Michael Mentele

learning-review

Book Review: The Gene

Book Author: Siddartha Mukherjee

Quotes:

Human beings are ultimately nothing but carriers – passageways – for genes. They ride us into the ground like racehorses from generation to generation. (Haruki Murakami)

Introduction

I wanted to learn the history of genomics. I’ve known of Mendel but I didn’t have a clear roadmap of how the field has progressed to the present day.

So, I picked up The Gene. This is a complete history of genetics from Aristotle to Mendel to Craig Venter by Suddartha Mukherjee in ~500 pages.

I’ll give you the cliff notes version though I highly recommend going back and giving it a read – there is nuance and stories from history like how Mendel’s paper–one of the most important in biology sat on Darwin’s desk unread and went undiscovered for decades after his death… (seems to be a theme for important work in biology). Or how Rosalind Franklin got screwed when it came to discovering the structure of DNA.

The Gene underscores that science is a far messier affair then one realizes. It is rampant with politics, bias, and confusion. Ego runs wild. We get eugenics and books like Galton’s ‘Hereditary Genius.’ Scientist’s themselves are incredibly flawed human beings but somehow there is a latent public ideal that scientists are somehow not susceptible to the normal human foibles. Looking at history, it is clear they are.

Eugenics in the US surprised me. The whole racial hygiene ideal seemed absurd. As an engineer I believe everything is tradeoffs. The idea that one group is better than another is silly. The idea that certain people with certain conditions are inferior could only hold water if you had consensus on what you are optimizing for. But you will never get that.

I support the positive ideas of eugenics, in that there is value in genetic enhancement and the elimination of disease – as long as it opt-in. That is, if I had a condition I could choose to have a gene therapy to change that condition. I believe it is a human right to have self-sovereighnty so for that reason I don’t think their is anything wrong with willful participation in designing your biology. I think we all have that right. But to have someone force a change upon us or take our lives from us is a horror and a violation of our social contract.

Timeline

What is interesting about the timeline is how backloaded it is. No notable progress has been made until the early 1900’s and then the more recent acceleration of the last 50 years coinciding wth molecular biology and recombinant DNA.

The book follows chronologically the fascinating journey of understanding and manipulating heredity. The key events:

  • 350 BC
    • aristotle argues heredity is passed as a message from the father’s semen and grown in the mother
  • 1859
    • Darwin publishes the origin of the species
  • 1865
    • Gregor Mendel identifies discrete units of inheritance through his experiments with pea plants
  • 1869
    • Galton writes Hereditary Genius and coins the term eugenics
  • 1900 - 1909
    • Mendel’s work is rediscovered and the term ‘gene’ is coined
  • 1908 - 1915
    • Morgan and his students prove genetic linkage (locality in the genome) and crossing over
  • 1927
    • Carrie Buck is sterilized in the eugenics movement in the US
  • 1934 - 1935
    • Nuremburg laws for the protection of hereditary health are passed – precursors to the brutal nazi eugenics that were to follow
  • 1933 - 1939
    • the german biological state launches a campaign for racial cleansing
  • 1943
    • the deranged Mengele launches brutal and scientifically useless studies on twins
  • 1941 - 1944
    • Avery proves DNA is the fundamental carrier of genetic information
  • 1953
    • Watson, Crick, Wilkins, and Franklin discover the hylical structure of DNA
  • 1945 - 1960
    • Genes are found to act by encoding RNA
    • Gene regulation is discovered
  • 1961 - 1963
    • the genetic code is solved!
    • three basepairs, a ‘codon’, code for an amino acide
  • 1968 - 1973
    • Berg, Cohen, and Boyer create recombinant DNA
  • 1975
    • the asilomar conference is held and rules for how to play with biology are established
  • 1970 - 1980
    • new techniques to clone and amplify genes are invented
  • 1976
    • cancer found to be a disease caused by genetic mutations
  • 1978 - 1988
    • disease linkage maps are created for diseases
  • 1990
    • a single gene – SRY is found to determine maleness
  • 1994
    • a massive genetic study debunks the concept of race (???)
  • 1998
    • human embryonic stem cells are derived
  • 1999
    • Jesse Gilsinger dies after attempted gene therapy
    • the wild west of genetics get’s clamped down on
  • 2000
    • draft sequence of the human genome is announced from the Human Genome Project
  • 2005 - 2008
    • studies on the human genome write the history of human migration and origin
  • 2009 - 2013
    • genes for acute disease like autism, bipolar disorder, and schrizophrenia discovered
  • 2010 - 2015
    • new methods for gene editing are invented such as CRISPR

Key Events

I see a few key moments in this timeline that are worth talking about:

  • The origin of species in 1859
  • the discovery of Mendel’s work in 1900
  • Thomas Morgan’s experiments from 1908 - 1915
  • The discovery of DNA as the carrier of genetic information in 1941
  • the discovery of recombinant DNA by Berg, Cohen, and Boyer in 1968 - 1973
  • the linkage of diseases to genes from 1976 onwards
  • the human genome project draft announced in 2000
  • the discovery and popularization of CRISPR in 2012

These in my opinion represent major turning points in our understanding and conceptualization of biology from the macro scale to the micro. Moving from understanding the mechanism of inheritance to just beginning to modify, engineer, and change it to suit our own purposes.

The origin of the species is significant because before that humans thought god had created all the creatures of the earth. No. This book outlines the concept of natural selection and how creatures have come to be by the process of gradual evolution (natural selection) over vast swathes of time. Now that the collective psyche has this idea in their head they can now perform tests against this idea. Make models and predictions. Instead of stupidly classifying “god’s creatures” into useless taxonomies.

A second major milestone is the discovery of Gregor Mendel’s work on pea plant hybrids in the early 1900’s. This was critical because a key flaw in Darwin’s theory was how there could be inheritance and variance. How could mutants arise? How could variation occur that could then be selected upon? It seemed paradoxical that information could be passed down with fidelity generation to generation but variatiton had to also be introduced. How did that occur?

Mendel’s study on pea plan hybrids demonstrated that there was discrete carriers of information, genes, that determined what an organism phenotype was. This revealed that what you see isn’t what you get. Just because you have brown eyes doesn’t mean you don’t have an allele for blue eyes. Mendel demonstrated that you had two alleles of a gene, one from each parent. He was able to show these ‘genotypes’ were true, that there was a dominant and recessive gene for exampls (two alleles) and they were both present and passed through to their offspring but the offspring could have a different phenotype than the parent. This could explain how variation could happen (to some degree) because the child’s phenotype could be different from the parents due to the alleles present while still having fidelity and conservation of genetic information.

Unfortunately, there were still problems. The key problem was that while we now had this idea of a unit of heredity it didn’t always hold true. Their were (exceptions)[https://www.glowm.com/section_view/heading/Mendelian%20Inheritance%20and%20Its%20Exceptions/item/342]

Thomas Morgan resolved some of these issues with two key discoveries:

  • the locality of genes or gene linkages
  • crossing over of genetic information

Then eventually we developed the technology to actually inspect and observe the genetic information. Physics provided us with a molecular description of biological components. Understanding rapidly accelerated from here on out.