Presentation Speech by Professor Björn Vennström of the Nobel Committee at the Karolinska Institute

Translation of the Swedish text

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

At the beginning of a life the newly fertilized egg divides and becomes two cells, then four, eight, and so on. At first, all the cells are alike. Later, however, they specialize, and what is to become head and tail, and front and back, respectively, is soon evident. This gradual specialization is governed by genes. But which genes? How many are they? How do they work?

These questions were addressed by this year’s laureates in physiology or medicine. They chose the fruit fly Drosophila melanogaster as their experimental animal since it is simple to study. The newly laid egg develops in 10 days, first to a larva, then to a pupa, and finally to a sexually mature fly.

Insect larvae have segments; recall the larva of a butterfly! Each segment has its own developmental program. Think about the wasp, with its head, the central section, and the striped posterior (“tail”) region: every part develops from a specific segment in the larva. Christiane Nüsslein-Volhard and Eric Wieschaus decided to find all the genes that cause the larva to develop exactly 14 segments, since the segments determine the body plan. Their chances of success were unclear. Nobody had done anything similar before, and a hopelessly large number of genes could be involved. They began their work, using a simple but ingenious experimental approach. After having tested more than half of the approximately 20000 genes of the fly, they found three groups of genes that govern segmentation. The first group of genes provides a basis for segmentation along the body axis. The next group of genes governs the development of every second segment, whereas the third group refines the structure of the individual segments.

Christiane Nüsslein-Volhard and Eric Wieschaus had opened a Pandora’s box filled with a seemingly unmanageable jumble of genes, and transformed their hope for success into a reality. They showed that it really was possible to identify and classify genes that govern early embryogenesis in a rational way. The genes they found were surprisingly few: only 15. This success has paved the way for other developmental biologists to make pioneering discoveries. How do seemingly identical segments in a larva develop into different parts of the mature fruit fly? Flies with an extra pair of wings had been found as early as the beginning of this century: one segment in the larvae had simply chosen the “wrong” developmental program. Edward Lewis studied the genes that govern the development of segments, and he found that they were arranged one after another in the DNA of the fly. The order of the genes in the DNA also corresponded to the order of the larval segments in which they exerted their effects. This, and much more, was a novel concept. We humans have genes that are closely related to the genes discovered by the laureates, and they perform important functions in our embryonic development. The genes that Edward Lewis discovered have in fact the same order in our DNA as in that of the fruit fly, and they work in the same way. The knowledge gained about the development of the fruit fly has thus been a prerequisite for the recent advances in understanding how vertebrates develop.

Edward Lewis, Christiane Nüsslein-Volhard, and Eric Wieschaus,

Your discoveries of genes that govern embryonic development have allowed us to comprehend how a single cell develops into a complex multicellular organism. On behalf of the Nobel Assembly of the Karolinska Institute I wish to convey to you our warmest congratulations, and I now ask you to step forward to receive your Nobel Prizes from the hands of His Majesty the King.