Washington: Carnegie Institution.
First edition, the very rare offprint issue, of the first of the papers documenting McClintock’s discovery of ‘control elements,’ for which she was awarded the Nobel Prize in Physiology or Medicine, 1983. “Between 1948 and 1951, McClintock carried out a series of sophisticated experiments with variegated maize that revealed mobile genetic elements that could move from one chromosome to another. Since the mobile elements possessed the ability to alter the function of neighboring genes, McClintock called them ‘control elements.’ Because of the focus, in the 1950’s, on the discovery by Watson and Crick of the structure of DNA and its genetic implications, McClintock’s discovery of ‘jumping genes’ was not appreciated at the time. Although she had suggested that mobile genetic elements were probably present in insects and higher organisms, it was not until the mid-1960’s that mobile elements were found to play a role in the spread of antibiotic resistance from resistant to sensitive strains of bacteria. In the 1970’s, the formation of antibodies was found to be based in genetic transposition. In the late 1970’s and early 1980’s, it was discovered that growth-regulating genes, or oncogenes, are transposed from one chromosome to another in certain forms of cancer … McClintock’s discovery of mobile genetic elements in maize has counterparts in bacteria, animals, and humans; more-over, it also helped to explain how genes can change during evolution and to elucidate a series of complicated medical problems” (Magill 3, pp. 1435-4). The second offered paper McClintock first suggested the existence of mobile genetic elements in bacteria.
“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” (Nobel Prize Award Ceremony Speech by Nils Ringertz).
F. N. Magill, The Nobel Prize Winners: Physiology or Medicine, 1991; L. Pray & K. Zhaurova, ‘Barbara McClintock and the discovery of jumping genes (transposons),’ Nature Education, Vol. 1 (2008).
‘Mutable loci in maize.’ Offprint from Annual Report of the Director of the Department of Genetics, Carnegie Institution of Washington Year Book No. 47, for the year 1947-1948. [Offered with:] ‘Some parallels between gene control systems in maize and in bacteria.’ Offprint from The American Naturalist, Vol. XCV, No. 884, September-October, 1961 8vo, pp. 155-169 & 265-277. Self-wrappers, McClintock’s name written on first page of both offprints, ink stamp of Norman H[enry] Giles (1915-2006) on the first. Giles was an American microbial geneticist who studied mutations of Neurospora crassa.