The Gene: An Intimate History, By Siddhartha Mukerjee

RATING

1 star

N/A = good but not on the scale

1 star = perspective supplementing

2 stars = perspective influencing

3 stars = perspective altering

SHORT SUMMARY (272 words or less)

I’m surprised at how recent the discipline of genetics has evolved (sic) compared to other fields like physics and chemistry.  Aside from some dabbling by Ancient Greeks, it wasn’t until Gregor Mendel and Charles Darwin that the area was explored.  Darwin’s theory of natural selection determined that organisms, over generations, adapted to survive external conditions, but he couldn’t place how this information was passed to progeny.  Mendel almost concurrently discovered the idea of plant hybridization.  This was only about 150 years ago.

The field of genetics exploded from there.  Mutagenetics and genetic variation theories were explored.  Ultimately the Nazis used eugenic experimentation in their Final Solution, and even before then, in some absolutely horrific ways.  The Soviets were just as macabre, but even in the United States, some terrible legal decisions were made on the basis of eugenics.

Interestingly enough, after fleeing Nazi Germany, physicist Schrodinger postulated the idea of a molecule that was sophisticated and strong enough to carry and replicate information.  DNA was discovered centuries earlier, but no one really knew what it did.  The chase towards identifying DNA function structure is just fascinating.  High drama with a cast of characters.  Franklin, Pauling, Watson and Crick.

The function of DNA is something that is just fundamentally magical and inspirational to me.  I appreciate it a lot more than I did when I learned this stuff in high school.  And what’s even more fascinating, we are just at the beginning of understanding this field.  Lot more info in this book, but these are the things that jumped out at me.

LONG SUMMARY

-Ancient Greeks first came up with the notion of shared genetic information.  Pythagoras thought that male semen traversed the male human body collecting mystical vapors.  He believed this information then transferred to the mother.  Basically, the thought was that the mother was just a vessel for the baby, not conferring any genetic information.  It wasn’t until 200 years later (seriously!?) that Aristotle realized that some babies look like their mothers more than their fathers and thus women must be contributing some sort of heredity.

-Fast forward a couple thousand years, and people thought that all people were homunculus–basically people within people.  The thought went that within each man was a miniature person carried in sperm.  And inside that miniature person, there was another miniature person.  And so on, human nesting dolls, all the way back to Adam.  It was an interesting thought that physically we were linked to the original biblical humans.

-Charles Darwin at the Galapagos formed his theory of evolution but could not explain the foundation for how organisms passed along favorable qualities.

-Gregor Mendel, Darwin’s near-contemporary discovered the idea of plant hybridization.  That tall plants that were cut short begat tall plants in one generation but could beget short plants in a subsequent generation.  Thus the idea of dominant and recessive genes (and genetic dormancy) was born.  Crazy to think that Gregor Mendel’s main discoveries were only like 150 years ago. Genetics, compared to other scientific disciplines, is pretty new.

-Genotype = specific genetic profile; phenotype = physical expression of the genetic profile

-Genetic variation–type of genes and order of expression affects phenotype.  So you can have ABC have one expression and CBA have a different expression.  Genes + variation/order + environment + other factors (such as favorable reproductive attributes) = phenotype expression.

-Herman Muller:  discovered mutagenesis (genetic mutations resulting from radiation).  He was doing his research in the 1910s and 1920s.  Moved to Germany in the 1930s, before the Nazi’s took full power.

-Nazi eugenics- The Nazi’s, starting in 1939 and before their Final Solution, had implemented an extermination policy called Lebensunwertes Leben, translated as “life not worthy of living.”  Basically, they designated a bunch of characteristics that they deemed subpar for humans (physical and/or mental disabilities) and sent children under the age of 3 to extermination centers where they were euthanized.  Ultimately, this practice spread to older children and then adults.  Overall, about 250,000 were killed and more sterilized under this program, a precursor to the larger Holocaust.  Interestingly enough, the term “genocide” shares the same root word as the word “genetic.”

-The Nazis also performed experiments on twins at their concentration camps.  Every time I read something about the Nazis, they set a new standard for the worst of mankind.  They would single out twins and segregate them from the rest of the camp population to perform sadistic experiments on them.  Things like exposure to extreme heat and cold, killing them to measure differences in organ size, injecting chloroform into subjects’ hearts, surgery without any anesthetics…depressingly the list goes on.  In one particularly evil example, a person with a hunch back had his back sewn together with his twin to see if the two people would be able to share a single spinal cord.

-The Soviets took an equally sadistic, but a different perspective than the Nazi’s with respect to genetics.  If the Nazi’s believed on a horrific scale the malleability of genetics, the Soviets saw genetic science as almost heretic (no pun intended).  Basically, the Soviets thought that genes didn’t really exist and that physical characteristics could be transformed through physical and chemical manipulation.  They tortured people through exposure to “transformation,” particularly shock therapy.  The author makes a good point–in both instances, government views and perspectives on genetics helped reinforce and promote nation states that used these views to promote killings and genocide.

-During the Nazi rule, many scientists, professionals and scholars left Germany.  Often, scientists who had moved explored areas of study other than their primary discipline.  Interesting fact–while in Dublin in the 1943, physicist Erwin Schrodinger postulated in his book “What is Life?” that genetic information must be carried and passed on by a strong and complex molecule, called an “aperiodic crystal.”  DNA was discovered centuries earlier, it was not known to have heredity importance.  This book helped contemplate the idea for a molecule resilient and strong enough to propagate genetic information.

-Super nerdy side note:  In doing more research about Schrodinger’s book, I came across another one of his paradoxes.  Most people know about, or at least heard of, his more famous paradox, the Schrodinger’s Cat thought experiment–an analogy to explain the idea of quantum superposition, the idea that quantum particles can exist in multiple states at the same time.  The Schrodinger’s Cat analogy goes like this:  say you lock a cat in a box with a radioactive particle that in one state may decay and release stuff to kill the cat or in another state not decay and thus not kill the cat.  According to quantum superposition, the radioactive particle would be in both states (in the decay state and the nondecay state) at the same time.  Thus, the cat would be both alive and dead at the same time.  It’s only until you open up the box and observe whether the cat is alive or dead does the superposition go away.  Sounds really crazy, but some modern quantum theories say that this is quite true.  That quantum particles can be in more than one state at the same time and that act of observation can effect the state.  Schrodinger’s other paradox in the book involves the second law of thermodynamics, which says in a nutshell that given enough time, all isolated system go from ordered states to states or disorder (a concept known as entropy).  However, since life appears as an ordered system, it appears that the entropy law is violated.  This paradox is resolved in two ways:  1. life itself is part of a biosphere and thus not it is not an isolated system and 2. though life organisms may be ordered, life sustains itself by adding more disorder to the universe to preserve it’s ordered state.  It’s an interesting thought, that to maintain order, life creates a net disorder.

-Griffith experiment and bacterial transformation:  In 1928, during the Spanish Influenza outbreak, Frederick Griffith designed an experiment where he injected mice with different strains of pneumococcus bacteria to try and derive a treatment for pneumonia, a byproduct killer of the flu pandemic.  The bacteria had two strains: rough strains, which were easier for an immune system to fight and smooth strains that were more difficult.  The rough strain alone did not kill the mice, the smooth strain alone did kill the mice.  A heat treated smooth strain did not kill the mice, but a combination of the rough strain and heat treated smooth strain did kill the mice.  In this last example, when each strain was injected individually and alone, they were not lethal, but in combination they were.  Thus, Griffith was able to infer that the bacteria was able to “transform”.  That is, even though the heat treated smooth bacteria by itself was not lethal, it’s genetic code still produced a combination killer strain.

-Avery experiment and the importance of DNA:  Oswald Avery built on Griffith’s experiment in 1944 by determining that the nucleic acids (specifically DNA) in cells, not protein, were responsible for bacterial transformation.  For a while after Griffith and before Avery biologists believed that it was all about protein and that DNA was just a dumb molecule.  Avery initially started this search with that perspective in mind, but he found that whenever he tried to breakdown and destroy proteins with enzymes, the transformation still persisted.  But when he broke down DNA with DNA-ase (a DNA reducing enzyme), the transformation qualities were lost.  Thus, it must be DNA and not proteins responsible for the bacterial transformation.

-The road to discovering of the DNA structure is just simply fascinating.  For anyone thinking about reading this book, the section related to this story is just gripping.  Basically, the idea by Maurice Wilkins was to take a picture of DNA and from the shadow deconstruct the structure.  Rosalind Franklin was really good at taking pictures of the crystalline structure.  Linus Pauling tried to create a replica triple helix structure from the deconstruction technique.  James Watson and Francis Crick were able to take the images generated by Franklin and derive the double helix structure.  Basically, Watson and Crick took physical objects that represented molecules to scale and fit them together to build the double helix structure.  They also discovered that the A-T, C-G pairs were complimentary, and thus, these nucleobases were able to fit in the center of the helical spine.  There’s a LOT more to this story, but my summary of it would take up pages and pages.  I suggest everyone read about it.  The author makes a point to say that the structure of DNA is one of the iconic structures in human history–where the form of the structure immediately conveys to the viewer the function of it.  Like a hammer, or a pyramid, the double helix immediately conveys the notion of an information carrying molecule

-After the discussion of the discovery of DNA’s structure, Mukherjee goes into a discussion of the role of DNA.  It’s something I learned about years ago in biology but didn’t really appreciate until now.  DNA is the molecule that contains the genetic information, but how is that information turned into actual proteins that manifest the physicality of the information?  The author uses a great analogy.  Think of DNA as being locked in a vault in the middle of a library.  You first need to access it before you can start building a structure from the information contained in it.  So the DNA is transcribed using messenger RNA (mRNA) and a process called transcription.  This is analgous to getting a photocopy of the DNA in the vault.  After transcription, the mRNA strand has to be translated into physicality.  Transfer RNA (tRNA) takes the mRNA and transfers amino acids from a cell’s cytoplasm to its ribosome for protein construction.  In the analogy, tRNA interprets or translates the photocopy.  So there you have it:  DNA -> mRNA -> tRNA -> protein synthesis.  Or analogously, structure housing genetic information -> copy of information -> translated information with building instructions -> building of molecular structures based on the housed genetic information.  This is just absolutely amazing to me.  I didn’t appreciate this at all when I learned about it in school.  It makes me want to relearn some basic biology.