Hacking Darwin

by Jamie Metzl

  No common legislation governs assisted reproduction in Europe, resulting in a patchwork of different laws and regulations. Most European states stipulate that PGT can only be used to select against serious and incurable diseases. Some countries, like Italy and Germany,74* are more restrictive, while others, like France and the United Kingdom, have established broader regulatory bodies, the Agence de la Biomédecine in France and the United Kingdom’s Human Fertilization and Embryology Authority, that tend to be more permissive when reviewing PGT applications.75 Because a 2008 European Commission directive makes all Europeans free to travel without penalty to other EU countries for treatments, including PGT, that may be restricted at home, the impact of various national restrictions is muted.

  In countries with strong religious leanings, including Chile, the Ivory Coast, the Philippines, Algeria, Ireland, and Austria, PGT is banned. If someone wants to get PGT in Chile or select a boy in China, they can find an underground clinic, travel to another country, or simply not have it done. A recent survey showed that 5 percent of those receiving assisted reproduction care in European clinics and 4 percent in the United States were people traveling from abroad to circumvent restrictions and other barriers in their home countries.76

  Among the more advanced countries, Australia, Belgium, Brazil, Canada, France, Germany, and the Netherlands prohibit gene editing embryos in ways that would be passed to future generations, most imposing criminal penalties against violators. Rather than banning germline manipulations up front, a second set of countries—including France, Israel, Japan, and the Netherlands—make it illegal to initiate a human pregnancy with a genetically modified embryo. A third set of countries, including the United Kingdom, carves out very specific exceptions to a ban and establishes regulatory structures for making case-by-case decisions about what types of heritable changes can be allowed.

  The United States doesn’t have a ban on heritable genetic alteration of embryos per se but has other regulatory structures that make this type of activity all but impossible. China, on the other hand, has decent laws restricting heritable human genetic manipulation but a weak and often inconsistent oversight culture, a Wild West mentality among some researchers, and a very large, unlicensed “gray market” of assisted reproduction clinics.77 That’s why it was no surprise the highly controversial alleged first gene editing of the human embryos apparently taken to tern in November 2018 happened in a Chinese laboratory with no oversight from the university or government. Other countries have no significant laws on human genetic alteration; some among these are positioning themselves as future destinations for unrestricted human reproductive tourism.78

  The maps on the following pages gives some indication of the diverse regulatory environment for genetic technologies around the world:

  HUMAN GERMLINE GENETIC MODIFICATION

  HUMAN REPRODUCTIVE CLONING

  HUMAN SOMATIC GENE THERAPY

  PREIMPLANTATION GENETIC DIAGNOSIS

  HUMAN RESEARCH CLONING

  HUMAN EMBRYONIC STEM CELL RESEARCH

  Source: R. Isasi, E. Kleiderman, and B. M. Knoppers, “Editing Policy to Fit the Genome?” Science 351 (2016): 337–339.

  Because genetic data will be so critical to both the personalized health care of individuals and the deciphering of human genetics more generally and also so susceptible to misuse by others, societies will have good reason to safeguard the genetic information of its citizens. Here again, national variation is big and growing. Different countries regulate and protect the privacy of genetic and other data very differently.

  America’s 2008 Genetic Information Nondiscrimination Act (GINA), Canada’s Genetic Non-Discrimination act, the United Kingdom’s 2010 Equalities Act, and Australia’s Genetic Privacy and Non-Discrimination Bill prohibit discrimination based on genetic information in health insurance and employment but provide far less sweeping consumer genetic data protections than in the European Union.*

  The EU has gone the farthest in protecting individual privacy rights. In May 2018, the EU’s revolutionary General Data Protection Regulation, GDPR, came into effect. By far the most aggressive data-protection law in the world, the GDPR enshrined the privacy rights of EU citizens to control access to data collected on them anywhere in the world and placed strong new obligations on companies to safeguard that data. Although the international debate over GDPR has largely centered on the pressure it places on U.S. tech giants like Google and Facebook, the implications for genetic privacy are equally significant. Under the GDPR, each subject must give explicit consent for his or her genetic data to be included in a specific data pool or study.79

  China, too, recently passed a comprehensive national data protection law with big implications for genetic information. The 2017 Network Security Law of the People’s Republic of China imposed privacy protection mandates on companies and required an individual’s consent for any data transferred outside of China. The law also bans the transfer of personal information outside of China if the transfer is deemed to damage Chinese vaguely defined national security, public, and national interests. This requirement applies to what the law calls “sensitive” personal information, a category including genetic data.80

  Although Europe and China’s privacy laws may at first seem similar, they are anything but. In Europe, the GDPR is being deployed to protect individual citizens from their data being used without their consent by anyone, including the government. In China, the new privacy law is ensuring a government monopoly over genetic and other data collected from and about people inside China.

  While the EU is working to prevent genetic data from being used to create a police state, China’s Ministry of Public Security is amassing the world’s largest DNA database as, among other things, an investment in social control. Chinese citizens in the country’s predominantly Muslim Xinjiang region and other ethnic minorities, migrant workers, potential dissidents, college students, and activists are being required to provide samples to be entered into the national database.81

  Privacy protection may seem like a justifiable human-rights issue in the EU and an Orwellian control issue in China, but the reality, as always, is more complex.

  For most people, the idea of a government or company tracking every aspect of our lives is frightening. From an individual rights perspective, privacy is essential. From a big-data-analytics perspective, however, it has the potential to be a barrier to pulling together the vast data sets from which actionable insights can be drawn.

  Because understanding what individual and groups of genes do is the ultimate big-data problem, the larger and higher quality the data sets, the more possible it will become to uncover genetic patterns underpinning more complex diseases and traits. Whoever gets the biggest and best data sets will be best poised to lead the genetic revolution with all of the wealth, prestige, power, and influence it will bring.

  It may end up being the case that China’s massive investment in AI, efforts to promote national leadership in life sciences and biotechnology, and ability bring together massive data sets of sequenced people paired with full access to their electronic medical records will put China in the pole position in global efforts to decode the human genome, transform health care, and lead the global genetics revolution. It could alternately be the case that greater privacy protection in the United States and Europe will lead to stronger and more coherent societies, higher standards of genetic and other data collection, and more quality discoveries. Whichever society makes the right bet will be poised to lead the future of innovation. But we should not delude ourselves about what’s at stake and the societal costs of making the wrong bet.

  The environmental, GM crops, abortion, and genetically engineered humans debates show how our different communities, with their diverse histories, cultures, economic pressures, and political structures, respond very differently to new technologies. These dissimilarities then lead to a wide variety of legal and regulatory environments around the world.

  The good news is that the
wide disparity of different approaches is creating a “laboratory of nations,” each finding its own path as it interacts and competes with other states. In this context, the most promising, and sometimes even the most aggressive, research on and applications of any new technologies will find a home, driving innovation forward.

  The potentially bad news is that the diversity of communal beliefs and national models could also move humanity toward the lowest common denominator approach to human genetic engineering. If this should happen, the most aggressive countries will set the bar for everyone else, who must keep up if they believe their future well-being, competitive advantage, and prosperity are at stake. Our diversity of approaches, like all forms of diversity, increases the odds of both positive and negative outcomes.

  Diversity, however, is a biological precondition but does not alone drive evolution. Evolution also needs that other essential ingredient: competition.

  If our different orientations about human genetic engineering establish a wide range of options, competition between us will propel our species into the genetic age.

  *Under the Donald Trump presidency, this burgeoning environmental progress slipped away, and the U.S. government pulled out of its previous commitments to address climate change, scaled down national parks, and gutted the EPA.

  *Genetically modified organisms are ones whose genes have been altered in ways that don’t normally occur through mating. Transgenic organisms are ones where the genetic modification involved adding genetic material from a different organism.

  *Until relatively recently, Germany had among the most restrictive laws in the world protecting the rights of human embryos, stemming largely from the country’s principled reckoning with its murderous Nazi past. Germany’s 1990 Embryo Protection Act forbade the fertilization of human eggs for research and embryos from being donated. In response, German prospective parents often traveled to Belgium to have PGT carried out. As public notions of parenting changed, however, the German government voted in 2011 in favor of allowing PGT under specific circumstances.

  *Interestingly, GINA does not apply to people in the U.S. military or to other forms of insurance, such as life insurance. Genetic nondiscrimination will become particularly important because universal sequencing will show that everyone has a preexisting condition of some type or an increased risk for multiple disorders relative to the general population.

  Chapter 10

  The Arms Race of the Human Race

  When given the opportunity to gain some type of advantage over others, even at a considerable risk, some subset of us takes it. We’ve evolved this way.

  From the moment life emerged, our ancestors entered a never-ending arms race with each other and other species for advantage and survival. We fought our way to the top of the food chain and avoided being ground up as burgers for some other species because we’ve (so far) won that competition.

  In our nomadic, hunter-gatherer days, human groups in many places competed relentlessly with each other, often stealing each other’s resources. When the advent of agriculture, writing, and other technologies made it possible to organize ourselves into larger communities, we wasted no time translating each little technological advantage into individual and collective opportunities to rob, subjugate, and oppress each other.

  The Mongols leveraged the stirrup to give their horsemen additional oomph to conquer much of the known world. The European colonial powers used their advanced ships and weapons to dominate and exploit big portions of the globe. The initial technological advantage the Germans and Japanese enjoyed in the Second World War was overcome by the even more powerful competitive advantage of the American, British, and European émigré scientists who developed the radar, advanced cryptography, radio navigation, and nuclear weapons that helped win the war. In these cases, and so many more, competition fueled technological development even when the technologies being developed had both great upsides and dangerous potential downsides.

  And although utopians for many centuries have imagined a world where we all fully embrace our Buddha-nature and escape the cycle of incessant competition with each other, that day has not yet arrived. Even though levels of large-scale conflict have been decreasing around the world for decades,1 it would be dangerous folly to believe that the genetics revolution with its great upsides and dangerous potential downsides will play out in the harmonious, noncompetitive world we can imagine rather than the highly competitive one we have known. Instead, the magnitude and consequences of this competition will grow as the technology advances.

  In the early years of this expanding revolution, particularly when our understanding of what genes do, how the body works, and what manipulations are most beneficial is in its infancy, an artificial distinction between therapy and enhancement will be maintained. We will be able to maintain the fiction that the genetics revolution is primarily and ultimately about enhancing health care and treating disease. In the early years, doctors working to prevent or treating a certain disorder or disease may want to overshoot the mark of normal by giving an embryo (or even a grown person) extra advantages. Because what is considered a therapy to one person might be considered an enhancement to another, our concept of what is “normal” will prove a moving target. As therapeutic applications of powerful genetic technologies become the norm, the distinction between what constitutes a therapy and a genetic enhancement will increasingly blur.

  We will ask, to give a few examples, whether there’s really a fundamental difference between genetically enhancing someone’s poor eyesight to be normal versus their normal eyesight to be great, or if there’s really a difference between genetically enhancing a patient’s cellular ability to fight a cancer or AIDS that’s already developed or their ability to never get cancer or AIDS in the first place. Parents, in other words, will increasingly wonder if there’s really a difference between giving their children advantages of nurture versus providing the same advantages through nature. The more enhancements like these become available and seen as beneficial, the more competition within and between communities will push our highly competitive fellow humans to want them.

  The sporting world provides a particularly illuminating window into how competitive pressures can and likely will spur a genetic arms race.2

  There is little doubt that genetics play a central role in achievement in sports at the highest levels, where the rules are clearly defined, the capabilities needed for success are relatively specific, and the distribution of nongenetic assets are evenly distributed. That’s why there are so few five-foot players in the National Basketball Association.

  As David Epstein describes in his 2013 book The Sports Gene: Inside the Science of Extraordinary Athletic Performance, Finland’s Eero Mäntyranta was one of the most dominant Nordic skiers in history, winning seven Olympic medals, including three golds, and two world championships between 1960 and 1972. A consummate champion, Mäntyranta had a tremendous work ethic and indomitable spirit. When he and his family were genetically sequenced in the early 1990s, however, it turned out that Mäntyranta and twenty-nine of his relatives also had a very rare single mutation of the EPOR gene. This mutation made them far better able than others to produce hemoglobin, the red blood cells that transport oxygen from the lungs to body tissues, which gave them a far greater than normal endurance capacity.3 Not every relative with this mutation was an Olympic champion. Few were. But having this mutation certainly increased their odds.

  Athletic success is a complex phenomenon that cannot of course be attributed to any one gene, even one like Mäntyranta’s. Lots of other factors like nutrition, parenting, drive, coaching, access, and luck play important roles. But that doesn’t mean single genes can’t be critically important.

  Lots of people have a mutation of their ACTN3 gene, one of the unknown larger number of genes influencing the speed at which muscles contract. Although many athletic performance-related genes have been studied, ACTN3 is so far the only one that correlates with performance across multiple po
wer sports. When researchers knocked out this single gene in mice, the mice lost significant levels of muscle power.4 Having the right ACTN3 variant won’t make you a great sprinter, but multiple studies have shown that if you have two disrupted copies of ACTN3 your chances of making it to the Olympic finals in any sprinting race are virtually nil.

  If you have a mutation of the MSTN gene impeding the production of myostatin, on the other hand, a protein that halts the production of muscles, your muscles keep growing far beyond most everyone else’s. Liam Hoekstra, a child with this myostatin mutation dubbed “the world’s strongest toddler,” could do challenging gymnastics tricks at five months old and pull-ups at eight months.

  Genetics are also proving highly influential in elite marathon running. The spectacular success of Kenya’s Kalenjin tribe, and even more of its Nandi subtribe, is a case in point. Most everybody knows that Kenyan runners have dominated distance running for decades. Between 1986 and 2003, the percentage of Kenyan male runners included in the top twenty fastest times ever in races 800 meters and longer increased from 13.3 percent to an astonishing 55.8 percent. Over the past thirty years, Kenyan-born men have won nearly half of all Olympic medals in distance running events and almost all of the world cross-country championships. But the Kenyan running success story is more precisely a Kalenjin success story.