1991 Albert Lasker Basic Medical Research Award

Genetic basis of early embryonic development

Edward Lewis
In fundamental discoveries made over the last 40 years, Dr. Lewis has laid the foundation for most of what is known today about the evolution, structure and function of control genes, which regulate development of specific regions of the body. Dr. Lewis's revolutionary investigations have also provided methods and materials for analyzing gene function, laying the groundwork for late discoveries of control genes in other organisms, especially vertebrates.

Dr. Lewis is particularly known for his use of the fruit fly, Drosophila, to study how genes determine heredity. Beginning with a small number of viable mutants of the fruit fly, he discovered what he called the Bithorax complex, a cluster of genes in the fly that controls how the body segments develop. Beginning in the late 1940s, Dr. Lewis showed that mutations in Drosophila that lead to striking abnormalities, such as embryos with multiple thoraxes or flies with four wings instead of two, are organized in giant clusters. 

This work established the concept that single genes can control the development of specific regions of the body. Further, Dr. Lewis established a direct relationship between the tandem repeat structure of the Bithorax complex genes and their orderly expression in the body. He then made what 30 years ago was considered a radical proposal: that such gene clusters evolved by repeated duplication of a single ancestral gene and that these clusters in modern organisms would show traces of their common origin.

Dr. Lewis's studies launched a new area of investigation into how genes regulate the entire course of growth of a living organism. Over the past decade, using new techniques of molecular biology, scientists have built on his observations about development. In particular, they have identified within the DNA of each gene of the giant clusters a region that differs very little from organism to organism, called the "homeobox." The nature of the homeobox and its precise function is a widely investigated area in developmental biology today. There is considerable speculation that it acts as a kind of master regulator of development.

To Dr. Edward Lewis, for his discovery of the Bithorax complex, through research on the fruit fly, which led to the establishment of fundamental principles for analyzing gene function in developing organisms, including human beings, this 1991 Albert Lasker Basic Medical Research Award is given.
 

Christiane Nüsslein-Volhard

Working with the fruit fly, Drosophila, Dr. Nüsslein-Volhard determined how genes control body patterns by showing that they give rise to a hierarchy of signaling molecules, each conferring spatial information by governing where and when other molecules are expressed.  By systematically identifying and characterizing about 120 genes, or nearly all of the genes involved in specifying embryonic pattern development, Dr. Nüsslein-Volhard and her colleague Eric Wieschaus have opened up the study of the body plan on the molecular level.  Through these investigations, Dr. Nüsslein-Volhard discovered the first defined molecular gradients which tell cells what to do based on their relative position within the embryo.

 

Dr. Nüsslein-Volhard has identified about 30 genes that directly affect the process of determination of the embryonic axis.  These “coordinate” genes define four systems that determine the anteroposterior axis (three systems) and the dorsoventral axis (one system) independently.  Although all four systems use different biochemical mechanisms, they share several properties.  First, the product of one gene in each system is localized in a specific region of the freshly laid egg and functions as a spatial signal.  Second, in each system this spatial information finally results in the asymmetrical distribution of one gene product that functions as a transcription factor.  Finally, this transcription factor is distributed in a concentration gradient that defines the spatial limits of expression of one or more zygotic target genes.

Dr. Nüsslein-Volhard’s research is considered awe-inspiring for its sheer daring and success.  Most of the genes she has identified in the past 12 years were previously unknown.  And in the brief period since their discovery, nearly all have been cloned and are the subject of intense analysis by hundreds of laboratories.  Moreover, her recent work on specific subsets of these genes, particularly those controlling dorsoventral and anteroposterior axis determination in early embryos, has helped provide a foundation that may prove comparable to that which we now have for Drosophila for understanding the development of higher vertebrate animals.

To Dr. Christiane Nüsslein-Volhard, for charting new paths in developmental biology through the discovery of nearly all genes responsible for organizing basic body patterns, this 1991 Albert Lasker Basic Medical Research Award is given.