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EXTRA CREDIT

A Family Matter
By Matthew Weiner

GENETIC INHERITANCE ISN'T AS

SIMPLE AS MENDEL'S SEEDS. SOME

FATAL CONDITIONS, PREVIOUSLY

CONSIDERED NON-GENETIC, MAY

ACTUALLY BE LINKED BY FAMILY

TIES. BY PAINSTAKINGLY COMBING

HUMAN DNA, GENETICIST ROBERT

FERRELL IS ON THE TRIAL OF AN

INHERITED GENE THAT MAY CAUSE

ABDOMINAL AORTIC ANEURYSMS.



Vascular surgeons Marshall Webster and David Steed had always suspected that abdominal aortic aneurysms (AAA) were more than a random complication of heart disease. They had treated AAA patients for years, wrapping the balloon-like swellings of the aorta in Dacron to reduce the chance of bursting--a fatal threat that makes AAA the 13th leading killer in the US. In 1987, though, these University of Pittsburgh Medical Center surgeons began to notice an unlikely pattern. Again and again, they were operating on relatives of former patients.

The surgeons looked at families of about 100 of their aneurysm patients. Sure enough, if a man was the brother of a patient, there was a one-in-five chance that he himself had had an aneurysm or was harboring one. This was well above the usual frequency of aneurysms--about 1.2 percent of men and .6 percent of women over age 65 die from them. If AAAs ran in families, the surgeons concluded, genes were most definitely at work.

"But it's not as if you can look at a family and say that the aneurysms are caused by a gene," says Pitt geneticist Robert Ferrell, part of the Webster aneurysm study. "It's not as clean as that." With so-called simple genetic diseases, such as cystic fibrosis, each person who has the gene, and no one else, develops the disease. But aneurysms have proven to have non-genetic causes as well, such as heart disease and smoking. All of the major killers in the United States--cancer, heart disease, diabetes--involve both genetic and non-genetic components, explains Ferrell. But finding the gene that may make people more susceptible to aneurysms will help physicians identify patients at greater risk.

Supported by a five-year grant from the National Institute of Health, Ferrell is now exhaustively searching for the AAA genes in the long, tangled strings that make up human DNA. Each person has the same genes in the same places in their DNA. The genes in a certain place determine eye color, in another place determine blood type, and so on. But scientists don't know yet where every gene is, or even whether or not a given stretch of DNA contains any genes.

"When we began the study, there were lots of known genes that we thought might cause aneurysms," says Ferrell, citing those genes that encode proteins that make up the aorta. "We've ruled out most of those. We're no longer making any assumptions about the genes. Now we're continuing to search in a more systematic way--with genetic markers." Each person's DNA is like a very long, dark street. Genetic markers, which are known pieces of genetic code spread throughout DNA, are like the regularly spaced streetlights along that street. Though they don't illuminate the whole length of DNA, the markers insure that no unknown gene is very far from a place we can see. If two people have identical DNA at a genetic marker, they probably have identical DNA at nearby places--between the streetlights.

If one marker occurs more often in people who have aneurysms than in people who don't, then Ferrell will know the AAA gene is near that marker. Since every gene is near some marker, he says, "eventually we should be able to find it." When a particular marker is linked to the disease, scientists will investigate the genes nearby to find the real AAA gene. In the meantime, doctors will be able to test people for the marker.

Genetic inheritance, it turns out, isn't as clear cut as Mendel's seeds, isn't simply a competition between dominant and recessive, isn't always as obvious as eye color and height. Until the human genome is completely deciphered, geneticists will continue their arduous walk through DNA. But Ferrell's study may help light the way.


A Shock in the Dark
By Valerie R. Gregg
TO COMPREHEND THE

INCOMPREHENSIBLE IS THE STUFF

OF PHYSICIST JEFFREY WINICOUR'S

BLACK HOLE RESEARCH--CREATING

MATHEMATICAL ALGORITHMS TOO

LARGE FOR COMPUTERS, BASED ON

AN EINSTEINIAN THEORY BARELY

ANYONE UNDERSTSANDS--ALL TO

DETERMINE THE COLLISION EFFECTS

OF BLACK HOLES, WHICH, IN

ESSENCE, ARE MASSES OF NOTHING.



What happens to a star when it dies, when the matter fueling its raging inferno is spent? It can collapse in on itself, according to Einstein's relativity theory, its center becoming ever more dense until its gravitational field is so strong that nothing, including light, can escape its pull. It condenses everything within its grasp into matter so small it doesn't exist--at least not on a level we now understand. It simply disappears. Such a star, if massive enough, becomes a black hole.

A tough concept, to be sure.

But Jeffrey Winicour of Pitt's Department of Physics and Astronomy has added even more factors to this equation. Imagine that the collapsed star is part of a binary star system--one in which two stars revolve around each other, solar systems and all. What happens if the second star collapses, becoming another black hole?

Don't forget to factor in the movement of the whole star system through the universe, courtesy of the Big Bang. Then, account for all the distortions in time and space that Einstein's Theory of General Relativity says exist around black holes. (A theory, by the way, that one computer encyclopedia claims is only truly understood by about 10 people in the world.) What you're left with is an impossibly long and complex physics problem, in which straightforward mathematics is skewed by deep-space collisions and warps in time and space.

Winicour and Pitt researchers Roberto Gomez and Luis Lehner, as part of an eight-university, NSF-funded consortium, have spent the last several years tackling this problem, developing the complex Einsteinian algorithms that could solve it. Only the largest computers in the world--as powerful as every person on earth crunching 1,000 large-number multiplications and writing out the answers every second--can handle this massive physics problem.

So far, Winicour and his colleagues have been able to simulate the head-on collision of two black holes of equal mass and dimension. This is what they've found: The immense gravitational pull from each black hole causes their orbits to accelerate and thus bend or wobble, forcing the holes to travel closer and closer together until the orbits inevitably collide, creating a new and even more massive black hole. Computer simulations show that when the black holes have the same dimensions, their collision path looks something like a pair of trousers. Imagine each black hole's orbit as the hem of each leg of the trousers. As the gravitational pulls become stronger, the holes' orbits move up the leg of the trouser until they meet, eventually smoothing out into what could be called the spherical "waistband."

This collision then creates a ripple effect--like throwing a pebble into a pond--sending out gravitational waves that, according to Einstein, distort time and space. Winicour hopes his research will help describe these waves more concretely to give giant observatories, under construction in Europe, a solid reference point for detecting and measuring gravitational waves in space.

"We can't study the actual black holes because, to us, they are masses of nothing," he explains. "With these observatories, we'll be able to see waves coming from just outside the surface of black holes. It's a chance to see exactly what's happening."

Now that the consortium has simulated the head-on collision, it is examining what happens when black holes merge in other ways--when they are different sizes or have different gravitational pulls. Even today's most advanced computer technology cannot handle the massive number of calculations necessary to account for these variables. But Winicour and his associates, working hand-in-hand with computer scientists, are getting ready for the day they can.

"Computers have revolutionized mathematics and science," Winicour says. "Equations that people weren't able to solve, that were infinite, we can now solve with a computer grinding away, doing something for you. It's a different way of finding a solution."

The continued development of this amazing tool promises to bring Winicour and company even closer to unraveling the greatest mysteries of the universe, lending more proof to Einstein's theories and reducing infinity to something we can understand. Imagine that.








Estrogenesis
By Elizabeth Starr Miller
DESPITE THE CONTROVERSY OVER ESTROGEN REPLACEMENT

THERAPY FOR WOMEN IN MENOPAUSE, EPIDEMIOLOGIST

JANE CAULEY HAS DISCOVERED THAT, IN SOME CASES, THE

BENEFITS MAY OUTWEIGH THE RISKS


Few changes in life have suffered more stereotypes than, well, than the Change of Life. In addition to putting up with jokes about hot flashes and mood swings, women in menopause also have to deal with some very real--and very unsettling--physical adjustments, including weaker bones and an increased chance of heart disease.

But thanks to new research by Pitt epidemiologist Jane Cauley, menopausal women (or at least their physicians) are now armed with new information. For six years, Cauley studied nearly 10,000 women nationwide who received estrogen replacement therapy--widely prescribed for menopausal women whose bodies no longer produce the hormone. Initially focusing on bone strength, Cauley discovered that estrogen slows down bone deterioration and ensures that a woman's bones maintain their constant state of renewal and repair.

"During menopause, as bones weaken," explains Cauley, "one in six women can expect to suffer a hip fracture or other bone fractures. By taking estrogen, women can greatly reduce these risks."

But Cauley soon found that the protective effect of estrogen did not stop with bone strength. On examining death certificates of women who had been involved in the study, Cauley concluded that older white women who had taken estrogen for at least 10 years had a 30 percent lower risk of dying from heart disease. Typically considered a men's disease, heart disease is the number one killer of women.

While estrogen seems to be shaping up as a woman's wonder drug, Cauley cautions that her study does not "end the controversy" over the use of the hormone. Though estrogen is no longer linked with a higher risk of strokes and high blood pressure, as it was in the 1970s, its long-term use may carry an increased risk of breast cancer. Weighing the risks of estrogen therapy against the benefits is difficult, says Cauley, and depends on each woman's medical history. "Every woman considering estrogen," explains Cauley, "should be treated as an individual case and should also treat her own decision with care."


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