Gene editing like Crispr is too important to be left to scientists alone
Two little girls called Lulu and Nana celebrate their first birthday this month. The Chinese twins are the first humans to have every cell in their body genetically modified using Crispr-Cas9, a revolutionary gene-editing process that allows the DNA in embryos to be edited to carry certain characteristics that can be passed down to their children and grandchildren.
When the twins’ birth was announced to the world by the US-trained biochemist He Jiankui, he described how he and his Chinese and American colleagues had used Crispr to introduce genetic mutations into otherwise healthy embryos in an attempt to minimise the girls’ susceptibility to HIV infection. Such an intervention was both unnecessary and possibly ineffective, and in direct defiance of scientific consensus and established ethical norms. As a molecular biologist who has spent over a decade in laboratories, I was horrified by the experiment.
The stories of these girls’ own experiences remain to be told. I sincerely hope theirs is a life filled with joy, playfulness and love, but it is likely to also feature health consequences.
In the months following, He was labelled a “rogue” scientist, and elements of the mainstream scientific community scrambled to distance themselves. Government bodies rushed to assemble expert groups to develop regulatory guidelines that could prevent similar actions from other “outliers”.
But there is a big difference between trying to insulate the scientific establishment from criticism and making science fit to be a meaningful participant in society. The culture of science must fundamentally transform itself – becoming more diverse and more open – or it will be unfit for the task ahead.
The global market for Crispr geneediting products as medicine, to develop new crops (such as spicy tomatoes or long-life mushrooms) and other uses is predicted to be $5.3bn by 2025. Continued advances in Crispr precision and ease of use, like the just reported prime editing approach, are likely to make that number even higher. Crispr gene editing has the potential to treat a myriad of monogenic diseases from sickle cell anaemia to muscular dystrophy and cancer. Parents may one day be able to genetically customise their children’s health, physical features and abilities. Crispr will be the genetic scissors that tailor the human gene pool.
With such power in hand, we must ask: whose vision of the future are we trying to create?
Most of us support a future where Crispr is used to treat over 10,000 monogenic diseases that impact 75 million people every year. But should Crispr also be used to “correct” deafness, for example, and by extension, eradicate a rich and vibrant deaf community? Should it be used to increase intelligence or muscle strength? What about changing children’s eye colour? Or their sexuality? The future becomes blurry when Crispr applications move beyond treating disease to instead perpetuate subjective perceptions of normalcy or supremacy.
And gene-edited children will be expensive, creating the potential to make the world more inequitable, to make those who are already vulnerable more vulnerable, and to further entrench the dominant view of the privileged. That is a future we must fight tooth and nail to avoid.
Experts in science, ethics and governance are making some efforts to ensure Crispr researchers heed these societal concerns. The World Health Organization (WHO) has enlisted an expert advisory committee chaired by the South African constitutional judge Edwin Cameron and Margaret Hamburg, head of the American Association for the Advancement of Science, to develop global governance recommendations for human genome editing. An International Commission on the Clinical Use of Germline Genome Editing has also been established by the US National Academy of Medicine and National Academy of Sciences, and the UK’s Royal Society. For far too long, regulatory officials and technology developers (either academic scientists or for-profit companies) have steered the direction of technology. In addition to clear research guidelines that support safe, therapeutic gene editing, I hope to see new recommendations that can help redistribute decision-making power. An open-access online registry of Crispr clinical trials, recently proposed by the WHO, will hopefully promote a more open and transparent process. Venues are also needed where early and sustained public deliberation can take place to help integrate the concerns of society in deciding how Crispr should be used.
However, guidelines for human gene editing were already in place prior to Lulu and Nana’s birth. Publicly available research guidelines clearly stated that it was still too early to safely or ethically implant Crispr-edited human embryos. Yet He has defended his experiments by arguing that he had “complied with all the criteria” laid out by those guidelines. And it has since been revealed that multiple American and Chinese scientists knew of He’s experimental intentions and yet allowed them to proceed. Guidelines for research and regulation can only go so far to safeguard ethical use of Crispr. Some argue that a moratorium on gene editing is needed until more effective guidelines are in place. But I worry that introducing more guidelines will only treat the symptoms of a diseased scientific system – one that lacks diversity in its scientists and is fuelled by competition.
Most of modern science, and by extension the technologies it creates, has been shaped by a very narrow and privileged worldview. The scientific enterprise has been dominated by men – even today women make up only 28.8% of researchers worldwide as of last June. It has been exclusionary to people of colour – a Nobel prize has yet to be awarded to a black scientist. And it rarely includes people with disabilities or the very people scientists are attempting to “treat”.
If our ultimate goal is for Crispr to equitably serve society, then we need to make sure those who steer its development realistically represent society. Scientists who come from historically marginalised backgrounds can introduce much-needed critical perspectives.
We need to bring more diversity into the lab, but we also need to get scientists out of the lab and into society. Scientists have often been isolated from the very issues and communities their research seeks to impact. We need to support channels that allow diverse members of society to inform scientific research: channels such as the proposed global observatory for gene editing and the Association for Responsible Research in Genome Editing, which gather scientists with patient advocacy groups and disability activists to inform Crispr research. More opportunities for scientists to learn from the public are also needed, such as Involve, a nonprofit organisation dedicated to public participation, and Editing Nature, an initiative I founded to empower impacted communities in deciding how Crispr is used. As a vital first step, we must create a scientific community that values diversity and openness.
Incentive structures – in large part created by scientific funding bodies, research institutions and publishers – are fuelling unhealthy competition and opacity among scientists. In a battle to be the first to discover, scientists are forced to shield their ideas and their research. This opacity hinders open collaborations within the scientific community and with the public.
As we saw with He’s experiments, this competition and opacity creates a dangerous scenario when Crispr is involved. To safeguard the scientific enterprise, cooperativity and humility need to instead become central virtues of science. Scientific incentive structures should reward scientists who engage with the public and participate in cross-disciplinary collaborations. Meanwhile scientists should be trained to appreciate the limits of their own knowledge, and to know when to incorporate outside expertise and worldviews.
This work doesn’t stop at the research bench, or even in the classroom. Crispr holds the potential to forever change the arc of humanity, making its ethical use everyone’s responsibility. As citizens, we must push for medical school deans, professors, grant officers, journal editors, regulatory officials and those who design global research guidelines to come from a wide variety of backgrounds.
We must also pressure our governments to uphold inclusive and open regulatory processes, as well as participating in public discourse to amplify historically marginalised voices. Only in working together can we make science more open and inclusive, and only then can its products benefit us all.
• Natalie Kofler is a trained molecular biologist and lecturer in bioethics at Yale University and Harvard Medical School
nisable casts, substantial budgets and experienced directors meant that they all looked like actual theatrical releases, too, making their drops feel like minievents to viewers who might not have been anticipating their release.
Inevitably, and ironically, the films that seemed to stand against the ongoing production line of predictable sequels being churned out by the wider industry are all now being envisioned as franchise-starters by those behind them. Murder Mystery 2 has been given the official green light, a follow-up to the Bird Box novel was announced earlier this year, leading many to speculate about an adaptation, while Triple Frontier director JC Chandor has expressed muted interest in a quadruple. Next year also sees sequels to the previous year’s hits The Kissing Booth and To All the Boys I’ve Loved Before.
2 Sometimes they (don’t) come back
By far, the platform’s biggest TV drop of the year is Stranger Things 3 (64 million viewers), an inevitable result given the frenzy surrounding the series since it began in 2016, but while it’s easy to equate its success to that of a big-screen sequel, especially given both its genre and how it’s been marketed, what’s most interesting is that it’s one of only two shows on the list that isn’t a first season. There’s no sign of Netflix staples like Orange is the New Black, Glow, Bojack Horseman, The Unbreakable Kimmy Schmidt, House of Cards, Black Mirror, The Crown, 13 Reasons Why and Mindhunter, and instead viewers have flocked to new shows like The Umbrella Academy (45 million viewers), You (40 million) and Sex Education (32 million), all also notably aimed at a younger audience.
It’s a sign that either original shows tend to lose viewers with each season or that Netflix has been algorithmically tweaking its output to fall more closely in line with its most impassioned younger viewers. With all new shows on the list coming back for a second season, it will be interesting to see what next year’s results highlight.
3 A tough watch is an easy binge
Importantly, the lists provided don’t include content acquired by Netflix from elsewhere which would inevitably mean that much-loved sitcoms like Friends and The Office would make an appearance. The success of both (Netflix extended the Friends deal for one final year for $100m before it was snapped up by HBO Max starting 2020) led many to believe that the practice of bingeing was mostly employed by those seeking lighter, snappier fare. But the appearance of two tough, issues-led dramas on Netflix’s TV list suggest that this might not always be the case.
In a short amount of time, Unbelievable (32 million viewers) and When They See Us (25 million) have shown there’s a big audience for fact-based shows dealing with difficult, timely topics. Unbelievable, a combination of a dogged crime procedural and a docudrama, focused on rape and how it can be mishandled by authorities while When They See Us, Ava DuVernay’s Emmy-winning Central Park Five miniseries, dealt with race and how it too often leads to false imprisonment, and both were eagerly consumed by viewers and critics. Expect a major awards push for both in time for the Golden Globes as well as further green lights for equally tough-minded dramas.
4 Dead genres come back to life
Genres that have long been cast aside by Hollywood have been carefully and cleverly resuscitated by Netflix for a while now with notable successes, such as 2018’s “Summer of Love” which saw a string of smash-hit romcoms, including Set It Up, To All the Boys I’ve Loved Before and The Kissing Booth (all of which Netflix has been happy to brag about). In comparison, before Crazy Rich Asians last year, the industry hadn’t seen a $100m romcom hit since 2011’s Just Go With It.
The latest top 10 is filled with similar examples with teen movie/romcom crossovers The Perfect Date (48 million viewers) and Tall Girl (41 million), psycho-thriller Secret Obsession (40 million), romcom Always Be My Maybe (32 million) and chick flick Otherhood (29 million) all scoring well. Apart from Otherhood, the films mentioned aren’t really star-led but their appeal is more about a tried-and-tested-and-forgottenabout formula being brought back to life. The success of “cheerfully trashy” thriller Secret Obsession, from longtime Hallmark and Lifetime channel director Peter Sullivan, is perhaps the most concerning given its rote plot and flat TV movie direction. It’s a cheap quickie that would usually be chucked on to cable but its large viewership on Netflix will lead to more of the same, a grubby inevitability and looking ahead at their schedule, there are similarly low-rent options in the coming months.
5 Big directors don’t lead to big audiences
The list of most-watched films, from Bird Box down to Fyre (20 million viewers) sees a gap of 60 million viewers, meaning that while some films hit big, there’s a great many that lag far, far behind. This doesn’t make them flops per se but it does mean that genuine phenomena are hard to find. The list also shows that while Netflix has put a great deal of funding into both their awards push and their splashy partnerships with respected auteurs, audiences are less invested in the outcome than they are.
The most conspicuous absence is Alfonso Cuarón’s Roma, the platform’s most critically acclaimed and awarded film to date. Netflix might have been proud to flaunt its reviews, nominations and eventual wins but they have yet to release any solid data about either its streaming viewership or its limited run at the box office. There’s also no love for the Coen brothers and their anthology western The Ballad of Buster Scruggs, Dan Gilroy’s Sundance-premiering art world horror Velvet Buzzsaw, the long-awaited Orson Welles drama The Other Side of the Wind, Paul Greengrass’s grim docudrama 22 July or Steven Soderbergh’s High Flying Bird. Of course, these films would have been unlikely to make the top 10 mostwatched films at the cinema, too, but the film list offers a picture of a far less demanding viewer than the TV list and show’s a great discrepancy in the films that Netflix chooses to promote over what viewers choose to watch.
Given the uptick in major directors who have been lured to the platform, this might not be the case in the next 12 months. Martin Scorsese’s extravagant crime saga The Irishman will surely be a rare critical and commercial crossover title for them, although its mammoth 210-minute runtime might prove a problem (Netflix counts more than 70% of a movie or episode as a watch). But for those who can’t make it through, there’s a film with Kristin Davis and Rob Lowe falling in love at Christmas while caring for elephants in Zambia. So, as appears to be the Netflix mantra, there really is something for everyone.