Carlo M. Croce: Seeking Truth and Beauty

Believe it or not, as a boy Carlo Croce liked to hang out in art museums, to his mother’s chagrin. There are a lot of art museums in Italy, so his mother started dropping him off and going off to the coffee bar to find more interesting company. He bought his first painting, an old master, at age 12 and that used all his savings. He didn't resume his old master collection until he was in his 30s and had saved some money from his job at the Wistar Institute in Philadelphia. He now has an exciting and growing collection.In the meantime, he received his MD degree from the University of Rome “La Sapienza” while reading textbooks and journals in English to supplement the old style medical education. He planned to join Karl Habel at Scripps Clinic in 1970 for a research fellowship just as Dr. Habel was struck in his prime by a monkey B virus infection, so Carlo was diverted from California to Philadelphia to join Hilary Koprowski's internationally known Wistar Institute of Anatomy and Biology. I was a Ph.D. student at Wistar at the time and witnessed the arrival of the quiet 25 yr. old Italian who was too shy to try out his textbook English.He began his work in somatic cell genetics and virology in a large laboratory where a number of us worked on related projects, including Barbara Knowles (now Associate Director for Research at Jackson Laboratory) and Davor Solter (now Director of Developmental Biology, Max Planck Institute, Freiburg, Germany).One of his first accomplishments was to map the very first viral integration site on chromosome 7q in an SV40 transformed fibroblast cell line, using human-mouse somatic cell hybrids that retained human chromosome 7, the SV40 T-antigen and the SV40 genome. Very recently, one of his hybrid clones was used by others to clone the SV40 genome integration site and to show that the SV40 genome had integrated into a common fragile site.Still using somatic cell hybrids, Carlo Croce and his laboratory began in the late 70s and early 80s to map genes important in cancer, such as the immunoglobulin genes that are rearranged in lymphomas, along with the MYC and BCL2 genes among others. These experiments took advantage of the leukemia/lymphoma specific translocation to walk from immunoglobulin loci, and later TCR loci, into the oncogene loci juxtaposed by translocation, the beginning of positional cloning of translocation breakpoints. These studies involved collaborations with valued colleagues, including Peter Nowell, the co-discoverer with David Hungerford, of the Philadelphia chromosome, the first reported cancer specific chromosome alteration. In the exciting decode of the 1980s, the Croce laboratory published 23 reports in Science, including the discovery of the BCL2 gene with Yoshiide Tsujimoto (now University of Osaka). They also observed that mistakes by immunoglobulin family rearrangement/recombination machinery was responsible for the type of chromosome translocations that involved the IG and TCR genes.Carlo Croce has been not only an outstanding laboratory scientist with numerous important discoveries to his credit; he has also been the Director of an NCI designated Cancer Center, first at the Fels Institute for Cancer Research, where he built a first class basic cancer research faculty from the ground up. In 1991, he moved his cancer research faculty to Jefferson Medical College, where it took the name of its benefactor, Sidney Kimmel, and became the Kimmel Cancer Center. At KCI the Croce laboratory continued to find and study genes involved in cancer development: oncogenes activated by translocation such as ALL1, involved in biphenotypic leukemias, discovered with another important collaborator, Eli Canaani and TCL1 (with Gianni Russo’s lab) activated by translocation to the TCRa locus in lymphomas of ataxia telangiectasia patients; or tumor suppressor genes, lost usually through deletions in epithelial cancers, such as FEZ1/LZTS1 at 8p22 lost in prostate, breast and other cancers and the FHIT gene at the 3p14.2 common fragile site (discovered in a collaboration with my laboratory), confirming a long held hypothesis that genes at chromosome fragile sites could contribute to cancer development through frequent chromosomal rearrangements. At the same time, Carlo Croce was living the nearly always tumultuous life of a Director of a Cancer Center, involving recruitment of faculty, constant bargaining with Deans, department chairman, University administrators, but he still manages to fit in a few skiing meetings, gossip sessions with colleagues like Web Cavenee, visits for good coffee, good food and TV appearances in his beloved Italy and most of all, he still manages to study, examine, buy, transport, restore, reframe and admire his old master paintings. I think he loves it as much as science because discovering a beautiful but misattributed painting at an obscure or even well known auction house, buying it and then proving that it is actually a painting by a Gentileschi or a Cavallino is as thrilling and elegant as discovering the connection between a specific gene alteration and its cancer.     

Thinking about Possible People: A Comment on Tooley and Rachels

Most people believe it would be wrong to bring a child into the world if in all likelihood its life would be miserable. But if pain and suffering count against bringing someone into existence, why do pleasure and happiness not count in favour of bringing them into existence? Recently in this journal Michael Tooley has re‐affirmed his rights‐based explanation for this asymmetry. In a nutshell: to create an individual whose life is not worth living would be to wrong that individual – to create an obligation that cannot be fulfilled – but it is not possible to wrong an individual who is not brought into existence. In the same issue of this journal, in an article covering a range of arguments for and against the claim that it would be good for additional people to exist, Stuart Rachels objects to Tooley’s account on the ground that it has counterintuitive implications. His most interesting argument involves a Parfit‐style counterexample: a woman is about to take a fertility pill that will result in twins, one of whom will be healthy and the other of whom will not. Does it make a difference, morally speaking, if the woman knows which of the twins will be healthy and which will not? In this paper I argue that both Rachels’ criticism of Tooley’s rights‐based account, and Tooley’s own defence of it, are unsuccessful due to their failure to come to grips with the semantics of names for possible individuals. Both of them implicitly assume that it is possible to have a potential person in mind, in a way that misleads them about the fairness of actions that involve possible people. The significance of this extends to other areas such as abortion, population policy, and embryo experimentation, where examples involving possible people are common.     

A Comment on La Vaque and Rossiter

The paper by La Vaque and Rossiter recommends that placebo-controlled trials only be conducted when best proven treatments are not available. In this comment, I review evidence suggesting that identifying best proven treatments is a complex task involving many variables and that making such a decision entails many real-world difficulties.