The field of human genetic engineering is on the brink of changing the world. But how did it get to this point, and what does the future hold? In Part 1, Allegra Chatterjee provided us with a history of genetics from the discovery of DNA’s structure to glow-in-the-dark pigs. Surveying the present capabilities of genetic engineering, Part 2 introduced us to the ways in which it is being applied to identify diseases and genetic traits, paving the way for the manipulation of human DNA. This week we are publishing the final part of the series, which considers new developments in genetic engineering in relation to ethics and bio-capitalism. Chatterjee’s central question is not how this new biotechnology will be used, but how will it be regulated? With private companies and biohackers alike pushing for deregulation, albeit on different grounds, Chatterjee’s urgent calls for governmental regulation of genetic engineering suggest that the fight for the future is already here.
“There are moments in history when new scientific developments open the doors to the applications of new technologies to vast new domains full of promise —and full of potential perils, as well…” 
Few discoveries have promised to so radically change the course of human history and the planet we live on as CRISPR-Cas9. The revolutionary new gene editing tool has surged in popularity among researchers in recent years due to its ability to precisely, cheaply and quickly edit DNA. It can be used to rewrite the genetic code in any cell type in any organism through simple cutting and pasting of DNA, making it arguably the most powerful biotechnology the world has ever seen.
With remarkable speed and specificity, CRISPR has made the previously inconceivable possible. For the first time ever, we are able not only to edit our own genomes in targeted ways, but also to rewrite the genetic code of future generations through the editing of sperm and egg cell DNA, giving us unprecedented control over the trajectory of human evolution.
But how will arguably the greatest scientific discovery of the last century change the world? Although CRISPR and other modern gene editing technologies hold great promise—of eradicating genetic diseases and creating climate change resistant crops, as well as a host of other scientific and social benefits—they also raise significant ethical concerns and present complex challenges around regulation and control. How and when should we use this new capability? Who should be allowed to use it (and to profit from it)? Who should regulate it? How can such regulations be enforced? As with any successful new technology, as well as changing the world for better, CRISPR may also change the way we live in unwanted ways that are difficult to predict.
Regulation and control
On 1 December 2015, scientists, clinicians, policy-makers, bioethicists and others from around the world gathered to debate the ethical, social and legal implications of human gene editing at the First International Summit on Human Gene Editing in Washington DC. The Summit was attended by some of the world’s most eminent geneticists including Nobel laureate Paul Berg, who created the first ever recombinant DNA (genetic material comprised of the DNA from two different organisms), and Jennifer Doudna and Emmanuelle Charpentier, the duo who developed the revolutionary CRISPR-Cas9 gene editing technology, who are tipped to receive Nobel prizes of their own for the discovery. A host of “deep and disturbing” questions were explored, including if and when gene editing should be used to alter human inheritance, when it will be safe to do so and, more controversially, when, if ever, it would be justified to use editing for genetic ‘enhancement’.
Based on discussions at the Summit, the delegates set out a series of recommendations describing their consensus view on how human genome editing should be carried out and regulated in the future. They recommended that somatic genome editing (the editing of all cells except sperm and egg cells), should be regulated according to existing rules that apply to human clinical research, but that altering the DNA of germline (sperm and egg) cells, should have additional regulations imposed, as any changes introduced would be heritable and potentially affect many people if passed down to future generations.
Currently, there is limited data on the long-term generational consequences of germline editing, and any unintended off-target effects could have dramatic implications for many individuals, in contrast to somatic cell editing which would affect just one individual. Germline editing also poses ethical challenges around consent, as descendants affected by sperm or egg cell changes from an ancestor are unable to give their consent, given that they have yet to be born. But on the flip-side, no organism ever gives consent to being born, so why should the situation be any different for genetically engineered organisms? The Summit recommended that germline research should only be permitted for trials concerning the treatment or prevention of disease, with rigorous oversight, and human trials for other applications, such as for the use of genetic ‘enhancements’, should be strictly prohibited.
Currently, no international regulatory framework exists for genetic engineering, and the above recommendations are merely that: recommendations. Each country must evaluate to what extent and in which contexts they will permit editing of both somatic and germline cells, and the laws around human genetic engineering vary from country to country.
UK legislation currently permits research for somatic cell editing, and trials are already underway to develop treatments for diseases including HIV, sickle-cell anaemia and some cancer treatments, amongst many others. Germline editing in the UK is currently only permitted for embryos up to 14 days old, where research is appropriately justified and supported by rigorous scientific and ethical review. The US government currently funds research into somatic cell gene therapy, but from 2016 federal funding for germline cell research has been banned, after a new law was passed through Congress.
Despite this, genetic modification of embryos has been carried out in the US for disease research, using funding grants from elsewhere. Canada is amongst the countries with the most prohibitive laws; human germline editing is criminalised, and punishable by up to 10 years in prison, and a fine of up to $500,000. However, the Canadian Institutes of Health Research is challenging this law, and calling for its legalisation. Other countries, such as India and China, which was the first country in the world to genetically modify human embryos, have more relaxed regulation.
Many are calling for an international agreement on the regulation of human genetic engineering. In a recent speech at the University of Pennsylvania Law School, legal scholar Gary Marchant argued that a lack of international harmony on research regulation may lead to genetic engineering being used by some without appropriate recognition of ethical concerns and potential damaging side-effects.
However, developing such an international agreement is an ambitious goal. The variation in countries’ approaches to the regulation of human genetic engineering are inextricably tied to cultural and religious attitudes, and public perception of science and new technology, which are in turn shaped by the historical context. For instance, Canada’s decision to ban human embryo research was influenced by the negative public reaction to the cloning of Dolly the sheep in 1996 in the UK. It is unlikely that a number of Western countries will ever allow the use of genetic engineering for genetic ‘enhancements’, whereas countries like China are much more open to such practices. Given the deeply ingrained values that individuals and nationals often attach to genetic practices, it may be an unrealistic fantasy to expect an international consensus to be reached.
However, as fear and suspicion of new technology inevitably softens over time, stigma may decrease and attitudes change. It is therefore not unlikely that national human gene editing regulations will become more relaxed in years to come, despite it currently being prohibited in much of the world. In fact, the goalposts are already beginning to shift; just one year after an international group of respected scientists stated that it would be “irresponsible to proceed” at the present time with altering germline cells as any changes would be heritable, an influential report was published by the US National Academy of Sciences and Medicine which endorsed support for the editing of human embryos in some instances. Time and time again, initially feared novel technology, such as IVF and mitochondrial replacement therapy, becomes normalised in the public consciousness, accepted and eventually embraced. A human gene-edited future may not be as far off as we think.
Modern day eugenics and bio-capitalism
“The lower the caste,” said Mr. Foster, “the shorter the oxygen.” The first organ affected was the brain. After that the skeleton. At seventy per cent of normal oxygen you got dwarfs. At less than seventy eyeless monsters.” – Aldous Huxley, Brave New World 
Although abhorrent to most people nowadays, the eugenics movement was tremendously popular in many countries during much of the 20th century. It was believed that through selective breeding of the ‘genetically superior’ and more sinisterly, through the forced sterilisation and murder of those believed to be of lower genetic quality, the advancement of the human race could be precipitated. Many US states initiated laws that legalised forced sterilisations, and the ultimate embodiment of the ideology promoted by the eugenics movement was the extermination of millions of Jews and other groups by the Nazis.
After World War II, eugenics became a dirty word, and today it is believed to be a thing of the past, a nasty stain faded into history. But, with the advent of modern gene editing technologies like CRISPR, realising the dreams of eugenicists has become scientifically more plausible than ever, and the ideology may make a resurgence under a different guise. In the not too distant future, people may choose to alter their own, or their children’s genomes, to render them free from genetic disease. Science and governments permitting, people may also choose to have certain genetic ‘enhancements’ to confer a raft of improvements such as higher intelligence, creative ability, and changes in appearance.
For those who might argue that such an approach would be socially unacceptable and that public outcry would prevent such practices, it should be pointed out that one form of eugenics is already commonplace; the selective implantation of embryos free from obvious genetic abnormalities that cause conditions such as Down’s syndrome in people undergoing IVF, and more brutally, the termination of pregnancies where the foetus is found to have genetic abnormalities. This watered-down form of eugenics is already deemed socially and morally acceptable by most – is it really so far-fetched that eugenics could make a more powerful resurgence under the more palatable guise of human self-improvement?
If such practices do arise, they are likely to do so from the bottom up, driven by consumer culture and ‘bio-capitalism’, in contrast to the state-directed, top-down regimes of the past. Once gene editing is deemed safe enough, and becomes commercialised, market pressures may demand that it be made available to paying consumers. Commercialised biotech companies may offer individuals and families the option of editing their own, or their children’s genes, to prevent illness, improve intelligence or artistic ability, or alter their appearance.
This could have dire consequences for a world already experiencing extreme inequality, with 1% of the global population predicted to control two-thirds of the world’s wealth by 2030. Although wealth already increases chances of success in life, through expensive education, better healthcare and cosmetic treatments, if the elite embark on genetic self-improvement as well, this could exacerbate inequality and social mobility to a whole new level; inequality could become encoded in our genomes, creating a society reminiscent of Aldous Huxley’s Brave New World, where humans are created and conditioned in laboratories according to society’s rigid caste system, controlled by a few at the top of the pile.
If policy-makers are to prevent this dystopian future, strict regulations need to be put in place in advance. Agreements reached should be global, as restrictions on biotechnology enhancement clinics would be ineffective if the rich can travel elsewhere to be ‘treated’ at offshore clinics. But with large vested interests, biotech companies may pressure regulators to permit the use of gene editing for both medical and enhancement aims, and to advertise services to consumers. Furthermore, as is often the case with prohibited commodities, such as illegal drugs, weapons or prostitution, consumer interests find a way around governmental control; enhanced legal measures often do not prevent trade, but merely push it underground making ensuring safe practice even more difficult. Speaking at the International Summit on Human Gene Editing, John Holdren, Barack Obama’s science advisor, asserted that human germline editing “is a line that should not be crossed at this time”. But if governments and regulators are unable to effectively police that line, and if market forces and consumers pressure people to cross it, how can this be enforced?
However, despite the recent rapid advances with gene editing technology, the dystopian future of genetic treatment clinics offering intelligence and good looks for large sums of money may still be a long way off. Few characteristics are known to be controlled by single genes, making them easy to control via gene editing. Despite decades of research, science currently has limited understanding of the combination of genes and environmental factors that determine many of the most sought-after traits, such as intelligence and attractiveness, making these traits thankfully out of bounds for gene editing, for now.
If bio-capitalism does lead to consumers demanding genetic self-improvements, the first things to be grasped will likely be the low hanging, less controversial fruit, such as removal of disease causing genetic variants and traits controlled by single or few genes. In fact, Nature, one of the world’s most prestigious scientific journals, argued in a recent article that genome editing could soon be used as a “panel of recommended vaccinations” on in-vitro fertilised (IVF) embryos to remove damaging, disease-causing mutations before they are implanted. Politicians and regulators need to be ahead of the curve and pre-emptively put measures in place to protect society as our understanding progresses and the prospect of genetic enhancements become ever more realistic.
Biohackers: the antidote to bio-capitalism?
But could a radical new movement prevent, or at least dampen, the potential of powerful biotech companies and research institutions from monopolising the human gene-editing market? In recent years, the do-it-yourself biologists known as biohackers have begun experimenting in makeshift labs and living rooms; these collectives of scientists, designers, artists and engineers experiment with biotechnology, outside of the traditional institutions, sometimes using themselves as human guinea pigs.
Josiah Zayner, now one of the world’s most famous biohackers, made headlines last year when he became the first person ever to use CRISPR to edit his own genome. The ‘procedure’, which involved Zayner injecting himself with CRISPR and other chemicals to modify his genes to give him greater muscle mass while giving a talk, in between shots of whiskey, was live-streamed on the internet.
A former NASA biochemist, Zayner’s philosophy, which reflects the general ethos of the biohacking community, is to promote the accessibility of biotechnology. He, and many others, believe that the democratisation of science promotes greater innovation, creativity and speed when it comes to developing new treatments or novel biological applications. Zayner uses the analogy of the computer hacking movement of the 90s, which led to the creation of the most used operating system ever, Linux, invented by Finnish student, Linus Torvalds, working in his bedroom. He also argues against the injustice of expensive paywalls on publications, many of which are taxpayer funded. Through controlling who and how biotechnology is used, Zayner believes that “overprotective” regulation may be doing more harm than good by stifling the future Linus Torvalds of biology, and argues that experimenting with our own biology is a form of freedom of expression.
Despite being prohibited by US Food and Drug Administration regulations, Zayner sells DIY genetic engineering kits online to anyone. His scepticism of regulation is evident in the live-stream, as when questioned on the risk of “off-target activity”, he argues that UV light and pollution also cause off-target effects, but “the FDA doesn’t regulate that shit… nobody complains about those off-target effects”.
By his own admission, Zayner, a self proclaimed “social activist”, never expected his CRISPR muscle injection to work. The purpose was instead to demonstrate that gene-editing treatments weren’t necessarily unsafe, in a dramatic protest against prohibitive regulations on genetic technology; taking practice what you preach to a whole new level. While he doesn’t encourage people to experiment on themselves, Zayner “wanted people to recognise what was possible with this technology. I wasn’t trying to give myself bigger muscles… I was doing it to provoke people in the industry”.
Since Zayner’s stunt, a number of other biohackers have followed suit; notably, Aaron Traywick, CEO of the biotech company Ascendance Biomedical, who injected himself with an untested herpes treatment onstage at a biohacking conference, one of several stunts that made him among the most infamous figures in the biohacking community. After watching these events, Zayner confessed in an interview with The Atlantic “there’s no doubt in my mind that somebody is going to end up hurt eventually. Everybody is trying to one-up each other more and more. It’s just getting more and more dangerous…” Another Ascendance biohacker later Facebook live-streamed himself injecting himself with an untested HIV medication.
With no medical or scientific background, Traywick and Ascendance Biomedical’s ambition was to cure cancer, HIV, ageing and herpes, which he hoped that the absence of regulatory pressures of conventional research institutions would enable him to do. In order to avoid contravening FDA regulations, Ascendance relied on self-experimentation, as a loophole puts testing on volunteers outside of the FDA regulation.
Earlier this year, disillusioned Ascendance employees/volunteers announced they would no longer be working with Traywick, after he reportedly put pressure on them to make scientific shortcuts in order to meet unrealistic deadlines, and was “defrauding investors”. However, they may still go ahead with a self-experiment of the second version of the HIV therapy.
In May 2018, Traywick was found dead in a spa floatation therapy tank, after accidentally drowning with the drug ketamine in his system. Many in the biohacking community were critical of Traywick’s methods, and he has been described as the “used-car salesman of the biohack world”. Zayner, the original pioneer of live-streamed self-experimentation himself described Ascendance Biomedical as “not legit in any measure”, and “making the biohacker community look like idiot scammers” in a polemic Facebook post in February 2018. Despite this, before and since his death, Traywick has been admired by many as a creative visionary pushing the boundaries of conventional science.
While no one can know what the future holds, one thing is certain; humankind is at a tipping point as, for the first time, our scientific ability has caught up with our ambition. While gene-editing has the power to change the world for the better, some individuals and organisations, particularly those who stand to profit, may not always have such noble intentions.
Typically, the pace of scientific advance is sufficiently slow that governments and regulatory institutions have years to debate and discuss, before preemptively regulating to mitigate against future harm and maximise benefits. The recent Facebook data scandal highlights how powerful organisations with vested interests can take advantage when technological advance is rapid, and capitalise on the inertia of governments that are slow to act. However, we must also be cautious of the potential by-products of regulation, including the stifling of innovation and increased concentration of power when democratisation of biotechnology is prevented.
The unprecedented speed with which CRSIPR-Cas9 has transformed the genetic landscape means that we must confront not only the scientific questions, but also the multitude of ethical, legal and political challenges it has thrust upon us. The future is here now, and we must act now.
 From the introduction to the International Summit on Human Gene Editing, US National Academy of Sciences, Washington DC, 1 December 2015.
Allegra Chatterjee works for the NHS as part of their Graduate Management Training Scheme, with a specialism in Policy & Strategy. Her current placement is with the NHS Innovation Accelerator, an organisation dedicated to faster up-take and spread of evidence-based medical innovations for increased benefits for patients, staff and the population. Before this, Allegra graduated from UCL with a BSc and MSc in Natural Sciences, where she majored in Genetics and minored in Organic Chemistry.