTO gene variants can be lessened by increased physical activity, a total of 704 healthy OOA adults were selected from the Heredity and Phenotype Intervention (HAPI) Heart Study, an investigation of gene x environment interactions in cardiovascular disease, for whom objective quantified physical activity measurements were available and for whom 92 single-nucleotide polymorphisms (SNPs) in FTO were genotyped.
Results Twenty-six FTO SNPs were associated with BMI (P = .04 to
Conclusions  Our results strongly suggest that the increased risk of obesity owing to genetic susceptibility by FTO variants can be blunted through physical activity. These findings emphasize the important role of physical activity in public health efforts to combat obesity, particularly in genetically susceptible individuals.
Obesity Genes and Physical Activity, An Interview with Dr. Evadnie Rampersaud – Fitness Rocks Podcast 114
drmonte
In this episode of Fitness Rocks I have a conversation with Dr. Evadnie Rampersuad about the effect of physical activity on the expression of a gene that is associated with obesity. Dr. Rampersaud is an Assistant Professor at the Miami Institute for Human Genomics at the University of Miami Miller School of Medicine.
Listen to Fitness Rocks Podcast 114