Nobel Laureate: Barbara McClintock

 

The Nobel Prize in Physiology or Medicine 1983.

"for her discovery of mobile genetic elements"

Barbara McClintock (1902-1992) received the Nobel Prize in Physiology or Medicine for discovering transposons, or mobile genetic elements [Transposons: Part I, Transposons: Part II].

Barbara McClintock began her interest in genetics while she was an undergraduate at Cornell in 1921. That was a time when genetics as a discipline was just being recognized [autobiography]. McClintock went on to earn a Ph.D. from Cornell in 1927 and then stayed on to lecture in genetics undergraduate courses. In 1936 she moved to the University of Missouri where she was a Professor until 1941 when she took a position at the Carnegie Institution of Washington, with a lab at the Cold Spring Harbor Laboratories (New York, USA). She remained there in an official position until 1967 but was still a frequent visitor until well into the 1970's.

Most of her scientific work was in the field of maize cytogenetics where she quickly established a reputation as a good experimenter with a very sharp mind. She received many accolades and awards throughout her career and was elected to the National Academy of Sciences (USA) in 1944. In 1945, she became the first female president of the Genetics Society of America.

Her work on mobile genetic elements in maize began in 1944 and this work soon led to the discovery of two transposons, Dissociator (Ds) and Activator(Ac).

The presentation speech was given by Professor Nils Ringertz of the Karolinska Institute and it explains, in easy-to-understand terms, the significance of McClintock's work.

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

The Nobel prize in Physiology or Medicine for 1983 recognizes a great discovery about the organization of genes on chromosomes and how these genes, by changing places, can alter their function. This discovery, made while investigating blue, brown, and red spots on maize kernels, resulted in new knowledge of great medical importance - information which provides the key to problems as diverse as hospital infections, African sleeping sickness and chromosome changes in cancer cells. In order to explain this link, we must start at the beginning; namely with Barbara McClintock's investigations of coloured spots on maize kernels.

The maize cobs that we buy at the supermarket usually have yellow kernels. This is not always the case with wild forms of maize. In Central and South America where maize originated, one can still find primitive types of maize where the kernels are blue, brown or red. The colour depends on pigments in the surface layer of the kernel endosperm. The endosperm is the food store for the developing seedling. The synthesis of kernel pigments is controlled by the genes of the maize plant. In some cases one finds differently coloured kernels on the same cob. The explanation for this is that the cob is formed from a group of female flowers. Each of these female flowers may be fertilized independently by a pollen gram from a male flower. Maize cobs with differently coloured kernels arise when the pollen grains do not carry the same genes for endosperm pigments. All these phenomena can be explained on the basis of the laws of the inheritance stated by Gregor Mendel in 1866. What cannot be explained, however, and what puzzled plant breeders in the 1920's, was that maize kernels sometimes have numerous spots or dots, rather than being evenly coloured as would be expected. It was suspected that the dots on the kernels were due to the instability of genes involved in the pigment synthesis. These genes were believed to undergo mutations during the development of the kernel. Should such a mutation be inherited by several generations of daughter cells it would result in a differently coloured spot. This idea received further support when it was found that maize with variegated kernels also had broken chromosomes. The problem of variegation in maize was of slight importance from a practical point of view, but it fascinated Barbara McClintock because it evidently could not be explained on the basis of Mendelian genetics.

McClintock analyzed this phenomenon by studying chromosome changes and the results of crossing experiments in maize with different patterns of variegation. She was able to identify a series of genes on chromosome number 9 that determine pigmentation and other characteristics of the endosperm. She found that variegation occurred when a small piece of chromosome 9 moved from one place on the chromosome to another close to a gene coding for a pigment. The usual effect was to switch off the gene, and furthermore, the chromosome frequently showed a break at the site of integration. McClintock called these types of genetic material "control elements" since they clearly altered the function of neighbouring genes. In a series of very advanced experiments carried out between 1948 and 1951, McClintock mapped several families of control elements. These elements affected not only the pigmentation pattern of the maize kernels but other properties as well. She also pointed out that mobile genetic elements were probably present in insects and higher animals. In spite of this, her observations received very little attention. This was because her findings, when first presented, were overshadowed by the discovery that the DNA molecule stores the genetic information in its structure. It also became evident that mutations involving only one change in one of the building blocks in the DNA molecule could have serious effects. Under these circumstances, it is not surprising that few geneticists were prepared to accept that genes could jump in the irresponsible manner that McClintock proposed for controlling elements. The "state of the art" in molecular genetics at that time made it difficult to accept "jumping genes", and thus McClintock had to await the development of methodological tools powerful enough to verify in biochemical terms her great discovery.

In the mid-sixties, mobile genetic elements were found to play an important role in the spreading of resistance to antibiotics from resistant to sensitive strains of bacteria. This type of transferable drug resistance is a serious problem in hospitals since it causes infections that are very difficult to treat. During the 1970's, more support was found for the medical significance of mobile genetic structures. It was found, for instance, that the transposition of genes is an important step in the formation of antibodies. It has always been a mystery how the body, using a limited number of genes, can form an almost endless number of different antibodies to foreign substances. Nature has solved this problem according to the building block principle. When an individual is born, the chromosomes carry a set of mobile building blocks for antibody genes. By recombining these blocks in various ways in different cells, the body is able to generate millions of genes for antibodies.

During the last few years mobile genetic structures have attracted great interest in cancer research. In certain forms of cancer, growth regulating genes called oncogenes, are transposed from one chromosome to another. Tumour viruses in birds and mice have been found to carry oncogenes which they, in all likelihood, originally picked up from a host cell. If a virus then introduces these genes in the wrong place on the chromosomes of a normal cell, the latter is transformed into a cancer cell.

McClintock's discovery of mobile genetic elements in maize, therefore, has been found to have counterparts also in bacteria, animals and humans.

What led McClintock to devote her research to the variegation of maize kernels was that it did not lit in with Mendelian genetics. With immense perseverance and skill, McClintock, working completely on her own, carried out experiments of great sophistication that demonstrated that hereditary information is not as stable as had previously been thought. This discovery has led to new insights into how genes change during evolution and how mobile genetic structures on chromosomes can change the properties of cells. Her research has helped to elucidate a series of complicated medical problems.

Dr. McClintock,

I have tried to summarize to this audience your work on mobile genetic elements in maize and to show how basic research in plant genetics can lead to new perspectives in medicine. Your work also demonstrates to scientists, politicians and university administrators how important it is that scientists are given the freedom to pursue promising lines of research without having to worry about their immediate practical applications. To young scientists, living at a time of economic recession and university cutbacks, your work is encouraging because it shows that great discoveries can still be made with simple tools.

On behalf of the Nobel Assembly of the Karolinska Institute I wish to convey to you our warmest congratulations and I ask you to receive your Nobel prize in Physiology or Medicine from His Majesty the King.

[Photo Credit (top): The Barbara McClintock Papers]