The Nobel Prize in Physiology or Medicine 2002 - Illustrated Presentation

The Nobel Prize in Physiology or Medicine 2002
	The Nobel Assembly at Karolinska Institutet has awarded the Nobel Prize in Physiology or Medicine jointly to Sydney Brenner, Robert Horvitz and John Sulston for their discoveries concerning "genetic regulation of organ development and programmed cell death". By using the nematode Caenorhabditis elegans as a model system, the Laureates have identified key genes regulating these processes. They have also shown that corresponding genes exist in higher species, including man.
	This year´s Nobel Laureates have identified key genes regulating organ development and programmed cell death in the nematode C. elegans. They have also shown that corresponding genes controlling these processes exist in humans.

 

Introduction

Male Female Programmed cell death eliminates unwanted structures during the development of the male and female inner reproductive organs.

The human body consists of hundreds of cell types, all originating from the fertilized egg. During the embryonic and foetal periods, cells increase dramatically in number, mature and become specialized to form tissues and organs. Lots of cells are formed also in the adult body – more than a thousand billion cells each day. To counter cell production and maintain an appropriate number of cells in the tissues, extensive cell death occurs both in the foetus and in the adult. This delicate, controlled elimination of cells is called programmed cell death.   In the human foetus, the interdigital mesoderm, initially formed between fingers and toes, is removed by programmed cell death. The intestinal lumen and other tissues are sculpted by programmed cell death.

Sydney Brenner
Sydney Brenner, born 1927, La Jolla, CA, USA.	Sydney Brenner realized, in the early 1960s, that the nematode Caenorhabditis elegans was an ideal model organism to study cell differentiation and organ development. This small worm has a short generation time and is transparent, which made it possible to follow cell division directly under the microscope. In 1974, Brenner demonstrated that specific gene mutations could be induced in the genome of C. elegans by the chemical compound EMS (ethyl methane sulphonate). Different mutations were linked to specific genes and to specific effects on organ development. Brenner´s discoveries, carried out in Cambridge, UK, laid the foundation for this year´s Nobel Prize.
Sydney Brenner established the nematode Caenorhabditis elegans as a novel model organism. This transparent worm is approximately one mm long and consists of 959 somatic cells.

Robert Horvitz
Robert Horvitz, born 1947, Cambridge, MA, USA.	Robert Horvitz used C. elegans to investigate whether there was a genetic programme controlling cell death. In 1986, he identified the first two "death genes", ced-3 and ced-4. He showed that functional ced-3 and ced-4 genes were a prerequisite for cell death to be executed. Later, Horvitz discovered that another gene, ced-9, protects against cell death by interacting with ced-4 and ced-3. He also identified genes directing the elimination of the dead cell, and he showed that the human genome contains a ced-3-like gene. We now know that most genes involved in controlling cell death in C. elegans have counterparts in humans and are evolutionarily well conserved. In the human signalling pathway ced-3-, ced-4- and ced-9-like molecules participate.
Robert Horvitz identified genes controlling cell death in C. elegans. Corresponding genes exist in mammals, including man.

John Sulston
John Sulston, born 1942, Cambridge, England.	John Sulston developed techniques to study all cell divisions in C. elegans, from the fertilized egg to the 959 somatic cells in the adult nematode. In 1976, Sulston described the cell lineage for a part of the developing nervous system. He showed that the cell lineage is invariant, i.e. every nematode undergoes exactly the same programme of cell division and differentiation. As a result of these findings, Sulston discovered that specific cells in the cell lineage always die by programmed cell death. This could be followed in the living organism. He described the visible steps in the cellular death process and demonstrated the first mutation of a gene participating in programmed cell death, the nuc-1 gene.
John Sulston mapped a cell lineage in the nematode C. elegans. He showed that specific cells undergo programmed cell death during the normal differentiation process.

The Implications of the Discoveries

Some diseases characterized by defective cell death (left) and excessive cell death (right).

The introduction of C. elegans as a novel experimental model system, the characterization of its invariant cell lineage, and the possibility to link this to genetic analysis have proven valuable for many research disciplines. For example, this is true for developmental biology and for analysis of the functions of signalling pathways in multicellular organisms. Research on programmed cell death is intense. Knowledge in this field has helped us to understand the mechanisms by which some viruses and bacteria invade and manipulate our cells. Some diseases, like cancer and certain autoimmune conditions, are characterized by a reduction in cell death, leading to the survival of cells normally destined to die. Many treatment strategies against cancer are based on stimulation of the cellular "suicide programme". This is an interesting and challenging task to further explore in order to reach a refined manner to induce cell death in cancer cells. We also know that in AIDS, neurodegenerative diseases, stroke and myocardial infarction, cells are lost as a result of excessive cell death. For instance, current research suggests that it is possible to reduce the damage caused by myocardial infarction and stroke by using drugs restraining programmed cell death.

 

 

Credits and References for the 2002 Nobel Poster for Physiology or Medicine

Scientific Advisors, Professors at Karolinska Institutet:Hans Jörnvall - Physiological Chemistry, Secretary of the Nobel Assembly
Urban Lendahl - Genetics
Sten Lindahl - Anesthesiology, Chairman of the Nobel Committee
Sten Orrenius - Toxicology

Art Director:
Urban Frank

Medical Writer:
Anders Nystrand

Printed by:
DB Media AB, Stockholm, Sweden 2002

Copyright © 2002:
The Nobel Committee for Physiology or Medicine
at Karolinska Institutet, SE-171 77 Stockholm, Sweden

Web Adapted Version:
Nobelprize.org

Every effort has been made by the publisher to credit organizations and individuals with regard to the supply of photographs and illustrations. The publishers apologize for any omissions which will be corrected in future editions.

 

 

 

http://nobelprize.org/nobel_prizes/medicine/laureates/2002/illpres