Labtimes 2017-06

page 64 Lab Times 6-2017 Book Review Not much more than a century has passed since the rediscovery of Mendel’s Laws of Inheritance – which were widely ignored by contemporaries – until the complete deci- phering of the human genome in 2003. The huge scientific progress, concerning the con- cept of genes as informational units of he- redity, fell into four phases that correspond roughly with the four quarters of the 20 th century. In the first phase, scientists estab- lished the cellular basis of heredity, the chro- mosomes on which genes could be localised by mapping. In the second phase, complet- ed by the discovery of the double helix struc- ture, DNA was pinned down as heredity’s molecular basis. In the third phase, scientists like Jacques Monod elucidated how genes actually work, forming the informational ba- sis of heredity. By decoding the genetic lan- guage and understanding the mechanisms by which cells process genetic information to coin a phenotype, scientists learned to har- ness genes for their own use. This led to se- quencing and cloning technologies that still have a tremendous impact on human society. The fourth phase was the era of genomics, in which complete genomes were deciphered. 100 years of genetics These four phases form the outline of The Gene , the almost 600-page masterpiece of cancer researcher Siddhartha Mukher- jee, Assistant Professor at the Columbia Uni- versity Medical Center in New York. Howev- er, The Gene goes beyond the completion of the Human Genome Project, expands to our times andwell into the future. While the first part is a highly informative history book de- scribing the quest of Gregor Mendel, Charles Darwin, Thomas Hunt Morgan and many more for a theory of heredity, the beginnings of gene technology and the development of gene therapies, the second part is of more philosophical nature. Here, Mukherjee de- livers a positioning of where human genet- ics and modern medicine stand today, what is already possible in regard to therapeutic manipulations of the genome and which im- pact it might have on patients and mankind altogether, if the decoding of individual ge- nomes became widely accessible. Quest for better genes Mukherjee is not only a scientist and a physician but also personally affected by a potential genetic disorder. Two of four un- cles from his father’s side and one cousin suffered from a psychiatric condition, ei- ther schizophrenia or manic depression. Mukherjee knows that these ailments are heritable, that his own and his children’s fu- ture lies in their genes. In spite of the enthu- siasm for new therapeutic and diagnostic possibilities, the author warns against re- ducing people to a potentially ailment-pro- voking gene variant and recommends that we consider the impact that a genetic diag- nosis might have on the concerned person: a previvor – as some of them call themselves – who knows that a given mutation will to some extent lead to a medical condition but who does not know when or how this con- dition will manifest. Previvors have to cope with an uncertainty that in some cases may be worse than the disease itself. Where we are about to manipulate complete genomes instead of single genes, Mukherjee sees humankind at a crossroad on the way to an accelerated human genome technology. He thoroughly deals with the approach of gene therapies to eradicate pathogenic mutations from the human gene pool and, although he acknowledges that gene therapies have the potential to spare patients immense suffering, reminds us of cases of eugenics both in the United States at the beginning of the 20 th century as well as inNazi Germany. In his opinion this negative eugenics must not be replaced by a positive one which sets about to improve the human genome by selectively manipulating it. Af- ter all, it is always a genome (of a designat- ed person) that defines, which gene variants are normal and which are mutant. The Gene is highly recommended for anyone, who is interested in the history of molecular biology and its protagonists as well as for those, who want to knowwhat is already possible in regards to gene editing, and what we can expect of the future. In ad- dition, the reader learns a lot about human descent and sexual identity. Mukherjee re- counts exciting stories about the first thera­ peutic protein ever to be produced recom- binantly, the race for the human genome and today’s approaches to producing the first transgenic humans using CRISPR-Cas gene editing technology in China. Along the way, he affords a touching insight into his own family history after the division of Ben- gal in North India, which led to the foun- dation of the sovereign Republic of Bang- ladesh and the traumatising displacement of Mukherjee’s grandmother and many oth- ers to West-Bengal’s (still Indian) capital Kolkata. Touching insights Even now, the story of Carrie Buck (to whom the book is dedicated) is still terri- fying. The young woman and her moth- er were forcibly transferred to the Virgin- ia State Colony for Epileptics and Feeble- minded in Lynchburg after a deliberate di- agnosis of ‘moronism’, and sterilised in the 1920s. This, from today’s point of view, un- thinkable procedure was meant to improve the human gene pool by preventing sexu- al reproduction of ‘unsuitable’ individuals. Through Carrie Buck’s example, Mukherjee demonstrates emphatically where the irre- sponsible use of scientific findings can lead a society. In the era of post-genomics, where the first human transgenic embryo might be about to be created, it is our responsibility to resist the repetition of any form of such genetic ‘cleansing’. The Gene: An Intimate History. By Siddhartha Mukherjee. Scribner, 2017. 608 pages, € 31 (hardcover), € 9 (softcover), € 10 (eBook). Larissa Tetsch Book Review: The Gene – An Intimate History Biography of the Gene The Indian-American cancer researcher, Siddhartha Mukher- jee, delivers nothing less than a complete history of genetics and heredity. His book is not only compellingly informative but also deeply philosophical. Photo: Columbia University Siddhartha Mukherjee during a lecture at Columbia University

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