Microcosm Week: Dreaming of a Complete Solution to Life

By Carl Zimmer | July 8, 2009 1:41 am

Last week, three teams of scientists published three massive studies in Nature on the genes behind schizophrenia. They scanned thousands of people to find variants of genes that tended to show up more in people with schizophrenia than in those without it. And they found a heap of genes. There are thousands of different variants that each may raise your risk of schizophrenia by a tiny amount.

Nicholas Wade, a veteran genetics reporter at the New York Times, has been following the quest to trace diseases to genes for a long time now. And when Wade tried his hand at blogging last week, he laid down a harsh verdict.

Press releases from five American and European institutions celebrated the findings, one using epithets like “landmark,” “major step forward,” and “real scientific breakthrough.” It was the kind of hoopla you’d expect for an actual scientific advance.

It seems to me the reports represent more of a historic defeat, a Pearl Harbor of schizophrenia research.

By “defeat,” Wade was not saying that the research was wrong. It was just not going to lead to any quick fixes for this devastating disease. While the risk of schizophrenia can be inherited, that does not mean that you can take a pill that compensates for a single broken gene and cure it.

These new results are depressingly similar to a string of searches for the genes linked to other conditions, such as diabetes and high blood pressure, as I explained in my recent essay for Newsweek, “The Gene Puzzle.” Now that scientists can read the human genome and scan thousands of people’s DNA, they’re not finding easy answers. They instead are finding networks upon networks of thousands of genes, that can be disturbed in a staggering number of ways.

It can be frustrating to discover just how complex our genes can be. But we really shouldn’t be too surprised. We’ve had plenty of warning about the complexity of life from a much simpler organism: E. coli.

E. coli only has 4,000 or so protein coding genes (we’ve got about 20,000, plus thousands of other important chunks of DNA). E. coli doesn’t have to develop into a brain or a heart or a toenail: all it needs to do is be E. coli, a single, tiny cell. As I explain in my book Microcosm: E. Coli and the New Science of Life, E. coli has been studied up and down and every which way for a century. It is the best-understood species on Earth. And by 1973, the great biologist Francis Crick, co-discoverer of the structure of DNA, decided  E. coli should be the subject of a singular scientific project–a kind of biological moon shot. He called for the “complete solution” to E. coli: a total explanation of how the cell sustained itself, grew, and reproduced.

It’s been 36 years since Crick’s call, but scientists have yet to figure E. coli out. For one thing, they don’t have a very good idea of what a lot of its genes are for. According to a study published in PLOS Biology in April, the function of a third of  E. coli‘s genes are uncharacterized. The authors of that study were able to come up with hypotheses for what all those 1431 genes do, but they are rough hypotheses at best. The scientists proposed the some genes are involved in building proteins, for example, or constructing membranes. They could not offer a detailed explanation for how the structure of each of those proteins allowed it to carry out some particular function.


It will take a lot of scientists doing a lot of experiments to figure out exactly what those 1431 genes are doing. And conversely, it will take a lot of work to figure out the interactions of genes that produce even the simplest things about E. coli. This diagram comes from a paper published last month in Molecular Systems Biology on one such simple thing (click on it for a bigger view). Scientists have been engineering E. coli to make an alcohol called isobutanol, which might serve as an alternative fuel. The only catch is that isobutanol is poison for E. coli. Even a tiny amount of the stuff will cause the bacteria to stop growing, which is the last thing you want to happen to microscopic fuel factories. So scientists at UCLA tried to figure out how isobutanol makes E. coli sick. This diagram sums up what they figured out: a single kind of molecule can trigger all kinds of changes in the activity of a number of proteins, and those changes cascade through the cell, as proteins shut down genes for other proteins or activate other ones.

That being said, the scientists did figure out the answer to this particular question, and they are figuring out how to tweak this network to help E. coli survive its self-made poison. While E. coli should make us skeptical of big promises about mastering the human genome in the near future, we can still have some hope for the distant future. Pearl Harbor, after all, did not end the war.

CATEGORIZED UNDER: Microcosm: The Book

Comments (4)

Links to this Post

  1. Michael Nielsen » Biweekly links for 07/31/2009 | July 31, 2009
  1. johnk

    Here’s my 2 cents.

    I think people are generally locked into the wrong model of what a disease is. The traditional, scientific model is that a disease is caused by something going wrong, such as a bad gene or a bad protein. This model is very good when it works. It defines diseases by causes, and, when there is a clear cause, especially a genetic cause, it seems very clean.

    But I think another category of disease is better defined by a state than a cause. Examples of defective states are epilepsy or cardiac arrhythmias. A state is a system property that, in healthy individuals, is hard to get into. Once in a state, it may be hard to get out of. A person suffering from a state disorder has a low barrier to defective-state entry; importantly, there may be many routes to defective state entry, so discovering a single route may account for very little of the population variance.

    In this way of thinking, the frustration in not finding simple genetic or cellular causes of schizophrenia (and other psychiatric disorders) suggests that these diseases may be state defects rather than defects based on singular cellular mechanisms.

  2. Speaking as a science journalist, when scientists and journalists perpetuate the idea that schizophrenia can somehow be “solved” by genetics, they’re either being naive or disingenuous. Read Liz Spikol and tell me what genetics is going to do about socioeconomics.

    Scientifically, I’d say the genetics is telling us schizophrenia is very closely tied to H. sapiens cognition, such that many different combinations of events can nudge a highly optimized system from state 1 toward state 2. And that makes it more important than ever to focus on the *what to do to help people suffering from schizophrenia.*

    See my posts on the missed opportunity here for journalists and how framing schizophrenia as a scientific problem can go awry.

    More intuitively, ask yourself what would happen if Jenny McCarthy’s son were to develop a condition that could be mistaken for schizophrenia.

  3. I know it’s frustrating for readers to realize that the myth of “a gene for this; a gene for that” really is just a myth. But I can’t help being awe-struck whenever the complexity of life is so beautifully illustrated. This example of E. coli and isobutanol deepens even more my profound respect and astonishment at the miracles of living cells. And the same for the tape worm! Wish I had one named after me!


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The Loom

A blog about life, past and future. Written by DISCOVER contributing editor and columnist Carl Zimmer.

About Carl Zimmer

Carl Zimmer writes about science regularly for The New York Times and magazines such as DISCOVER, which also hosts his blog, The LoomHe is the author of 12 books, the most recent of which is Science Ink: Tattoos of the Science Obsessed.


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