Clinical OMICS

MAY-JUN 2019

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

Issue link: https://clinicalomics.epubxp.com/i/1117801

Contents of this Issue

Navigation

Page 46 of 50

www.clinicalomics.com May/June 2019 Clinical OMICs 45 humor and an acerbic wit (see Genetic Engineering & Biotech- nology News, May 2019). One comment I remember he made when a leading scientist from one organization left to go to a start-up Biotech company was "well that should put the average IQ up at both places." Sydney was eminent without being pompous, and he could not abide scientists, laureates, or anybody else for that matter, who were full of their own self-importance. He turned down a British knighthood (as you might expect), but he was a Companion of Honour (and there are only 65 of them at any one time in the U.K.). In the early 90s, DNA sequencing (chiefly dideoxy Sanger sequencing) was used to get a better understanding of the number of genes in the human genome. The cataloguing of mRNAs coding for all proteins was called "Expressed Sequence Tag" (EST) sequencing. Sydney didn't discover EST sequencing because it was essentially a logical exten- sion to sequencing cDNA clones (something I did a lot of at Celltech), but he certainly was a proponent of the util- ity of EST analysis (popularized by Craig Venter). How many genes were there actually? I remember estimates of anything between 20,000 to 65,000, varying from week to week, before we finally got the draft of the genome. Sydney's ingenuity was also evident in develop- ing the concepts of multi- plex parallel sequencing. His role in this should not be underestimated. Syd- ney was a founder of Lynx Therapeutics. Lnyx, which was bought by Solexa (a company that developed dye-based chain termina- tors) in 2005, deployed the concept of MPSS (massively parallel signature sequenc- ing) allowing the analysis of millions of individual DNA molecules in a single assay. Their Megaclone system pioneered the use of bead technol- ogy to capture and analyze these multiple DNA molecules. Together, these two companies formed the basis of the next- gen sequencing (NGS) platform acquired by Illumina in 2006. The transformation in biomedical research made pos- sible by NGS is obvious. Somewhat lost however, given the magnitude of his other discoveries, is Sydney's fundamental role in the development of this transformational technology. I remember fondly one particular conversation with Sydney, glass of wine in hand, watching the sun set over the Pacific Ocean after the draft human genome sequences had been published. He told me that he was reading the human DNA sequence from the beginning of chromosome 1 all the way to the end of chromosome 23. At the time I wasn't sure that was true. In retrospect, I'm fairly sure that it was. It sums up the man—he was so inquisitive about how the whole genome all fitted together. His interest in the Fugu genome came from the fact that the Fugu genome is eight times smaller than the human genome but with essentially the same number of genes. I'm not sure he needed the smaller scale to help him to understand the human genome. He got it anyway. So how do you capture the essence of this eminent man and his mind? Not the way the majority of his obituaries have been written. Instead, listen to the wit and humor in his voice, enjoy his endless anecdotes for people and places, and remember what his contributions to molecular biology and biotechnology actually have been. It is not all about C. elegans—that's a bit of a distraction. His real contributions lie in the development of current genetics and genomics based on his pioneer- ing work understanding how DNA is transcribed into mRNA and, in turn, translated into protein. Fundamental, don't you think? Tim Harris is a Venture partner at SV Health Investors and a consultant to various Biotechnol- ogy companies. He is a founder and Board member of Rheostat Therapeutics, a Cambridge, MA-based company discovering compounds affecting mitophagy. He started in Biotechnology in 1978 cloning foot and mouth disease virus RNA. Sydney Brenner at a 2011 symposium at the Okinawa Institute of Science and Technology. Photo: OIST ANDRZEJ WOJCICKI / Science Photo Library / Getty Images O P I N I O N

Articles in this issue

Links on this page

Archives of this issue

view archives of Clinical OMICS - MAY-JUN 2019