The Gene: An Intimate History

By Sunil Kumar

Only the 2nd post this month; another review. A long rambling philosophical cum scientific book by Siddhartha Mukherjee.

Genetics is a new science – you can plausibly date it from the rediscovery around 1900 of Gregor Mendel’s then practically unknown 1866 paper on the breeding of peas, and the naming of the “gene” in 1909 as a discrete, stable, heritable unit – but its infiltrations into modern institutions and senses of the self are pervasive.

It was scarcely a moment from the first attempts to characterise heritable traits to the emergence of concerted efforts to put those understandings to work in engineering better people. In 1905, the English biologist William Bateson presciently wrote that once “the facts of heredity” became known, “mankind will begin to interfere … When power is discovered man always turns to it. The science of heredity will soon provide power on a stupendous scale.”

So; cut the science fiction and move straight into probable fact. Mukherjee’s vivid descriptions of DNA, RNA, proteins, gene sequencing, eugenics and probable future scenarios are fascinating and offer insightful glimpses into the science and the future.

However; I was slightly put off by his Western worldview and repeated references to Aristotle etc. Indic thought and the Hindu religion is only referred to in the concept of “bheda” and “abheda”. Gene expression plus the mapping of diseases to specific points in the genome; the number of research studies and the unconventional ways in which this was achieved made fascinating reading.

Darwin’s cousin, Francis Galton, aggressively advocated “eugenics” – the improvement of human society through selective breeding. He knew nothing of what a gene might be, but he urged that the intelligent, the strong and the beautiful should breed more, and the unfit should breed less. Galton reckoned that a proper appreciation of how racial power depended on heredity would institutionalise eugenics and keep the British from becoming even nastier and shorter.

By the 1930s, British and American programmes for the sterilisation of the “genetically defective” inspired the development of Nazi Rassenhygiene. The almost immediate adoption by Hitler’s new regime of a sterilisation law and the later “research” on twins by Auschwitz “doctor” Josef Mengele momentarily ruined the brand for any systematic attempts to account for human traits in genetic terms and to use that knowledge to intervene. By the mid-20th century, Mukherjee writes, the gene had become “one of the most dangerous ideas in history”.

Genetic knowledge has historically been secured largely through the experimental manipulation of peas, primroses, fruit flies, nematodes and micro-organisms and, while Mukherjee has little to say about the hugely important agricultural technologies resulting from plant and animal genetics, the ultimate prize of genetics has always involved ourselves – how to understand ourselves and how to make better versions of ourselves. Geneticists, of all scientists, have had least need to be reminded that “the proper study of mankind is man”.

The “gene” was originally an abstraction, then came knowledge of where such things might live in the cell and on chromosomes; then what they were made of; how they carried information about physiological functions; how they controlled those functions and were, in turn, regulated.

The stages from Watson and Crick’s 1953 discovery of the structure of DNA, to working out how DNA coded for proteins, to the sequencing of the human genome in 2000, all absorbed enormous quantities of intelligence, labour and instrumental ingenuity. In fact the tussle between Craig Venter and the American NIH National Human Genome Research Institute and the different approaches in an eventual compromise and a public announcement by former U.S president Clinton was a glimpse into the enormous scientific pride associated with the genome project.

https://www.genome.gov/10001356/june-2000-white-house-event/

But they did not depend on fundamentally new scientific visions. Once it was understood that genes had a discrete chemical identity, it was envisaged that, someday, with work, luck and the right sorts of instruments, knowing all the rest would be possible. But what geneticists did not then imagine was the rapidity with which their instrumental powers would change.

Very few geneticists in the 1960s foresaw the development of genetic techniques, to make new things at biochemical, cellular and organismic levels. The technologies of recombinant DNA, emerging in the early 1970s, allowed geneticists to take DNA from different species, engineer new genes and produce lots of “clones” of the new entity.

What initially appeared as an ethical and political concern – “playing God” and taking undue risks with nature – was soon overwhelmed by the golden prospect of using genetically modified micro-organisms as “factories” for making drugs and other biologics for which there was a need and a market – insulin, for example.

And that idea was itself transformed into an institutional reality that few had foreseen: genetically engineered entities, or the methods for making them, might be patented, legally protected, powered up by private equity, and made into the foundation of immensely profitable new companies – among the first, Genentech in San Francisco’s Bay Area and the Harvard-linked Biogen in Geneva. Genetics first intruded into the public consciousness as eugenics, then as biotech.

Gene function responds to the body’s internal environment: cells tell other cells what to do. Your nerve cells and your liver cells have the same genes, but, as geneticists have understood for a long time, some genes that are turned on in one type of tissue are toggled off in others.

Your genome is a palette, not a painting. Mukherjee wants us to understand that our genome may also respond to the external environment.

Some of those environmental influences may affect chemical switches turning genes on and off, acting as an “epigenetic” layer of control sitting above the genome, and, he writes, in certain cases etching themselves as “permanent, heritable marks” that may be passed on to future generations. Our heredity is our environment at one remove, and the flow of biological information is not a straight line but a circle.

Mukherjee makes a pertinent point that genetics; the genome and human destiny are not cut and dry; black and white conclusions. Genes are not wholly responsible for our phenotype; and our physical and mental identity. A haematologist and oncologist by training; Mukherjee describes dreaded diseases including cancer, haemophilia and AIDS; although in sparse detail.

We are all a very complex mix of choices; the environment; destiny and the very elusive factor of a supernormal force or divinity which agnostics are still seeking.The cautionary element in Mukherjee’s tale is that genetic predispositions should not be used as a stick by governments and health bodies to legislate and determine the fate of humanity.

Twentieth century advances in cell biology and understanding how evolution worked revealed that not only do humans not sit on top of the evolutionary ladder but that there is no ladder.

Whether it’s Oswald Avery’s brilliantly straightforward 1944 pinpointing of DNA as the carrier of genetic information, Watson and Crick’s building and rebuilding of their man-sized model of its structure in the 1950s, or the quest to isolate the gene for Huntington’s disease in the 1980s and 1990s, what shines through is the sheer ingenuity of the scientists who have demystified the genome, searching for ‘laws’ that might undergird biology as they do physics.

The human can be just another ape, a mere twig, in the relentlessly branching tree of life. Also, the design and body-plan of organisms were mediated by strange pieces of chemical blocks — genes — that worked the same way in bacteria as they do in humans; there are no ‘human genes’ but just various permutations that sometimes lead to humans. When he mentions that the basic constituents(genetic factors) of almost all life are similar; one is tempted to think about natural origins and the presence of a master planner; a creator.

Mukherjee  wrongly states that “classical Darwinian evolution is that genes do not retain an organism’s experiences in a permanently heritable manner… Darwin discredited that model [of Lamarck].” But Darwin had no idea of the gene—the concept of which was established only in the 20th century.

What of the future? In The Gene’s final section, we get a little on embryo selection, a little on gene editing and a little on stem cells, all of which may soon be used to ‘engineer’ healthier, smarter or otherwise altered humans.

The book’s coverage of these techniques — on which the importance of a full, frank debate cannot be overstated — is accompanied by a vague ‘manifesto’ on some of their pitfalls and caveats, but the whole treatment feels rushed, as if Mukherjee didn’t wish to scare the horses by getting too far into the ‘newgenic’ implications.

To sum up; this book is worth reading for a brief introduction to the field. Curious researchers and inquisitive minds can dig further.

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