Thomas H. Jukes (1906–1999)
James F. Crow

TOM Jukes accepted our invitation to write a Perspectives on the early history of molecular evolution, and in August 1999 he sent a rough beginning containing some now-forgotten early history. He planned an extensive revision and continuation, but on November 1 his death intervened. We have decided to publish his early draft, realizing that it was but a start toward the article that he had planned.

Tom, along with Jack L. King and Motoo Kimura, formulated the neutral theory of molecular evolution. Earlier, the idea had been foreshadowed by Sueoka (1962) and Freese (1962). They had each suggested mutation pressure of near-neutral changes to account for the much greater diversity of DNA than of amino acid content among bacterial species. Remarkably, they had these insights before the redundancy of the code was recognized.

The neutral theory of molecular evolution in eukaryotes started with Kimura (1968). He argued that the rate of protein evolution was too fast to be compatible with Haldane's (1957) cost of natural selection, and therefore most of the changes must be neutral, driven by mutation and random drift. King and Jukes (1969) had independently arrived at the same conclusion and discovered Kimura's paper while writing theirs. They submitted a manuscript to Science, only to have it turned down. One reviewer said it was obviously true and therefore trivial; the other said that it was obviously wrong. King and Jukes appealed, and the second time it was accepted. This time I was a reviewer; if my recommendation was decisive, I am pleased. The King and Jukes approach was quite different from Kimura's and included a number of arguments. It was more convincing, partly because of their marshaling a larger variety of evidence and partly because of growing doubt of the applicability of Haldane's principle.

The King-Jukes paper had the intentionally provocative title, “Non-Darwinian evolution.” The theory produced an immediate outcry from traditional students of evolution, undoubtedly abetted by the title. In the ensuing polemics, Kimura played the major role. King died prematurely in 1983 and Jukes wrote mainly about other things, although he did participate in one joint paper (Jukes and Kimura 1984). One of his interests was the evolution of the genetic code (Jukes 1983). I particularly liked his showing how, in an orderly sequential way, mutation pressure in the codon and anti-codon could produce the unexpected codes in bacteria and mitochondria (Jukes 1985). He also developed a widely used correction for multiple undetected changes in evolutionary base substitutions (Jukes and Cantor 1969).

Kimura became a crusading advocate for the neutral theory and spent the rest of his life on the subject. In one paper after another, he offered further, increasingly convincing evidence. He also developed a solid mathematical theory, much of it carried over from his own earlier work, which turned out to be remarkably well preadapted for use in molecular evolution. His book The Neutral Theory of Molecular Evolution (Kimura 1983) became a landmark. The jury is still out as to the full extent of random changes in determining the course of molecular evolution, but the neutral theory has formed a basis for phylogenetic reconstruction and the molecular clock; it has also become the null hypothesis for numerous selection experiments. Kimura died in 1994 (Crow 1995).

Happily, there was never a public rivalry among the three discoverers. King and Kimura were frequent friendly correspondents. Jukes (1991) acknowledged Kimura's great contributions and sent him a reprint with “best wishes and thanks.” Kimura rightly receives the lion's share of the credit, but we should not forget the independent discovery by King and Jukes and the two forerunners, Sueoka and Freese.

Jukes was primarily a nutritionist, with a number of solid accomplishments, especially in vitamins. Some of these have been mentioned by Maddox (1999). Jukes was also an outspoken polemicist and did not hesitate to speak clearly and forcefully against what he thought was bad science or faulty logic. An example is his strong critique of Pauling's advocacy of massive doses of vitamin C. He could be cantankerous, but he was usually right and always honest. Among other things, Tom waged a spirited battle against creationism. His wide-ranging scientific and social interests are reflected in his frequent columns, along with book reviews and letters, in Nature. I counted 72 such contributions in the years 1975–1980.

Each of Tom's friends has a favorite remembrance. Here is mine. Tom greatly admired Aldous Huxley, “the most imaginative of the Huxleys” (Jukes 1996). We both enjoyed Huxley's masterpiece, Point Counter Point, a brilliant, erudite, witty satire on the excesses of British society in the 1920s. The book abounds in sophistication and esoterica; one needs The Brittanica within reach (which Huxley is rumored to have read). Tom introduced me to Huxley's short stories, particularly Young Archimedes, the tragedy of a mathematical prodigy whose lesser musical talent was mercilessly exploited. And he admired Brave New World. He called attention to Huxley's prescience when he described conditioning test-tube embryos for different roles in life; those that were to be rocket engineers were kept in constant rotation so they would have a better sense of balance in space (this was published in 1932!).

Tom loved music. In his last years he went to the lab in the morning and spent the afternoons at home listening to records. He admired Huxley's structuring of Point Counter Point after the Bach B minor suite for flute and strings. He also loved the Beethoven String Quartets and marveled at Huxley's use of the heiliger Dankgesang (holy song of thanksgiving) from the A minor quartet at the climax of the book. When Huxley or the heiliger Dankgesang comes to mind, I shall always think of Tom Jukes.

Following is the rough draft as Jukes submitted it, except for a few bibliographic corrections. It complements an earlier paper (Jukes 1991), and Tom was trying not to duplicate. He planned extensive additions, and obviously he intended to say more about the nearly neutral hypothesis of Ohta. His draft is presented here, not as what Tom would have liked for it to be, but as a final tribute to an admired colleague.