title: Henry Friesen Award Lecture. Work, the clinician-scientist and human biochemical genetics.
abstract: The pursuit of human biochemical genetics has allowed us to understand better how the person with the (genetic) disease differs from the disease the person has and to develop the concept that genetics belongs in all aspects of health care. It is a perspective that comes quite readily to the clinician-scientist, and the restoration of that "species" in the era of functional genomics is strongly recommended. Garrod, the initial founder of human "biochemical genetics" belonged to the clinician-scientist community. Archibald Edward Garrod introduced a paradigm, new for its day, in medicine: biochemistry is dynamic and different from the static nature of organic chemistry. It led him to think about metabolic pathways and to recognize that variation in Mendelian heredity could explain an "inborn error of metabolism." At the time, Garrod had no idea about the nature of a gene. Genes are now well understood; genomes are being described for one organism after another (including Homo sapiens) and it is understood that genomes "speak biochemistry (not phenotype)." Accordingly, in the era of genomics, biochemistry and physiology become the bases of functional genomics, and it is possible to appreciate why "nothing in biology makes sense without evolution" (and nothing in medicine will make sense without biology). Mendelian, biochemical and molecular genetics together have revealed what lies behind the 4 canonical inborn errors described by Garrod (albinisn, alkaptonuria, cystinuria and pentosuria). Both older and newer ideas in genetics, new tools for applying them (and renewed respect for the clinician-scientist) will enhance our understanding of the human biological variation that accounts for variant states of health and overt disease. A so-called monogenic phenotype (phenylketonuria) is used to illustrate, in some detail, that all disease phenotypes are, in one way or another, likely to be complex in nature. What can be known and what ought to be done, with knowledge about human genetics, to benefit individuals, families and communities (society), is both opportunity and challenge.
authors.affiliation: Department of Human Genetics, McGill University and McGill University Health Centre, Montreal, Que. charles.scriver@mcgill.ca
authors.forename: C R
authors.initials: CR
authors.lastname: Scriver
mesh_terms: D000818:Animals; D001363:Awards and Prizes; D001671:Biochemistry / Q000266:history; D002170:Canada; D005823:Genetics / Q000266:history; D049672:History, 19th Century; D049673:History, 20th Century; D016045:Human Genome Project / Q000266:history; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000266:history; D010661:Phenylketonurias / Q000235:genetics / Q000266:history; D010820:Physicians; D012108:Research Personnel; D012955:Societies, Medical; D014937:Work