Nobel Prize

BARBARA MCCLINTOCK

Nobel Prize in Physiology or Medicine 1983

Throughout her career, Barbara McClintock studied the cytogenetics of maize, making discoveries so far beyond the understanding of the time that other scientists essentially ignored her work for more than a decade. But she persisted, trusting herself and the evidence under her microscope.

A few labelled samples of Barbara McClintock’s maize, with microscope.

Photo: Smithsonian Institution. National Museum of American History

Corn stalk specimen.

Photo: Courtesy of the Barbara McClintock Papers, American Philosophical Society

Barbara McClintock almost didn’t go to college. She was a talented student, but her mother believed a college degree would harm her chances of marriage and vetoed her plan to go to Cornell.

The McClintock children, ca. 1907. Barbara McClintock is second from the right.

Photo: National Institutes of Health. Courtesy of the Barbara McClintock Papers, American Philosophical Society. Photographer unknown

A McClintock family photograph, ca. 1914. Barbara McClintock is third from the right, leaning on the piano.

Photo: National Institutes of Health. Courtesy of the Barbara McClintock Papers, American Philosophical Society.

Fortunately, McClintock’s father returned from the Army Medical Corps in France in time to intervene. In 1919, at the age of 17, McClintock enrolled in the Cornell College of Agriculture. She thrived at college: she joined the student government, played banjo in a jazz band, and excelled in the classroom. It was there that she took the course that would change the course of her life: genetics.

Genetics as a discipline was still new in the 1920s; Cornell offered only one undergraduate course. But McClintock took to it immediately, conceiving a lifelong interest in the field of cytogenetics – the study of chromosomes and their genetic expression.

A letter from Lewis Stadler (pictured) to Milislav Demerec. A close friend and supporter from Cornell days, Stadler had helped McClintock procure a position at the University of Missouri. Six years later, Demerec brought her to Cold Spring Harbor Laboratory on leave from the university. Stadler writes that although he wants McClintock to return to Missouri, “I hope she will stay at Cold Spring Harbor if she is convinced that would be better for her work.”

Courtesy of Cold Spring Harbor Laboratory

Page two from a letter from Lewis Stadler (pictured) to Milislav Demerec. A close friend and supporter from Cornell days, Stadler had helped McClintock procure a position at the University of Missouri. Six years later, Demerec brought her to Cold Spring Harbor Laboratory on leave from the university. Stadler writes that although he wants McClintock to return to Missouri, “I hope she will stay at Cold Spring Harbor if she is convinced that would be better for her work.”

Courtesy of Cold Spring Harbor Laboratory

Barbara McClintock’s colleague and supporter Lewis Stadler, with geneticist Esther M. Lederberg at the University of Missouri in the 1950s

Courtesy of Joshua Lederberg

She earned her bachelor’s, master’s and doctoral degrees at Cornell and had great success in her research on the cytogenetics of maize. Even so, it wasn’t easy to find a permanent position in the midst of the Depression. Finally, McClintock was hired as an assistant professor at the University of Missouri in 1936.

McClintock loved working in the lab. “I was just so interested in what I was doing I could hardly wait to get up in the morning and get at it,” she once said.

But for her, teaching was a distraction. She left her university job in 1941 for Cold Spring Harbor Laboratory, a research facility funded by the Carnegie Institution. Freed to focus exclusively on her experiments, McClintock stayed at Cold Spring Harbor until her retirement in 1967 – and even beyond, as a scientist emerita, until her death at the age of 90.

Early in her research at Cold Spring Harbor, McClintock began to study the mosaic colour patterns of maize at the genetic level. She had noted that the kernel patterns were too unstable, and changed too frequently over the course of several generations, to be considered mutations. What was responsible for this? The answer contradicted prevailing genetic theory.

Labelled maize. Barbara McClintock discovered that genes could “jump” by studying generational mutations in maize.

Photo: Courtesy of Cold Spring Harbor Laboratory. Photo: Jan Eve Olsson

An illustration of corn kernel specimens, included in Barbara McClintock’s article in the ‘Cold Spring Harbor Symposia on Quantitative Biology’ in 1951.

Photo: Courtesy of the Barbara McClintock Papers, American Philosophical Society

As McClintock observed by studying successive generations of maize plants, instead of being locked into place giving fixed instructions from generation to generation, some genes could move around or “transpose” within chromosomes, switching physical traits on or off according to certain “controlling elements.”

Aware that her work departed from the common wisdom, McClintock put off publishing her theories on genetic transposition and controlling elements until other researchers had confirmed her results. At last, in the summer of 1951, she gave a lecture on her findings at the annual symposium at Cold Spring Harbor Laboratory. It didn’t go well. As she later recalled it, the audience was either perplexed by or hostile to her theories. “They thought I was crazy, absolutely mad.”

In the face of such resistance to her theories, McClintock stopped publishing and lecturing – she stopped trying to convince others – but she never stopped pursuing her theories. “I just knew I was right,” she said later. “Anybody who had had that evidence thrown at them with such abandon couldn’t help but come to the conclusions I did about it.”

McClintock’s diagram of the BreakageFusionBridge cycle.

Courtesy of the Barbara McClintock Papers, American Philosophical Society

Corn specimens photographed in 1966, when Barbara McClintock was studying the evolution of maize in South America.

Photo: Courtesy of the Barbara McClintock Papers, American Philosophical Society

Finally, in the mid-1960s, the scientific community began to come to the same conclusions, validating her findings and giving her the credit that was long overdue. McClintock received the Nobel Prize more than 30 years after making the discoveries for which she was honoured.

Barbara McClintock made discovery after discovery over the course of her long career in cytogenetics. But she is best remembered for discovering genetic transposition (“jumping genes”). Understanding the phenomenon is still fundamental to understanding genetics, as well as related concepts in medicine, evolutionary biology, and more.

Beyond her discoveries, though, McClintock’s legacy is one of uncommon persistence. As she put it, “If you know you are on the right track, if you have this inner knowledge, then nobody can turn you off… no matter what they say.”

Barbara McClintock – Nobel Lecture

Read the Nobel Lecture
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Barbara McClintock – Other resources

Links to other sites

The Barbara McClintock Papers at the U.S. National Library of Medicine

‘Barbara McClintock and Transposable Genetic Elements’ from DOE R&D Accomplishments 

Barbara McClintock – Banquet speech

Barbara McClintock’s speech at the Nobel Banquet, December 10, 1983

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen

I am delighted to be here, and charmed by the warmth of the Swedish people. And I wish to thank them for their many courtesies.

I understand I am here this evening because the maize plant, with which I have worked for many years, revealed a genetic phenomenon that was totally at odds with the dogma of the times, the mid-nineteen forties. Recently, with the general acceptance of this phenomenon, I have been asked, notably by young investigators, just how I felt during the long period when my work was ignored, dismissed, or aroused frustration. At first, I must admit, I was surprised and then puzzled, as I thought the evidence and the logic sustaining my interpretation of it, were sufficiently revealing. It soon became clear, however, that tacit assumptions – the substance of dogma – served as a barrier to effective communication. My understanding of the phenomenon responsible for rapid changes in gene action, including variegated expressions commonly seen in both plants and animals, was much too radical for the time. A person would need to have my experiences, or ones similar to them, to penetrate this barrier. Subsequently, several maize geneticists did recognize and explore the nature of this phenomenon, and they must have felt the same exclusions. New techniques made it possible to realize that the phenomenon was universal, but this was many years later. In the interim I was not invited to give lectures or seminars, except on rare occasions, or to serve on committees or panels, or to perform other scientists’ duties. Instead of causing personal difficulties, this long interval proved to be a delight. It allowed complete freedom to continue investigations without interruption, and for the pure joy they provided.

Barbara McClintock – Photo gallery

HRH Prince Bertil of Sweden and Barbara McClintock, checking out the programme for the evening, at the Nobel Banquet in the Stockholm City Hall, Sweden, on 10 December 1983.

Copyright © Svensk Reportagetjänst 1983 Photo: Ulf Blumenberg

Barbara McClintock delivering her Nobel Lecture at Karolinska Institutet in Stockholm, 8 December 1983.

Source: National Institutes of Health. Courtesy of the Barbara McClintock Papers, American Philosophical Society Photographer unknown

Barbara McClintock with Alfred Hershey, 1969 Nobel Laureate in Physiology or Medicine. Date unknown.

Source: National Institutes of Health. Courtesy of the Barbara McClintock Papers, American Philosophical Society Photographer unknown

Barbara McClintock with staff at the Banbury Center, Cold Spring Harbor Laboratory. Barbara McClintock is standing third from the left in the first row. Photo taken in August, 1984.

Source: National Institutes of Health. Courtesy of the Barbara McClintock Papers, American Philosophical Society Photographer unknown

Photograph of Barbara McClintock's five ears of corn and a microscope.

Source: Smithsonian Institution. National Museum of American History Photographer unknown

Barbara McClintock in the lab at Cold Spring Harbor, April, 1963.

National Institutes of Health. Courtesy of the Barbara McClintock Papers, American Philosophical Society. Photographer unknown

Barbara McClintock arrived at Cold Spring Harbor on Long Island in 1941 and spent most of her remaining research years at the facility. Photo taken ca 1950.

Source: National Institutes of Health. Courtesy of the Barbara McClintock Papers, American Philosophical Society Photographer unknown

Barbara McClintock shown in her laboratory at the Department of Genetics, Carnegie Institution at Cold Spring Harbor, New York, 1947.

Source: Smithsonian Institution/Science Service; Restored by Adam Cuerden, via Wikimedia Commons Photographer unknown

Barbara McClintock with her family. From left to right: Mignon, Malcolm Rider "Tom", Barbara, Marjorie, and Sara (at the piano). Photo taken ca 1914.

Source: National Institutes of Health. Courtesy of the Barbara McClintock Papers, American Philosophical Society Photographer unknown

The McClintock siblings. From the left: Mignon, Malcolm Rider "Tom", Barbara, and Marjorie. Photo taken in 1907.

Source: National Institutes of Health. Courtesy of the Barbara McClintock Papers, American Philosophical Society Photographer unknown

Barbara McClintock – Prize presentation

Press release

NOBELFÖRSAMLINGEN KAROLINSKA INSTITUTET
THE NOBEL ASSEMBLY AT THE KAROLINSKA INSTITUTE

The Nobel Assembly of the Karolinska Institute has today decided to award the Nobel Prize in Physiology or Medicine for 1983 to

Barbara McClintock

for her discovery of “mobile genetic elements”.

Summary

Barbara McClintock discovered mobile genetic elements in plants more than 30 years ago. The discovery was made at a time when the genetic code and the structure of the DNA double helix were not yet known. It is only during the last ten years that the biological and medical significance of mobile genetic elements has become apparent. This type of element has now been found in microorganisms, insects, animals and man, and has been demonstrated to have important functions.

Genetic instability was originally discovered in maize (Zea mays) in which it was found to cause altered patterns of pigmentation of the kernels. Instead of being evenly pigmented, the kernels have sectors of more intense pigmentation. The spots vary in size and colour. At the same time, the cells show chromosome breaks and other abnormalities. McClintock examined the relationship between the pigmentation pattern the kernels and chromosome changes. Variegation in the colour of the kernels was found to be parallelled by transposition of structural elements within or between chromosomes. Because transpositions result in inactivation of neighbouring genes, McClintock used the term “controlling elements” to describe the mobile chromosome structures. Another effect of transposition was chromosome breaks at points where the mobile elements were integrated.

During the mid-1960s mobile genetic elements were demonstrated in bacteria and shown to play a role in the transmission of resistance to antibiotics from one bacterium to another.

Such elements were also found to have an important function in the ability of unicellular parasites (trypanosomes) to change their surface properties, thereby avoiding the immune response of the host organism. Recombination of DNA segments proved to be an essential factor in the ability of lymphoid cells to produce a seemingly infinite number of different antibodies to foreign substances. In recent years, evidence has accumulated that transposition of genes or incomplete genes are involved in the transformation of normal cells into tumour cells. Thus, genes controlling cell growth have been found to undergo translocation from chromosome to another during cancerogenesis. The initial discovery of mobile genetic elements by Barbara McClintock is of great medical and biological significance. It has also resulted in new perspectives on how genes are formed and how they change during evolution.

When McClintock began the work that led to the discovery of mobile genetic elements, genetic instability had been demonstrated in plants and insects (Drosophila). In maize, the instability caused the kernels to show differently coloured patches. This variegation was believed to reflect a greater fragility of certain chromosome regions, causing genes for pigmentation to mutate more easily than other genes. As daughter cells multiplied and inherited the mutant genes, colonies of cells with an altered pattern of pigmentation were formed.

McClintock first examined the structure of chromosomes in maize plants showing variegation in pigmentation. By combining results from these studies with those from genetic crosses she was able to localize genes for e.g. type of starch, storage protein, anthocyanin pigments on the individual chromosomes. Of the ten pairs of chromosomes pair number 9 turned out to be of particular interest.

The choice of maize presented several experimental advantages. Each ear (Fig. 1) has several hundred kernels, each of which is the result of an independent fertilization event. The inheritance of a series of characteristics can easily be studied simply by examining the structure, starch content or pigmentation of the individual kernels. Mutations affecting pigmentation are particularly useful, not only because they can be easily observed, but also because they do not harm the multiplication of the cells. Therefore, if a single cell undergoes a mutation or other form of heritable change during the development of the kernels, this will result in altered pigmentation of several successive generations of daughter cells. The number and size of the differently coloured spots, therefore, provides important information on the extent of genetic instability and the point during development at which the genetic change took place.

Figure 1. Schematic summary of the maize plant, its maize cobs and maize kernels.

Another advantage of maize as an experimental system was that individual chromosomes are easily studied. During the 1930s McClintock made an important contribution to plant genetics by describing the detailed morphology of normal and altered maize chromosomes. This work was a necessary condition for the discovery of mobile genetic elements.

The first mobile element characterized by McClintock was found on chromosome number 9, where it caused chromosome breaks (Fig. 2). Since the chromosome was divided into two parts, this element was named “dissociation” or Ds. As it was transposed along chromosome 9 it caused breaks and inactivitation of neighbouring genes. McClintock, therefore, referred to the mobile elements as “control elements”. In order for Ds to be transposed, a second genetic element called “activator” (Ac) had to be present. Together Ds and Ac represented a two element system controlling gene activity. McClintock also identified different forms of Ds, some causing complete gene inactivation while others resulted in different degrees of partial gene inactivation. The role of the Ac element was shown to be a coordinating one. By signalling to Ds elements, Ac triggered the transposition of one or several such elements. Also the Ac element occurred in different forms. Some of these produced signals early during the development of the kernel, while others induced transpositions late in development. The type of Ac element could be detected by examining the size of differently pigmented spots on the surface of the kernels.

 

In later work, McClintock demonstrated regions of genetic instability on other maize chromosomes. Also in these cases the phenomena observed turned out to be due to genetic elements moving from one chromosome to another.

The most important features of the control elements discovered by McClintock are the following:

The control elements behave as ordinary genes in genetic crosses, and can be localized to specific chromosome regions. When they transpose along, or between, chromosomes, they cause inactivation of neighbouring genes. In some cases, they also result in structural instability at the sites of integration, causing chromosomes to break easily at these sites. When control elements leave a certain region, the previously inactived genes resume normal functions.

Control elements can be classified into groups. Within a certain group, one element acts as a superior element (regulator) signalling to subordinate elements (receptors) when to transpose. By doing so, the superior element controls the exact time during development when transpositions are to occur.

Control elements can assume different states. They can be part of regulatory systems consisting of two or more elements. They can also appear as independent or autonomous elements. Some elements act by programming neighbouring genes to become active at a later time, which may be several cell generations later.

McClintock’s experiments were carried out with great ingenuity and intellectual stringency. They reveal a whole world of previously unknown genetic phenomena. In spite of this, they failed to attract the attention of contemporary scientists. This might have been due to the fact that her results were reported in not so widely read publications such as the annual report of the institute where she worked and in special newsletters exchanged by plant breeders working with maize. A contributing factor was that she was far ahead of the development in other fields of genetics. Her most important results were published before the structure of the DNA double helix and the genetic code had been discovered. Furthermore, useful as they were from an experimental point of view, the pigmentation patterns of maize kernels was of little practical significance.

In recent years, mobile genetic elements have been demonstrated in a number of species. This has given new insights into the mechanisms involved in the evolution of genes and has resulted in a much more dynamic picture of the organization and function of genes. In bacteria, short DNA segments known as “insertion sequences” or IS elements have been found to move from the bacterial chromosome to smaller DNA molecules known as plasmids or from one plasmid to another. The effect of their transposition is inactivation of genes. Genes surrounded on both sides by IS elements become mobile (Fig. 3). This type of gene is known as “transposon”, and is of great importance in clinical medicine. Often, these structures carry genes for resistance to antibiotics. The spread of such resistance genes from resistant to sensitive bacteria is a major problem in the treatment of infectious diseases.

Figure 3. Schematic summary of how a gene for resistance to an antibiotic can jump from a bacterial chromosome to a plasmid using a transposon as a vector (step 1). The plasmid (R-factor) may then be taken up by a sensitive bacterium (step 2) which becomes resistant to the antibiotic. In this way resistance to an antibiotic may spread from one bacterium to another making treatment difficult.

Mobile genetic elements have also been found in bacteriophages, i.e., viruses that infect bacteria. In trypanosomes, a type of parasite that causes African sleeping sickness, mobile genetic elements cause changes in the surface molecules of the parasite, making it possible for the parasite to evade the immune response of the host organism.

In insects (Drosophila), several mobile genetic elements have been identified and shown to be closely related to genes found in RNA tumour viruses. One such element, known as “copia”, can occur in nuclear DNA as a mobile gene. It can also be copied into RNA and become part of an RNA virus. The RNA form can again be copied back into DNA when a new cell is infected. The DNA copy then becomes a mobile gene in the nucleus of the infected cell.

The correlation between mobile genetic elements and RNA viruses (retroviruses) is of interest also in relation to animal and human cells. Some genes that cause normal cells to become tumour cells (oncogenes) can occur both as viral genes (v-onc) and as cellular genes (c-onc). In some cases the abnormal growth pattern of tumor cells has been linked to transposition of c-onc genes or to integration of mobile genetic elements close to the c-onc genes.

The discovery of mobile genetic elements by McClintock is of profound importance for our understanding of the organization and function of genes. She carried out this research alone and at a time when her contemporaries were not yet able to realize the generality and significance of her findings. In this respect, there are several similarities between her situation and that of another great geneticist active 100 years ago, Gregor Mendel, who, studying the garden pea, discovered other basic principles of genetics.

Award ceremony speech

Presentation Speech by Professor Nils Ringertz of the Karolinska Institute

Translation from the Swedish text

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.

The Nobel Prize in Physiology or Medicine 1983

Barbara McClintock – Biographical

In the fall of 1921 I attended the only course in genetics open to undergraduate students at Cornell University. It was conducted by C. B. Hutchison, then a professor in the Department of Plant Breeding, College of Agriculture, who soon left Cornell to become Chancellor of the University of California at Davis, California. Relatively few students took this course and most of them were interested in pursuing agriculture as a profession. Genetics as a discipline had not yet received general acceptance. Only twenty-one years had passed since the rediscovery of Mendel’s principles of heredity. Genetic experiments, guided by these principles, expanded rapidly in the years between 1900 and 1921. The results of these studies provided a solid conceptual framework into which subsequent results could be fitted. Nevertheless, there was reluctance on the part of some professional biologists to accept the revolutionary concepts that were surfacing. This reluctance was soon dispelled as the logic underlying genetic investigations became increasingly evident.

When the undergraduate genetics course was completed in January 1922, I received a telephone call from Dr. Hutchison. He must have sensed my intense interest in the content of his course because the purpose of his call was to invite me to participate in the only other genetics course given at Cornell. It was scheduled for graduate students. His invitation was accepted with pleasure and great anticipations. Obviously, this telephone call cast the die for my future. I remained with genetics thereafter.

At the time I was taking the undergraduate genetics course, I was enrolled in a cytology course given by Lester W. Sharp of the Department of Botany. His interests focused on the structure of chromosomes and their behaviors at mitosis and meiosis. Chromosomes then became a source of fascination as they were known to be the bearers of “heritable factors”. By the time of graduation, I had no doubts about the direction I wished to follow for an advanced degree. It would involve chromosomes and their genetic content and expressions, in short, cytogenetics. This field had just begun to reveal its potentials. I have pursued it ever since and with as much pleasure over the years as I had experienced in my undergraduate days.

After completing requirements for the Ph.D. degree in the spring of 1927, I remained at Cornell to initiate studies aimed at associating each of the ten chromosomes comprising the maize complement with the genes each carries. With the participation of others, particularly that of Dr. Charles R. Burnham, this task was finally accomplished. In the meantime, however, a sequence of events occurred of great significance to me. It began with the appearance in the fall of 1927 of George W. Beadle (a Nobel Laureate) at the Department of Plant Breeding to start studies for his Ph.D. degree with Professor Rollins A. Emerson. Emerson was an eminent geneticist whose conduct of the affairs of graduate students was notably successful, thus attracting many of the brightest minds. In the following fall, Marcus M. Rhoades arrived at the Department of Plant Breeding to continue his graduate studies for a Ph.D. degree, also with Professor Emerson. Rhoades had taken a Masters degree at the California Institute of Technology and was well versed in the newest findings of members of the Morgan group working with Drosophila. Both Beadle and Rhoades recognized the need and the significance of exploring the relation between chromosomes and genes as well as other aspects of cytogenetics. The initial association of the three of us, followed subsequently by inclusion of any interested graduate student, formed a close-knit group eager to discuss all phases of genetics, including those being revealed or suggested by our own efforts. The group was self-sustaining in all ways. For each of us this was an extraordinary period. Credit for its success rests with Professor Emerson who quietly ignored some of our seemingly strange behaviors.

Over the years, members of this group have retained the warm personal relationship that our early association generated. The communal experience profoundly affected each one of us.

The events recounted above were, by far, the most influential in directing my scientific life.

This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/ Nobel Lectures/The Nobel Prizes. The information is sometimes updated with an addendum submitted by the Laureate.

Barbara McClintock died on September 2, 1992.