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The anti-DNA story

The presence of DNA-binding antibodies in the serum of patients with lupus was reported by three independent groups in 1957, from Milan, New York and Paris. Science does not operate in a vacuum, and there was a slender thread that linked the three discoveries: the youngest and least experienced of all the researchers involved. Still a medical student, I unwittingly played this role, and since I have a vivid memory of my first assignment, I have agreed to write down how all of this happened. In Milan, third-year medical students could apply to become ‘interns’ in a University Department. In 1953 I filed my application to the Medical Clinic. The applicants exceeded the openings: when I was accepted I felt like I had won the lottery, and reported to the Laboratory of Hematology. Head of the Lab was Elio Polli, one of the senior Assistant Professors. A pleasant but strong personality, years later he would be called upon to succeed the legendary Luigi Villa as Director of the Clinic, and number one internist in town. However, his powerful influence on the first steps of my career came from a visionary conviction of his: the solution of the leukemia riddle was in the DNA, and the hopeless patients that crowded his infirmary could only be saved if he could determine what the difference was between normal and leukemic DNA; that is, what went wrong in the latter. Each intern student had four beds to tend to in the morning, but immediately after the ‘visit’ (a procession-and-discussion of cases by the Professor and his Assistants) I ran to work in the lab. My assignment was to purify DNA, from any source we could lay our hands on: calf thymus from the slaughterhouse, leukocytes from the blood bank and, of course, and foremost, cells of different types of leukemia from patients bedded in the clinic. I worked singlehandedly and my equipment was state of the art, directly imported from the USA following the specifications of Erwin Chargaff (to whom Polli had paid regular visits in Chicago): four Beckman centrifuges, looking like flying saucers on tripods (that had to be run in the cold room); a Waring Blender (which had been the most difficult piece to obtain because nobody in Italy knew what it was, nor that it could be replaced by a local piece of kitchenware); and a custom-made precipitation chamber with a rotating arm to collect threads of pure white DNA materializing in 10 C absolute ethanol. As soon as a preparation was done, I delivered it to a team of young doctors in the next room; they seemed very competent and a bit status conscious (several of them – DiMayorca, Semenza, Basilico – would become internationally known basic scientists), but their analysis was crude: they measured the viscosity of DNA solutions at different pH. The probability of discovering meaningful differences by this method was low, and reflected what was then known (this was the epoch of the tetranucleotide model of DNA, years before the double helix became the consensus paradigm): hopelessly little. Polli realized it: he struggled and searched for new, more discriminating ways to fulfill his mission. In the Spring of 1955, the opportunity for a 2-month studentship from the French government landed in the University of Milan. The Rector sent it to Prof Villa, and Prof Villa asked his Assistants to find the student who had worked hardest: it was me. I was asked which Institution I wanted Correspondence to: Franco Celada, MD, PhD, Division of Rheumatology, Room 1611, NYU Hospital for Joint Diseases, 301 East 17th Street, New York, NY 10003, USA Email: franco.celada@nyumc.org Received 10 November 2010; accepted 11 November 2010