Control, p.18
Control, page 18
When it comes to genetic diseases, which have very serious implications, then the game is not so funny. Even with the best understood genetic diseases such as cystic fibrosis, the picture is very messy. Around two-thirds of people of White European descent with CF have the same mutated version of the gene CFTR. The ΔF508 version makes a protein that is truncated, like a sentence that is several words too . . . The truncated CFTR doesn’t work well in its role for moving salts in and out of the cells that line the lungs, and the result is a thick mucus that inhibits breathing. This genetic etiology may sound confidently clear, yet more than fifteen hundred other mutations in this one gene have been described that can also cause CF. Furthermore, even for the majority of people who have the common ΔF508 version, the severity of the symptoms is far from identical, and in 2015, five genetic modifiers were identified that were not part of the CFTR gene at all but had significant roles in how severe the disease was. How these genetic variations affect the patients is not known.
These are the traits and diseases that we know the best, the ones we teach as the basics in schools. And yet they are riddled with complexities that to my mind preclude gene editing interventions as a means of eugenically removing or altering them from an individual and from future generations. Because of the nature of our DNA, the permutations are effectively infinite. Yes, variants in MC1R are part of the cauldron that cause red hair, but the variants are endless. Yes, versions of OCA2 significantly influence eye color, but the variants are endless. Yes, the vast majority of CF patients have the same mutation in a single gene, but thousands do not, and to understand the endless variants in this disease and thousands of others is the ongoing work of some of the best scientists in the world.
For complex traits, obviously, the picture is only going to get much, much more complex. Those genetic variants associated with traits or disorders such as intelligence or schizophrenia number in the hundreds, each individual version tilting the scales ever so slightly toward one end or the other. However many genes are involved—several hundred or a thousand, according to the most recent studies—each one of them contributes a tiny fraction of the total heritability that we can measure.
When it comes to intelligence, yes, there are variants in hundreds of genes that load the odds toward slightly greater success in the metrics of cognitive abilities when we look at populations with similar ancestry. This is good knowledge, and worth knowing. It takes real expertise to figure out just what is going on in our genomes, but real chutzpah to suggest action based on this incomplete knowledge. The predictive value of knowing the genes involved in height or intelligence (or any trait, for that matter) is worked out by correlating them with the known outcome in a population—you look at the DNA in adults and match them to their heights or cognitive abilities, or whatever you’re interested in. We can’t do that in the same way for embryos because this technique has been available for only a couple of years, and those embryos could still only possibly be babies at this time. The variants are known because we can look at the genes in huge populations, hundreds of thousands, from which statistical significance emerges. But embryos generated during IVF come in batches of very small numbers, maybe eight or ten, if you’re lucky. A team of American and Israeli scientists modeled the possible utility of embryo selection in 2019, as proposed by people like Stephen Hsu. The results are not very impressive. The researchers used a battery of statistical techniques to work out what range of height or intelligence might emerge during a hypothetical round of IVF. The answers came out at just under an inch, and 2.5 IQ points. The typical error margins around IQ are about plus or minus 5 points, meaning that when you get an IQ score of say 120, it was actually somewhere between 115 and 125 when you took the test. And as for height, well, I can get up to six feet tall with the right shoes and hair product.
So, from a practical point of view, embryonic selection for complex polygenic traits is barely viable. It’s a costly, technical procedure for arguably marginal gains that could be applied to a handful of people already undergoing IVF. And let’s not forget that IVF is not exactly an easy procedure. Any woman who has been through it will confirm this readily. It’s a lot less fun than sex, and people who go through this arduous, emotionally fraught and often physically painful process mostly do it as a last resort to have kids when the standard options have not borne fruit.### It’s not fun and it’s not a game. You may have noted that most of the people who knock around the idea of embryo selection tend not to be the ones who will have to endure the daily rounds of injections to induce ovarian hyperstimulation, or the needle through the vaginal wall to get access to the ovarian follicle. The people who seem most excited by the idea of eliciting molecular control over reproduction don’t tend to have wombs at all.
Would I want to select embryos with those variants, or even edit the genomes of embryos to harbor those variants? No. Not while the roles of those bits of DNA are poorly understood. Not when we don’t know if selecting for something means you are inadvertently selecting against something else. One study found that IQ positively correlates with anorexia, anxiety disorders, attention deficit hyperactivity disorder and asthma. Though, as I’ve argued, the gains might be slight, a nudge taller or smarter, you may also be nudging that child toward an eating disorder or other unforeseen health problems.
I would also not want embryo selection when the gains of those variants are so marginal that they can be overwhelmed by solutions that are known, and understood, and can be deployed to populations instead of individuals—things as radical as education for all without privilege, tailored to individual needs. Things like better nutrition, health care, exercise, welfare. If we want the betterment of our people—and who doesn’t?—we don’t need to turn to a scientific creed that is at best poorly understood. When people preach about the possibility of improving a person or a nation’s cognitive abilities, they almost never have done the legwork to understand the issue. We don’t have the knowledge or the tools, and the expense would be colossal for the probability of a gain that could easily be swamped by the inherently uncontrollable nature of biology and life. Biology is unruly, and therefore cannot be ruled. I struggle to imagine a time when this will ever be different.
My caution is not derived from fear, nor from a political stance about liberty or control. It is from a position of expertise. I know that what I’ve written in the last few pages is technical and possibly difficult for a lay reader. You didn’t pick up this book to get an undergraduate university course in human genetics, and I’ve barely skimmed the surface. But that is kind of the point. The glibness with which nonexperts start waffling on about a new eugenics enabled by current technology is frustrating to hear, because it is only in the technical nuts and bolts of basic biology that we can comprehend how wrong they are, or how improbable or impossible the proposals might be. Or that they are flirting with an idea that in history caused so much harm, without the knowledge to back up the claim that it might be different this time. Just as the first time round, and probably the next time, they simply turn to a science they don’t fully understand.
DID EUGENICS WORK?
As I hope you can see, I am extremely skeptical about the possibilities of enhancing or removing genetic traits or diseases from populations using the technologies available to us (or rather, to some) today. Whether these qualify as eugenic interventions is up for debate, but in some ways I don’t really care. I think it’s reasonable to assume that if these technologies were available to the Victorians or Edwardians or Nazis, then they would be excited at the prospect of changing biology as a means of population control.
The eugenics enacted in the first half of the twentieth century defined cultures and conflict, and became a central pillar of the global stage. Science as policy is never clean or tightly controlled as it would be in a lab, but the mass sterilizations and murders did happen, justified by their scientific beliefs, naïve and political though they were, which means that we can ask questions about how successful they became.
We can look at the actions and extract some kind of information about heredity in populations. Obviously, just as eugenics in the Third Reich merged with deranged, racist, homophobic and hate-filled ideologies, many of those actions will not survive much scientific scrutiny.
Homosexuality cannot be eradicated because it is natural and not maladaptive. Of course, homosexuality is heritable (as per the first rule of behavior genetics), but sexual behavior is not a binary; some people are exclusively gay, others bisexual, some exclusively heterosexual. Some people change their sexual preferences during their lives. Others hide stark differences between their thoughts, words and deeds. There is a genetic component to sexual behavior and that includes homosexuality, but those genes don’t make you gay. You don’t have to be a world-class geneticist to notice that every homosexual person who has ever existed was the result of heterosexual sex.**** If your deranged, hate-filled desire was to murder every single gay person in a country, well, first you wouldn’t be able to identify them, and second, in the very next generation after this horrific genocide, you’d still have a proportion of gay people, and a rainbow spectrum of all the sexual proclivities that humans enjoy. Indeed, one study from August 2021 cautiously suggests a possible reason for the persistence of same-sex behavior despite its superficially appearing to be something that nature would select against—as homosexual people tend to have fewer children. What was found is that the genetic elements that associate with same-sex behavior also associate with an increased number of sexual partners in heterosexual people. It’s a preliminary study, and the data limited to people in the United States and United Kingdom, but if correct, whatever those individual bits of DNA that correlate with an increased probability of homosexual behavior are, they are being preserved in heterosexual people anyway. Killing gay people would not alter the existence of the genetic architecture that comes with gay people.
Very obviously, the largest part of the Holocaust was an intention to purify the Nordic race. This was folly squared, because there is no Nordic race, and there is no such thing as racial purity. The tangled web of ancestry that is the genealogical truth of human history precludes even the vaguest concepts of racial purity, and every Nazi had Jewish ancestors, just as every White supremacist today has North African, southern African and Middle Eastern ancestors, if only they bothered to look at and understand the basics of population genetics. The only thing pure about the Nazis’ focus on Jews, and on Roma and Slavs, is its racism. There is no possible scientific justification for this hatred.
But what about the diseases that the Nazis sought to eradicate? Under the 1933 sterilization law, many diseases and conditions were included, and some specified: schizophrenia, bipolar disease, hereditary epilepsy, Huntington’s disease, severe alcoholism and others.
As institutionalization grew, the number of patients in psychiatric care had increased radically in Germany in the first few decades of the twentieth century (as it had done in Great Britain and America as well), but with the introduction of the principle of “lives unworthy of life” in 1920, these patients’ continued existence was increasingly precarious. A psychiatrist named Berthold Kihn calculated that the number of psychiatric patients in German hospitals was costing the state 150 million Reichsmarks per year, and Hitler agreed that this justified their killing: “It is right,” he said in 1933, “that the worthless lives of such creatures should be ended, and that this would result in certain savings in terms of hospitals, doctors and nursing staff.”
Around a quarter million patients were killed or sterilized—astonishingly, this represents somewhere between three-quarters and all diagnosed schizophrenics in Germany in the years 1933 to 1945. Again, the numbers are not straightforward to verify, but in various studies, the prevalence of schizophrenic patients—that is, the number of people in Germany already living with the condition—was low in the years immediately after the war, lower than other European countries at the same time. But the incidence—that is, the number of new cases—was high and increasing. A study encompassing the years 1974 to 1980 revealed an average of 59 schizophrenic patients in the Mannheim area of Germany per 100,000. This compared with an average of 24 per 100,000 for eleven studies done in the Netherlands, Italy, Denmark, Norway, Iceland, the United Kingdom, the United States and Australia.
There are many factors that could account for this. Better and more specific diagnoses is one, though this should mean the prevalence would also increase postwar, but it did not, and the diagnostic criteria are the same in other countries. It is not entirely clear what the precise diagnoses were for schizophrenia before 1945, but it is likely that they were actually broader than when criteria were formalized and defined in the modern era. Another possible reason is a changing demographic; in the Mannheim study in the 1970s, 13 percent of the population were immigrant workers. But on inspection it was found that the immigrants had a significantly lower rate of schizophrenia than in the established German population.
Whatever the reasons, the fact that the incidence of schizophrenia had significantly increased within three decades since the last patient was murdered or sterilized shows that the policy was ineffective and scientifically specious. They should have known that: it was already well established that the majority of schizophrenia patients do not have children themselves, and do not have a family history of the disease. Though it is unequivocal that there is a significant genetic contribution to the risk of schizophrenia, the environmental influences are quite capable of amplifying the incidences without regard to its biological heredity.
Ironically, the Nazis’ combination of scientific ignorance, naïveté and a steadfast commitment to action may well be the cause of the increase in schizophrenia in Germany. Many psychiatric conditions are associated with poverty and living in hardship. It is possible, though difficult to account for, that the state of war, and a broken country in the aftermath of devastating destruction of its people and infrastructure, increased the environmental risks for individuals to develop mental health problems. In at least one scenario, this phenomenon is verifiable.
In September 1944, the Nazis were aware that they were in the endgame and were going to lose the war. In a bitter act of defiant retaliation, they blockaded a large part of western Holland. They embargoed food transports and removed cattle and other food stocks. The canals had frozen by November, and very quickly famine struck. The Hunger Winter lasted until April 1945, when the U.S. Army Air Forces and the Royal Air Force (and other Allies) enacted Operations Chowhound and Manna—eleven thousand tons of food drops that the Nazis agreed not to shoot at. Hundreds of thousands of Dutch were starving, and some eighteen thousand people died in those six or seven months. With rationing records from this time, and good demographic data about who was present and who was conceived during this cruel famine, scientists have followed up with the survivors and their children, and have garnered a huge amount of data on the effects of starvation on people—effectively, an experiment that should never have happened. It is well-known that children conceived during the famine have hugely increased incidences of a whole range of conditions, which include both the physical and psychiatric. Of these, the risk for schizophrenia doubled. The Third Reich’s eugenics program was an attempt permanently to eradicate the cause of a disease, but what they actually did was only temporarily quash the symptoms and simultaneously create an environment in which it would flourish. Recall that calculation that psychiatric care was costing the state 150 million Reichsmarks per year in 1933. It’s not a linear conversion calculation, but in today’s money that is roughly $925 million. The most recent assessment of the cost of treating schizophrenia in contemporary Germany puts the bill at around $13 billion.
Unlike schizophrenia, Huntington’s disease does have a single-gene cause, and it is invariably lethal. It’s a brutal disease, with rapid degeneration of physical control, starting with fidgety movements, slurred speech and difficulties in swallowing. It also comes with depression and other mental health problems, including obsessive-compulsive disorder and bipolar disease, and after a few years from the first signs, people die without any control or basic bodily autonomy. One of the key characteristics for the majority of people with Huntington’s is that symptoms tend to show up only when carriers of a single copy of the mutated gene are in their forties, which typically is after they have had children. A child of a person carrying the Huntington gene has a 50–50 chance of inheriting it, and if they do, they will suffer the disease in adulthood (if they don’t die of something else first). This means that until very recently, people often passed on the disease gene to their children before they knew that they had it themselves. Today, we can identify children that have inherited the disease gene from a parent at birth, and in the cases of IVF, in utero, but that was not possible in the days before prenatal genetic diagnoses.
A policy that sterilizes adults who have Huntington’s symptoms is already too late to remove the defective gene from the germline and the population. This is one of the reasons that Huntington’s disease persists. Part of the first crucial work on the inheritance pattern of Huntington’s was done in 1916, again by America’s chief eugenicist, Charles Davenport, who claimed that most cases in the Americas could be traced back to three immigrants, probably brothers, from the seventeenth century. If this were true, it serves the eugenics principle that Huntington’s disease would not exist at its current frequency if these brothers had not become fathers. It also served the narrative that went hand in hand with eugenics, which is that immigrants are undesirable.
With that relatively simple inheritance pattern, Huntington’s path through families led geneticists of the 1980s to the mutated gene that causes it. There are two ways that Huntington’s can be eradicated for future generations. The first is that all carriers of the disease are identified before they have children of their own, and using a combination of genetic counseling, prenatal diagnosis, and if necessary pre-implantation genetic diagnoses, only embryos that do not carry the disease gene are allowed to survive. This basically is what happens today in the wealthy West, but owing to the fact that Huntington’s is often not identified in people until after they have had children, and this type of intervention is expensive, that ship has already sailed. The second option is to do the same, but sterilize the children who carry the disease gene before they have children. Either way, we erase Woody Guthrie from existence.
