This year's recipients of the highest honors in science and medicine have been selected by the Nobel Foundation's judging committees. The 1998 medals bring to 11 the number of researchers at Bell Labs to be honored and mark the fourth consecutive award for scientists at Stanford University.

Here are sketches of the achievements in physics, chemistry and medicine.


PHYSICS

Virtual Electrons

Robert B. Laughlin
ROBERT B. LAUGHLIN

When a student named Edwin H. Hall observed an unexpected electrical phenomenon in 1879, he had little idea of what he had started. Researchers have studied the Hall effect for more than a century and their investigations have resulted in a string of important discoveries about the nature of matter.

This year marks yet another step in the Hall effect saga: The 1998 Nobel Prize in Physics will be awarded to two scientists, who discovered a new state of matter called the "fractional quantum Hall effect" in 1982-- Horst L. Strmer of Columbia University and Bell Labs, and Daniel C. Tsui of Princeton University--and to Robert B. Laughlin of Stanford University, who explained its theoretical basis a year later.

According to the Nobel citation, the three researchers are receiving the award "for their discovery of a new form of quantum fluid with fractionally charged excitations." What they found was that electrons acting together in strong magnetic fields can form new types of "particles," with charges that are fractions of electron charges. "The contributions of the three laureates have thus led to yet another breakthrough in our understanding of quantum physics and to the development of new theoretical concepts of significance in many branches of modern physics," says The Royal Swedish Academy of Sciences.

 Horst L. Strmer
HORST L. STRMER

Edwin Hall's initial finding was that when electrons moving along a metal strip are subjected to a magnetic field perpendicular to the plane of the strip, they are deflected toward the one side of the strip where they cause an excess electrical charge to build up. This Hall voltage is proportional to the strength of the magnetic field. The Hall effect can be used to determine the density of charge carriers (negative electrons or positive holes) in conductors and semi-conductors, and has become a standard tool in physics.

The Hall effect could easily be explained by the laws of classical physics until researchers started looking at it in two-dimensions. In 1980, Klaus von Klitzing of the Max-Planck-Institute for Solid State Research conducted experiments on the behavior of electrons confined to two dimensions at the interface between two semiconductors. These experiments took the Hall effect into the strange world of quantum mechanics where the electrons took on the properties of a fluid.

In this "quantum fluid," a plot of Hall resistance versus field strength was no longer linear: it had become a staircase. Klitzing's discovery of the "quantized Hall effect" won him the physics Nobel Prize in 1985; so precise were the steps, or quanta, that his experiment has been used to define the unit of electrical resistance.

This year's laureates, who where then at Bell Laboratories, now the research arm of Lucent Technologies, would carry the research further in experiments in the semiconductor gallium arsenide, using even lower temperatures and more powerful magnetic fields. To do so, they created a unique environment, a trap in which to restrain electrons on a two-dimensional plane. This was done by sandwiching two dissimilar semiconductor wafers--gallium arsenide on one side and gallium aluminum arsenide on the other. Electrons accumulated at the interface between the two semiconductors and were tightly confined. Next, the researchers cooled the electron trap down to a tenth of a degree above absolute zero.

What they discovered was that there were steps within the steps observed by Klitzing--the next step in the Hall resistance was three times higher than von Klitzing's highest recorded step. Later, Tsui and Strmer found more steps, which initially could not be explained. The heights of the new steps could be expressed with the same constant used in earlier work, but were now divided by different fractions -- thus, the term fractional quantum Hall effect. This would be impossible, since electrons cannot have fractional charges.

Daniel C. Tsui
DANIEL C. TSUI

The task of explaining the theoretical basis for the observations fell to Laughlin. "When I saw their data I knew that they had found a fractional charge," he recalls. In a thin sheet of electrons inside a semiconductor, the electron appears to break up into several identical pieces - but this is due not to the disintegration of the electron, but to the motion of many electrons forming fractionally charged quasi-particles. The particles possess exact fractions of electrical charges, such as one-third, one-fifth or one-seventh. "In this case," said Strmer, "the amazing thing is that by electrons cooperating with one another and not disintegrating, you get something smaller than the initial object." Laughlin surmised that the electrons were combining with the flux quanta of the magnetic field. Electrons are fermions, spin-half particles, and normally do not like to condense into a shared quantum state, but in combination with the flux quanta they would become bosons, spin-zero or spin-one states, which are not averse to sharing a quantum state.

A similar process occurs in low-temperature liquid helium and in superconductors. In superconductors, electrons pair up (into Cooper pairs, which are bosons) and then condense into the shared superconducting quantum state in which all the electrons in the supercurrent act as an ensemble. A side effect of Laughlin's conjecture was that the electron ensembles could have fractional charges by acting as if they were particles (quasiparticles) with an electrical charge which was a non-integral multiple of the basic electron charge. Laughlin later determined that the magnetic field had created "holes" in the two-dimensional sheet of electrons. Called vortices, these were similar to a whirlpool in a lake; in the absence of water, the vortices represent an absence of charge.

In 1997, this hypothesis was experimentally verified by groups in Israel and France. In its statement, the Nobel committee said that Laughlin "showed that the electrons in a powerful magnetic field can condense to form a kind of quantum fluid related to the quantum fluids that occur in superconductivity and in liquid helium. What makes these fluids particularly important for researchers is that events in a drop of quantum fluid can afford more profound insights into the general inner structure and dynamics of matter."

Earlier this year, the three researchers were honored by the Franklin Institute, which awarded them its Benjamin Franklin Medal in Physics. But this is the big one. Laughlin's mother, who rushed to his campus home after hearing the news, told him, "I never thought it would happen. I thought it was just your childhood dream."

FURTHER READING:

ELECTRONS IN FLATLAND. S. Kivelson, D.H. Lee and S.C. Zhang in Scientific American; March 1996.

WHEN THE ELECTRON FALLS APART. P.W. Anderson in Physics Today October 1997.

THE FRACTIONAL QUANTUM HALL EFFECT. J.P. Eisenstein and H.L. Strmer in Science June 22, 1990. Cover illustration and caption.

CHEMISTRY

Understanding Bonding

Ever since chemists realized that the elements could bind to one another to form new compounds with unique properties, they have struggled to understand how those bonds worked. In the early years of this century, it seemed clear that the new science of quantum mechanics held important clues. But the mathematics needed to predict behavior on a molecular level was daunting.

Paul Dirac, one of the founders of quantum physics, summed up the problem in 1929:

"The fundamental laws necessary for the mathematical treatment of large parts of physics and the whole of chemistry are thus fully known, and the difficulty lies only in the fact that application of these laws leads to equations that are too complex to be solved."
Walter Kohn
WALTER KOHN

It took until the 1960s for those equations to begin to fall before the increasing calculating power of computers and a new branch of chemistry now known as "quantum chemistry" to emerge. In just a few decades the pace of the research has accelerated as theoretical insights and computational developments have combined to revolutionize chemistry.

This year's chemistry Nobel recognizes two scientists who laid the groundwork for an era in which chemists can design molecules and predict their properties on a computer screen. Walter Kohn of University of California at Santa Barbara is a physicist whose work formed the basis for simplifying the mathematics in descriptions of the bonding of atoms. Meanwhile, chemist John A. Pople of Northwestern University developed the quantum-chemical methodology now widely used in chemistry.

In its announcement of the award, the Royal Swedish Academy of Sciences cited Kohn and Pople for their "pioneering contributions in developing methods that can be used for theoretical studies of the properties of molecules and the chemical processes in which they are involved."

John A. Pople
JOHN A. POPLE

Today, chemists using computers can analyze the structure and properties of matter in detail. Experiments are often conducted to verify the computer data--not vice versa. Nor do the calculations require huge mainframe computers; most can be handled by scientific workstations. Behind that computational simplicity is Kohn's insight that it was not necessary to consider the motion of each individual electron. Instead, he devised the density-functional theory, which is based on the far less complex calculation of the average number of electrons at any one point in space. The simplicity of the method makes it possible to study the reactions of very large molecules, such as enzymes.

It was Pople who brought that calculating power to the fingertips of chemists in 1970, when he introduced the first version of a computer program called GAUSSIAN. The program, based on the fundamental laws of quantum mechanics as discovered by physicist E. Schroedinger, allows chemists to enter the particulars of a molecule or a chemical reaction to predict the properties of the resulting molecule or how a chemical reaction may take place. At the beginning of the 1990s Pople was able to include Kohn's density-functional theory in his modeling software, opening new possibilities for analyzing ever-more complex molecules. Present versions of GAUSSIAN are now a standard tool of academic and commercial chemists.

With the techniques of Kohn and Pople, not only can scientists produce accurate renderings of the intricate folds of complex enzymes, they can study the composition of interstellar dust clouds and observe reactions between pollutants and ozone in the upper atmosphere.

Both Kohn, who was born in Vienna, Austria, in 1923, and Pople, born in Burnham-on-Sea in Somerset, United Kingdom in 1925, are still active at their respective universities. And each, according to the Nobel announcement, has the satisfaction of seeing how the fruits of their long careers "afford a deeper understanding of molecular processes that cannot be obtained from experiments alone."

FURTHER READING:

A. Pople et al. AB INITIO: MOLECULAR ORBITAL THEORY, John Wiley & Sons, New York, 1996

R. G. Parr and W. Yang, DENSITY-FUNCTIONAL THEORY OF ATOMS AND MOLECULES, Oxford Science, Oxford, 1989


MEDICINE

The Answer is 'NO'

Robert Furchgott
ROBERT F. FURCHGOTT

Three medical sleuths who demonstrated that a common air pollutant created in auto exhaust is a potent regulator of the cardiovascular system are the winners of the Nobel Prize in Physiology or Medicine. The presentation in July 1986 of their conclusion that nitric oxide--a gas--was a chemical signal that regulated the dilation of blood vessels created a sensation. The findings touched off an avalanche of research aimed at improving treatments for atherosclerosis, shock, cancer--and impotence.

The first piece of the puzzle was provided by Robert F Furchgott, a pharmacologist at the State University of New York (SUNY) Health Science Center. Furchgott, who was studying the effects of various drugs on blood vessels was frustrated by contradictory results--sometimes the same drug would cause a dilation, other times a contraction. He wondered if the different response depended on the condition of the endothelial surface cells that line blood vessels.

In 1980, he proved that the cells only relaxed in the presence of the dilator acetylcholine when the endothelium was intact. His conclusion: it must be the endothelial cells that respond to acetylcholine by producing an unknown messenger molecule that caused the vascular smooth muscle cells to relax.

Louis J. Ignarro
LOUIS J. IGNARRO

Furchgott called his mystery molecule EDRF, for endothelium-derived relaxing factor; others soon took up the quest to identify it. But the answer had already been discovered by Ferid Murad, now at the University of Texas Medical School at Houston. He was studying the mechanism of blood vessel dialating compounds such as nitroglycerin. In 1977, he discovered that they release nitric oxide (NO), which relaxes smooth muscle cells. Murad was intrigued that a gas could regulate important cellular functions and speculated that other factors such as hormones might also act through NO.

The experimental evidence that proved Murad's intuition correct was provided by a participant in the quest for EDRF, Louis J Ignarro of the UCLA School of Medicine. Working both together and independently, he and Furchgott concluded that that EDRF was identical to NO.

That discovery marked a turning point in the understanding of cellular regulation. Here was not a peptide or a protein but a simple and common gas so unstable that it is converted to nitrate and nitrite within 10 seconds of being created. "Signal transmission by a gas that is produced by one cell, penetrates through membranes and regulates the function of another cell represents an entirely new principle for signalling in biological systems," says the Nobel Assembly at the Karolinska Institute in its announcement of the award.

Subsequent research quickly confirmed that the role of NO was an important one, indeed. As well as being of key importance for the cardiovascular system, it acts as a signal molecule in the nervous system, as a weapon against infections, as a regulator of blood pressure and as a gate keeper of blood flow to different organs. Once thought to be a curiosity produced by certain bacteria, researchers now know that NO is present in most living creatures and made by many different types of cells.

Ferid Murad
FERID MURAD

The finding that NO is a ubiquitous cellular signaler has sent drugmakers rushing to find ways to manipulate its activity to treat a variety of diseases. For example, in atherosclerosis, the endothelium has a reduced capacity to produce NO, which can now be furnished by nitroglycerin--the very chemical that formed the basis of Alfred Nobel's fortune. Developing new cardiac drugs could have the same impact on a drug manufacturer as Nobel's discovery that the capricious explosive power of nitroglycerin could be tamed if mixed with porous diatomaceous earth: Dynamite.

Other projects are aimed at finding ways to treat sepsis and circulatory shock as well as cancer and other conditions. Sepsis, which are caused when white blood cells react to bacterial products by releasing enormous amounts of NO that dilate the blood vessels and cause catastrophic drops in blood pressure, might be controlled by NO inhibitors. On the other hand, white blood cells use NO not only to kill infectious agents such as bacteria, fungi and parasites, but also to defend against tumors. Scientists are currently testing whether NO can be used to stop the growth of tumors since this gas can induce programmed cell death, apoptosis. And, of course, there is impotence. As Pfizer researchers found when they developed Viagra, NO can initiate erection of the penis by dilating the appropriate blood vessels.

Alfred Nobel passed up a chance to benefit from NO. When he was taken ill with heart disease, his doctor prescribed nitroglycerin for his chest pain. Nobel refused. In a letter, he wrote: "It is ironical that I am now ordered by my physician to eat nitroglycerin." It probably would have worked but it would take 100 years until it was clarified that nitroglycerin acts by releasing NO.

FURTHER READING:

THE OBLIGATORY ROLE OF THE ENDOTHELIUM IN THE RELAXATION OF ARTERIAL SMOOTH MUSCLE BY ACETYLCHOLINE R. F. Furchgott and J. V. Zawadzki in Blood Vessels, Vol 17, 1980

NITRIC OXIDE: BIOCHEMISTRY, MOLECULAR BIOLOGY, AND THERAPEUTIC IMPLICATIONS Ferid Murad and Louis J. Ignarro in Advances in Pharmacology, Vol. 34, 1995