Fish with cinnamon sauce. Chicken dressed in peacock feathers. A wild boar's head, glazed in two colors of sauce and breathing real fire.

The haute cuisine of medieval Europe tended, says Paul Freedman, toward "trompe l'oeil, color, and special effects." Spices, often very hot ones, were a central part of the show: the meals served in the homes of the well-to-do featured combinations of as many as a dozen. Contrary to the popular impression today, spice wasn't used to cover the off-taste of rank and rotting ingredients. "People in the Middle Ages simply liked spices," says Freedman, who is the Chester D. Tripp Professor of History and an expert on medieval social history.

Their desirability fueled explorations, commerce, and culinary adventures. Freedman's forthcoming book, Flavor, Fragrance, and Fashion: Spices in the Middle Ages, explores how the widespread use of such exotic ingredients as cubeb, asafetida, galanga, and grains of paradise also functioned as a cultural divide. "When I studied how peasants were seen by the upper classes, I was struck by how often the emphasis was on diet," he says. "Peasants were people who ate porridge, root vegetables, garlic, cheese, dairy products, and other plain foods that were considered lowly. The upper classes ate meat and game, but what truly made these prestigious foods was that they were prepared with spices."

Part of their popularity involved medieval notions about health, particularly the idea that the key to well-being was keeping the four fundamental body fluids in harmony. A cook could bring these "humors" into balance by, say, using a hot and dry spice to counteract a cold and moist fish. But taste was pivotal too, says Freedman. "It's clear that gastronomy overlapped with medicine."

Spices were also a manifestation of good taste. "It was common to give them away as gifts and feature them in the household as a kind of aromatherapy that created a healthy environment in the home," he notes. "The way in which we now have much less certain frontiers between medicine and conspicuous consumption is definitely a medieval idea."

Freedman's book, due out next year, will provide a look at an era that no longer seems so alien. "The stereotype of the Middle Ages is that it was a grim and penitent era," says the historian. "However, people who lived then were surprisingly pleasure-loving. To them, spices offered tastes and aromas that provided sensuous and refined sensations. Medieval times were dangerous, but also fun -- and with very interesting food."

One day, Richard Lifton received a referral from another doctor: a patient with high blood pressure and low magnesium levels, conditions that put her at risk for heart problems. The case seemed fairly routine at first. "If you look at patients with hypertension, they often have low magnesium," says Lifton, a geneticist at the Yale School of Medicine. "What wasn't known was the reason for the connection."

When he chatted with the patient, Lifton was intrigued to learn that several of her female family members also had low magnesium levels. He invited these relatives in for study, and a surprising number of them had hypertension and high cholesterol, as well. Lifton's team eventually zeroed in on a single DNA defect many of the family members shared: the first mutation ever found that contributes to a broad range of risk factors for heart disease and stroke, including high cholesterol, a weakened heart, high blood pressure, and low magnesium. The researchers announced their discovery in the October 22, 2004, online edition of the journal Science.

In following the clues, Lifton's team benefited from the cooperation of the woman's relatives, 142 of whom underwent genetic testing. Initial screening showed that 32 of them had low magnesium levels -- and many of them were on the same maternal lineage. This pattern suggested a possible defect in the mitochondrial portion of the genome, because these genes are passed only from mothers to their offspring.

The culprit emerged after genetic sequencing: an errant fragment of DNA in a gene that coded for a particular type of transfer RNA. Transfer RNA plays a critical role in shuttling amino acids back and forth during the manufacture of proteins in the cell. Such a genetic defect -- in this case for the transport and delivery of the amino acid isoleucine -- would create faulty proteins. The more Lifton probed, the more evidence he found of other health problems, from migraine headaches to weakened heart muscle, that are related to mitochondrial mutations.

"There's never been a report of a common genetic link among any of the three traits we found -- low magnesium, hypertension, and high cholesterol," says Lifton. "Because these traits are frequently found together in the general population, our finding raises the question of whether the loss of mitochondrial function that accompanies aging might contribute to all three."

But the mutation is not the entire story, for it didn't always lead to the same outcome. Lifton and his sleuths are now looking for genetic and environmental modifiers -- and treatments.

Mice with tans
by Marc Wortman

"Attacking sacred cows again, are we?" a colleague asked Douglas Brash at a science conference recently. Brash, a professor of therapeutic radiology, genetics, and dermatology, shook up his field a decade ago by proving that sun damage to a particular gene can lead to skin cancer. Lately, he's been going after melanin.

Fair-skinned people are significantly more vulnerable to skin cancer than those with darker skin. The cause, according to standard scientific notions, is their relative lack of melanin -- the polymer that lends skin and hair their color -- which has long been assumed to provide shade protection from ultraviolet radiation. But Brash had puzzled over the fact that fair-skinned blondes and redheads in particular develop skin cancer at very high rates, while people with dark hair and fair skin have a substantially lower risk. "I wondered," he says, "if the variation in susceptibility might not be related to their particular melanin genetic variant."

To find out, Brash's laboratory used mice engineered with pigmentation for yellow or black hair, as well as albino mice with no pigment at all. His team then set up a murine tanning salon and irradiated the mice under UV light in miniature tanning beds.

In the October 19, 2004, Proceedings of the National Academy of Sciences, the researchers report that UV-induced cell death -- the sunburn precursor to skin cancer -- took place mainly around the hair follicles, the only areas where
melanin occurs in mice. Dying cells were particularly numerous in the yellow mice, rarer in the black mice, and absent altogether in albino. The findings indicate that melanin's role in skin cancer is much more complicated than scientists had thought. "What this tells us is that melanin is not only good for you, it also can be bad," says Brash, noting that in some cases melanin can actually magnify the surrounding cells' susceptibility to UV light damage. "It very likely depends on your particular melanin variant."

The FDA, which is trying to determine whether it should regulate tanning salons, has taken a keen interest in Brash's findings. As a next step, he plans to expose samples of differently pigmented human skin cells to UV radiation. Eventually, such studies may help pinpoint the precise variants that make people more susceptible to skin cancer.

What you don't know can hurt you
by Bruce Fellman

Even at supposedly acceptable concentrations, ozone, a key component of city smog, can kill, says Yale epidemiologist Michelle L. Bell. After analyzing data from 95 U.S. urban communities, Bell and colleagues at Yale and Johns Hopkins estimated that levels of ozone which are well within legal limits are associated with significant and unexpected increases in mortality.

Smog is produced mostly in the summer, when car exhaust, power plant fumes, and other forms of air pollution are "cooked" by the sun and combine to form ozone, a caustic chemical that can inflame lung tissue. When ozone readings are high, public health officials warn the most vulnerable people, particularly asthmatics and the elderly, to stay indoors. But the threat is more widespread than anyone imagined, says Bell, a professor at the School of Forestry and Environmental Studies: "It's a problem for everyone."

The study, published in the November 17, 2004, Journal of the American Medical Association, looked at air pollution, weather, and mortality data collected from 1987 through 2000 for urban areas that include about 40 percent of the U.S. population. The deaths were due primarily to heart and lung ailments. Bell says that 4,000 lives every year could be saved in the areas that were surveyed if ozone levels were reduced by about a third -- "a modest reduction achievable with already available technology."

Ronald Breaker unearths fossils from the earliest ages of life. But you won't find rock hammers in his laboratory at Yale's department of molecular, cellular, and developmental biology. Instead, Breaker is discovering ancient molecules -- some four billion years old -- that are essential to the survival of living cells.

Scientists generally agree that the earliest organisms on Earth were probably much simpler than life today. Every living thing on this planet is based on three kinds of molecules: proteins, DNA, and RNA. Proteins give the body structure and carry out chemical reactions such as digesting food. The recipe for building each of these proteins is stored in a gene, a stretch of double-stranded DNA. And in order to use that recipe, a cell must first make a copy of the gene with a single-stranded version of DNA called RNA.

In the late 1960s, Francis Crick and other scientists began to argue that before there were proteins, DNA, and RNA, there was only RNA. They suggested that RNA-based life forms used a single molecule to store genetic information and to carry out chemical reactions. Only later did these primordial creatures evolve DNA and proteins. When Ronald Breaker joined the faculty in 1995, he decided to test this so-called "RNA World" theory. "The RNA World theory holds that RNA could carry out the basic functions you need for a living entity to survive," says Breaker. "One of those key needs is to sense their surroundings."

Living cells rely on proteins that can respond to changes in their environment by turning on some genes and shutting off others. Breaker discovered that he could create RNA molecules that did the same thing. He and his colleagues have fashioned RNA-based "switches" that can sense a wide range of signals, from cobalt ions to antibiotics to ultraviolet light. When these molecules sense particular signals, they respond by changing their chemical behavior. Some molecules simply destroy themselves. Others gain the ability to grab other molecules.

"It was clear we could make dozens and dozens of engineered RNA switches, almost at will," says Breaker. He wondered whether RNA-based switches had survived the end of the RNA world and continue to play an important role in cells. It turns out that they do. Since 2002, Breaker's lab has published details about nine so-called "riboswitches" they've discovered in bacteria. (Ribo is short for ribonucleic acid, the full name of RNA.) Other switches have been found in plants and fungi.

Breaker is discovering that riboswitches can be remarkably sophisticated. In the October 8 issue of Science, for example, he and his colleagues reported on a riboswitch that senses an amino acid called glycine. Cells use glycine to build a wide range of proteins, and they can also burn any extra glycine for energy. Breaker's new riboswitch lets cells know when they've got extra glycine to burn, but also shuts down glycine-burning genes when the levels get too low. "It's the most extraordinary riboswitch we have so far," says Breaker.

Breaker is investigating ways to kill bacteria by exposing them to drugs that shut down their riboswitches. Certain cancers may be caused in part by cells producing too many proteins; it may be possible to manipulate human riboswitches in order to turn those cells off. As Breaker and other scientists discover more and more complex RNA molecules in living cells, it's becoming clear that the RNA world isn't just where we come from. We live in an RNA world today.