We are on the verge of a scientific revolution that will change life and death as we currently know it. In the Code of the Wild documentary film, Cody Sheehy (award winning producer and director) and CRISPR scientist Samira Kiani explore the controversial and secretive world of genetic engineering.
The making of the documentary took Sheehy and Kiani to China, where they stumbled across and brought the world's attention to the work of the infamous CRISPR scientist, Jiankui He. He shook the scientific community and broke ethical boundaries when he utilized the CRISPR Cas-9 system to genetically edit human embryos, his intention being to make the babies immune to HIV.
Whilst Code of the Wild is still in production, a recently released trailer hints that it will make for a fascinating, insightful and gripping watch.
In an interview with Kiani and Sheehy, we cover all aspects of Code of the Wild, including the making of the documentary film, the discovery of He's experiment and the concept of being able to "purchase" a longer life span.
Molly Campbell: Can you please tell us about process of creating Code of the Wild. What inspired you to make it? Why did you choose to specifically film in China? Did you face any resistance from scientists in the field when asked to discuss their research?
Samira Kiani (SK): There are many rapid advances taking place in the field of genomics and genome engineering technologies, and these advances are not only bringing around a technological revolution but also a societal revolution, as they are changing how we will live and how we will die.
I first reached out to Cody who is a film maker with Rhumbline Media and we decided together that this would be a very interesting topic for a documentary film. The Code of the Wild idea started initially with brainstorming as me and Cody tried to decide how to tell a story and engage the public in conversations about genomic revolutions that will change their future.
Cody Sheehy (CS): As we learned more about genetic engineering, we realised that many countries are involved in genetic engineering and some of them are racing ahead. Why did we choose to specifically film in China? The first human embryos were edited in China, the majority of papers that have actual data from trials with embryos are from China and our intuition was that some of the leading work when it comes to human enhancement might be there. We knew that we would have to go there ourselves to find out what was going on, and it just so happened that our intuition was correct.
SK: In terms of resistance, a lot of scientists were very reluctant to be filmed on camera and that’s completely understandable. We tried to really talk to them in advance and had a member of our crew in China about six months before our trip so that we could clear our way and apply for necessary permissions.
MC: Dr Kiani, as a CRISPR scientist, what do you view as the most exciting breakthrough in this field thus far?
SK: I would say, like many other scientists who are working this field, I feel like the most exciting CRISPR breakthrough is its ability to specifically change the DNA code, specifically in human embryos without really, as far as we know right now, having so much deleterious effect on the development of embryos.
A lot of work has started to be done in nonviable human embryos by a number of scientists and their preliminary data shows that these embryos can really develop, at least to the point that are allowed to be tested (matter of days) without much negative effect on the developmental process. This is very exciting in terms of what we can do in future with regards to modulating genetic diseases and understanding the different form of genetic malfunctions. That is, for me, the most exciting part and obviously, the most challenging part as well because of the ethical considerations that as scientists and society, we need to deal with in order to take this approach in embryos.
CS: I would add that as a layperson entering the world of CRISPR, I was excited and shocked to find out about the applications of CRISPR in fully grown adults in addition to embryos. Learning about the ideas that are on the table, such as being able to reverse aging, was a real eye opener for me.
MC: Filming the documentary led to the discovery of Dr Jiankui He's genetic editing of two human embryos. In your opinion, had it not been for this documentary, would his research have been discovered and widely publicised?
CS: I think it’s pretty conclusive that his research was going to be known by the entire world without us being part of the equation. Although, perhaps the timing of when that information came out had a lot to do with our project. It wouldn’t seem that that’s important – however, the timing that we helped create allowed the second summit on human genome editing in Hong Kong, where all the world-renowned scientists were meeting, to discuss the controversy with He at the meeting.
The research team were going to reveal their work to the world, on their own schedule, as they were trying to get ethical support from various other scientists. By breaking the story ahead of the time, we exposed the research to the public before they were ready, allowing scientists to have that conversation at the summit.
Read more about He's gene editing of human embryos here.
MC: The trailer alludes to other scientists that are using CRISPR to edit human embryos. Do you believe that this is a widespread issue in areas of the world other than China?
SK: One of the advantages of CRISPR has been the ease of engineering, lower cost and accessibility of this technology and I think what we saw in China is just one example of what’s going on in the world. Scientists and all other stakeholders need to start learning that they have to communicate more about this subject because it has the potential to happen all over the world and not only in China. We need to learn to engage underrepresented voices in the conversations.
CS: In some war-torn countries that have scientists that are willing to do things that are less ethical and with less high-functioning equipment, the quality of the genetic editing may be a lot poorer. It's possible that some of the potentially bad outcomes of gene editing that people worry about may happen in a lab that is not as well-funded as He's, which is something that I worry about.
MC: What are the key benefits and dangers associated with gene editing research? In your opinion, how can we regulate the research conducted in the field so that it moves science forward in a safe, ethical manner?
SK: The key benefit is the ability to change the DNA code in a relatively precise, specific and safe manner. If there is an inherited form of genetic disease or acquired disease that is somehow happening because of the changes in DNA code, we now, theoretically, have the potential to go and correct that. Also, we have the capability to potentially treat many other diseases such as cancer through tissue regeneration etc. This also means that we need to deal with many technical hurdles to implement gene editing in an efficient manner in humans, but we are moving in that direction. The danger is that we need to make sure gene editing is specific, meaning that we are only targeting the specific gene that we want, and we are not changing any other parts of our genome accidentally. We also need to make sure that we are targeting only the target tissue or organ we want, and not changing other organs inadvertently.
Another danger is that this technology is not only helpful in treating diseases in humans but also has deeper implications with regards to other animals and nature. There is the potential to accidentally release a genetically edited organism into nature without really having conducted proper research before the release happens, meaning we could influence the environment in an unwanted manner. As the technology is easy to use, readily available and adaptable, it’s possible that untrained professionals could start to work with it, and bio-errors may occur.
It’s very important that we start thinking about regulation and this is a very challenging conversation. I would say the first step is communication, and after communication is established, then we can put forth regulations based on the discussions that people from different fields have together.
CS: One key thing in my opinion is that most people in the world, so far it seems, really are okay with the idea of editing babies for medical problems and to correct genetic disorders. When it comes to enhancing people, making babies more intelligent or creating soldiers with more muscle, these are are the ethical areas that some countries, it seems, would like to go there, and others not so much. What is ethical and what is unethical? That's a huge part of the conversation going forward. I think also, on the other side of the equation, how do you regulate this? DNA is everywhere, it’s hard to detect, it’s complicated, this technology is cheap, easy and it’s going to get easier. George Church suggest that the key to regulating gene editing is surveillance, as prohibiting it is not going to do anything in the future.
MC: Nessa Carey recently stated in an interview discussing her new book, Hacking the Code of Life, that the controversial work of Dr He has set the gene editing field back "10 to 15 years". Would you agree with this statement? If so, how can we combat this?
SK: My thinking, as a CRISPR scientist, is no. Actually, I would say it ignited the conversation and discussions that were much needed, and we were all avoidant to do that. I think he broke a taboo. Also, I don’t believe that Jiankui He might be the first scientist and only scientist who attempted this. I believe that he was the first scientist publicly known to actually do that.
CS: I agree. I'd like to paraphrase some things that I’ve heard from other people in our film, such as Antonio Regalado, who made a very good point. When IVF first happened, it was a very similar controversial topic, but now, there’s been over eight million babies born from IVF. It’s amazing how quickly public perception can shift on these matters. He also said too, which I thought was insightful, that "maybe the jury is still out on this."
Whether or not it’ll set things back, or whether He has accelerated the field and broke through the barriers, will most likely depend on how healthy the babies are. If they’re very unhealthy, and we won’t know this for a while (the data has not been released), then the public may decide that gene editing should not be pursued. If everything is healthy, it might just be a footnote in the whole process and encourage the creation of the guidelines that scientists require.
MC: The gene editing field has received negative press since the China conspiracy. As a CRISPR researcher, Dr Kiani, what would you choose to say to those who view gene editing in a negative light?
SK: I would say that it’s very important, before taking any side as to whether a technology is negative or positive, to really try to understand the technology. Can it benefit or harm the human race? After really evaluating that, then try to take a side. I would say that as a CRISPR scientist who is actually entrusted in working in this technology, I see a lot of benefits to treating human diseases through gene editing, though I wouldn’t say that the therapeutic benefits are completely developed at this point. Perhaps we are talking about five or ten years from now. Or maybe even CRISPR is not going to be the one that changes human health, but it’s going to be another readily available gene editing tool.
If there is a technology that can help the human race, we should really think and look into it more carefully, the same as what we did with vaccines, the same as what we did with antibiotics. This is natural evolution in medical technology that we shouldn’t necessarily rapidly take sides with.
As with many other technologies that humankind has developed, there are side-effects that both scientists and other people who are developing and using this technology need to discuss. What are the boundaries of this technology? Should be, for instance, used only for clinical applications? Or enhancement?
CS: It's been really interesting for me thinking about this topic in terms of the long arc of history. Right now, we have this whole new field of medicine that’s opening up and so many diseases have a genetic component. Gene editing could transform medicine, and it is right in front of us - we can almost touch it. What it also means is that ultimately, the evolution of how our genes change over time and what makes us human will be increasingly under our control. Will we decide exactly what makes a human? What makes a desirable human for, say, space travel, in the future?
That is the power, ultimately, that we’re choosing to take now, and we won’t understand the full consequences of that for potentially hundreds or thousands of years. It’s going to be profound and I just hope that we’re going to live in that future. It sounds like it could be a positive place but also, humans don’t always make the best decisions when it comes to managing ecosystems.
MC: What key points would you like people to take away from the film?
CS: There are so many but the main point I think from my point of view, is that this is real and that this is here. In some cases, once a technology is real and it’s here and it has great usefulness, it is inevitable that it will be applied.
If you don't like cell phones, you don't have to have one, just opt out – but everyone seems to have one. I think gene editing may fall into the same category for lay people. Once gene editing becomes normalized, and this technology transforms society, we're all going to live in in this advanced world.
SK: I would like the film to ignite the conversation, showing both the positive aspects of gene editing but also, the dark side of it, and let the public start a discussion surrounding all the information they receive from the film. It’s a more stimulating movie to ignite thought process and conversation.
MC: What do you envision to be the next big breakthroughs in the field of gene editing?
CS: For me, I think there’s so many millions of things going on in all these little labs and there’s no way to know exactly what the next CRISPR type of technology will be - although it will be big something and it will be revolutionary. But in general, I think everyone right now in the public is focused on the editing of babies and human enhancement. I think some of this anti-ageing stuff that’s going on will really change how people think about the world. Once we start understanding that very wealthy people are maybe going to live a lot longer than the rest of us, I think that’s going to be a big conversation.
SK: In terms of breakthroughs, I would say multiplexing, meaning the ability to modify multiple genes, maybe thousands of genes at the same time, will be the next exciting development in gene editing.
Samira Kiani and Cody Sheehy were speaking with Molly Campbell, Science Writer, Technology Networks.