Learning Potential / Utility: ★★★★★ (5/7)
Readability: ★★★★★★ (6/7)
Challenge Level: 1/5 (None) | 384 pages ex-notes (432 official)
Blurb/Description: Following up on the memorable Disappearing Spoon, pop science writer Sam Kean is back with a well-researched yet story-driven romp through the history and implications of genetics.
Summary: For better or worse, The Violinist’s Thumb finds itself compared not only against Kean’s prior work on chemistry (The Disappearing Spoon, which I thought highly of), but also against Siddhartha Mukherjee’s The Gene (which I did not think highly of – see TG review + notes).
Where “The Gene” suffers from interspersing far too much opinionated and irrelevant social commentary amidst some very good science/history writing, The Violinist’s Thumb has a number of digressions as well that, while amusing and enjoyable, make the beginning of the book seem more “pop” than “science.” Thankfully, the majority of the book – as well as the appendix / endnotes – delivers a lot more scientific punch and learning opportunities.
Highlights: While I wanted The Violinist’s Thumb to be good enough that I could recommend readers ignore The Gene entirely, I come away thinking that they’re complementary books. The Gene covers the pre-modern history and underlying elegant “central dogma” science very well, whereas The Violinist’s Thumb does a far better job of relating genetics to everyday life, as well as certain modern scientific topics like epigenetics.
Kean also does a much better job of sidestepping house bias and controversy; on the rare occasion he offers a social or philosophical insight, it is – totally unlike Mukherjee’s – actually thought-provoking and worth considering, which I wasn’t expecting from a pop-science book.
Lowlights: I was a big fan of the elemental periodic-table organization of The Disappearing Spoon; while that was a bit of a one-trick pony that would be admittedly hard to do with genetics, I thought The Violinist’s Thumb was a bit harder to follow. Similarly, I found that some of the “diversions,” while usually amusing/enjoyable, led too far astray from the science – which I did not find with Disappearing Spoon.
Kean also clearly (based on the endnotes and his casual use of abbreviations like mtDNA) did a lot of reading and learning that I’m not sure translated fully into the pages of the book, which often (in my estimation) seem to provide the “Cliff notes” version of the science and didn’t go deep enough into some of the ideas – I think Kean (or his editor, hard to tell) underestimated the capacity of a lay audience to understand some of the more technical concepts.
Mental Model / ART Thinking Points: salience, utility, disaggregation, ideology, feedback,nonlinearity, trait adaptivity, luck, sample size, margin of safety, n-order impacts, tradeoffs, stress,agency, culture, complexity, multicausality
You should buy a copy of The Violinist’s Thumb if: you want a well-researched and very thoughtful journey through the history and practical implications of genetics, occasionally beset by “shiny new object” syndrome.
Reading Tips: I assumed that because it was a pop-science book it would be a quick read; it’s actually somewhat longer than I expected, so skim appropriately (particularly through any anecdotes that don’t seem like they’re going anywhere scientifically). Tolerate the ADD in the first 100 pages; the rest of the book is better. The book is also fairly modular, so if a certain section isn’t really striking your intellectual match, don’t feel bad about moving on.
Finally, DON’T SKIP THE ENDNOTES – Kean has put a lot of work into them and they are very interesting (in some cases, more so than the non-endnotes they refer to). I read them all at the end, but if you’re more inclined (i.e. less lazy), you could flip back and forth after every mention, or every chapter.
“The Disappearing Spoon” by Sam Kean – a similar (albeit more focused and, in my view, better-written) romp through the elements of the periodic table
“The Gene” by Siddhartha Mukhjerjee (N&A) – it deeply pains me to have to recommend The Gene, as to say that I have serious problems with a substantial portion of the book would be severely understating it. However, stripping away Mukherjee’s extraneous social commentary and odd, scientifically-contradicted presentation of certain issues, The Gene (and especially its first half) provides a much cleaner and more elegant picture of the history and “central dogma” of genetics.
Reread Value: 2/5 (Low)
More Detailed Notes + Analysis (SPOILERS BELOW):
IMPORTANT: the below commentary DOES NOT SUBSTITUTE for READING THE BOOK. Full stop. This commentary is NOT a comprehensive summary of the lessons of the book, or intended to be comprehensive. It was primarily created for my own personal reference.
Much of the below will be utterly incomprehensible if you have not read the book, or if you do not have the book on hand to reference. Even if it was comprehensive, you would be depriving yourself of the vast majority of the learning opportunity by only reading the “Cliff Notes.” Do so at your own peril.
I provide these notes and analysis for five use cases. First, they may help you decide which books you should put on your shelf, based on a quick review of some of the ideas discussed.
Second, as I discuss in the memory mental model, time-delayed re-encoding strengthens memory, and notes can also serve as a “cue” to enhance recall. However, taking notes is a time consuming process that many busy students and professionals opt out of, so hopefully these notes can serve as a starting point to which you can append your own thoughts, marginalia, insights, etc.
Third, perhaps most importantly of all, I contextualize authors’ points with points from other books that either serve to strengthen, or weaken, the arguments made. I also point out how specific examples tie in to specific mental models, which you are encouraged to read, thereby enriching your understanding and accelerating your learning. Combining two and three, I recommend that you read these notes while the book’s still fresh in your mind – after a few days, perhaps.
Fourth, they will hopefully serve as a “discovery mechanism” for further related reading.
Fifth and finally, they will hopefully serve as an index for you to return to at a future point in time, to identify sections of the book worth rereading to help you better address current challenges and opportunities in your life – or to reinterpret and reimagine elements of the book in a light you didn’t see previously because you weren’t familiar with all the other models or books discussed in the third use case.
Page 15: Kean separates the physical entity of DNA from the concept of a “gene” as information… disaggregation.
Pages 17 – 18: the antiquated theory of “homunculuses” – little humans inside sperm or eggs that, of course, had their own little humans inside of them (little humans all the way down!) The advantage of this theory was ideology: it supported the notion of original sin.
Pages 21 – 24: in the late 1800s, scientists determined that nuclein (the old name for DNA) contained phosphates, sugars, and the four bases adenine, cytosine, guanine, and thymine. Kean discusses the double helix form. Scientists noticed that chromosomes were neatly divided when cells split; they also figured out that all cell nuclei contain DNA, but DNA seemed too “dull and simplistic” to carry cell information – proteins seemed more complex (and thus more likely candidates). ( Salience?)
Pages 26 – 27: Kean discusses Mendel’s famous pea-plant experiments (including in the appendix, Pages 363 – 364). What made Mendel successful?
Obviously, it helped that only he (not bees or the wind) could pollinate his peas, but the bigger deal was the “binary, either-or nature of pea plants.”
Kean explains that:
“this focus on separate, independent traits allowed Mendel to succeed where other heredity-minded horticulturists had failed. Had Mendel tried to describe, all at once, the overall resemblance of a plant to its parents, he would have had too many traits to consider
[…] but by narrowing his scope to one trait at a time, Mendel could see that each trait must be controlled by a separate factor.”
Essentially: eat the elephant one bite at a time. Disaggregation.
Pages 29 – 30: Mendel was not appreciated until well after his time (see The Gene for more info).
Pages 33 – 35: Scientists started to grow skeptical of Darwin’s proposition of natural selection as the mechanism for evolution: the two problems were:
A, he didn’t really explain where variations came from, and,
B, he didn’t explain how variations persisted through generations or how, outside of geographic situation, dilution didn’t prevent movement in traits.
More ideology. Many also didn’t like the intellectual implications: George Bernad Shaw despised the “hideous fatalism about it, a ghastly and damnable reduction of beauty and intelligence.”
Pages 40 – 44: Thomas Morgan’s fly experiments mirrored Mendel’s 3:1 ratio; he also noticed that some mutations occurred and transmitted exclusively on male flies – suggesting the notion of chromosomes being gene carriers. He also found that while “linked” genes usually traveled together, they unlinked a smaller proportion of the time – with the frequency of separation being related to how far apart on the chromosomes they were. This was the “pearls on a string” model – genes at fixed locations on a chromosome string.
This process of “crossing over” not only explained uniqueness, but also heredity.
Pages 48 – 49: a couple important concepts here: first, Darwinism and Mendelism complement each other. How? Genes control traits (via RNAs and then proteins, as we’ll learn elsewhere), and natural selection “selects for” those organisms with better genes. Crossing over puts new genes together, which along with mutation, accounts for variation.
Genes aren’t instantly diluted because they’re discrete, so adaptive genes will propagate themselves. Biologists in the 1930s and 1940s found, per Kean, that:
Pages 54 – 57: The story of Tsutomu Yamaguchi, the only officially recognized person to be present for both Hiroshima and Nagasaki (there are far more unofficial people, per Keene). See also the end of The Making of the Atomic Bomb ( TMAB review + notes), by Richard Rhodes (30 or so of the most impactful pages I’d ever read).
Page 59: How DNA is transcribed into proteins: first, the DNA is copied into RNA, which is like DNA but single-stranded and has U (uracil) rather than T (thymine). Biochemists studied it because its concentration spiked around the time of protein synthesis.
The transcribed RNA string is called messenger RNA – it leaves the nucleus and goes to the ribosomes. The ribosome grabs the end triplet; another kind of RNA, a transfer-RNA, arrives bearing an amino acid, but only the transfer-RNA with the right kind of bases will pair. One the right one arrives, the amino acid is transferred, and the messenger RNA shifts down to the next triplet.
Page 64: on the genetic benefits of redundancy / margin of safety: while each triplet only encodes for one amino acid, in some cases, multiple triplets encode for the same amino acid: for example, GCT, GCC, GCA, and GCG all encode for alanine. So many mutations are “silent” and don’t cause problems.
Pages 64 – 71: Kean goes into quite some detail here on DNA mutations. Although we have DNA-repair mechanisms, everyone has some, and the number increases as we age. Ultraviolet rays can fuse Ts together; gamma rays and other forms of radioactivity can delete chunks of DNA or create free radicals which can cleave one or both strands. One-strand breaks are fixable easily; widespread two-strand breaks, however, are often just patched up where a few bases meet, with missing letters filled in, leading to what Kean calls “frameshift” mutations where an extra base is inserted or removed, causing the entire sequence to go badly.
Cells with bad DNA can initiate apoptosis, but if this happens en masse, it can be bad for the organism (this is where many of the horror stories in Japan come from, in addition to the direct burns).
Pages 74 – 76: some interesting notes on “knot theory” – DNA, having to pack its sun-to-pluto-and-back length into a relatively small human body, has to do a lot of contortions, which leads to a lot of gnarly knots (Kean analogizes to what happens when you shove earbuds in a bag.) So we have lots of mechanisms (like “topoisomerases”) to deal with these knots.
Pages 78 – 79: on the linguistic properties of DNA
Pages 81 – 82: on the syntactical and grammatical nature of mutations
Pages 84 – 87: Restriction enzymes in microbes can cut through palindromic DNA; consequently, most microbes avoid palindromes in their DNA. Higher organisms avoid palindromes two, both because it can form self-bonding H=hairpins, and also because it can make crossing over harder.
On the other hand, the Y chromosome can recombine with itself thanks to palindromic effects.
Pages 89 – 92: Kean makes a parallel between data analysis, information theory, and genetics. He notes that pioneer Claude Shannon actually did a genetics thesis. I need to look for books in this area. The Information was terrible (TIG review).
Pages 95 – 102: The story of nun Miriam Stimson is quite interesting (for many reasons). At the time, the base pairing between a, T, C, and G was not known; hydrogen bonding was thought to be impossible in DNA. She didn’t actually come to the right conclusions on the shape of DNA bases, but some of her experimental techniques ended up helping other scientists figure it out.
Pages 102 – 107: Mitochondrial DNA (mtDNA) and the endosymbiosis theory: evidence in favor of it includes that mitochondrial DNA is stored in circles, like that of bacteria, and that there are living relatives of mitochondria.
Kean posits that mitochondrial power (they “store as much energy per unit size as lightning bolts”) removed a bottleneck forevolution. Apparently “primitive microbes expend 2% of their total energy copying and maintaining DNA, but 75% of their energy making proteins from DNA.” Which makes it a bit hard to keep a lot of extra DNA around.
There’s also the concept of mitochondrial Eve here, and the fact that we get mitochondria from our mothers.
Pages 109 – 113: Barbara McClintock, studying corn, discovered “jumping genes” (more formally, transposons) that hop around in the genome. (The “alu” gene is an example.) They can help regulate the expression of other genes.
Pages 121 – 125: hox genes are highly conserved and tightly linked, regulating other genes (and regulated by maternal factors as well as Vitamin A) to ensure correct head-to-toe alignment.
There is a gene called, no joke, “sonic hedgehog.” It helps maintain left right symmetry.
Pages 125 – 136: If you think grizzly bears (Ursus arctos horribilis) are terrifying (and you should), polar bears make grizzlies look like teddies. Where grizzly bears just often aggressively defend their territory if surprised and usually don’t hunt humans, polar bears actively hunt. They’re also, as the various anecdotes on these pages reveal, kind of difficult to kill even with a full complement of weaponry.
There’s some great writing on these pages (“naturally the ship’s carpenter up and died immediately,”) but Kean actually has a scientific point to the story: polar bears can kill you from beyond the grave.
Poisons accumulate At higher and higher doses toward the top of the food chain. Vitamin A Is a fat-soluble rather than water-soluble vitamin, so it can’t be excreted in urine. There is thus compounding as you go up the food chain in a process called bioaccumulation (which is why you’re not supposed to eat swordfish).
Polar bears like eating seals; vitamin A helps seal pups quickly add lots of skin and blubber to protect them from the cold. So when polar bears eat seals, they end up ingesting a lot of vitamin A, which is sequestered in their livers (Kean analogizes and calls it a high-tech biohazard containment facility).
As discussed earlier, two important concepts regarding DNA are that even though the same DNA is present in every cell in the body, it is obviously expressed meaningfully differently in different cells; at the same time, DNA is sort of packed up very tightly, and bits of it have to be unwound or untangled to be transcribed.
DNA wraps itself around protein spools called “histones,” which keeps it tidy but also controls its expression. Acetylating the histone (adding a COCH3) unspools DNA, while methylating cytosine (adding a CH3) can effectively eliminate expression of a gene by preventing other molecules from locking on.
Later, this ends up playing a role in “epigenetics” – but for now, what’s more important is that vitamin A is a “transcription factor” that stimulates growth. It happens to be especially active in skin, so if you eat polar bear liver, and survived to tell the tale, you’re likely going to find your skin peeling off. Fun times.
I’ve recently been on a kick trying to increase my consumption of vegetables, and my natural reaction to this story was concerned that I would accidentally overdosed on vitamin A (I made caramelized carrot soup, kale puree risotto, and 2.5 pounds of roasted brussels sprouts in the span of a few days – all of which I believed to be relatively high in vitamin A.)
After some reading, my fears were allayed – other than the case of a Japanese woman with an eating disorder who was surviving entirely off pumpkin, it seems like it’s difficult to overdose on vegetables, because much of their “Vitamin A” is really in the form of beta-carotene, which our bodies convert to Vitamin A in a regulated fashion.
On the other hand, livers and fish liver oils do contain vitamin A in retinol form, and if you eat enough of those and take a bunch of vitamin A supplements, you probably can cause yourself some problems.
Pages 138 – 146: At one point, the central dogma of biology (DNA leads to RNA leads to proteins) assumed that information can only flow in that one direction, kind of like water only flows downhill. Unfortunately, it turns out that the real world is a little more complicated: there is in fact an enzyme, reverse transcriptase, that does what it says on the tin: it “transcribes” RNA in reverse, creating DNA. Some viruses, notably HIV, function in this manner.
So, why bother with DNA to begin with? The answer is that DNA is more stable and less corruptible than RNA.
In terms of our self-identity, it’s interesting to note that we harbor:
“10 times more microorganisms… than cells”
and that 8% of our genome is actually comprised of virus genes, with only 2% to making us specifically human. (Later in the book, though, I seem to recall the distinction is made between complexity at the genome level and complexity of the organism level: the point is made that if a gene instructed to stop neurons from doubling simply waited two additional codons, that would explain all of the intellectual difference between humans and lower animals, or something like that. Another interesting example of exponential growth)
Not all of this nonhuman DNA is anything bad, though: Kean points to virus genes as helping our immune systems and allowing us to taste starchy foods as sweet.”
Pages 148 – 152: Kean discusses Toxoplasmoa gondii, which is yet another reason to be a dog person: cats literally carry parasites that can cause what Wikipedia refers to as “epigenetic remodeling.” The short version: it can make rodents into paradoxical lovers of cat urine, or form cysts in human amygdalas, impacting the way we process pleasure and fear. And, perhaps (I’m editorializing here), explain how someone could come to love that unlovable-est of creatures, the cat.
Note: your faithful book reviewer may be a dog person.
Other fun stories include: the Cordyceps (zombie ant) fungus!
Pages 158 – 160: It turns out that only about 1% of our genome codes for proteins. What is the rest do? Some of it codes for features that have been disabled, a bit like nerfed semiconductor chips selling at lower prices.
Much of it is “introns” – a bunch of filler between the actual code – the advantage being that you can slice and dice the genome in various ways. For example, if the word “chromosome” was a gene, it might look like:
c…. h… r… o…. mo… so… me…
So, by choosing where to splice, you could create “chromosome,” or words like:
Chrome, come, homo (as in sapiens), Romo (as in Tony), home, rome, some, ho (as in Santa), so, me…
This is generally adaptive, but in some instances, can lead to things getting messed up.
Page 161: Our friend Toxo reappears. The placenta is apparently pretty good at keeping threats away from the fetus, but doctors advise pregnant women to stay away from kitty litter, because apparently Toxo can make it through the placenta and destroy fetal brains. (As if dogs needed another chalk mark in the victory category… the running tally is dogs 7,392,948, cats 0.)
Pages 162 – 164: Placentas are mostly a defining feature of mammals, and according to Kean, apparently evolved from retroviruses. It’s generally pretty good at keeping out threats,But is particularly susceptible to certain types of cancer like leukemia, given that it absorbs a lot of blood and has a lot of growth hormones.
Page 167: On the benefits of breastmilk: it apparently activates genes.
Pages 167 – 170: the “major histocompatibility complex” (MHC for short) is “among the most gene-rich stretches of DNA we have.” It’s extremely unique to people; even relatives have very different ones. What does it do?
It helps us identify cells: it puts stuff from the inside of cells on the outside of cells so roving killer cells from our immune system know not to kill cells that don’t have bacteria or cancer or so on; it also simply identifies cells as being part of us rather than as part of someone else, so our immune system doesn’t decide to terminate them arbitrarily.
This is usually very adaptive, until you need an organ transplant or have a baby growing inside you. The placenta basically hides the baby from Mom’s immune system so it doesn’t get eaten.
Page 172: “atavisms” – ancestral traits that usually don’t show up, but are still latent in our genomes. The punchline: it turns out humans are occasionally born with tails (which I did not know).
Pages 174 – 175: one of our vestigial organs allows us to respond to pheromones, leading to the only rational defense of attraction as a useful input in deciding who to marry: people with different MHCs tend to smell more attractive to each other, and (at least on that dimension) will produce babies with stronger disease resistance.
Page 181: can humans and chimpanzees cross? In what seems like the setup for a bad reality-TV show, one Soviet scientist did try to investigate that.
Page 184: on why sex chromosomes tend to converge
Pages 205 – 206: a gene called apoE separates us from monkeys in allowing us to more effectively metabolize fats and get rid of dietary toxins. I bring this up because A, it’s interesting, and B, nutrition is sort of the Wild West of science.
I once ran across a post citing some research that claimed (based on monkey models) that unsaturated fat and saturated fat are equally bad for you. I’m not enough of an expert to really opine, but if what Kean says here is true, then it’s hard to believe that a monkey model really helps us understand human biology much on the issue of fat metabolism.
Pages 215 – 216: our DNA suggests that, at some point in our past, we were cannibals. ick.
Pages 221 – 230: the history of human migration, as told by DNA. There is more genetic diversity inside of Africa than outside it. also, we all have some Neanderthal DNA – apparently Nordic people have the most.
A big brain in general does make an animal smarter, but it’s not a one-to-one correlation – Neanderthal skulls actually had slightly more room than humans goals.
Nature does not always evolve in the direction more intelligence: brains are biological gas guzzlers, consuming roughly 20% of our caloric intake, and as such, under certain conditions – such as food scarcity – creatures that need less food to power their brains (or, at least, those that are more efficiently able to access food relative to their intelligence) were selected for. Apparently the island “hobbits” might be a function of this phenomenon.
Also, while we gotten bigger since the Middle Ages, apparently were actually 5 inches shorter and have 10% smaller brains since the year 30,000 BC.
Pages 233 – 240: Attempting to study Einstein’s brain did not result in a whole lot of interest. However, we do know a few things about how our brains develop.
One gene, “aspm,” helps us grow a thick cortex and have a high neuron density (which Kean says correlates strongly with intelligence – thankfully, he doesn’t make bizarre sociopolitical arguments like Mukherjee in The Gene, and instead sticks to science.)
Our friend apoE apparently also helps brains by managing cholesterol and promoting brain plasticity. Our intelligence may not have taken off until 6,000 years ago. Finally, neurons Seem to have a much higher incidence of transposon activity than other genes, leading some researchers to believe there’s a relationship to brain function.
Page 245: On complementary technology: chromosomes are so named after the Greek word chroma meaning color (incidentally, also the name of a fantastic album by Cartel that I can’t even believe is 15 years old now). Anyway, European chemists developed new dyes and pigments in the 1800s that scientists used two stain and study chromosomes.
Page 250: Apparently chimpanzees like painting and will throw temper tantrums if you take their canvases away. Here is a chimpanzee painting. Why he occasionally tastes the paint is not clear, unless he’s trying to get the bottle unstuck.
Page 251 – 254: Once again, Kean demonstrates his ability to tackle complex scientific issues with much more objectiveness and thoughtfulness than Mukherjee despite his relative lack of scientific training: discussing linguistic skills or lack thereof (dyslexia), which show strong genetic correlation, Kean notes that while it’s clear that there is a genetic contribution, it’s not always clear which genes are involved (and their function in different people can vary). There is one gene, foxp2, however, that seems to clearly play an important role.
Pages 254 – 262: Perfect pitch is genetic. More to the point of the title of the book, the most talented violinist of all time, Niccolo Paganini, Was able to do incredible things because of a genetic condition that is believed to be Ehlers-Danlos syndrome (EDS), which makes synthesis of collagen difficult. This has benefits like extreme flexibility, but also creates debilitating ailments elsewhere. Trait adaptivity tradeoffs, and n-order impacts…
Kean also brings up the concept of sexual selection. Death/survival is one pressure, of course – you either die a hero, or live long enough to, oh wait, nevermind, wrong quote – but of course, someone who lives a really long time but doesn’t pass their genes along isn’t going to be terribly useful.
Kean notes that this can lead to the transmission of traits that are maladaptive in a strict fitness sense, and may be an explanation for the persistence of artistry (even when it occasionally goes along with crazy, or in the case of Paganini, worse). Kean, making what I find to be an insightful observation on utility and local vs. global optimization:
“It just goes to show that people’s sexual desires can all too easily get misaligned from the utilitarian urge to pass on good genes. Sexual attraction has its own potency and power […]”
See also Helen Fisher on how love is like cocaine for our brains.
This also pops up in birds; Jennifer Ackerman’s “The Genius of Birds” (Bird review + notes) has a section discussing whether or not song performance is a good indicator of a male bird’s genetic fitness. There is some reason to believe there is a plausible causal mechanism, but ultimately, Ackerman observes:
“It’s not clear whether a male’s song performance actually correlates with his performance on other cognitive tasks. The evidence is mixed.”
She notes Ronald Fisher’s “pioneering model of sexual selection” which posits that “extravagantly beautiful traits – even when not useful – may have evolved simply because they were preferred by the opposite sex.”
So, yeah. Interesting to think about.
Finally, of course, there’s this bit from Nudge ( Ndge review + notes) by Sunstein/Thaler, which may be getting a little off-topic but I’d just like to leave it here for your enjoyment. On overconfidence, hyperbolic discounting, and base rates…
“Unrealistic optimism is at its most extreme in the context of marriage. In recent studies, for example, people have been shown to have an accurate sense of the likelihood that other people will get divorced (about 50 percent).
But recall the fact that they have an absurdly optimistic sense of the likelihood that they themselves will get divorced. It’s worth repeating the key finding: nearly 100 percent of people believe that they are certain or almost certain not to get divorced!
It is in these circumstances, and in part for that reason, that people are immensely reluctant to make prenuptial agreements[,] believing that divorce is unlikely, and fearing that such agreements will spoil the mood…”
Pages 262 – 264: if you wanted the gruesome scientific explanation of why incest is bad.
Page 276: more on why incest sucks, Tutenkhamen edition
Page 278: Kean says “hereditary madness was endemic among European royalty between about 1500 and 1900.”
No wonder democracy was so attractive.
Page 279: JFK had an autoimmune disease, Addison’s, which ruined his adrenal glands and depletes the body of cortisol. Too much cortisol (the stress hormone) is bad, but too little is bad too. Nonlinearity / dose-dependency.
Pages 286 – 291: on Darwin’s mysterious illness(es), which could have been caused by anything from Chagas disease to genetic flaws to a combination. Also, more incest.
Page 293: As stated in the review, Kean, unlike Mukherjee, doesn’t inject opinion or philosophy into the science very often – but when he does, unlike Mukherjee, it’s worth listening to and thinking about. This might be my favorite quote from the whole book: in reference to several people with hereditary ailments, Kean notes:
“This [groping about in DNA sequences for the roots of illnesses] misses a deeper point about Darwin and others – That they persevered, despite their illnesses. We tend to treat DNA is a secular soul, our chemical essence. But even a full rendering of someone’s DNA reveals only so much.”
Applause for that. Agency.
Pages 311 – 313: on the complexity and multicausality of biological systems: reminding me a bit of the radiology and Dr. Lock portions in Jerome Groopman’s excellent How Doctors Think ( HDT review + notes), Kean notes that the Human Genome Project (HGP) hasn’t revolutionized medicine the way some thought it would. Kean provides a rare interpretation and it’s a really good one:
“As Venter and others have pointed out, virtually no genetic-based cures have emerged since 2000; virtually none appear imminent […] the pace of discoveries has frustrated everyone.
It turns out that many common diseases have more than a few mutated genes […] it’s nigh impossible to design a drug that targets more than a few genes. Worse, scientists can’t always pick out the significant mutations from the harmless ones. And in some cases, scientists can’t find mutations to target at all.
Based on inheritance patterns, they know that certain common diseases must have significant genetic components – and yet […] the “culprit DNA” has gone missing.”
Kean goes on to note some of the potential causes: different function of the noncoding DNA “introns,” which scientists understand less well, gene-gene interactions, the potential for duplicate copies elsewhere, the potential for chromosome-structure effects that are not captured in sequencing, the fact that there are many pathways (via small factors) to the same end result (say, high cholesterol).
“[in the HGP], many scientists lost sight of [a point] in the rush to sequence: the difference between reading a genome and understanding it. [earlier on the page:]
Sequencing confirmed how few genes humans have.[..] and forced scientists to realize that the exceptional qualities of human beings derive not so much from having special DNA as from regulating and splicing DNA in special ways.”
Pages 314 – 315: epigenetics, the idea that the environment can imprint changes on our DNA that may actually be passed (in a limited way) between generations, is a throw-back to Lamarckian genetics
Pages 320 – 327: an intriguing discussion of epigenetics
Page 334: in the “drugs are bad, mmkay” category: heroin and cocaine can permanently misspool DNA.
Page 338: on “secrecy”
Pages 341 – 343: returning to the “genetic determinism” argument (as propagated, for example, in The Moral Animal), Kean notes that genes “deal in probabilities, not certainties.” He points out that clones would only be as alike to their parents as identical twins are to each other: which is, in some cases, surprisingly not. probabilistic thinking and, again, complexity.
He also discusses the Greek story about planks that is in The Gene as well, and goes on to very briefly review the genetics of sexuality.
Pages 344 – 348: On the importance of not mixing sociopolitical ideology with science: in discussing some geneticists’ refusal to think in terms of race, Kean notes that “for one thing, some ethnic groups respond purely – for purely biochemical reasons – to certain medications for hepatitis C and heart disease, among other ailments.” In other words, idealistic sociopolitically-driven race-blindness doesn’t make for good medicine. Mukherjee could take a tip from Kean here.
On page 347, Kean offers some more philosophy about the difference between “what’s natural” and “what’s right,” and the importance of not being sensational on both sides of the political spectrum. Amen.
Pages 348 – 354: An interesting note I wish Kean had dived deeper into: “[geneticists] need to determine how culture – itself a partial product of DNA – bends back and influences genetic evolution.” Also some Feynman-like imagining about the future of genetics.
Pages 363 – 364: the endnotes display just how much work Kean put into researching this book. 363 – 364 contains some nice discussion of Mendelian genetics and recessive/dominant genes.
Page 366: getting nerdy on the central dogma
Page 368: some ridiculously expensive book recommendations
Pages 373 – 374: an example of DNA splicing in the fruit fly. Also a recommendation for A Cabinet of Medical Curiosities.
Page 376: Craig Venter’s team apparently encoded quotes about Robert Oppenheimer and by Richard Feynman into DNA as a tracking tag.
Page 378: here’s ther eference I mentioned earlier: in the endnote for page 235, Kean notes that a stem cell programmed to divide 32 times would end up with 4.3 billion neurons; a stem cell programmed to divide 34 times would end up with 17.2 billion neurons – the difference between chimpanzees and humans. compounding
Page 381: on lactose intolerance
Pages 382 – 383: on how an amateur scientist noticed something professional geneticists failed to spot
First Read: early 2018
Last Read: early 2018
Number of Times Read: 1
Review Date: early 2018
Notes Date: early 2018