Nobel prizes: The sweet smell of success

Olfactory genes, subatomic particles, and the molecular kiss of death

Physiology or Medicine

In recognition of more than a decade of pioneering exploration of the sense of smell, two Americans received the 2004 Nobel Prize in Physiology or Medicine on Oct. 4. The researchers, Richard Axel of Columbia University and Linda Buck of the Fred Hutchinson Cancer Center in Seattle, will share the nearly $1.4 million prize.

The award largely honors the pair’s close collaboration on a paper published in Cell in 1991 and their continuing independent efforts. Before the paper appeared, scientists knew little about the cellular and molecular mechanisms underlying the olfactory system, which transmits information on odorant molecules from the nose to the brain. Anatomical studies had shown that olfactory neurons project hairlike cilia into the nasal cavity. However, researchers were unable to pinpoint olfactory receptors on these cilia or explain how such receptors might work.

According to Kerry Ressler, an associate professor of psychiatry at Emory University in Atlanta and Buck’s first graduate research assistant in the mid-1990s, the olfactory system had been largely ignored by sensory scientists who were more apt to explore the mechanisms behind other senses, such as sight and hearing. The reasons were twofold: The sense of smell is the most expendable of human senses. In addition, says Ressler, “there was a lack of good tools for how to dissect this system in the right way.”

At the time of the Cell paper, Buck was a postdoctoral fellow in Axel’s lab at Columbia. Taking advantage of a then-novel DNA-copying technique known as polymerase chain reaction, the colleagues searched for genes that encode olfactory receptors in rats. After several false starts, the two researchers achieved success.

Since publishing preliminary information about 18 rat olfactory genes in the 1991 paper, the researchers have discovered almost 1,000 others. The number discovered so far in people is only about 350. Scientists estimate that these genes allow a healthy person to distinguish and remember upwards of 10,000 different scents.

The seminal 1991 discovery of this specific family of genes enabled researchers to probe the sense of smell using modern molecular- and cellular-biology techniques. Subsequent studies by Axel, Buck, and others have shown that each olfactory neuron expresses only one type of receptor on its surface. Scents composed of several different odorant molecules bond to these receptors in a particular pattern. For example, the odorant molecules wafting from sizzling bacon might stimulate only receptors 2, 45, and 54.

These odorant-receptor interactions trigger neurons to send signals to the olfactory bulb, a structure located in the front of the brain. The bulb then relays information about the scent to the brain’s thought and emotion centers.

Andrew Chess, a former postdoctoral fellow in Buck’s lab and a current olfactory researcher at the Whitehead Institute in Cambridge, Mass., says that Axel and Buck were an “excellent choice” to receive this year’s Nobel prize. “Their work basically started this field of applying modern molecular biology approaches to this sensory system,” he says.—C. Brownlee


Three physicists who developed a theory to explain the strong interaction that holds together atomic nuclei—one of the four basic forces in the universe—have won the 2004 Nobel Prize in Physics.

David J. Gross of the University of California, Santa Barbara, H. David Politzer of the California Institute of Technology in Pasadena, and Frank Wilczek of the Massachusetts Institute of Technology (MIT) will share the $1.36 million prize.

Early last century, scientists discovered that atoms—once thought to be the smallest building blocks of matter—actually are made of protons, neutrons, and electrons. Atom-smashing experiments in the late 1960s confirmed what theorists had begun to suspect earlier that decade: that protons and neutrons are themselves made of smaller components dubbed quarks. However, none of those high-energy experiments ever produced an isolated quark. The strong force apparently always withstood the high-energy violence of the experiments, and the quarks presumably remained confined within protons and neutrons, which measure only about 10–15 centimeters across.

In 1973, when Gross and Wilczek were at Princeton University and Politzer was at Harvard University, the three researchers independently discovered a property of the strong interaction that they called “asymptotic freedom.” According to this phenomenon, the force of attraction between quarks actually gets weaker when the quarks are close together. Somewhat like the stretching in a rubber band being pulled, the force of attraction gets dramatically stronger as the distance between quarks increases—a result that explains why quarks are never found in isolation.

Before the researchers came up with the concept of asymptotic freedom, any relationship among the plethora of new particles observed during atom-smashing experiments remained hidden. The concept “cleared away the fog” surrounding the strong interaction, comments Edward Witten, a physicist at Princeton University. For the first time, scientists could predict what types of subatomic particles would result from high-energy collisions, he notes.

Experiments and current theories suggest that quarks existed in isolation only in the first 0.1 second or so after the Big Bang, says Wilczek. That’s how long it took the young universe to cool down to about 10 trillion°C, a point at which quarks glommed in triplets to create the neutrons and protons that make up atomic nuclei.

The understanding of the strong interaction between quarks that stems from Gross, Politzer, and Wilczek’s Nobel-winning work is “one of the great cornerstones of our understanding of modern physics,” says Marc A. Kastner, head of the physics department at MIT.

“This is a Nobel that’s been overdue,” says Alfred Mueller, a physicist at Columbia University.

Although the fundamental theory behind the strong interaction is well supported by data, it’s also very complicated. Physicists are still trying to figure out how all the subatomic particles that result from high-energy collisions are created, Mueller notes.

Because announcements of the Nobel prizes often occur around midday in Sweden, American recipients receive notification that they’ve won in the exceptionally early hours of the morning, sometimes at inopportune moments. For Wilczek, the phone call came at 5:12 a.m., when he was in the middle of a shower. Dripping wet, sans towel, he ended up chatting with a series of people from the Nobel committee. “It was quite a long call,” he notes.—S. Perkins


And this year’s Nobel Prize in Chemistry goes to three scientists for their discovery in the early 1980s of how cells mark proteins for destruction. The key turned out to be the molecular tag called ubiquitin. Doomed proteins get the label and then are shuttled off to a cell’s disposal apparatus, called a proteasome, which slices the proteins into pieces. This selective destruction of unwanted proteins is involved in a number of diseases, including cervical cancer and cystic fibrosis.

Aaron Ciechanover and Avram Hershko of the Technion-Israel Institute of Technology in Haifa and Irwin Rose of the University of California, Irvine will share the prize, which was announced at press time. More on their research will appear in next week’s Science News.—A. Goho

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