NEW KEYS TO LIFE PROCESSES MELVIN CALVIN* It seems entirely appropriate as part of this occasion to have a tribute from biology to physics in general and to the reactor in particular and to Fermi as its creator. Physics has frequently and repeatedly provided biochemistry and biology with new tools for the advancement ofthe sciences. However, in the provision ofan almost unlimited supply ofradioisotopes ofvery nearly all of the elements in the periodic table, physics has provided a tool of immense power and diverse application in biology that has rarely been equaled in the history ofthe two sciences. It is my hope that I will be able to review for you some ofthe highlights ofthe contributions which the availability of these new keys has made possible in the evolution of our knowledge of the construction and behavior of living organisms, from the molecular level to that of man. This is a task which would have been done much better by George Von Hevesy, the man who first conceived of the utility of radioisotopes in learning how living organisms are made and work. And I regret very much that he is not here to do it for you; however, time moves on, and I will do my best. Shortly after the discovery by the physicists of their ability to induce radioactivity in elements which normally were not so, it was clearly evident that thisability, ifitcould be brought to bear on theprimary elements of living organisms, such as hydrogen, carbon, oxygen, nitrogen, phosphorus , and some of the others, would have an enormous value to the investigation ofthe structure, construction, and behavior ofliving organisms . And the search was on. Even with the development ofthe accelera- * Professor ofchemistry and molecular biology, University of California, Berkeley. This paper was presented at the Twenty-fifth Anniversary Observance ofthe First Nuclear Chain Reaction, at the University ofChicago, December I, 1967. Publication in Perspectives is supported by the Dow Chemical Company. 555 tors, particularly the early cyclotrons ofErnest Lawrence in Berkeley, the idea that they might be used for such a purpose grew concomitantly. As soon as cyclotron time became available, it began to be used under Lawrence's prodding for the development of biological problems, both directly as an irradiation instrument and indirectly as a device for producing possibly useful radioisotopes. Since the principal material ofwhich living organisms are constructed is carbon, it was quite obvious that a radioisotope ofcarbon would have immense value in disentangling the current activities ofa living organism from the structure of the machinery which was performing the work. For this reason and other such reasons, the search for radiocarbon isotopes was under way almost as soon as the accelerator was functioning. And it didn't take long for Drs. Ruben and Kamen to produce the first ofthese, namely, the carbon of mass 11 which was radioactive with a half-life of about 20.5 minutes. As you are undoubtedly aware, it is produced by a deuteron bombardment of boron-?? with the emission of a neutron to produce Cu. Most ofthe early work using radiocarbon was with this isotope . However, its short life limited its usefulness, and Ruben had clear reason to search on the other side ofthe stable range for another radioisotope having mass greater than 13. He and Kamen first produced such an isotope by bombarding C13 with deuterons from the 60-inch cyclotron— by a (d,p) reaction giving rise to C14. But they knew that a large number ofneutrons were escaping the cyclotron whenever a deuteron bombardment was underway, and they recognized thepossibility ofcreating C14 by an (n,p) reaction on N14. They therefore surrounded the cyclotron with cans ofammonium nitrate solutions which after a period ofmonths were worked up for C14 and its production confirmed. But since its lifetime was so long (half-life about 5,000 years) and the number ofneutrons available by this method so small, only minuteamounts ofC14were available by this route. About this time, the work toward this end had to stop because ofthe beginning ofthe war, which in addition to everything else took the life of Sam Ruben. Some three years later, the event we were celebrating here today took place, and then...