A note from our collaborators: With scientific guidance from geneticists Dr. Ting Wu and Dr. Ruth McCole, the filmmakers developed a story that builds upon research in Ting’s laboratory. In particular, the filmmakers have focused on DNA elements called UCEs, which the Wu laboratory has hypothesized to protect people from genome damage. In ANYA, the filmmakers pursue a theoretical extension of the UCE model. Note that the UCE model has not been proven; it is still under investigation. In addition, the filmmakers collaborated with Ting and her team at the Personal Genetics Education Project (pgEd.org), who provided insights on ethical issues related to genetics. While participation of the Wu laboratory and pgEd in the making of ANYA reflects support for the use of film to promote awareness and dialogue about genetic technologies, it should not be taken as an endorsement for the application of genetic technologies to humans.
Fiction and fact are colliding fast.
A tsunami of genetic technologies is coming our way offering a largely unsuspecting public everything from seemingly harmless insights into heredity like 23andMe to breathtaking cures to designer babies to the terrifying prospect of a new wave of eugenics. Each time a patient or budding genealogist chooses to map their DNA they add to our knowledge of the only recently mapped human genome and to a growing store of genetic data that can be ever more effectively mined to find long lost relatives, genes responsible for hereditary diseases, or potential suspects leaving evidence at forensic crime sites.
Each choice to test DNA or pursue a new line of research adds potential knowledge and risks. Before this week, grappling with the complex cost/benefit analysis of genetic technologies seemed more the domain of a vanguard of academics, medical practitioners and their patients, science journalists, and sci-fi writers.
This week, mainstream headlines heralded the arrival of the tsunami. Chinese scientist He Jiankui’s yet-to-be-verified announcement of the first gene-edited baby tells us it’s time to figure out how we, as individuals and as a society, will navigate the opportunities and risks of this new terrain.
It is our hope that our upcoming film, ANYA, will in some small way help guide the discussion.
ANYA scooped the gene-editing headlines!
In this short clip from ANYA, geneticist “Dr. Seymour Livingston” (Motell Foster) fields questions from “Narval” community members who have just discovered they carry a gene that prevents them from reproducing with non-Narval people. Like so many people facing infertility, they want to know whether or not new genetic technologies can help them have babies.
The answer, in both fact and fiction, is a highly qualified “yes.”
Narval Woman: Do you think they can have a baby?
Dr. Seymour Livingston: Yes. I think it’s possible. That’s why I need more samples. To confirm that you’re all alike in the same way.
Fausta: And then what?
Dr. Seymour Livingston: It’s a little complicated. We have the technology to edit people’s genes. That part’s pretty straight forward. But it’s only been used in China. There could be unintended consequences.
Narval Widower: What does that mean?
Dr. Seymour Livingston: Well. To start with. Medical side effects. It’s hard to know without years of testing. I’m not trying to obfuscate. I mean. Look. Even if everything works out, and it might, there could be social consequences. […] Maybe no one would care but we humans don’t have the best track records with appreciating diversity.
How did genetics become a part of ANYA?
intial focus: A plausible cause for “speciation”
We didn’t set out to write a story about genetics or gene-editing. After creating the space/math/art documentary, PAINTING THE WAY TO THE MOON, Jacob and I continued to be fascinated by the often accidental, messy, and contested nature of scientific discovery. We decided to write a feature film to explore a discovery from the perspective of both researcher and research subject. Our early drafts of ANYA were focused on what it might be like — at a very human, lived level — to discover another species of humans alive on the planet today. What would it be like for those involved? How would the rest of the world react?
Drawing on my background in anthropology, we constructed a plausible scenario for there to be a second species of humans living in Queens today, isolated from the rest of New York (and humanity) by their infertility with the general population. An accident of genetic mutation of a single gene that made it impossible for the “Narval” people to reproduce with outsiders. The Narval culture and language grew from there.
In search of a plausible genetic variation that could cause such infertility, we turned (on the recommendation of the NAS Science & Entertainment Exchange) to Harvard Medical School’s Dr. Ting Wu, Dr. Ruth McCole, and the Personal Genetics Education Project (pgEd). The research in Ting’s lab on a mysterious set of DNA sequences, called UCEs, offered a particularly intriguing backdrop for our story. We also found a helpful resource in Ting’s pgEd group, which is dedicated to increasing public awareness and dialog about genetics. In 2015 Jacob and I made several visits to the Wu Lab to go over screenplay drafts, write new scenes, observe lab meetings, and attend a “chalk talk.”
Ting and Ruth shared their research on chromosomal structure with us, particularly on “ultra-conserved elements” (UCEs). These tiny bits of DNA remain unchanged over millennia and across species. Based on their research, they reasoned that during reproduction small discrepancies between UCEs of egg and sperm cells could cause an embryo to fail. This became the source of our fictional couple’s infertility. If everyone in a population shared the same varient UCEs, they’d be able to have children with each other, but not outsiders. We had a plausible explanation of infertility and speciation for the story!
Gene-Editing was a later addition
We learned through them, that while we were working hard to get the genetic science of ANYA right, scientists around the world were working hard to get the rules of engagement right around a burgeoning area of research: gene-editing.
We became fascinated with the relative ease of powerful new gene-editing techniques. It was hard to imagine that it would be straight forward enough for a scientist with expertise in another area of biology or genetics would be able to get up to speed fast enough to conduct an illicit experiment. Could our fictional evolutionary geneticist even learn how to edit genes without raising awareness? Apparently so, even if it would be highly unethical. While we were considering whether or not our fictional geneticist might risk pursuing gene editing to help his ex-girlfriend have a baby with her new husband, real geneticists around the world were agreeing to in place a voluntary moratorium on editing the human germline that hoped might give regulations and the public time to catch up with the science..
Gene editing and the effectiveness of the voluntary moritorium continue to be highly contested territory among scientists. For instance, on November 29, 2018, days after Dr. He’s announcement, the Second International Summit on Human Genome Editing in Hong Kong rejected a blanket ban of gene-editing of human embryos, arguing that He Jiankui’s actions were the failure of an individual not the scientific community and that while using genetic-modification to eliminate genetic diseases in human embryos is premature, it may someday help eliminate genetic diseases.
In 2015-2016, pgEd invited us to a series of Congressional Briefings they were organizing to inform lawmakers about the benefits and implications of advances in genetics, including CRISPR. We saw just how far behind our laws — and our lawmakers understanding — lag behind the science. (The last major legislation was “GINA,” the Genetic Information Nondiscrimination Act of 2008.) While we were in DC, we observed a session of the Supreme Court and wrote a scene envisioning Seymour defending his use of CRISPR. We cut the scene and opted not to mention CRISPR by name. However, we expect to be back at the court watching a real gene editing case before long. This particular watershed can’t hold for long.
In 2016, we returned to Boston to participate in a pgEd Industry Forum and the Festival of Genomics. None of the scientists or vendors batted an eye when I shared the plot of the film. They knew all too well that gene-editing was plausible. Now.
During this period of development, I became aware that scientists were able to create modifications in the genes of mosquitos that would passed on to other mosquitos in the wild through “gene drives.” Such a use of gene-editing could dramatically reduce the transmission of mosquito born illnesses such as malaria and zika.
It became more and more clear that gene editing wasn’t the stuff of a distant future. It was the stuff of a week from tomorrow. Literally it turns out. Gene-edited human babies — something we thought was fiction when we started writing ANYA in 2014 — were born weeks after we finished editing and polishing the film.
In the earliest versions of the script “anya” was the name of the curse, the “Narval” people’s cultural explanation for their biological difference. In these drafts, the couple at the heart of ANYA overcame infertility by swapping babies with another couple. It was a cultural solution to a biological problem.
In the shooting script and finished film, “Anya” refers to the name of the first gene-edited Narval baby. The couple has to decide whether or not to edit the mother’s egg cell from the non-Narval to the Narval gene variant to combine with the Narval father’s sperm cell prior to in-vitro fertilization. We focus on the ethics and decision making process. It’s up to the viewer to decide whether or not Anya is the product of gene-editing.
What do we think they did? I’ll give you a hint. I started writing the title in all caps because ANYA reminds me of AGCT, the building blocks of DNA.
What’s our take on gene-editing?
We knew going into ANYA that gene modification wasn’t new. It’s the precision, pace, and potential for unforeseen consequences that are new.
If He Jiankui’s claims are true that he successfully delivered twin girls designed to be immune to HIV through the gene-editing technique, CRISPR, then the world’s first recognized genetically-edited babies — babies who will pass on their edited genes to their children and their grandchildren — were conceived while Jacob and I were beginning to edit ANYA.
As we selected and strung together clips in a Premiere timeline, He Jianku used the CRISPR protein to “cut and paste” a bit of genetic code into the DNA of the girls’ single-cell, undivided embryo that would hopefully allow them to be immune to HIV as a adults. The risks are incredible. Medically, the girls could be fine or the “fix” could work or not (it appears to have worked in one girl and not the other) or there could be unintended consequences (such as a diminished immune system). Some of the consequences may not show up until later in life. (Here’s a one minute video explaining how CRISPR works as a “cut and paste” tool.)
Geneticists, like any other community, are not all in agreement about the use of gene editing in human embryos. Even geneticists who hope we will one day use gene-editing regularly on human embryos argue that that time has not yet arrived. Even so, with the level of interest and potential for profit in genetic testing and curing disease, it seems the race is on.
From my understanding, most scientists and funding agencies are voluntary putting the brakes on this type of research until more of the building blocks are in place and they deem it safer to proceed. There are laws governing the release of genetic information and the practice of medicine by non-medical doctors, which in the U.S. includes those holding research PhDs, such as ANYA’s “Dr. Seymour Livingston.” Yet there is a LOT of uncharted and unregulated territory. It’s reassuring to know that organizations like pgEd are working overtime to bring lawmakers, educators, researchers, business people, clergy, and the broader public into the conversation.
When it comes to new technologies, Jacob and I are neither Luddites nor early adopters. When it comes to genetic technologies, we’re reserving judgement until more data is in.
As a documentarian and an anthropologist, we’re observers and students of history. We’re keenly aware that discoveries are messy. We can never fully foresee the risks and benefits nor the winners and losers of new technologies, nor can we predict the winners and losers left in its wake. One of the most important concepts I learned from twenty years studying international development was that even the most well-intended actions have unintended consequences. (The book that first brought this home for me was James Ferguson’s “The Anti-Politics Machine: "Development," Depoliticization and Bureaucratic Power in Lesotho“ (1994).)
What can we learn about gene-editing from agriculture?
My introduction to genetic editing came years ago through agriculture. I think agriculture helps demonstrate the tremendous lag between technical expertise and public understanding as well as the impossibility of predicting all outcomes of a particular technology.
In the most basic sense, humans have been actively modifying genes since we began selectively breeding plants and animals for food and pets. Since the 1970s with advent of genetically modified foods (GMOs), humans have been honing an unprecedented ability to tinker with biology. Apart from glamorous crops like Vitamin-A infused “golden rice,” GMOs rarely make headlines. Almost fifty years after GMOs arrived, there is still a major gap between the scientific consensus of their safety, the public’s mistrust, and little understood consequences for health or agriculture. We’re far from knowing how to feel about these advances much less how to regulate them.
Through my academic work on rural development and migration, I talked a lot with small farmers and agricultural extension agents in rural Honduras, Ecuador, and Colombia. I learned from them how dramatically industrial agriculture affected their ability to sustain themselves and their families by growing their own food. GMO seeds had had the most profound impact. Extension agents (including some from major international corporations like Cargill and Monsanto) often gave GMO seeds for free or at deep discount. When farmers opted to plant GMO seeds they belatedly discovered that the plants required more agrochemicals to survive and bore no usable seeds. The once self-sufficient farmers were stuck buying seeds, pesticides, and fertilizers—products they had not previously needed. And their stores of local seeds dwindled. Long story short, the aggregate effect was to make it impossible for them to feed themselves and their families without finding money to buy the new products. Some found local work. Some migrated elsewhere in the country. Some came to the U.S.
Based on my research, I would argue that industrial agriculture and GMOs are one of the root causes of outmigration from rural Honduras. Put differently, another piece of news this week, the so-called caravan of Central American migrants arriving at the U.S./Mexico border, is an indirect consequence of gene-modification (GMOs) that I’m pretty sure no one foresaw.
What about ANYA?
In ANYA, we say neither that gene-editing is good nor bad. We simply say what we believe to be the truth: gene-editing is here now and no matter how careful we are, there will be unintended consequences.
We’re confident that ethical scientists like those we’ve met through ANYA are working overtime to improve the science and put in place appropriate guidelines. For our part, Jacob and I feel a responsibility to educate ourselves and share ANYA as widely as possible so that the film can help scientists and non-scientists get ready for the tsunami of genetics technologies coming our way.
Carylanna Taylor is an applied cultural anthropologist (PhD, University of South Florida, 2011; MS, Cornell University, 2003; BA, Penn State, 1997) with research and teaching experience throughout the Americas. She became a filmmaker over the past six years and is now co-owner, with Jacob Okada, of First Encounter Productions which emphasizes nuanced content informed by anthropology, science, and current events. ANYA is their first fiction feature. Together they wrote, directed, produced, and edited ANYA (80 minutes, available 2019) with the collaboration of genetics professionals at Harvard’s Personal Genetics Education Project, Carnegie Mellon University, and Frontline Genomics.