William French Anderson
William French Anderson (born December 31, 1936) is an American physician, geneticist and molecular biologist. He is known as the Father of Gene Therapy. He graduated from Harvard College in 1958, Trinity College, Cambridge University (England) in 1960, and from Harvard Medical School in 1963. In 1990 he was the first person to succeed in carrying out gene therapy by treating a 4-year-old girl suffering from severe combined immunodeficiency (a disorder called "bubble boy disease"). In 2006, he was convicted of sexual abuse of a minor and in 2007 was sentenced to 14 years in  prison. He was paroled on May 17, 2018, for good behavior. Early life and education. Anderson was born in Tulsa, Oklahoma. His father was a civil engineer, his mother was a journalist and writer, and he had two older sisters. His was a very happy childhood. He was recognized in high school for his scholarship, interest in science, and prowess on the track team. He won an Honorable Mention in the Westinghouse Science Talent Search for a project demonstrating how Roman numerals could be used in arithmetical procedures. He was a 1954 graduate of Tulsa Central High School. Anderson went  to Harvard College, where he published several papers as an undergraduate: his high school work on Roman numerals in classical philology in 1956, arithmetical operations using Minoan linear B numerals in the "American Journal of Archaeology" in 1958, a physical chemistry research paper in the "Journal of the American Chemical Society" in 1958, and a research study on the effects of irradiation on DNA in the "Journal of Cellular and Comparative Physiology" in 1961. In its March 19, 1956 issue, "Time" magazine called Anderson a "Harvard Prodigy" for his research work on ancient numerical systems. He graduated from Harvard in  1958, and spent two years at Trinity College, Cambridge University (England), where he obtained an M.A., worked in the laboratory of Francis Crick, won a Full Blue on the track team, and met, and in 1961 married Kathy, who was a fellow medical student at Cambridge. He returned to Harvard, to the medical school, and was joined there by Kathy a year later. Anderson graduated in 1963 and spent a year internship in pediatric medicine at Children's Hospital in Boston. His wife graduated in 1964 and went on to have a very distinguished career in pediatric surgery. Anderson, after  his intern year, spent a year conducting bacterial genetics research at Harvard Medical School and published his work in the "Proceedings of the National Academy of Sciences USA" in 1965. Career. Anderson then spent two years, 1965–1967, in the laboratory of Marshall Nirenberg at the National Institutes of Health, where he helped finish the decipherment of the genetic code. Nirenberg rewarded his efforts by allowing him to make the first public presentation of the final genetic code before an audience of approximately 2,000 scientists at the April 1966, meeting of FASEB in Atlantic City. After his successful post-doctoral fellowship  with Nirenberg, Anderson was given his own laboratory in the NIH in July 1967. He made clear from the beginning that his goal was to develop a way to give a normal gene to children with a genetic defect in order to cure the genetic disease. He, therefore, decided to begin by studying human disease on the molecular level. Over his career he has published more than 400 research papers, 39 editorials, and 5 books, and has received numerous awards and honors including 5 honorary doctorate degrees. Discovery of eukaryotic protein synthesis initiation factors. As Anderson began his own career , protein synthesis in bacteria was at the forefront of molecular biology research. He set out to discover protein synthesis initiation factors in mammals. His first major accomplishment, in 1970, was the isolation from rabbit reticulocytes (immature red blood cells) of several factors that initiated hemoglobin synthesis on reticulocyte ribosomes. It was later learned that these factors also initiated protein synthesis in essentially all eukaryotic systems. Development of a cell-free protein synthesizing system. In order to isolate the predicted molecule "messenger RNA", a cell-free protein synthesizing system of mRNA-free ribosomes was needed. Initially, a cell-free tRNA-dependent  protein synthesizing system was developed from rabbit reticulocytes ribosomes, using the endogenous mRNA on the ribosomes. An analogous system was developed with human reticulocyte ribosomes. Isolation of human messenger RNA. A procedure was developed for stripping the putative mRNA from the ribosomes. This ribosomal wash from rabbit reticulocyte ribosomes was incubated in a cell-free system and rabbit hemoglobin was produced. The procedure for stripping endogenous mRNA from rabbit reticulocyte ribosomes was used on human reticulocyte ribosomes to obtain human globin mRNA. Synthesis of normal and mutant globin proteins using human globin mRNA. Stripped rabbit reticulocyte ribosomes were programmed with  mRNA isolated from thalassemia, sickle cell anemia, or normal human reticulocytes. The rabbit ribosome cell-free system was able to produce normal human globin from normal human mRNA, sickle cell globin from sickle cell mRNA, and the abnormal alpha/beta globin chain abnormality of thalassemia from thalassemia mRNA. Microinjection of globin DNA into mammalian cell nuclei. As a first approach for developing a human gene therapy procedure, standard microinjection techniques were modified to permit the injection of DNA plasmids into the nucleus of mammalian cells. Human globin genes were microinjected into mouse fibroblasts and into mouse oocytes and shown to  express human globin mRNA. Development of retroviral gene therapy vectors. Microinjecting a few non-stem cells was clearly not an efficient procedure for a clinical protocol. In 1984, Anderson published a major review in "Science" in which he analyzed the "Prospects for Human Gene Therapy" and concluded that the most promising approach was to use retroviral vectors as a delivery vehicle. He immediately established a close, long-term collaboration with one of the top retroviral vector scientists: Eli Gilboa, then at Princeton. Together they developed vectors that could efficiently carry a gene package into mouse or human cells in culture . The most efficient vector, N2, carrying a neomycin resistance gene, was used to transduce mouse bone marrow cells. The N2-transduced cells were injected into lethally irradiated mice where they repopulated the marrow. The presence and expression of the N2 vector could be detected in the repopulated mouse bone marrow cells by testing for the resistance of the marrow cells to the toxic antibiotic neomycin. Once the procedure was working successfully in mice, successful studies were done in non human primates. In addition, extensive safety studies were done in the vector transduced animals. Successful gene therapy of a human patient . Attempting to perform gene therapy by inserting recombinant DNA into a human being was extremely controversial after an illegal attempt was made in 1980. Anderson, together with bioethicist John Fletcher, set the ethical standard for this type of clinical protocol in his 1980 article in "The New England Journal of Medicine" entitled: "Gene Therapy In Human Beings: When Is It Ethical To Begin?" An extensive regulatory process was established during the late 1980s, including the creation of the Human Gene Therapy Subcommittee as a first round of regulatory oversight. Only after approval by that formal public governmental review did the  gene therapy clinical protocol move on for review by the Recombinant DNA Advisory Committee (RAC), the FDA, and other ethics/regulatory committees. The media followed every step closely. Anderson teamed with Michael Blaese, a prominent immunologist in the National Cancer Institute (NCI), and Steven Rosenberg, a prominent cancer surgeon and immunotherapy advocate, also in the NCI. The initial protocol was a safety study where only the N2 vector, previously shown to be safe when used in non-human primates, was administered to cancer patients, on Rosenberg's NCI clinical cancer service, who volunteered for the study. A full "gene therapy