Dear SMBE Members,

On the morning of July 4, 2021, population geneticist Richard “Dick” Lewontin passed away at the age of 92, just three days after his high-school sweetheart and wife of 73 years, Mary Jane. Both had been in poor health. Lewontin was an emeritus Professor in the Department of Organismic & Evolutionary Biology and Curator in the Museum of Comparative Zoology at Harvard University.

Lewontin has left an indelible imprint on the field of evolutionary biology through his research, writing, and mentorship.

After finishing his undergraduate degree at Harvard, Lewontin trained under the supervision of the famous Drosophila geneticist Theodosius Dobzhansky at Columbia. Dobzhansky was often away collecting flies, which provided Lewontin freedom and independence. But, when Dobzhansky was back in the lab, they purportedly argued intensely about population genetics, an activity both parties enjoyed immensely.

Fresh after earning his PhD from Columbia, he moved to North Carolina State University, where he remained for just 4 years (1954-1958) before moving, first to the University of Rochester, and then to the University of Chicago. In his early work, Lewontin was known for bringing a mathematical modeling approach to the field of genetics. While most population genetics was focused on a single gene, his early work with Ken-Ichi Kojima essentially founded two-locus theory and introduced the term “linkage disequilibrium” to describe the statistical association between the variation at each of a pair of genes. This work laid the foundation for now commonly used, association-mapping approaches.

However, the primary reason Lewontin moved to Chicago was because he recognized the exciting work of biochemist Jack Hubby, a new faculty member, who was pioneering the method of gel electrophoresis. As Lewontin put it: Hubby had a method but no question, and he had a question but no method. Together, they published two ground-breaking papers in Genetics: Hubby & Lewontin (1966) and Lewontin & Hubby (1966). The first focused on the method by which one could assay genetic variation via gel electrophoresis, and the second applied this method to assess genetic variation in a population of Drosophila pseudoobscura. Lewontin complained – even decades later – how the latter paper was more highly cited, and Hubby wasn’t adequately recognized for his contributions. Nonetheless, together, these papers laid the foundation for the field of molecular evolution, by (1) demonstrating the surprisingly high amount of genetic variation (heterozygosity) in natural populations and (2) setting the stage for the still ongoing debate about how much of this variation was due to natural selection and how much was due to chance. See Charlesworth et al. (2016) for more detail. As a direct consequence of these studies, Motoo Kimura and his colleagues developed the neutral theory, which tries to explain in quantitative terms the observed pattern of genetic variation expected in the absence of any form of natural selection. Thus, effectively, these papers set the agenda, for both empirical and theoretical population genetics, for the ensuing decades and to the current era of population genomics.

In 1973, Lewontin was lured to Harvard University and the Museum of Comparative Zoology (MCZ) to serve as a “Curator of Population Genetics”, a new position designed for him. He was offered the entire third floor of the MCZ, which he had renovated to his specifications. Most notably, in the center was an expansive meeting room (including a large table brought all the way from the University of Chicago), designed to bring together students, postdocs and a long line of visiting natural and social scientists as well as philosophers, providing them an open space to freely discuss science and exchange ideas. Visitors were greeted by an enormous, mounted moose head that his early lab members were rumored to have “borrowed” from the MCZ Mammal Department.

This year also marked the publication of the landmark paper by Lewontin and Krakauer that suggested the use of the variation in the Fst statistic across loci to detect selection - an approach that presages much of the current population-genomic tests of selection. A year later, the publication of his book The Genetic Basis of Evolutionary Change solidified Lewontin’s position as a leader in the field. While the parts of the book that focused on molecular methods quickly became outdated, the book is one of the clearest expositions of the battle between selectionists and neutralists. The first chapter of the book outlined a path forward for the field, emphasizing the role of population genetics in helping to link genotype to phenotype to fitness, inspiring a generation of scientists (including both of us).

The scientific environment that Lewontin was able to create in the MCZ attracted many talented trainees and visitors. One of these was Marty Kreitman, a postdoctoral researcher, who extended the protein electrophoresis survey to DNA sequencing. In 1983, he published in Nature the first survey of DNA sequence variation in the recently cloned gene Adh in D. melanogaster, the paper that in many ways started the field of molecular population genetics at the DNA sequence level. Lewontin refused to put his name on the paper, claiming he only contributed ideas. This was Lewontin’s modus operandi – his students frequently published papers without his name.

In addition to his work in Drosophila, Lewontin also made profound contributions to the field of human genetics throughout his career. On a work trip, Lewontin – armed with a pad of paper, hand calculator, table of logarithms and several books on human genetics – recorded, compared and summarized data on human variability. From these data, Lewontin’s early calculations suggested that upwards of 90% of genetic variation in all humans is also segregating within geographically distinct human populations. This observation allowed Lewontin to effectively argue that the notion of race had little evidence in human genetic differentiation. He also made important critiques of the frequently made inference that genetic differences were the cause of variation between populations or social groups in phenotypes, such as IQ. These criticisms resonate today in the era of genome-wide association studies and political racism  

Lewontin’s impact extended substantially beyond population genetics into many areas of science. One of his most famous papers, written together with Harvard colleague Stephen Jay Gould, “The spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme”, provided a blistering critique of uncritical adaptationist thinking in biology and established the need for rigorous and quantitative approaches for understanding biology that include a large variety of possible causal explanations. The quantitative and statistical thinking in biology that is so important and so ubiquitous today owes a great deal to this work.

Part of Lewontin’s criticism of “just so story-telling” in biology was focused specifically on the application of evolutionary biology in social sciences. Most famously, Lewontin made a withering denunciation of evolutionary psychology, in general, and the book Sociobiology by EO Wilson, another Harvard colleague (and the person who recruited Lewontin to Harvard), specifically. Lewontin argued strongly, most prominently in his book with Richard Levins The Dialectical Biologist, that scientific inquiry is always placed in a social and political context, and it is important not to turn the gaze away from this reality. 

While Lewontin is best known as a biologist, he left a strong imprint on the field of Philosophy of Science and as a public intellectual particularly through his popular books and many deeply insightful and brilliantly argued articles in The New York Review of Books.

In 2015 Lewontin was awarded the Crafoord prize and in 2017 the Genetics Society of America’s highest honor, the Thomas Hunt Morgan Medal. As a testament to this legacy, his nomination for the Morgan Medal was co-signed by 160 faculty members from around the world.

Lewontin’s scientific and intellectual legacy is more than the work he did, it was the environment he created, the students he trained and a lasting intellectual contribution to society. His contribution is also ethical in his insistence for the need for people to have intellectual freedom and to fully enjoy the fruits of their own labor.

He was deeply loved and revered by those close to him.

He will be deeply missed and not soon forgotten.

Authors:  Dmitri Petrov (Lewontin PhD student) and Hopi Hoekstra (Lewontin faculty colleague)

References:

Charlesworth B, Charlesworth D, Coyne, JA and CH Langley.  2016. Hubby and Lewontin on protein variation in natural populations: When molecular genetics came to the rescue of population genetics. Genetics 203(4): 1497–1503.

Gould SJ and RC Lewotin. 1979. The spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme. Proc Roy Soc B.  205(1161): 581-598

Hubby JL and RC Lewontin. 1966. A molecular approach to the study of genic heterozygosity in natural populations. I. The number of alleles at different loci in Drosophila pseudoobscura. Genetics 54(2):577–594.

Kimura, M. 1968. Evolutionary rate at the molecular level. Nature 217: 624-626.

Kreitman, M. 1983. Nucleotide polymorphism at the alcohol dehydrogenase locus of Drosophila melanogaster. Nature 304:412–417.

Levins R and RC Lewontin. 1987. The Dialectical Biologist. Harvard University Press. p. 336.

Lewontin RC. 1974. The Genetic Basis of Evolutionary Change. Columbia University Press. p. 346.

Lewontin RC. 1972. The apportionment of human diversity. In Evolutionary Biology Vol. 6 (Ed. TB Dobzhansky, MK Hecht, WC Steere). Springer, New York. p. 381-398.

Lewontin RC. 1974. Annotation: the analysis of variance and the analysis of causes. Amer J Human Genet. 26(3):400–411.

Lewontin RC and JL Hubby. 1966. A molecular approach to the study of genic heterozygosity in natural populations. II. Amount of variation and degree of heterozygosity in natural populations of Drosophila pseudoobscura. Genetics 54(2):595–609.

Lewontin RC and K Kojima. 1960. The evolutionary dynamics of complex polymorphisms. Evolution 14(4):458-472.

Lewontin RC and J Krakauer. 1973. Distribution of gene frequency as a test of the theory of selective neutrality of polymorphisms. Genetics 74(1):175-195.

Sent on behalf of SMBE President, Dr. Harmit Malik