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World: Humble Worm Leads To Nobel-Worthy Discoveries In Cells, Diseases

By Margot Buff

This year's Nobel Prize in physiology or medicine was awarded to three scientists who have shown how genes control both the creation and the death of cells in living creatures. The laureates spent years conducting experiments using tiny worms, and their work paved the way for important developments in medicine, including AIDS and cancer research.

Prague, 10 October 2002 (RFE/RL) -- The Royal Swedish Academy of Sciences in Stockholm awarded an American and two British scientists this year's Nobel Prize in physiology or medicine for demonstrating that some healthy cells are designed to kill themselves -- a discovery that's led to a new understanding of many human diseases.

But the research that earned the prestigious $1.1 million award was not conducted on human beings. The three scientists received the honor for their work over the past three decades with a species of nematode, a transparent worm less than 1 millimeter long.

Greg Lemke is a neurobiologist and the chair of the Salk Institute for Biological Studies in California, where Sydney Brenner, one of the laureates, now works. Lemke says discoveries crucial to understanding human life often emerge from humble origins like the nematode: "One of the lessons of modern biology is that much of what we know about how these things work in you and I, and in other mammals, is really dependent on their activity first having been identified and studied in these simpler organisms."

Brenner, a South African-born scientist working in Cambridge, England, pioneered research on the worm in the 1970s, demonstrating that its simple body provides a clear model for the growth of living things. He was later joined in his work by another Briton, John Sulston, who helped prove that some of the worm's cells are genetically programmed to die, or to commit "cell suicide," as a normal part of the creature's development and adult life.

The third Nobel laureate, Robert Horvitz, was responsible for identifying the genes that tell certain cells to commit suicide. Horvitz also expanded the research beyond the petri dish. He discovered that human DNA contains a "death gene," similar to the worm's, that instructs cells to kill themselves in certain situations. For example, when cells are old, abnormal, or malfunctioning.

Over many years of research, the scientists showed that the creation of different types of cells and the necessary deaths of other cells are balanced in the normal functioning of organisms -- whether they be worms or human beings.

One of the most important applications of the study of programmed cell death lies in instances where the system fails. Lemke of the Salk Institute says a wide range of illnesses are linked to the genetic program for cell death: "We now appreciate that if there's a problem with executing programmed cell death, or with executing the program, that this can lead to a whole series of disease states."

One such disease is cancer. When a cell forms abnormally, in most cases the mechanism for cell suicide kicks in. But when this mechanism fails to act, cancerous cells begin duplicating and can thrive in the body.

Lemke says auto-immune diseases, in which the body's immune system malfunctions and attacks its own tissue, are also characterized by a failure of programmed cell death. In illnesses such as lupus, multiple sclerosis, and rheumatoid arthritis, cells that would be eliminated in a healthy system somehow manage to survive.

Other illnesses can be understood as an overworking of the "cell suicide" function. In neurodegenerative conditions like Parkinson's disease and Alzheimer's, cells in the nervous system die too soon. Lemke says researchers are exploiting their understanding of cell death to try to inhibit it. Biotech firms are seeking drugs that would block the program for cell suicide as a way to treat neurodegenerative disease.

Aaron Klug is an earlier Nobel laureate and the former director of the Laboratory of Molecular Biology in Cambridge, where much of the work on programmed cell death was performed. He says the work at his laboratory led to another discovery about the same worm within the last few years. Scientists found that the same genes responsible for killing certain cells can also "silence" cells, or make them stop functioning.

Klug says the genetic codes for silencing cells may yield treatments for the HIV virus, which causes AIDS, if genes can be manipulated to kill or silence cells infected by the virus: "You might be able to use this gene-silencing technique, which is now understood in the worm, and also in certain plants, to try to silence HIV genes when they get switched on and when the virus gets in and causes AIDS. That might actually be something that might happen in the next few years. People are trying it already."

Both Klug and Lemke stress that cures for human diseases based on manipulating programmed cell death are still years away. But they also note the discoveries made by Brenner, Sulston, and Horvitz have laid the groundwork for ongoing research in genetics, microbiology, and human health. Klug says their work is responsible for the current understanding of how all cells live and die: "All this kind of understanding of what happens during the cell cycle, which is when cells multiply in higher organisms, all that -- the basic biology of all that -- all came ultimately from the work on the worm."

Other Nobel prizes have been awarded this week, as well.

The Nobel Prize in literature was awarded today to Imre Kertesz of Hungary.

Masotoshi Koshiba of Japan and Raymond Davis and Riccardo Ciacconi of the U.S. won the Nobel Prize for physics. They were recognized for their pioneering work on astrophysics, which led to the discovery of cosmic X-ray sources.

American Vernon L. Smith and Israeli-American Daniel Kahneman won the economics prize. The academy praised Smith for laying the foundation in the field of experimental economics and Kahneman for integrating insights from psychology into economics.

John Fenn of the United States, Japan's Koichi Tanaka, and Kurt Wuethrich of Switzerland won the chemistry prize for their work on proteins, which has led to increased understanding of the processes of life.

The Nobel Peace Prize will be awarded tomorrow in Oslo, Norway, the only Nobel Prize not awarded in Sweden.