April 15, 2009

Breaking News: Your genes didn't evolve to kill you

Genetic reporter Nicholas Wade, who has been on book break, is back with an NY Times front page story "Genes Show Limited Value in Predicting Diseases:

"The era of personal genomic medicine may have to wait. The genetic analysis of common disease is turning out to be a lot more complex than expected.

Since the human genome was decoded in 2003, researchers have been developing a powerful method for comparing the genomes of patients and healthy people, with the hope of pinpointing the DNA changes responsible for common diseases.

This method, called a genomewide association study, has proved technically successful despite many skeptics’ initial doubts. But it has been disappointing in that the kind of genetic variation it detects has turned out to explain surprisingly little of the genetic links to most diseases.

As Matt Ridley has said, no matter what you might think from reading the Health & Science section of your newspaper, your genes didn't evolve in order to kill you. So, this hunt for Killer Genes was always a little dubious, as I've been pointing out all decade.

Instead, your genes evolved to help you survive and reproduce. So, these expensive genome studies have so far proven better at finding the causes of differences in capabilities between individuals and between extended families (a.k.a., racial groups).

Dr. Goldstein argues that the genetic burden of common diseases must be mostly carried by large numbers of rare variants. In this theory, schizophrenia, say, would be caused by combinations of 1,000 rare genetic variants, not of 10 common genetic variants.

This would be bleak news for those who argue that the common variants detected so far, even if they explain only a small percentage of the risk, will nonetheless identify the biological pathways through which a disease emerges, and hence point to drugs that may correct the errant pathways. If hundreds of rare variants are involved in a disease, they may implicate too much of the body’s biochemistry to be useful.

An alternative theory, proposed by Greg Cochran and Paul Ewald in the 1990s is that more diseases are caused by infections than we currently assume. (Here's the 1999 Atlantic Monthly cover story on them.) Of course, genes and germs are not mutually exclusive causes. It could be that, say, you'll only get Disease X if you are both exposed to Germ Y and your immune system lacks Gene Variant Z.

My published articles are archived at iSteve.com -- Steve Sailer


Pie Hole said...

Cochran is an insufferable knowitall. But hey the man does know a hell of a lot.

And he is right about the undercounting of diseases actually caused by as yet to be determined infections. Someday he will get much wider recognition for his work in this area.

Chief Seattle said...

To the credit of the genome researchers, the same tools to quickly sequence Human DNA work just as well on pathogen DNA.

If a disease strikes after reproductive age, does it diminish Darwinian fitness? Probably, but only through family survival effects which are weaker than direct reproduction. So old-age diseases, which is what most health dollars are spent on, may well be correlated with genes.

Also, fitness is a combination of genes plus environment, and the modern environment hasn't been around long. Type II diabetes is a huge problem today. But 500 years ago, packing on the pounds in good times was probably a good idea in most parts of the world.

Chief Seattle said...

BTW, Steve, what's the best way to donate anonymously to VDare? Or is that crime think? Seriously, someone's got to combat the numb-nuts at SPLC who never miss a chance to compare anyone who's anti-immigration with a lynch mob.

Shara said...

Pie Hole said,

"Cochran is an insufferable knowitall. But hey the man does know a hell of a lot."

Maybe I just have a thing for brainy science types, but Cochran's insufferability is matched...no, is *surpassed* by his sense of humor. He's a pussycat underneath it all. It takes a woman to see that, boys.

Anonymous said...

It's not as obvious as you make it seem that hopes were elusive because "your genes didn't evolve to kill you," as explained by Wade:

"Unlike the rare diseases caused by a change affecting only one gene, common diseases like cancer and diabetes are caused by a set of several genetic variations in each person. Since these common diseases generally strike later in life, after people have had children, the theory has been that natural selection is powerless to weed them out."

Anonymous said...

A lot of the human genome hype about improving medicine was always pure hype, but it's important to understand why.

For instance, we know all there is to know about the genetics of cystic fibrosis, and are no closer to a cure. What made anyone think whole genome scans would help with more complicated diseases like cancer?

The truth is that a lot of people made money from the bubble built around inflated medical hopes, but there were a lot more Levis and Wells Fargos than people panning for gold.

Companies like Affymetrix have sold expensive microarrays to universities and government labs, and there's been a huge bioinformatics push by giants like IBM to sell hardware and software to the same groups. Academics from biologists, computer scientists, and statisticians have published hundreds of papers on intermediate technical problems.

That's by design, and that's why the NIH so lavishly funds genomics research. It's a form of Keynesianism or industrial policy, just like a lot of defense spending and prison construction.

The problem is our leaders and media don't like to admit that's how we run our economy, although big bailouts make it harder to conceal. Republicans particularly won't admit that big companies sometimes succeed because of the state sector.

When politicians want to support biotech hubs in their districts, they tell the public they're spending tax dollars to cure cancer. Who could object?

My problem actually isn't with our de facto Keynesianism. It would just be more effective and less corrupted by special interests if it wasn't always masked as something else.

Anonymous said...

Don't forget about alleles that are advantageous in the heterozygous state. Sickle cell anemia is the classic example for this. There is also speculation that cystic fibrosis is similar in this sense. Having only one allele for cystic fibrosis might confer some advantage.

rob said...

If a disease strikes after reproductive age, does it diminish Darwinian fitness? Probably, but only through family survival effects which are weaker than direct reproduction. So old-age diseases, which is what most health dollars are spent on, may well be correlated with genes.Chief, your missing something big. Pathogens evolve too.

Anonymous said...

When I was in college in the late 90s. "Genetic counselor" was one of the hot new career fields.

Anonymous said...

Your genes did not evolve to kill you before you reproduce -- but it's not such a stretch to imagine genes that evolved to kill you at the age of fifty to seventy, when in tribal societies you'd be a net drain on social welfare but in modern societies you'd really rather not drop dead.

Anonymous said...

One man's taxes are another man's greens fees.

Anonymous said...

I remember reading a few years ago that a small number of scientists believed that cancer was the result of extreme deficiency of certain nutrients.

roger rogaine said...

"your genes evolved to help you survive and reproduce"

I'm curious. What is the survival value of male pattern baldness?

Epicurean said...

"Your genes didn't evolve to kill you."

Question: Who is the "you?" Genes may operate at a personal level, but they do not evolve that way. Suppose that a certain gene is lethal to 0.00001% of the population, but is otherwise beneficial to the other 99.99999%. Did that gene evolve to kill anyone, even an unfortunate small percentage?