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A Chronicle on Genetics and the March of Darwinian and Mendelian Medicine Diddahally R

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A Chronicle on Genetics and the March of Darwinian and Mendelian Medicine Diddahally R Govindaraju Evo Edu Outreach (2020) 13:15 https://doi.org/10.1186/s12052-020-00129-5 Evolution: Education and Outreach BOOK REVIEW Open Access A Chronicle on Genetics and the March of Darwinian and Mendelian Medicine Diddahally R. Govindaraju* Abstract Ken Burns, a well-known documentarian has produced a flm titled, “The Gene: An Intimate History” based on Sid- dhartha Mukherjee’s book by the same name. The flm focuses sharply on the history of genetics, the science of inheritance and variation, in particular, the gene, the central player in genetics, its discovery, structure and function as well as its myriad infuence on development, growth, health, disease and evolution of all organisms. Importantly, he has shown how geneticists, physicians, patients and their families as well as society at large must cooperate, develop mutual trust and share ethical responsibilities in order to predict, prevent, manage and cure many inherited disorders. Mr. Burns has reinforced these ideas beautifully with illustrations, archived flm footage, location flming and com- mentaries. The flm also hints at the need for taking a unifed Darwinian-Mendelian and Hippocratic approach toward building a healthier human society. In short, this is a beautiful and engrossing documentary on the future of Genetic Medicine. Keywords: Ken Burns, Siddhartha Mukherjee, Garrod, Genetic disorders, Huntington disease, Precision medicine, Genome editing, Genetic medicine Details of the documentary flm euphoria about genetic research, toward predicting, pre- Burns, K. Te Gene: An intimate history presented in venting and potentially curing inherited disorders, being two parts on April 7, and April 14, 2020 on PBS. popularized as precision medicine. His narrative sharply “As to what constitutes ftness to survive, man and focuses on the common thread shared among genes in Nature do not see eye-to-eye… Te whole aim of medical the human genome, their structure, the vision to map art, whether therapeutic or preventive, has been to coun- and sequence them as well as the opportunities genetic teract the laws of Nature”-Archibald Garrod (1931). research ofers for alleviating human sufering from dis- A two-part documentary flm titled, “Te Gene: An eases of genetic origin. Te focused approach makes the Intimate History” by Ken Burns, a celebrated documen- documentary more engaging relative to the book. Te tarian, was aired on PBS on April 7, and April 14th. Te objectives of this review are to: (a) briefy introduce the flm is an adaptation from a book with the same title by scope of the original book source, (b) discuss the history Siddhartha Mukherjee (2016). Te frst and the second of genetics and its application to human health as fea- part of the documentary deal with respectively: (a) dawn tured in the documentary, and (c) refect on the emerging of the modern age of genetics, and (b) revolution in the trends toward integrating the Darwininan and Mendelian treatment of (genetic) disease. In the documentary “ava- principles with other advances in modern medicine, and tar” of Mukherjee’s book, Mr. Burns traces the anteced- the plausible impact of such an alliance on future health ent roots of genetics and articulates the contemporary care. In his book, Mukherjee frst refects on the inherit- *Correspondence: [email protected] ance and distribution of mental illness among his family Institute for Aging Research, Albert Einstein College of Medicine, 1300 members as a prelude to describing the discovery of the Morris Park Avenue, Bronx, NY 10461, USA laws of inheritance and variation among a set of crosses © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Govindaraju Evo Edu Outreach (2020) 13:15 Page 2 of 6 of garden pea varieties and their progenies by Gregor scientists with children and their parents, and patients Mendel in 1865 within the confnes of a “Walled Gar- and their families. Tese scenarios seamlessly intercalate den” in Brno, Czechoslovakia. In the same period, Men- with each other and provide a rich tapestry of the sci- del’s contemporaries, Darwin and Wallace successfully ence of genetics (and its evolutionary roots and trajec- advanced the Teory of Natural Selection. While Darwin tories) and what it could ofer to improve human health was inspired by variation exploited by plant and animal in the years ahead. Mr. Burns focuses sharply on genes breeders, Mendel meticulously recorded and analyzed infuencing human traits and specifc inherited disorders, the observed the pattern of variation among his cross- their structure and organization, and illustrates with the ing experiments involving specifc parental lines, their aid of case studies how to predict, prevent and possibly hybrids and the progeny of those hybrids. Note that Dar- cure genetic disorders using genomic information. win also carried out extensive studies on the efects of Te flm opens with the presentation of a bold, but pro- cross and self-fertilization in plants. He notably struggled fessionally and socially irresponsible gene editing experi- to provide a tangible explanation for the inheritance and ment conducted by a Chinese scientist, Dr. He Jiankui. He distribution of variation (both in nature and among his used a novel genome editing technique called “CRISPR- crossing experiments), which provides the raw material Cas9” (clustered regularly interspersed short palindromic for all evolutionary processes. Darwin was, however, cog- repeat) system on human embryos (germ-line editing) nizant of the health consequences of inherited variation, in order to cure twin girls from HIV. Te embryos were especially consanguinity (inbreeding), which took a toll developed from in vitro fertilization involving HIV posi- on the health of his children and grandchildren owing tive father and HIV negative mother. Note that individu- to his marriage to his frst cousin. Indeed, health and als who are heterozygous to “Delta 32” mutation in the disease are inextricable aspects of evolutionary process CCR5 receptor gene are susceptible to HIV, but homozy- (Haldane 1949). Te Mendelian principles rediscovered gous ones show greater levels of resistance. Germ line 120 years ago, were quickly extended to study human editing is irresponsible because the genetic modifca- health and disease (Garrod 1902). Subsequent applica- tions to the developing embryos are inherited and their tion of both Darwinian and Mendelian principles to crop life-course consequences on development and health as and animal breeding has contributed greatly toward ame- well as evolution have not been thoroughly investigated liorating world’s food scarcity. Could these discoveries be by a panel of international body of responsible citizen sci- employed to cure diseases and manage human health? entists. Mutations at the CCR5—Delta 32 site occurred Despite a few major omissions and a clear bias toward many generations ago in Europe and spread in human molecular biology (Govindaraju 2016), Siddhartha populations, obviously much before the appearance of Mukherjee’s historical narrative of the science of genet- HIV. ics or heredity and variation remains as an important Pediatric geneticist Dr. Wendy Chung introduces us guide to study the origin and growth of genetics, and to rare childhood diseases, which follow a Mendelian its relevance to modern medicine. It also mirrors the pattern of inheritance. Te introduction is facilitated abuses of genetic discoveries to propagate racism, the through the anxious and devoted couple, Luke and Sally fallacy of biological determinism and warns about the Jackson, and their beautiful young child Susanna. Unfor- consequences of tinkering the human genome with bad tunately, Susanna carries a defective (mutant) in “KiF1A” intentions, which could seriously impede the progress gene, which leads to a degenerative neural disease, of not only genetics and evolutionary biology, but also “Hereditary Spastic Paraparesis.” Te disease would not the entire human society. He has also discussed that only take away her childhood but also eats away her brain genetic discoveries made using the same principles that bit-by-bit over time. Dr. Chung patiently plays with the Nature has tinkered with, over billions of years, could be child and observes her subtle movements for diagnos- employed to managing and curing a number of diseases. ing the disease progression. Here we glimpse not only Such changes, prudent or imprudent, could also chart the dedication of Susanna’s parents to discovering the novel trajectories of human evolution. cause of their daughter’s illness, but also of Dr. Chung’s Ken Burns, like other great flm directors, has taken (and many physicians like her) palpable devotion to her only the scafoldings from the original source, and has patients in order to alleviate their sufering and fnd a retold the history of genetics in this documentary from purpose in her profession and life. Te consequences of an astonishingly fresh perspective. In a way, it feels like the mutation on protein and disruption of cellular func- watching a new and independent flm! Te documentary tion and its eventual manifestation as a disease are beau- is rich with appropriate illustrations and commentaries, tifully illustrated.
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