A Conversation With Professor Newton Ennis Morton

Authors


Editor's Note

We plan to publish “conversations” with eminent scientists from time to time so that graduate students and younger scientists can develop an appreciation for the foundations of genetic epidemiology established by early leaders. This is the first such effort to showcase Professor Newton Ennis Morton.

Professor Newton Morton was born in 1929 in Camden, New Jersey. He received a BA in Zoology in 1951 from the University of Hawaii and his PhD in Genetics in 1955 from the University of Wisconsin, Madison. From 1952 to 1953, he worked as a geneticist in Japan with Professor James Neel and colleagues on Atomic Bomb Casualty Commission, NRC-NAS. He was Assistant Professor, and then Associate Professor at the University of Wisconsin. Subsequently, he moved to Hawaii as Professor and Director of the Population Genetics Laboratory at the University of Hawaii. He left Hawaii in 1985; after 2 years at the Memorial Sloan-Kettering Cancer Center in New York, he joined the Southampton University in 1988 and retired in 2011. He has made ground breaking contributions to human and population genetics. He is one of the founding fathers in developing the field of genetic epidemiology. He is the first recipient of the William Allan Award, the major prize given by the American Society of Human Genetics that recognizes substantial and far-reaching contributions to human genetics. He was elected as a member of the United States National Academy of Sciences in 1990 for his pioneering contributions to Human Genetics.

Author's Note

It has been a real privilege to have worked with one of the greatest population geneticists and founding fathers of genetic epidemiology and I feel even more privileged to have earned his fatherly affection. I am grateful for the opportunity to have interviewed Professor Morton on behalf of the Journal. This report was compiled based on phone and e-mail conversations with Professor Morton, which also drew pieces from other materials made available by him. In a couple of places, I took the liberty of adding a few parenthetical clarifications to Professor Morton's answers (italicized).

Question: Please tell us where you were born and grew up, describe the household composition, and any relevant childhood experiences.

Answer: I was born in Camden, NJ, USA, the first child of parents who were descended from pilgrims settled in Massachusetts. When I was three months old we moved to New Haven, Connecticut where my brother was born several years later. I became interested in science through collecting butterflies as a child and thought I wanted to become an entomologist. My father was very interested in and worked in transportation with the railways. During the war he became an instructor in transportation at Yale. When the war was over, he decided he enjoyed teaching so much that he went to Kent State University in Ohio, where he spent the rest of his life teaching.

Question: What schools/colleges did you attend and why those schools?

Answer: I attended the all-male Hopkins High School, followed by the more diverse Swarthmore College in Pennsylvania for 2 years. As an undergraduate, I lost my enthusiasm and realized that I did not want to make a career of entomology. Feeling very depressed about this realization, I visited the biology library at a time when a small library could have everything of consequence and read voraciously to find something on which to focus my career.

I came across books by Theodosius Dobzhansky, Ernst Mayr, and George G. Simpson and spent about 2 weeks there just reading furiously, looking for something to replace entomology. After reading Dobzhansky's book, Genetics and the Origin of Species, it became very clear genetics was exactly the right thing for me to study and lead to a lifelong fascination with genetics.

I married young to a girl from Hawaii, and when combined with my interest in insular speciation, I was drawn to the University of Hawaii in Honolulu where I earned my BA in Zoology in 1951. Insular speciation was a very popular subject there and I saw a wonderful opportunity to study Drosophila (fruit flies). I actually worked my way through graduate school studying Drosophila.

As described in the Allan Award [Morton, 1962], my curiosity about human genetics extended to the University of Hawaii. I took my first genetics course from Gordon Mainland, who reinforced its attraction and advised me to apply for postgraduate study in Wisconsin with James Crow at the University of Wisconsin to continue as my mentor. I began working on my MS degree the very first day in Wisconsin and completed it in one year in 1952. At that time I enjoyed my master's thesis on Drosophila, stimulated by James Crow and Sewall Wright, but later became more interested in human genetics. Jim Crow greatly stimulated my interest in human genetics as well and encouraged me to spend 1952–1953 with James Neel working as a geneticist for the Atomic Bomb Casualty Commission in Japan. James Neel was looking for someone who would be competent to analyze the data, but was not sufficiently senior to take it out of his hands. So I was happy, he was happy and I had a marvelous time there. During that year I became very much interested in human genetics.

Upon returning to Wisconsin I had further stimulus from James F. Crow, Sewall Wright, Herman J. Muller, Joshua Lederberg, and Motoo Kimura. Intrigued by exposure to linkage analysis in Hiroshima, Japan, my PhD thesis was based on Wald's sequential analysis applied to common logarithms of exact probability ratios called lods [Morton, 1955c]. I earned a PhD in Genetics in 1955 from the University of Wisconsin, Madison.

Question: What type of jobs have you held that have been a contributing factor and enhancement to where you are today?

Answer: As described by the William Allan Award, my stimuli included a few colleagues who encouraged working in genetics (Dobzhansky, Mainland, Crow), linkage (Haldane, Smith, Renwick), mutation (Muller and Crow), segregation analysis of major genes (Chung), interracial crosses (Chung and Mi), and population genetics in Brazil. Then, and later, my joint interest in genetics and epidemiology led to many populations and problems.

I spent 1952–1953 as a geneticist in Japan with James Neel and colleagues with the Atomic Bomb Casualty Commission, NRC-NAS. The focus of our research was the effect of exposure of parents to the atomic bombs on the first generation offspring in Hiroshima and Nagasaki, Japan. Among the byproducts of these data were papers on nonrandomness in consanguineous marriage [Morton, 1955a] and inheritance of human birth weight [Morton, 1955b]. Of greater stimulus were two papers on linkage of blood groups with diseases of simple dominant inheritance [Fujii et al., 1955; Morton et al., 1954]. The samples were small and nonsignificant, but they stimulated my interest that led two years later to my PhD in Wisconsin, which was my first major research contribution [Morton, 1955c]. In 1955–1956, I was a National Cancer Institute Postdoctoral Fellow at the University of Wisconsin.

I continued to work in faculty positions at the University of Wisconsin as Assistant Professor (1956–1960), and then Associate Professor (1960–1962). My first linkage success in 1956 was with elliptocytosis, which was shown to map to more than one locus [Morton, 1956]. This was a familiar situation in Drosophila genetics, but a novelty in human genetics. It provided a strong incentive to extend linkage analysis with an ever-expanding discovery of new markers. I introduced a consecutive gene code that 23 years later was internationally adopted for loci with similar functions.

The two decades after 1957 were a time of change as monogenic analysis stabilized and the double helix was leading to preliminary understanding of DNA coding for proteins. In this interregnum, it seemed a good idea to take other directions, of which the first was analysis of the genetics of interracial crosses. During 1958–1959, we collected data on nearly 180,000 live births and late fetal deaths from 1948 to 1958 to answer questions primarily about genetic effects of outcrossing. Hawaii was the best place for such a study, first because of the relative equality and short outbreeding history of many racial groups and, secondly, because colleagues there were helpful in providing research space. (This was the first application of the extended diallele cross to human genetics, using methods that were introduced by experimental geneticists. Despite limitations of observational data, interracial crosses provide a useful adjunct to consanguinity studies. As shown by Morton et al. [1967], first generation hybrids between races in man are intermediate in size, mortality, and morbidity between the parental groups).

On return to Wisconsin with the preliminary analysis of Hawaii data, I became interested in high-mortality populations and chose emigrants from northeastern Brazil passing through the Hospediaria de Imigrantes in Sao Paulo where we studied more than 1,000 large nuclear families comprising almost 7,000 tested people. Our research in 1962 extended beyond my Allan Award. During the year in Sao Paulo, I accepted an offer from the University of Hawaii to initiate a department of genetics. After 2 years, I realized that administration inevitably interfered with science and created a Population Genetics Laboratory (PGL) devoted solely to research. In 1968, I was appointed the Director of the PGL at the University of Hawaii where I stayed until 1985. This gave me great satisfaction for the next twenty years, with a wonderful succession of graduate students, postdocs, junior colleagues, and international visitors. (During its existence the PGL, as it was fondly called, under the insightful leadership of Professor Morton revolutionized the field by providing many of the early methods in genetic epidemiology. Some of Professor Morton's students, colleagues, and collaborators included C. Robert Cloninger, P. Michael Conneally, John Grove, Henry C. Harpending, Yoko Imaizumi, Bronya J. B. Keats, Robert L. Kirk, Henrique Krieger, Jean-Marc Lalouel, Charles J. McLean, D. C. Rao, Stephanie Sherman, Mark H. Skolnick, John A. Sved, Peter Workman, Wick R. Williams, and Norikazu Yasuda).

I then spent 2 years at the Memorial Sloan-Kettering Cancer Center in New York as Head of the Department of Epidemiology and Biostatistics (1985–1987) and as an Adjunct Professor at Rockefeller University. I subsequently accepted a position in Britain as a Professor and the Director of the Cancer Research Campaign (CRC) Research Group in genetic epidemiology at Southampton University (1988–1995). Since 1995, I have been a Senior Professional Fellow in Human Genetics at Southampton.

Question: How/when did you become interested in genetic epidemiology?

Answer: Interracial crosses in Hawaii led to recognition that “traditional human genetics was concerned with rare traits of simple inheritance, while epidemiology dealt with common nongenetic diseases. In time the two disciplines may achieve a synthesis of methods and goals” for which genetic epidemiology was introduced [Morton et al., 1967]. During those years, epidemiology had failed to provide approaches to genetics, while population genetics tended to regard the environmental variables dear to epidemiologists as ambiguous noise. We suggested the term genetic epidemiology because epidemiology has methods often neglected by geneticists to analyze differences between noninterbreeding populations [Morton, 1982]. A variety of definitions were later introduced [Khoury et al., 1993]. (Professor Morton was very supportive of the launching of the International Genetic Epidemiology Society (IGES). He was very happy that it was led by James V. Neel as its founding President).

Question: Who/what were some of the major influences in your educational studies and your career?

Answer: The first William Allan Award generated major influences in my educational studies and subsequent career, continuing during later years at the University of Hawaii and elsewhere. James Crow, James Neel, and Sewall Wright, among others, had considerable influence on my career.

Question: What are some of the challenges faced throughout your career and how did you overcome them?

Answer: Great challenges included the small number of opportunities for employment in the early years from 1952 to 1962. Advantages were good colleagues, libraries, contact with the small number of human geneticists internationally, and the computers available in the United States (including Hawaii) but not in other countries. I was fortunate that my PhD provided that experience.

Question: How has genetic epidemiology changed since you entered/launched the field? What do you feel were/are the major changes in the field of genetic epidemiology that you've seen over the years (negative/positive)? And, in your opinion, what does it take to do this type of work well?

Answer: Genetic epidemiology rose slowly from its origin in 1967, with a clearer definition in 1978, and the journal, Genetic Epidemiology, launched in 1984 by D. C. Rao. (The Genetic Analysis Workshops (GAW) lead by Jean MacCluer and colleagues provide a platform for comparative discussions of methods and data analysis. Launching the International Genetic Epidemiology Society (IGES) in 1990 with James Neel as the founding President was another major advance). It flowered for about 15 years, until the success of genetic research with genes of high penetrance was succeeded by early work on complex traits as reviewed at a workshop held in 1999 in St. Louis in honor of my 70th birthday (see Rao and Province [2001] for published proceedings) (Photos 7-9). After much more identification of genetic factors that to variable degrees has been somewhat successful, genetic epidemiology will recover some of its older influence by detecting environmental effects.

Photo 1.

Newton Ennis Morton on pony, near New Haven, Connecticut (1934).

Photo 2.

Newton with three sons, Hawaii (1963).

Photo 3.

Newton, MD (Honorary), University of Umea, Sweden (1976).

Photo 4.

Sewall Wright and Newton Morton at the Population Genetics Lab (PGL), University of Hawaii (1979).

Photo 5.

PGL group photo with Sewall Wright (1979).

Photo 6.

Newton and Pat at home in Hawaii (1983).

Photo 7.

Newton's 70th birthday at D. C. Rao's home—“4 generations”—Stephanie Sherman, P. Michael Conneally, Newton E. Morton, James F. Crow (1999).

Photo 8.

Newton's 70th birthday at D. C. Rao's home—“4 generations”—James F. Crow, Newton E. Morton, D. C. Rao, Michael A. Province (1999).

Photo 9.

Seventieth birthday group photo with (front row sitting): Robert C. Elston, Arno G. Motulski, James F. Crow, Pat Jacobs, Newton E. Morton, William Jack Schull, C. C., and Clara Li (1999).

Question: Where do you see the future of genetic epidemiology heading?

Answer: Until more genetic factors are identified and their environmental influences characterized, the effect of genetic epidemiology will be small, genetic or not. An exception is racial IQ, which has been shown to be of no significant effect when environmental factors are carefully measured, contrary to prejudices by at least two distinguished scientists who neglected to consider the evidence. Apart from such examples, the hope is that genetic epidemiology will in time detect medically important environmental effects that can be identified and controlled for cases and relatives. Prenatal or youthful recognition are obstacles that should be overcome. With revolutionizing advances in genomics, sequencing, epigenetics and the like, the future of genetic epidemiology may be secure.

Question: Which of your publications/events would you consider your most important to date?

Answer: I favor my early publications [Morton, 1955c, 1956] that received the William Allan Award (which preceded my introduction of genetic epidemiology), next the later Outline of Genetic Epidemiology [Morton, 1982] and my membership in the USA National Academy of Sciences (1990). The 500 articles and eight books are assigned to major research groups as summarized at the “American Society of Human Genetics (2009): Session 13—The Evolution of Human Population Genetics and Genetic Epidemiology, 1955–2009. A symposium in Honor of Newton Morton's Birthday” (organized by Bronya Keats and Neil Risch), with contributions from D. C. Rao, N. J. Risch, A. Chakravarti, and H. Tang (Photo 10). As the summary notes, history before 2002 created linkage analysis and related subjects, including genetic epidemiology, but major developments in molecular genetics and computer science have transformed population genetics and genetic epidemiology.

Photo 10.

Hawaii group photo (2009; courtesy Dr. Yan Sun).

Question: What are your plans for the future?

Answer: My plans for the future are limited by reasons of my age and health. I retired from the Human Genetics Division, School of Medicine, University of Southampton in April, 2011 at the age of 81. Recently I have had three incidents that resulted in my being fitted with a pacemaker. This has been very successful and I have returned to elderly tennis and long walks as usual. Unfortunately for over 3 years I have had Alzheimer's disease. My wife is still active in the United Kingdom, and my five children and seven grandchildren live in western United States, Alaska, and Hawaii. My memory is decreasing and I may not live to see exciting future development in genetics. Our department has abandoned genetic epidemiology to exploit genome-wide scans, and others are following. I wait in retirement for the next development.

Question: If there was one thing that you would want people to know and/or remember about your contributions in the field of genetics and genetic epidemiology, what would it be?

Answer: My science contributions are briefly summarized in the short paragraph prepared for the ASHG Symposium in my honor [Morton, 2009], which includes linkage analysis, population genetics, and genetic epidemiology (reproduced next). My favored publication depends on the time and subject.

“In 1955, genetic disease studies were based on statistical analysis of inheritance patterns in families, and linkage analysis using a small number of blood groups and serum protein markers. Human population genetics similarly focused on limited genetic material. As a graduate student and young faculty member, Newton Morton contributed novel approaches to analyzing data from family aggregation studies, linkage analysis and population genetics. He was instrumental in defining the emerging field of genetic epidemiology. In the 54 years since, major developments in molecular genetics and computer science have transformed population genetics and genetic epidemiology. Sequencing of the human genome and identification of millions of polymorphic variants have provided unprecedented opportunities to advance understanding of human evolution and the genetic and environmental basis of disease. This symposium will demonstrate how these novel technologies are now impacting our understanding of human evolution and disease, from a perspective first defined by Newton Morton.”

Acknowledgments

This project was only possible with extensive help from Professor Patricia Jacobs (Newton's wife) and absolutely critical assistance from one of my colleagues, Ms. Sherri Turner. I greatly appreciate the opportunity provided to me by the Editor-in-Chief, Dr. Sanjay Shete.

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