Monday, January 1, 2018

Book Review: The Gene - An Intimate History by Siddhartha Mukherjee


During grad school days we used to joke that the prestige of a journal paper you publish is inversely proportional to the length & complexity of the journal's name. You can be sure that I have never published anything in journals like "Nature" or "Science". :-) 

I have developed a similar, admittedly snobbish notion about books written by non-fiction writers. There are authors who publish a lot vs. those who write just a couple of books in their lifetime. While the so called prolific writers take a small idea and quickly churn out a 300 page drivel by adding a lot of fluff (that are no doubt easy to read), there are others who write comprehensive works in their field of expertise that makes you feel glad you picked them up to read. Siddhartha Mukherjee's new book titled The Gene - An Intimate History clearly falls into the second category.

After Emperor of All Maladies that chronicled the history and current status of cancer research, he understandably felt so exhausted and thought he will never pick up the pen to write another book ever since he had written out everything he knew, narrated all the stories he had and so felt he was done once and for all. But then eventually wrote this book to talk about the normal functioning of the human genes as opposed to the EoAM book that talked about abnormal functioning of genes that had gone haywire. 

Book spans roughly 2500 years starting from Greek philosophers. He weaves personal family history that has a liberal sprinkling of mental disorders nudging him to wonder about genetic causes with research conducted by stalwarts like Mendel & Darwin all the way to CRISPR/Cas-9 in the present day. Centuries past, Pythagoras cohorts believed that the sperm traverses through the male body collecting signals from all the different body parts as to how it should grow up and then uses those instructions to grow into an entity that looks similar to the father. During Mendel's time he had figured that there is some indivisible unit entity in biological beings that is able to transmit flower color or height in pea plants from parent plant to child plant in a binary mode (i.e. characteristic quality gets either transmitted or not transmitted but doesn't get diluted half way when different parents are crossed) and can even remain hidden for multiple generations before revealing itself in a descendant further down the line. Then subsequently the DNA double helix structure, how the genes are made of just 4 alphabets (GACT), stretches of parts of the DNA forms a gene, how genes encode a recipe for making proteins that in turn creates cells that contains copies of DNA were all understood step-by-slow-and-painful-little-step. The amount of thoughts, efforts, extremely painful research and notes keeping that has brought our understanding of human genome to where it is today is simply humbling. 

Author has a knack for visual metaphors found allover the book. Many are quite useful to visualize the enormity of tasks on hand. He states that the human DNA when laid out in a straight line can stretch from US to Europe in which clusters of genes may be found like small islands found as pin pricks in the ocean! Collecting all the pin prick land masses may form something like Tokyo's metro train line equivalent. This mental picture helps you easily understand the sparseness with which genes are distributed in the DNA structure. Mapping the genome is described as climbing a rope to scale a mountain by moving your hands up the rope one palm at a time without leaving any gap. Another approach called "shot gun" used to decode human genome is described as breaking down the sequence into thousands of little pieces (as if blown by a shot gun), reading them and then trying to sequence them by noticing the overlapping letters found in adjacent segments. He also paints nice visuals as in the case of describing cell biologist Thomas Morgan's lab where he was studying fruit flies saying, "Bunches of overripe bananas hung from sticks. The smell of fermented fruit was overpowering, and a haze of escaped flies lifted off the tables like a buzzing veil every time Morgan moved". Even in my little writing attempts I have tried to paint such visuals as it tends to brings a sense of immediacy to the story. But in my case, I was describing some time/place I personally knew & had experienced. But since Morgan's lab was functioning during the first decade of the twentieth century, we can be sure that the author is not describing what he saw. :-) But with a smile, we can move on since it certainly helps the reader visualize the image well. 

I tend to wince when I read articles or books that tend to describe how one particular event or discovery transformed the entire human history. Good but simple example will be a write up of how if that apple hadn't landed on Newton's head, we wouldn't have discovered the notion of gravity and so won't have planes/GPS, etc. While such stories may sound amazing/nail biting, I tend to think sooner or later some other fruit or thing would have landed on Newton's or someone else's head and we would have understood gravity. So, I liked how the author, despite describing several monumental discoveries related to cell biology, genes and DNA, chronicles them as impressive discoveries but treats them as one in a series of steps that lead us to the present state (which still has lot more things left to discover). 

There are so many details in this domain of genetic research that are fascinating. Just to give one example, Cystic Fibrosis is a disease caused by genetic mutation and is very prevalent in European gene pool. If so, you'd wonder why evolution didn't cull it out by survival of the fittest selection process. It turns out that the mutation prevents salt and water loss in the host and so can prove to be an advantage when there are cholera epidemic that can kill people through dehydration! So, single mutation could be advantageous. But if a man and a women both with single mutation have a child, it can inherit double mutation that results in CF! 

Similarly, I had wondered as to how an entire organism like a human being is formed from a single fertilized cell. We know about cell division and the DNA in the cell serves as the recipe to make the human being. But as the cells divide, how does the process knows not to grow a thumb where your head is? If you don't have the patience to read this 600 page book, you can read this old but small article that lays out the details to a good extent. Research done on C. elegans (a small worm) to understand this phenomenon discussed in the book is fascinating. Author covers Nazi Germany and segregated US's eugenics efforts, development of companies like Genentech, inventions created to use viruses to carry bits of DNA that need to be implanted into bacteria and then animal/human cells, all the Nobel prizes harvested over the decades, latest ethical concerns in labs in China rushing to modify human genome that may propagate endlessly into future civilizations and concluding with the need for a deliberate well thought out mandate to guide this field into an appropriate future that we could be proud of. 

One thing I didn't like is the lack of drawings/pictures/images. I think the work is extremely well suited to carry a lot of illustrations. But the author states that he prefers to paint word pictures so that readers can generate their own vivid mental images. I couldn't agree with this view. I certainly would have appreciated lot more drawings close to the text describing them. (Even few photographs included are bundled into a contiguous section of few pages in the middle of the book.)

I am sure before my time is over, I am going to see at least two major revolutions that will reshape human lives phenomenally. One is going to be in the IT (Information Technology) area with the advent of ubiquitous high speed wireless networks (think 5G and beyond) combined with machine learning/AI. The other is going to be in genetic engineering. While the front seat view should be fascinating, hopefully the journey and destinations will be as safe in biotechnology as self-driving cars promise them to be!! :-)

Happy New Year!
-sundar.

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