By Jamie Metzl | 1 May 2016
After 4 billion years of evolution by one set of rules, our species is about to begin evolving by another.
Overlapping and mutually reinforcing revolutions in genetics, information technology, artificial intelligence, big data analytics, and other fields are providing the tools that will make it possible to genetically alter our future offspring should we choose to do so. For some very good reasons, we will.
Nearly everybody wants to have cancers cured and terrible diseases eliminated. Most of us want to live longer, healthier and more robust lives. Genetic technologies will make that possible. But the very tools we will use to achieve these goals will also open the door to the selection for and ultimately manipulation of non-disease-related genetic traits — and with them a new set of evolutionary possibilities.
As the genetic revolution plays out, it will raise fundamental questions about what it means to be human, unleash deep divisions within and between groups, and could even lead to destabilizing international conflict.
And the revolution has already begun.
Today’s genetic moment is not the stuff of science fiction. It’s not Jules Verne’s fanciful 1865 prediction of a moon landing a century before it occurred. It’s more equivalent to President Kennedy’s 1962 announcement that America would send men to the moon within a decade. All of the science was in place when Kennedy gave his Houston speech. The realization was inevitable; only the timing was at issue. Neil Armstrong climbed down the Apollo 11 ladder seven years later.
We have all the tools we need to alter the genetic makeup of our species. The science is here. The realization is inevitable. Timing is the only variable.
Not everyone has heard of Moore’s Law, the observation that computer processing power roughly doubles every 18 months, but we’ve all internalized its implications. That’s why we expect each new version of our iPhones and laptops to be smaller, do more, and cost less. But it’s looking increasingly possible there may be a Moore’s Law equivalent for genomics. In our world of exponential scientific advancement, the genetic future will arrive far faster than most people think or are prepared for.
This future is arriving, quite literally, in baby steps. In fact, the first state-authorized genetically altered babies will be born in the UK later this year.
The British Parliament voted in February last year to allow clinical trials of Mitochondrial Transfer, a process designed to eliminate the passing of mitochondrial disease from mother to child. The transfer of mitochondrial DNA from the female donor to the mother’s egg or nuclear parents’ early-stage embryo in this procedure is small, adding less genetic material than in a blood transfusion.
‘Three-person’ baby boy born in Greece https://t.co/dCtVkN4FbH
— Dr Greg Wilson (@uk_oncologist) April 11, 2019
But the third-party donor’s mitochondrial DNA will pass through the generations forever. The first of these facetiously called “three-parent babies” are set to be delivered as early as this summer.
Mitochondrial Transfer is a first and in many ways relatively small step. But the use of heritable genetic alterations to reduce or eliminate genetic diseases will not and cannot end there. If we can eliminate mitochondrial disease with genetic transfer, won’t people with other genetic diseases want us to spare their future children? They will and we will do it, and our collective comfort level with genetic manipulation will increase.
The birth of Louise Brown, the first “test tube baby,” in 1978 shows how quickly a new technology can shift from being revolutionary to normal.
Then, her birth shocked the world and was called a “moral abomination.” Today more than 5 million babies have been born through IVF and the rate is increasing annually.
According to Pew, only 12 percent of Americans feel IVF is “morally wrong,” and having an IVF baby doesn’t surprise anyone. Enhanced reproduction will follow the same trajectory. As it does, our genetic future will unfold in three overlapping stages, each already in progress.
Preimplantation genetic selection
First, we will use the existing technologies of IVF and preimplantation genetic selection (PGS) to a more focused effect.
With PGS, two cells are generally removed from three- to five-day-old embryos that have been fertilized outside the mother, and then sequenced. The average woman having her eggs extracted produces 15 viable eggs. Younger women tend to produce more and older ones less. If all of these eggs are fertilized during IVF, the parents would usually have around the same number of preimplanted embryos from which to choose.
Currently, PGS is used primarily to screen for single gene mutation diseases such as Huntington’s and Sickle Cell Anemia and, in rarer circumstances, for gender selection. With scientists around the world conducting massive amounts of genetic research and our knowledge of the genome expanding by the day, this process will eventually be used to screen for more complex diseases such as forms of cystic fibrosis and type 1 diabetes that are influenced by more than one gene.
Once we understand how to spot diseases or disease susceptibilities in the genome, parents using IVF and PGS will have the option of choosing to implant embryos likely to avoid these outcomes.
Given the choice of which of their natural embryos to implant, most will choose ones with the greatest perceived potential for optimal health. As the prevalence of this spreads, preimplantation embryo screening will begin to eliminate many of the terrible genetic diseases that have plagued our ancestors for millennia.
But as IVF and PGS increasingly become the way people around the world conceive their children to avoid disease, many will want to know what the already-sequenced genomes of their unimplanted embryos say about other traits.
When the Human Genome Project was completed in 2003, the program had cost a billion dollars and taken 13 years. Today, sequencing a genome takes a day and costs around a $1,000. By the end of the decade it is projected to cost around $50 and require just a few hours.
The cost of sequencing a human-sized genome.
From $100,000,000 to $1,000 in less than 20 years.
— Max Roser (@MaxCRoser) June 6, 2019
But most reasonably advantaged people will have their genomes sequenced as the necessary foundation of personalized care in the coming age of precision medicine even before those costs decline – a process being sped up by President Obama’s Precision Medicine Initiative.
As the massive amount of raw genomic data is compiled and compared to people’s life experiences and new tools are utilized to switch genes on and off in animal models, scientists will make even greater progress understanding complex polygenic traits and the broader ecosystem of the genome.
The genetics of intelligence, for example, is influenced by thousands of genes.
Michigan State Professor Stephen Hsu argues convincingly that we’ll be able to predict people’s IQs from their genomes with significant accuracy within a decade. Height is also the result of hundreds or more genes making different parts of the body a little longer, which is why tall humans aren’t just tall because they have necks like giraffes. According to Hsu, we’ll probably be able to predict height within a couple of years.
In most cases, these predictions will not be absolute but mathematical propensities. An embryo might have a disproportionate genetic overlap with Olympic sprinters or winners of the Fields Medal for math or people who don’t get Alzheimer’s, and parents will be able to make relatively informed decisions on which embryo to implant based on big data genomic analysis.
Because all of the embryos will contain the unadulterated genetic material of the two parents, we won’t need to have a complete understanding of the genome to make this approach appealing. A relatively well-informed guess will do.
Armed with this information about which of their 15 or so embryos has the potential to have the lowest risk for genetic disease, the highest IQ, and the greatest potential for living a long and healthy life, many parents will choose to have that embryo implanted first if they are in or can get to a jurisdiction where this is allowed.
An increase in eggs
The second overlapping phase of the human genetic revolution takes a further step by promising to bump up the number of eggs available in IVF.
The average male ejaculation contains hundreds of millions of sperm, but human females can produce eggs in the low teens at most in the extraction process. Researchers have already developed technologies to induce unlimited numbers of mouse stem cells into egg cells and then actual eggs.
Although this process is not close to being safe for humans, it is a good bet that one day it will be.
If so, women undergoing IVF would be able to have not just 15 or so of their eggs fertilized, but hundreds. Instead of screening the smaller number of eggs as in traditional PGS, these parents would be able to review screens for hundreds of their own unadulterated embryos, supercharging the embryo selection process.
Choosing from among hundreds of early-stage preimplanted embryos significantly increases the probability that genetic outliers — geniuses in one form or another, people with extraordinary skills — could be selected. It may even someday be possible to breed genetically selected male and female embryos together to speed up the generational genetic enhancement process.
Although embryo selection, empowered by big data analytics, is the near-term future of assisted reproduction, other technologies are likely to push the process forward even more.
In the third phase of the genetic revolution, many parents will consider the possibility of not just genetic selection but of genetic alterations for their children. The application of precision gene editing to alter the genetics of early-stage embryos is the farthest away from widespread human adoption but getting the most attention in the scientific community and popular media today.
Gene editing tools have been around for years, but the recent development of the CRISPR-Cas9 (and lesser known cpf1) tool allows scientists to edit the genomes of all species with far greater precision, speed, flexibility and affordability than ever before — a breathtaking advance with enormous potential for good.
CRISPR uses the cell’s own immune system to target, cut, and sometimes replace fragments of DNA. Its use is exploding in plant and animal research and applications. Just last year, scientists used CRISPR to fix defective genes in mice that had caused Duchenne muscular dystrophy and a rare, inherited form of liver disease. Preliminary lab work is underway exploring alterations of human cells to correct inherited blindness. Many other genetic diseases are in the queue.
Preliminary experiments have recently begun in China and the UK with non-viable human embryos to explore potential ways to prevent certain blood disorders, miscarriages and HIV. It will be some time before CRISPR will safely be used to alter the heritable traits of humans, but that day will come because, like embryo selection, precision gene editing will help us fight disease and live healthier and longer.
The scientific concepts behind CRISPR are complicated, but the actual application is not. Gene editing and other genetic technologies are no longer confined to governments, clinics, and large corporations. The DIYbio, or biohacking, movement is exploding around the world. High school kids can now engineer genes in their basements, hobbyists in their garages.
With CRISPR, it will ultimately be scientifically possible to give embryos new traits and capabilities by inserting DNA from other humans, animals, or even synthetic sources. If splicing a single gene from a macaque monkey into a human embryo ensured the future child would not get Alzheimer’s or from a Naked Mole Rat to eliminate the possibility of cancer, would those crossings of the human-animal barrier be worth it? Would the answer be different if we were not selecting against disease but for traits like better vision, smell, or hearing?
Of course, life experience will still matter in a genetics age. Being loved and cared for, eating healthy food, and having access to good schools and health care will always be essential for helping children of all types realize their potential. There’s no way to determine the balance between nature and nurture in human development. Both are important. But twin studies suggest genetic inheritance determines between 50 percent and 80 percent of who we become. Within that range, there is really no limit to the traits that can, over time, be better understood and potentially selected for or altered in some way on a genetic level.
Our ever-striving species, which has embraced every technology promising to deliver enormous benefits but also bringing potential dangers — nuclear energy is an example — will not be able to resist the genetic revolution. Opposing it would be more like opposing agriculture because we have concerns about GMOs. We cannot and should not. We will want to eliminate genetic diseases in the nearer term, enhance human capabilities in the medium term and, perhaps, prepare ourselves to live on a hotter Earth, in space, or on other planets in the longer term.
But we should make no mistake. The genie is already out of the bottle. The genetic era has begun.
If ours was an ideologically uniform species, this transformation would be challenging. In a world where differences of opinion and belief are so vast and levels of development so disparate, it has the potential to be cataclysmic.
For starters, not everyone will be comfortable with genetic enhancement based on some people’s understandable ideological or religious beliefs or for real or perceived safety concerns. Life is not just about science and code. It involves mystery and chance and, for some, spirit.
For people of faith and many others, we will never understand what makes a human no matter what we know of genetics or body chemistry. And no matter what we think we know, history is littered with the corpses of past scientific certainties later proven wrong at best and deadly at worst.
As recent advances in understanding the epigenome, virome and microbiome have shown, the human body is always far more complex than we appreciate.
These types of concerns are largely intuitive to Americans and others.
A January 2016 poll of a thousand American adults conducted by STAT and Harvard’s Chan School of Public Health found that although 69 percent of Americans had heard nothing or not much about genetic enhancement, nearly the same number felt that genetically altering unborn babies to reduce their risk of developing serious diseases should be illegal. Eighty three percent felt that genetic alterations to improve the intelligence or physical characteristics of unborn babies should be banned.
— Julian Savulescu (@juliansavulescu) December 3, 2019
Those opposing the application of genetic technologies to their offspring for whatever reasons will always have the ability to opt out. Those choices, however, on both the individual and societal levels, will have consequences.
If the division and violence that has stemmed from the genetically modified crops and abortion debates is any guide, the coming struggle over genetically selected and modified humans could well become a defining conflict for future generations.
And just as conflicts over the future of human genetic engineering will likely emerge within societies, conflicts between states could easily break out as well.
In the February 2016 Worldwide Threat Assessment America’s Director of National Intelligence delivered to Congress, genome editing merited its own section for the first time ever. Although the applications for biological warfare are currently America’s most pressing genetics-related national security concern, the broader set of genetic challenges are clearly not far behind.
Beyond conflicts between groups and countries, the potential dangers to the species as a whole are also very real.
Our evolution and survival to date have been based upon random mutation and competition. Might genetic technologies push us toward a dangerous genetic monoculture if we start selecting the traits of our children based on uniform, narrow, and culturally biased categories like IQ? No matter what the intention of parents, might genetic selection of children become a form of liberal or not-so-liberal Eugenics that challenges the moral core of our humanity? Might it encourage us to devalue the critically important and varied contributions everyone makes in a diverse society? Could it inspire parents to push their specifically-enhanced children toward predetermined destinies that could make them miserable?
There are no easy answers to any of these questions.
Recognizing this challenge, the United Nations General Assembly and other international bodies have tried to create global frameworks for genetic technologies. Because no global consensus exists, it should be no surprise they have failed completely. Leading scientists around the world also understand the implications and challenges of the genetics revolution and have been meeting regularly to discuss how to balance ethical and scientific goals.
Whatever the intentions of diplomats and scientists, the fact remains that the science is surging exponentially, popular understanding of it is advancing linearly at best, and the regulatory framework surrounding it is only creeping forward glacially.
This mismatch between what the science can do and how poorly people understand and are prepared for it is creating an extremely dangerous public tinderbox.
Absurd numbers of Americans panicked a year ago when four cases of Ebola showed up in the United States. The American public had not been socialized to the challenge even though Ebola had been plaguing parts of Africa for decades.
Because a rational conversation about the need to build infrastructure in West Africa to stanch the disease was therefore not possible, the American conversation, when it finally showed up so late in the game, sowed fear and forestalled a more logical and helpful response.
A far more irrational and dangerous panic will likely emerge when genetically modified humans start appearing among us unless we can have an informed conversation today about the opportunities and challenges of human genetic enhancement.
A species-wide conversation on our future has never before been carried out. We didn’t do it at the dawn of the industrial or nuclear ages for understandable reasons, even though we might have avoided some terrible outcomes if we had.
With a growing percentage of the world population connected to the information grid in one way or another, we now have a limited opportunity to avoid making the same mistake and begin laying a foundation for decisions we will need to collectively make in the future. Given the political divisiveness of this issue, the window will not stay open long.
Such a conversation would involve connecting individuals and communities around the world with different backgrounds and perspectives and varying degrees of education in an interconnected web of dialogue.
It would link people adamantly opposed to human genetic enhancement, those who may see it as a panacea, and the vast majority of everyone else who has no idea this transformation is already underway. It would highlight the almost unimaginable potential of these technologies but also raise the danger that opponents could mobilize their efforts and undermine the most promising work to cure cancers and eliminate disease.
But the alternative is far worse. If a relatively small number of even very well intentioned people unleash a human genetic revolution that will ultimately touch most everyone and alter our species’ evolutionary trajectory without informed, meaningful, and early input from others, the backlash against the genetic revolution will overwhelm its monumental potential for good.
Homo Sapiens of the world, let us begin this conversation.
Reprinted with permission from the author.
— Patrick J. McGinnis (@pjmcginnis) August 19, 2019
Are You Ready for the Genetic Revolution? | Jamie Metzl | TEDxPaloAlto
Homo Sapiens 2.0: The Future of Human Genetic Engineering – Jamie Metzl (Atlantic Council)
This Is How We Will Live Longer & Healthier | Jamie Metzl | TECH | Rubin Report
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