Where the Cloning Discussion Began

Today understanding of DNA and RNA is fundamental to all biology. In the mid-1950s, however, the annual Gordon Conference was the only venue where those interested in DNA and RNA could meet, while still having to share the forum with protein chemists. Watson and Crick’s double-helix model was still news, and for some it was still controversial. A few biochemists and renegade chemists and biologists were struggling to understand these large molecules. Money for science was scarce, as Sputnik had not yet been launched. Some biochemists and geneticists foresaw their fields merging into molecular biology, but the relationship was rocky, and the wedding date was indeterminate. Through most of the 1950s the annual Gordon Conference called Proteins and Nucleic Acids was at the center of this dynamic. The conference was held at the New Hampton School, where the countryside was beautiful, but the facilities (with their narrow, lumpy beds) seemed primitive, contrasting starkly with the meeting’s revolutionary science and influx of new insights and colleagues each summer.

Geneticists appeared occasionally at the conferences: Alfred Hershey was on the program in 1954, the year after he and Martha Chase nailed down Oswald Avery’s earlier proposal that genes are made of DNA. In 1956 there were initial reports on protein synthesis and the first descriptions of the enzymatic synthesis of polyribo- and polydeoxyribonucleotides by Severo Ochoa and Arthur Kornberg, respectively. Starting in 1957, proteins and nucleic acids were emphasized in alternate years; this was formalized in 1959 when GRC leadership deemed the scope of research in both areas “so wide” that each would have its own conference. Though still titled Proteins and Nucleic Acids, the first meeting devoted entirely to nucleic acids took place in 1960. Finally, in 1962, a conference called simply Nucleic Acids was held, chaired by Leon Heppel and Cyrus Levinthal.

Throughout the 1960s precise new enzymatic tools for analysis of DNA and RNA and fresh fundamental understandings were described at the Gordon Conferences, including the biosynthesis of DNA and RNA, the semiconservative replication of DNA (the idea that replicated DNA molecules are composed of one original strand and one newly synthesized strand), the genetic code, the sequence of tRNAs (transfer RNAs), and the chemical nature of mutation. The general excitement forged lasting collegial relationships and friendships among those in a passionate and growing, but not yet enormous, community. Dieter Söll and I appreciated the great honor of being elected cochairs for the 1973 conference.

Daniel Nathan’s report at the 1971 conference had unlocked vast opportunities for manipulating DNA in ways previously unimaginable. He showed us how, using the newly understood restriction endonuclease enzymes, the genome of SV-40 (and by implication all other genomes) could be reproducibly divided into smaller segments by cleaving its sugar-phosphate backbone. By the 1973 conference the entire Thursday-morning session was reserved for the discussion of results obtained with restriction enzymes. It was then that Herb Boyer electrified us by describing how foreign DNA segments could be cloned in Escherichia coli using a plasmid vector and pointed out the general applicability of this new method.

The story of what followed has been told often. Many in attendance that week began to imagine the enormous scientific potential of this new technique. Some raised questions about potential associated risks. John Sedat and Edward Ziff, two of the younger scientists at the conference, urged Söll and me to take time from the final scientific session on Friday morning to consider the implications of DNA cloning, or what came to be called “recombinant DNA” experiments. Because of time restraints the Friday discussion focused only on how to ensure that serious attention would be paid to the potential possible risks. Two actions were approved by the majority of those remaining (and eventually by a mail ballot, in order to include participants who had already left the conference on Friday). The first decision instructed Söll and me to send a letter to the presidents of the National Academy of Sciences and the Institute of Medicine describing the new method, summarizing the concerns that had been raised at the conference, and asking the academy to establish a study committee to recommend appropriate actions. The second decision was to publicize the letter more widely by submitting it for publication to the journals Science and Proceedings of the National Academy of Sciences.

Neither Söll nor I had foreseen that the opportunity to chair the conference would lead to new responsibilities for initiating the public discussion of this new science. The ensuing public and scientific debates, which have been documented in many books and articles, made the 1973 Nucleic Acids Gordon Conference famous. This event in history, however, marked what was to be only the beginning of the conference’s enduring legacy as a major venue for the remarkable advances of biomedical re-search over the last thirty years.