Thursday, 19 January 2017

The Gene: An Intimate History



Three profoundly destabilizing scientific ideas ricochet through the twentieth century, trisecting it into three unequal parts: the atom, the byte, the gene. Each is foreshadowed by an earlier century, but dazzles into full prominence in the twentieth. Each begins its life as a rather abstract scientific concept, but grows to invade multiple human discourses – thereby transforming culture, society, politics, and language. But the most crucial parallel between the three ideas, by far, is conceptual: each represents the irreducible unit – the building block, the basic organizational unit – of a larger whole: the atom, of matter; the byte (or “bit”), of digitized information; the gene, of heredity and biological information.
Siddhartha Mukherjee, as a cancer physician and researcher, made a name for himself with The Emperor of All Maladies, and when he was done writing it, he felt so completely drained that he knew he had no other book inside him. Eventually, Mukherjee realised that he did have one more story – that of the “normal” gene; its makeup, the history behind its discovery, and current applications – and he wrote The Gene as a sort of prequel to Emperor. While the history behind theories of heredity (from those of Aristotle and Pythagoras to Darwin and Mendel) made for an interesting narrative, I realised as I went along that there wasn't much here that I hadn't learned in high school. And as the story picks up steam into the modern day – with philosophical warnings about the future of genetically modified humans – again, it felt like you'd need to be hiding under a rock not to know what the current debate is. So, this isn't some paradigm-shifting exposé of the shadowlands of science, but it does have value: with his assured and easy voice, Mukherjee is able to make both history and science interesting and accessible (something not always achieved by my own erstwhile teachers), and to have assembled everything in one volume connects all of the dots in a satisfying manner. This is light science and I enjoyed it quite a bit.
Freaks become norms, and norms become extinct. Monster by monster, evolution advanced.
As I said, I don't think the history of thought about heredity has many surprises for someone who took grade nine Biology, and even its corruption into the Eugenics movements of the early/mid twentieth century (culminating not just in the horrors of Nazi Germany and Mengele's twin experiments, but the forced sterilisations found throughout North America) is common knowledge. When this historical narrative took off for me began with Watson and Crick trying to figure out the structure of DNA, and while a neighbouring researcher like Rosalind Franklin was perfecting her techniques for actually photographing the now famous helices, Watson and Crick were going at the problem obliquely: using Tinkertoys to assemble the various ways in which what little was known about genetic material could possibly be turned into a stable structure. What I liked best about this idea – besides Mukherjee always being careful to note the contributions of researchers like Franklin who might otherwise be forgotten in the historical narrative – was that this idea of researching the gene obliquely seems to be the only way it works. You want to efficiently write out the genome of a worm? Use a “shotgun” approach to separate and analyse random strings of DNA and hope they overlap enough to solve the entire sequence like a cryptogram. Want to discover the location of a single mutated gene that causes a disease like Cystic Fibrosis? First assemble massive family histories of sufferers and carriers and discover what other traits might be passed along in tandem with the mutation, thus narrowing the search for the real culprit. This notion of not really being able to study a gene directly led to something that was a surprise to me: When the Human Genome Project announced that they had succeeded at mapping the human genome, I thought that meant that we now knew the location and function of every gene in the human body. Turns out it “only” meant that the three billion or so base pairs were mapped (which includes long strings of exomes and introns and other non-true DNA as I understand it) and that only then could researchers begin to decipher what it all meant. We're not actually as far ahead as I had assumed.
That one of the most elemental diseases in human history happens to arise from the corruption of the two most elemental processes in biology is not a coincidence: cancer co-opts the logic of both evolution and heredity; it is a pathological convergence of Mendel and Darwin. Cancer cells arise via mutation, survival, natural selection, and growth. And they transmit the instructions for malignant growth to their daughter cells via their genes. As biologists realized in the early 1980s, cancer, then, was a “new” kind of genetic disease – the result of heredity, evolution, environment, and chance all mixed together.
I appreciate that we are living in an era of fake news and viral conspiracy theories, but I was stunned when a bright and educated young woman told me just last week that she knows that “they” have found the cure for cancer and are suppressing it for profit. As a cancer specialist, Mukherjee really shines when describing the genetic (and nongenetic) components of various forms of cancer, and if there were a magic drug or gene therapy that could simply enter the body and fix the various cancer-related mutated cells, I'm going to assume that at least one of the life-long lab-bound researchers who is working on it would rather publish than be bought off (while watching friends and family members succumb to the disease). I need to pick up The Emperor of All Maladies.

More interesting ideas: There is more genetic variation within a troop of Chimpanzees than within a random grouping of humans; indeed, there is more genetic variation within so-called “races” of humans than between races. I loved the idea of Mitochondrial Eve: Because the mitochondrial information within every human cell is passed on only from mother to daughter, every time a woman has only sons, her own information is lost. Tracing back the vast human family tree through its dead ends and branches, we all end up at a common female ancestor (mentally, that doesn't feel true. I'd be impressed with twenty or a hundred common mitochondrial lines – does the fact we all share the same mitochondrial information really mean one common ancestor? Have they actually found variants in so-called dead ends? I still liked the idea, though.) And I loved that every time the genetic researchers felt they were on the brink of something morally questionable – mixing human and animal DNA, creating designer human embryos – they would call their own conferences and decide on self-imposed moratoriums (yet, what can they do when Chinese researchers say they intend to proceed with whatever they like?) 

History repeats itself, in part because the genome repeats itself. And the genome repeats itself, in part because history does. The impulses, ambitions, fantasies, and desires that drive human history are, at least in part, encoded in the human genome. And human history has, in turn, selected genomes that carry these impulses, ambitions, fantasies, and desires. This self-fulfilling circle of logic is responsible for some of the most magnificent and evocative qualities in our species, but also some of the most reprehensible. It is far too much to ask ourselves to escape the orbit of this logic, but recognizing its inherent circularity, and being skeptical of its overreach, might protect the weak from the will of the strong, and the 'mutant' from being annihilated by the 'normal'.
Throughout The Gene, Mukherjee intersperses stories from his father's family that feature schizophrenics and manic-depressives. Because of their unhappy and destructive lives, Mukherjee is understandably concerned about passing on the genes for undesirable qualities. Yet, he also makes the point that many of the most creative figures in history – poets and composers and scientists – were probably bipolar; their incredible creative output coming in fits of mania. If we could track down the mutant gene responsible for a Beethoven or a Munsch or a Plath, would the world be better off for eliminating their future ilk? It seems inevitable that we will eventually “perfect” the human genome – eliminating all future variation and putting the brakes on the processes of evolution – and if I'm alive for it, it will be fascinating to see how we decide what the desirable “wild type” human will be. Again, there was nothing earth-shattering in The Gene, but it's well written and full of interesting linkages; a fine primer for the layperson.