Blogs / The Loom

Deep down, we are all cannibals. In tomorrow’s issue of the New York Times, I take a look at the science of autophagy: how our cells destroy themselves to live again. It turns out that this cellular cannibalism is crucial for our well-being in many ways. Scientists are now trying to improve our ability to destroy ourselves as a potential treatment for diseases like cancer and Huntington disease, and perhaps even to slow the process of aging itself. Check it out.

(Note to link-lovers: the article takes you directly to some of the primary literature. Progress!)

[Image: Royal Academy of Arts]

Congratulations to Elizabeth Blackburn, Carol Greider, and Jack Szostak, who just won the Nobel Prize in Physiology or Medicine this morning. They won for their discovery of telomeres, the caps on the ends of chromosomes that keep them from degrading and ward off aging. The Nobel site has posted some useful information about why this was such a profound discovery.

As a science writer, I often find it sobering to read scientific history. Science works slowly, even though we wish it would work in nanosecond breakthroughs.

In 1913, for example, a Russian scientist named Nikolai Anichkov ran an experiment in which he had egg yolks fed to rabbits. On this cholesterol-heavy diet the rabbits developed atherosclerosis. The more cholesterol the rabbits ate, the bigger the deposits on their blood vessels became. It was a tremendous discovery, considered by some one of the greatest in medical history.

But it did not lead overnight to a treatment for heart disease. In fact, it did not even lead, on its own, to a clear understanding of how cholesterol ends up in the blood vessels. Instead, it focused the attention of later scientists on the question of cholesterol. It took many years for scientists to figure out the steps by which enzymes produce cholesterol molecules. Then scientists began searching for drugs that might interfere with those enzymes.

In 1971, six decades after Anichkov ran his egg-yolk experiments, Akira Endo of Tokyo Noko University and his colleagues, decided to see if microbes made natural cholesterol-fighting compounds (free pdf). They reasoned that such a compound would be a potent weapon against microbial competitors, since cholesterol and related molecules are essential for building cells. In 1973 they found a fungus that blocks a key enzyme in the cholesterol pathway. It took more than another decade before drugs based on Endo’s explorations, known as statins, reached the market. Today drugs like Lipitor are prescribed to millions of people.

If a journalist wrote an article on Anchikov’s intial research, the most accurate headline would have been something like: “RUSSIAN SCIENTIST DISCOVERS LINK BETWEEN MOLECULE AND HEART DISEASE. WILL LEAD TO POWERFUL NEW MEDICINE IN EIGHTY YEARS.”

Of course, it would be a rare journalist who would be able to see eighty years in the future like that. And headlines about events readers won’t be alive to see can seem awfully remote. Anchikov’s discovery did not change the lives of the people who could have read about it at the time. Their grandchildren, yes.

I’ve been thinking about Anchikov recently, after having read a letter to the New England Journal of Medicine. It’s by Joel Hirschhorn of Harvard, on the subject of genomes.

A decade ago a complete sequence of the human genome was still a dream, although a dream close to becoming real. In a typical article from 1999, a reporter wrote that “scientists hope to treat diseases in much the same way that software engineers fix faulty computer programs, by isolating flaws in the code.” Once we could read the entire human genome, the article promised, nothing would be the same: “By identifying the genetic roots of illnesses like cancer and heart disease, some experts say, the science of the genome, or genomics, may make it possible for a child born today to live to 150–or, some say, much longer.”

What a difference a decade makes. Scientists have been finding many genetic markers for common diseases like heart disease and diabetes, but they’re not pointing the way to obvious treatments. The falling cost of DNA is letting scientists sequence genomes left and right–not just people’s genomes, but the genomes of their cancer cells and their microbes. And for now, scientists are drowning in data rather than plucking out new cures.

Hirschhorn wants the growing number of skeptics to keep history in mind. In his NEJM letter he writes,

New biologic insights do not guarantee a rapid translation into clinical practice; the latter will require great effort by basic, translational, and clinical researchers. The difficulty in translation is not unique to genetic discoveries: nearly a century and three Nobel Prizes separate the determination of the chemical composition of cholesterol from the development of statins. Each discovery of a biologically relevant locus is a potential first step in a translational journey, and some journeys will be shorter than others. With a more complete collection of relevant genes and pathways, we can hope to shorten the interval between biologic knowledge and improved patient care. 

In the next issue of Newsweek, I consider the near-term and the long-term future of genomes. My essay is called “The Gene Puzzle.” Check it out.

[Animation: Wikipedia]

Here’s a vision of how science may work in the future.

Last month I scrambled to write a story about the evolution of swine flu for the New York Times. I talked to some of the top experts on the evolution of viruses who were, at that very moment, analyzing the genetic material in samples of the virus isolated around the world. One scientist, whom I reached at home, said, “Sure, I’ve got a little time. I’m just making some coffee while my computer crunches some swine flu. What’s up?”

All of the scientists were completely open with me. They didn’t wave me off because they had to wait until their results were published in a big journal. In fact, they were open with the whole world, posting all their results in real-time on a wiki. So everyone who wanted to peruse their analysis could see how it developed as more data emerged and as they used different methods to analyze it.

Now, a little over a month later, they’re publishing their results in the journal Nature. Normally we press folks would get a press release about the paper a week before publication, and it would be under strict embargo till it appeared in the journal. This morning, however, I got a press release pointing me to the published paper. And while Nature normally requires you to subscribe to read a paper, the flu paper is published under a Creative Commons license, which means anyone can get it and use it under the license’s terms.

While that’s all very exciting, the paper itself is an anxiety-triggering read. The new swine flu (which the authors now call S-IOV S-OIV) is only distantly related to other known swine flus, which means that there are a lot of flu viruses circulating around about which we know very little. And, as I mentioned in my article, it had already entered the human population several months before it came to light earlier this spring. Be sure to check out figure 1 (I’m inserting it below from the wiki–thanks, Creative Commons!), which shows how lots of bird, swine, and human season flu viruses mixed together to produce the new beast. The authors warn that the pattern of evolution they see is the sort of pattern the big flu pandemics followed when they emerged in the past.

With this sort of urgent situation at hand, the patient process of old-fashioned science publishing may have to be upgraded.

[Image: CDC]

3quarkdaily just picked up my little rant about an awful piece of science writing. They accompanied their post with a picture of the scientist profiled in the article, Hina Chaudhry. That juxtaposition made me a bit queasy–let me just make clear that I was not criticizing Dr. Chaudhry, just the article about her. Dr. Chaudhry is doing what scientists should: running experiments and getting her results published in peer-reviewed journals. Here’s a free link to a 2007 paper of hers on regenerating heart tissue. It’s up to us science writers in turn to find a better way to describe a scientist than as a “a pretty lady.”

Cancer is not just a terrible disease but a strange one. Tumor cells must switch on certain genes in order to thrive and multiply. You might expect that natural selection would have eliminated those genes, because they kill off their owners. Far from it.  A number of cancer genes, known as oncogenes, have actually been favored by natural selection over the past few million years. Oncogenes, in other words, have boosted the reproductive success of their owners, and have even been fine-tuned by evolution.

Humans are not alone in getting cancer. In fact, it seems to be a pretty inescapable risk of being an animal. As cells divide and mutate, some mutations may make cells ignore the needs of the body and multiply madly. That’s too bad for other animals, but there’s a silver lining for us: by studying other animals, scientists can get some clues to how cancer evolves in us.

The delicate swordtail (Xiphophora cortezi) is particularly prone to getting melanomas (the bottom picture here shows a fish with a tumor in its tail). When Andre Fernandez and Molly Morris of Ohio University went fishing for delicate swordtails in mountain streams in Mexico, they found six fish with melanomas in a single day’s catch. These melanomas are particularly nasty–instead of striking old fish that are going to die soon anyway, they turn up in young breeders and kill them over a few months.

Melanomas develop from pigment-producing cells in the skin. As these tumors develop, the cells inside them produce lots of extra proteins from a gene called Xmrk. Despite Xmrk’s harm, it has survived in good working order for a long time. Functioning versions of Xmrk exist not just in delicate swordtails, but in related swordtail speices that descend from a common ancestor that lived a few million years ago.

How does such a dangerous gene continue to survive for so long? Fernandez and Morris have just published an experiment that might solve the mystery.  A lot of delicate swordtails have large dark spots on their tails, like the one shown on the top fish here. Xmrk is essential for producing those spots. Other fish have been shown to use stripes, spots, and other visual patterns to attract mates. So Fernandez and Morris wondered what the female delicate swordtails thought of the Xmrk spots on males.

Turns out, they like them a lot. When offered a chance to pay a visit to one of two male fish, female delicate swordtails from two populations in Mexico spent more time with spotted males than spotless ones. And they also preferred to consort with males with big spots over males with little ones.

The Xmrk gene definitely imposes an evolutionary cost on fish. But that cost may be erased by the benefit it gives male fish through sexual selection. By the time a male delicate swordtail dies from an Xmrk tumor, he may have mated with a number of females, which will pass down the gene to their young.

We humans may also be shaped by the trade-off between sexual selection and the cost of cancer.  Testosterone and related hormones latch onto androgen receptors on the surface of some cells. It’s important for the development of men’s bodies, for example, and the growth of body hair. It also plays a role in the production of sperm. These kinds of traits can affect the success men have in finding mates and having children. But the androgen receptor gene also becomes active during prostate cancer. In fact, versions of the gene that increase sperm count in men also raise the risk of cancer.

For more on the sexy side of cancer, check out my article in Scientific American which, I’m happy to report, was selected by author Sylvia Nasar to be included in The Best American Science Writing 2008, which has just been published. (Take a browse online here.)