Book Review: Carl Zimmer - She Has Her Mother's Laugh

The most important decision you can make in your life is who to have children with. This is understood more or less unconsciously by practically everyone, but the true nature of heredity - precisely what traits we inherit from our parents, and how we bequeath them in turn to our own children - is far more complex and subtle than we give it credit for. Zimmer traces our conception of heredity from one kind of ignorance to another, from our historical innocence of its genetic basis to our current incomprehension of what the ultimate consequences of our newfound power over it will be now that we have powerful tools like CRISPR. He does a great job balancing the pop sci elements of genetics 101 with the more complex cultural consequences at each stage of our understanding, so as concepts like X-inactivation, mosaicism, or epigenetics get discovered, you get crucial context as to how people used that new knowledge for both good and ill. The word "eugenics" casts a long shadow over our current attempts to consciously affect how our own heredity works, as it should, but the incandescence of real scientific knowledge is enough, or should be, to give us confidence that as we begin to use genetic engineering to deliberately reshape our genes that we don't have to simply repeat the old bigoted mistakes of the past. Our DNA might blindly attempt to replicate itself, but we don't have to, and a clear-eyed assessment of the possibilities in front of us should give us a great deal of optimism for our descendants.

The first genetics class I took was in 7th grade, and the Darwin vs Lamarck debate was one of the first things we covered. I often take a dim and impatient view of science classes that insist on walking students all the way back through the buried strata of ancient debates like that - much like "ontogeny recapitulates phylogeny", in Ernst Haeckel's famous line, most intro classes force students to recapitulate the history of the development of the subject matter by dredging up lots of discarded hypotheses - but genetics is complicated enough to be worthy of a comprehensive review, since some aspects of Lamarck's hypothesis are still being debated. I'm always amazed how ancient peoples could simultaneously spend hundreds or thousands of years patiently turning teosinte into corn or wolves into sheepdogs, yet be foggy on what exactly children share with their parents or why specifically it might be unwise to follow in your ancestor's footsteps and marry your first cousin, or think it was plausible that giraffes have long necks due to stretching. Pioneers of fruit and vegetable breeding like Luther Burbank, or even Gregor Mendel himself, had to spend an ungodly number of hours untangling phenotypes, proposing, rejecting, and concocting ever more elaborate hypotheses to explain why successive batches of peas and raspberries exhibited maddening almost-regularities, so retracing their thought patterns is still valuable and relevant. I particularly sympathized with Mendel, since in class when we learned about Punnett squares, the simple example of a dominant/recessive trait we were given was eye color. This confused me since both of my parents have green eyes yet I and my two siblings all have brown eyes. Theory destroyed? No; this is perfectly explicable given that eye color is in reality controlled by multiple genes, but if I were a 19th century monk trying to figure it out I'd have thought it was quite improbable given my naive monogenetic heterozygotic model.

So in that light it's not so surprising that the ideology behind inbred dynasties like the Ptolemies, Hapsburgs, or Romanovs lasted so long: if you want your children to inherit "royalty", then the more royals in their lineage the better! And of course the notion of heredity has been used to justify not only the continued rule of the strong, but also the subjugation of the weak, such as in the awful cases of the so-called "feeble-minded" individuals Zimmer profiles who were sterilized or otherwise dissuaded from having children due to stupid ideas about inherited cretinism. Intelligence remains the most hotly-debated form of heredity, since both nature and nurture seem important. Most people, including geneticists, freely acknowledge that there is at least some environmental influence, but it doesn't seem like anyone really believes that the choice of person who provides the other half of your child's genes is completely irrelevant to their welfare. If who you had kids with truly didn't matter at all, the world would look a lot different! This knowledge that your partner matters is also true for inherited diseases, as seen by the many techniques to reduce the chances of passing on congenital conditions via genetic testing and deliberate matching. A more innocuous trait like height, which is no longer as adaptive as it used to be (instead of a reliable marker of superior health, now that basically everyone has enough to eat it usually just signifies a difficulty fitting into tiny sports cars or airplane seats), falls somewhere in between, and so it took polymath Francis Galton, Charles Darwin's cousin, many hours of staring at height charts to come up with innovative statistical concepts like regression to the mean in order to explain why the children of the tall were not always the size of their parents, or how the odd pair of short people often produced average children. He was also the guy who first systematically fitted human attributes to Gaussian distributions, vastly improving our ability to analyze psychological and behavioral traits.

But many of the more fascinating aspects of heredity had to wait for modern science to come around in order to be studied in more detail. The discovery that not all cells are the same (mitosis-using somatic cells which make up your body vs meiosis-using zygotic cells that make up sperm and eggs) was fairly recent, as was the distinction between totipotent cells (which can turn into anything), pluripotent cells (which can become any type of somatic cell), and multipotent cells (which are limited to specific cell genres). Also interesting to me were things like lyonization/X-inactivation, where clumps of cells decide at once whether or not to express certain traits and produce things like calico patterns in cats, or the distinction between mosaicism (different cell lineages inside the same organism, so your body is generating multiple lines of mutation within yourself) vs chimerism (where your body can include cells from other organisms, meaning a mother can actually back-inherit genes from her baby via reverse travel up through the placenta). The idea that your body depends on other organisms that you don't share any DNA with - things that are in you but not of you - is worth a ponder. Zimmer got the bacteria in his belly button analyzed, and found that he had 53 distinct species present, including 17 species that hadn't been seen before. Your specific intestinal ecosystem of gut bacteria is crucial for digestion. Less whimsically, mitochondria, which are crucial because they provide the body's energy via conversion of oxygen and sugar into ATP, are also separate organisms, yet are inherited almost but not quite entirely exclusively from our mothers (ancestry services like 23andMe use mitochondrial DNA to infer maternal lineage). He also relates the fascinating case of a form of infectious canine cancer which has been spreading from dog to dog for an almost unfathomably long time:

Contagious cancer is not all that different from an ordinary tumor that becomes metastatic and spreads from one organ to another. The new organ is, in effect, another animal. But unlike ordinary tumors, contagious cancers no longer face an inescapable death. Instead of gaining a few years' worth of mutations, they can gain centuries of them. After eleven thousand years circulating among dogs, for example, CTVT has acquired an impressive arsenal of mutations in genes linked to immune surveillance. And just like ordinary cancer cells, CTVT cells have stolen mitochondria to replace their own. The only difference is that they steal mitochondria from a series of dogs - at least five different dogs over the past two thousand years. From the days of the Roman Empire onward, CTVT has recharged itself like a vampire, with the youth of its canine victims.

More difficult for people to accept was the idea that the same DNA can be expressed differently based on environmental stimulus; epigenetics and gene expression seemed dangerously close to the ideas of Lamarck or Lysenko, the Soviet charlatan who thought that you could breed winter-resistant wheat by sowing the seeds in snow. Zimmer quotes geneticist Keven Mitchell expressing extreme skepticism that your life experiences as stored in your neurons could affect your sperm/eggs in order to thereby affect your children's neurons:

For transgeneration epigenetic transmission of behaviour to occur in mammals," he wrote, "here's what would have to happen:Experience --> Brain state --> Altered gene expression in some specific neurons (so far so good, all systems working normally)-->Transmission of information to germline (how? what signal?) --> Instantiation of epigenetic states in gametes (how?) --> Propagation of state through genomic epigenetic "rebooting," embryogenesis and subsequent brain development (hmm...) --> Translation of state into altered gene expression in specific neurons (ah now, c'mon) --> Altered sensitivity of specific neural circuits, as if the animal had had the same experience itself --> Altered behaviour now reflecting experience of parents, which somehow over-rides plasticity and epigenetic responsiveness of those same circuits to the behaviour of the animal itself (which supposedly kicked off the whole cascade in the first place)

Put that way, it does sound science fictional, like the genetic memory in the Dune series. Particularly that last part: if our minds are shaped by our parents' life experiences, how would we then pass down our own experiences to our children in turn without our experiences being overridden, unless all we're doing is transmitting Nth generation photocopies of particularly vivid days in the lives of our cavemen ancestors ceaselessly unto the future? But, fascinatingly, it seems that it is actually possible for plants to inherit certain gene expressions of their ancestors; whether due to patterns of DNA methylation (coatings around DNA that affect their transcription), different RNA interactions during DNA replication, or the distinct sequences of plant germ cells transforming into somatic cells, plants seem to have different tools of heredity than animals do.

Zimmer uses those teases of cellular recollection to segue into a brief discussion of the distinctly human tools of mimesis, social learning, and culture that allow us to pass on far more than our genes to the next generation. Joe Henrich's book The Secret of Our Success is my current favorite book on cultural evolution, and some of Henrich's work on importance of our cultural heritage, which Zimmer estimates as extending back to about 7 million years (!), is cited here. But it's the possibilities of genetic engineering, particularly new tools like CRISPR, that are the most exciting, as the ability to selectively edit individual genes to precisely insert desired traits opens up all kinds of obvious avenues for genetic improvement. I don't think anyone but the most determined GMO conspiracy theorist would have issues with the kind of accelerated horticulture that plant scientist Zachary Lippmann wants to do to ground cherries, like Luther Burbank on fast forward:

He would edit genes that controlled when the fruits fell from the bushes, so that farmers wouldn't have to rummage on the ground for them. He would make a change to get the plants to ripen their fruits in batches rather than a few at a time. He would adjust the plants' response to sunlight so they would start producing fruit early in the growing season. They would grow to a fixed height so that farmers could use machines to gather them.

But people are rightly more worried about what this power could mean for human beings. We still have some time to ponder the ethical boundaries of deliberate gene editing, because it's unfortunately not quite as simple as cutting and pasting genes to make ourselves supermen, though we have already taken some steps into that world. In addition to the fact that CRISPR techniques themselves are still new and unperfected (Zimmer relates the example of some edited female mosquitoes that were somehow able to revert their CRISPR edits during their development from eggs; see also the saga of Chinese scientist He Jiankui from a month ago, well after this book was published), many of the traits we're most interested in depend on thousands of genes working together in ways that are still not well understood. Furthermore, even were we to develop a gene drive that would spread some new ability throughout humanity as fast as we're able to reproduce, there are still countless potential unintended consequences of a mutagenic chain reaction. Personally I'm all for getting rid of genetic diseases, and even conscious editing to encourage health and intelligence, but we have a while before we get there. The dream of a completely deterministic heredity has not yet been achieved, and so in the meantime we can still marvel at how the characteristics that we find most attractive or unique in each other get carried on to each new generation. "Life finds a way" indeed.