Nobel Laureates: Richard Roberts and Phillip Sharp

 
The Nobel Prize in Physiology or Medicine 1993.

"for their discoveries of split genes"

Richard J. Roberts (1943 - ) and Phillip A. Sharp (1944 - ) received the Nobel Prize in Physiology or Medicine for their discovery of interrupted genes and splicing in eukaryotes [see RNA Splicing: Introns and Exons and Monday's Molecule #31].

Roberts and Sharp discovered that the genes in adenovirus were split into various segments that were combined during RNA processing. The results started to become widely known in 1975-76 and the key papers were published in 1977. Later this gene organization was found to be common in chromosomal eukaryotic genes. Unlike many Nobel Prize discoveries, this one really was revolutionary. Here's the presentation speech by Professor Bertil Daneholt of the Nobel Assembly of the Karolinska Institute.

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

Why do children resemble their parents? This question has probably always fascinated humans, but not until the advent of natural science have we arrived at an increasingly satisfactory answer.

In the middle of the last century, the Austrian monk Gregor Mendel conducted his famous breeding experiments with the garden pea. He concluded that every trait of an individual plant is determined by a set of two genes, one obtained from each parental plant. To Mendel a gene was an abstract concept, which he used to interpret his breeding experiments. He had no idea of the physical properties of genes.

Only in the mid-1940s could it be established that in terms of chemistry, genetic material is composed of the nucleic acid DNA. About ten years later the double helical structure of DNA was revealed. Ever since then, progress within the field of molecular biology has been very rapid, and several Nobel prizes have been awarded in this area of research.

Initially, genetic material was studied mainly in simple organisms, particularly in bacteria and bacterial viruses. It was shown that a gene occurs in the form of a single continuous segment of the long, thread-like DNA, and it was generally assumed that the genes in all organisms looked this way. Therefore, it was a scientific sensation when this year's Nobel Laureates, Richard Roberts and Phillip Sharp, in 1977, independently of each other, observed that a gene in higher organisms could be present in the genetic material as several distinct and separate segments. Such a gene resembles a mosaic. Both Roberts and Sharp analyzed an upper respiratory virus, which is particularly suitable for studies of the genetic material in complex organisms. It soon became apparent that most genes in higher organisms, including ourselves, exhibited this mosaic structure.

Roberts' and Sharp's discovery opened up a new perspective on evolution, that is, on how simple organisms develop into more complex ones. Earlier it was believed that genes evolve mainly through the accumulation of small discrete changes in the genetic material. But their mosaic gene structure also permits higher organisms to restructure genes in another, more efficient way. This is because during the course of evolution, gene segments - the individual pieces of the mosaic - are regrouped in the genetic material, which creates new mosaic patterns and hence new genes. This reshuffling process presumably explains the rapid evolution of higher organisms.

Roberts and Sharp also predicted that a specific genetic mechanism is required to enable split genes to direct the synthesis of proteins and thereby to determine the properties of the cell. Researchers had known for many years that a gene contains detailed instructions on how to build a protein. This instruction is first copied from DNA to another type of nucleic acid, known as messenger RNA. Subsequently, the RNA instruction is read, and the protein is synthesized. What Roberts and Sharp were now stating was that the messenger RNA in higher organisms has to be edited. The required process, called splicing, resembles the work that a film editor performs: the unedited film is scrutinized, the superfluous parts are cut out and the remaining ones are joined to form the completed film. Messenger RNA treated in this manner contains only those parts that match the gene segments. It later turned out that the same parts of the original messenger RNA are not always saved during the editing- there are choices. This implies that splicing can regulate the function of the genetic material in a previously unknown way.

Roberts' and Sharp's discovery also helps us understand how diseases arise. One example is a form of anemia called thalassemia, which is due to inherited defects in the genetic material. Several of these defects cause errors in the editing process during splicing; thus, an abnormal messenger RNA is formed and subsequently also a protein that functions poorly or not at all.

The discovery of split genes was revolutionary, triggering an explosion of new scientific contributions. Today this discovery is of fundamental importance for research in biology as well as in medicine.

Dr. Richard Roberts and Dr. Phillip Sharp,

Your discovery of split genes led to the prediction of a new genetic process, that of RNA splicing. The discovery also changed our view of how genes in higher organisms develop during evolution. 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 the Nobel Prize from the hands of His Majesty the King.