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 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").Lyon, Jeff and Peter Gomer (1995), Altered Fates: Gene Therapy and the Retooling of Human Life, W.W. Norton & Company, Thompson, Larry (1994), Correcting The Code: Inventing the Genetic Cure for the Human Body, Simon & Schuster,
Early life and education Anderson was born in Tulsa, Oklahoma to his two parents. His father was a civil engineer, his mother was a journalist and writer, and he had two older sisters. He had 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 graduated in 1954 from 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,Anderson, W.F.: Arithmetical computations in Roman numerals. Classical Philology, LI: 145-150, 1956. arithmetical operations using Minoan linear B numerals in the American Journal of Archaeology in 1958,Anderson, W.F.: Arithmetical procedure in Minoan linear A and in Minoan-Greek linear B. Amer. J. Archaeology, 62: 363-368, 1958. a physical chemistry research paper in the Journal of the American Chemical Society in 1958,Anderson, W.F.; Bell, J.A.; Diamond, J.M., Wilson, K.R.: Rate of thermal isomerization of cis-butene-2. J. Am. Chem. Soc., 80: 2384-2386, 1958. and a research study on the effects of irradiation on DNA in the Journal of Cellular and Comparative Physiology in 1961.Marmur, J.; Anderson, W.F.; Matthews, L.; Berns, K.; Gajewska, E.; Lane, D.; Doty, P.: The effects of ultraviolet light on the biological and physical chemical properties of deoxyribonucleic acids. J. Cell. and Comp. Physiol., Suppl. 1, 58: 33-55, 1961. In its March 19, 1956 issue, Time magazine called Anderson a "Harvard Prodigy" for his research work on ancient numerical systems."The Prodigies", Time magazine, March 19, 1956, page 83 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.Anderson, W.F.; Gorini, L.; Breckenridge, l.: Role of ribosomes in streptomycin activated suppression. Proc. Natl. Acad. Sci. USA, 54: 1076-1083, 1965.
Career Anderson then spent two years, 1965–1967, under the tutelage of Marshall Nirenberg in a laboratory 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.Nirenberg, M.; Caskey, T.; Marshall, R.; Brimacombe, R.; Kellogg, D.; Doctor, B.; Hatfield, D.; Levin, J.; Rottman, F.; Pestka, S.; Wilcox, M.; Anderson, W.F.: The RNA code and protein synthesis. Cold Spring Harb. Symp. Quant. Biol., 31: 11-24, 1966. 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.Prichard, P.M.; Gilbert, J.M.; Shafritz, D.A.; Anderson, W.F.: Factors for the initiation of haemoglobin synthesis by rabbit reticulocyte ribosomes. Nature, 226: 511-514, 1970. 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.Gilbert, J.M. and Anderson, W.F.: Cell-free hemoglobin synthesis, II. Characteristics of the transfer ribonucleic acid-dependent assay system. J. Biol. Chem., 245: 2342-2349, 1970. An analogous system was developed with human reticulocyte ribosomes.Gilbert, J.M.; Thornton, A.G.; Nienhuis, A.W.; Anderson, W.F.: Cell-free hemoglobin synthesis in beta-thalassemia. Proc. Natl. Acad. Sci. USA, 67: 1854-1861, 1970.
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.Nienhuis, A.W.; Laycock, D.G.; Anderson, W.F.: Translation of rabbit haemoglobin messenger RNA by thalassemic and non-thalassemic ribosomes. Nature New Biology, 231: 205-208, 1971.
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.Nienhuis, A.W. and Anderson, W.F.: Isolation and translation of hemoglobin messenger RNA from thalassemia, sickle cell anemia, and normal human reticulocytes. J. Clin. Invest., 50: 2458-2460, 1971.Nienhuis, A.W.; Canfield, P.H.; Anderson, W.F.: Hemoglobin messenger RNA from human bone marrow: Isolation and translation in homozygous and heterozygous thalassemia. J. Clin. Invest., 52: 1735-1745, 1973.
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.Anderson, W.F. and Diacumakos, E.G.: Genetic engineering in mammalian cells. Scientific American. 245: 106-121, 1981. Human globin genes were microinjected into mouse fibroblasts and into mouse oocytes and shown to express human globin mRNA.Anderson, W.F.; Killos, l.; Sanders-Haigh, L.; Kretschmer, P.J.; Diacumakos, E.G.: Replication and expression of thymidine kinase and human globin genes microinjected into mouse fibroblasts. Proc. Natl. Acad. Sci. USA, 77: 5399-5403, 1980.Humphries, R.K.; Berg, P.; DiPietro, J.; Bernstein, S.; Baur, A.; Nienhuis, A.W.; Anderson, W.F.: Transfer of human and murine globin-gene sequences into transgenic mice. Am. J. Hum. Genet.• 37: 295-310, 1985.
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"Anderson, W.F., Prospects for human gene therapy. Science, 226: 401-409, 1984. 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.Yu, S.-F; von Ruden, T.; Kantoff, P.; Garber, C.; Seiberg, M.; Ruther, U.; Anderson, W.F.; Wagner, E.F.; Gilboa, E.: Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells. Proc. Natl. Acad. Sci. USA, 83: 3194-3198, 1986.Gilboa, E.; Eglitis, M.A.; Kantoff, P.W.; Anderson, W.F.: Transfer and expression of cloned genes using retroviral vectors. Bio Techniques, 4: 504-512. 1986.
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.Eglitis, M.A.; Kantoff, P.; Gilboa, E.; Anderson, W.F.: Gene expression in mice after high efficiency retroviral-mediated gene transfer. Science, 230: 1395-1398, 1985.
Once the procedure was working successfully in mice, successful studies were done in non human primates.Anderson, W.F.; Kantoff, P.; Eglitis, M.; Mclachlin, J.; Karson, E.; Zwiebel, J.; Nienhuis, A.; Karlsson, S.; Blaese, R.M.; Kohn, D.; Gilboa, E.; Armentano, D.; Zanjani, E.D.; Flake, A.; Harrison, M.R.; Gillio, A.; Bordignon, C.; O'Reilly, R.: Gene transfer and expression in nonhuman primates using retroviral vectors. Cold Spring Harb. Symp. Quant. Biol., 51: 1073-1081, 1986.Kantoff, P. W.; Gillio, A.P.; Mclachlin, J. R.; Bordignon, C.; Eglitis, M.A.; Kernan, N. A.; Moen, R. C.; Kohn, D. B.; Yu, S.-F.; Karson, E.; Karlsson, S.; Zwiebel, J. A.; Gilboa, E.; Blaese, R. M.; Nienhuis, A.; O'Reilly, R. J.; Anderson, W. F.: Expression of human adenosine deaminase in nonhuman primates after retrovirus-mediated gene transfer. :!.:. Exp. Med., 166: 219-234, 1987. In addition, extensive safety studies were done in the vector transduced animals.Cornetta, K.; Morgan, R.A.; Gillio, A.; Sturm, S.; Baltrucki, L.; O'Reilly, R.; Anderson, W.F.: No retroviremia in long-term follow-up of monkeys exposed to a murine amphotropic retrovirus. Hum. Gene Ther., 2: 215-219, 1991.
Successful gene therapy of a human patient