Brave New World

CAMBRIDGE, Mass. - The Biotech Connection at Boston, along with Gen9 and the Harvard Biotechnology Club, were honored to host Harvard’s Dr. George Church for a fireside chat titled Brave New (Genetics) World: Into the Era of Personal Genomes, Synthetic Biology, and De-Extinction. Standing at 6’5”, Dr. Church is a literal and figurative giant in genome sequencing and synthetic biology. His laurels include membership in the National Academy of Sciences and the National Academy of Engineering, the Bower Award and Prize for Achievement in Science, and over 60 patents. While Dr. Church strikes an imposing figure, he immediately set the audience at ease with his conversational style and wonderful sense of humor. When the moderator, Johnny Hu, asked him to briefly explain what he works on, Dr. Church replied, “Well, you said as brief as possible, so ‘DNA’.” Despite this initial brevity, Dr. Church went on to provide his valuable insights about how science is shaping our future.

The first question Dr. Church addressed was the impact of personal genomics on health care. One of his concerns was cost, saying that, “one of the fears of personalized medicine, instead of selling to everyone, like aspirin, [is that] now with orphan drugs, there might be 100 people worldwide that you’re selling to, and as a consequence they’re paying $200,000 per year. I’m very positive about it, but it’s inappropriate that long term will be so expensive.”

Dr. Church also pointed out that genetics already play a large part in the health care system. “I think the biggest barrier is convincing people that we already have meaningful information…the general attitude is that genomes are meaningless mush. 23andMe has been great in educating people that genetics is…not necessarily so scientific that you can’t understand it, but it’s also given people the impression that there’s not much you learn from the genome, and I think that’s false. Emphatically today, there’s a lot you can learn from the genome. The fact is, there are a lot of things you can learn pre-conception, about adult onset, about cancers…Angelina Jolie was a prime example. Something a lot of parents don’t know is that we already test newborns, but it’s usually for 40 genes.”

However, a major concern of personal genomics is that patients worry about information privacy. As director of Personalgenomes.org, Dr. Church is an advocate for open genomic data, but he acknowledged the need for balance between open data and privacy. “Keep in mind that myself and the 13,000 others that are doing (Personalgenomes.org) are not doing it to get a medical service…at least I hope not. We probably don’t need all 7 billion people on the planet to behave this way…a small number can be beneficial to a large number.” He drew an important distinction between sequencing for research and for medical purposes. “With sequencing, as long as it’s kept personal and voluntary, that’s a big difference. I think it’s going to be a much more thoughtful conversation. One thing that people worry about (with sequencing) is getting too much information, that’s something that’s totally negotiable, just like with any medical information. If you don’t want to know your cholesterol, but your doctor wants to do a blood test, you can say, ‘Just leave cholesterol off the report’.“

He also raised a word of caution to diagnostic companies that depend on private databases of sequences as part of their business model, pointing out that “when cDNAs were being privatized, Merck funded a public effort to put all the cDNAs out in the public to undermine Human Genome Sciences; when Celera wanted the whole genome privatized, there was an equal and opposite response to that, and it will almost certainly happen with personal genomes.”

Dr. George Church (left) and moderator Johnny Hu (right).

Dr. George Church (left) and moderator Johnny Hu (right).

Shifting to synthetic biology, the main focus was on public perception of genetic engineering. Addressing its potential as a clinical tool, Dr. Church said, “Gene therapy has changed radically and not so obviously to the public over the last 14 years. In 1999, Jesse Gelsinger died (from an) adenovirus vector and a couple years later a couple of kids died in Europe, so that seemed like a death knell for gene therapy, but what it resulted in was much greater caution in the field. Fast forward 14 years and now you have a very healthy ecosystem with over 2000 gene therapies in Phase I, II, and III and a lot of them have already emerged and been approved in Europe, like Glybera.” This led to perhaps the most memorable line of the night, when Dr. Church said, “[Glybera creates] the interesting situation of having genetically engineered Europeans not eating genetically engineered food.”

He addressed potential public backlash against genetic engineering (similar to GMOs), saying “There are a number of significant differences that we don’t need to manipulate between us and GMOs. GMOs are out in the public and potentially changing the structure of your wheat to be herbicide resistant, so that’s kind of like it being inflicted on you. Sequencing is a much longer buildup, so people would have been exposed to human genetics and as I said, every kid gets testing at birth. It’s going to take new things, I think gene therapies will make people take genetic modifications more seriously; modifying disease vectors with gene drives will cause people to take more notice.”

Dr. Church also acknowledged a role for government policy in regulating synthetic biology, likening it to the worries about recombinant DNA back in the earlier days of molecular biology. “Some will say it’s downright invasive and distracting because it overregulates and causes setbacks and delays, but I have observed no threat of that. I was there during recombinant DNA, and frankly, I saw a lot of research advance because there was so much attention to it; investors got more excited about it, young students like myself have better facilities, and it brought better insight into things like biological safety levels.”

Moving on to the more fantastic applications of his research, like de-extinction, Dr. Church said that “My lab sometimes takes on a fair number of things that sound like science fiction. Faster than light and time travel may not be the right choice, but bringing back some DNA diversity might actually be beneficial to agriculture and ecosystems. Now it’s not all about bringing back the perfect good old days, it’s about adapting our current ecosystem to the reality of change. To maintain the ecosystems that are most useful to humans, we need to be thoughtful about maintaining keystone species to help maintain those systems.”

The theme of caution and thoughtfulness was again brought up in a response concerning his efforts to bring back the wooly mammoth, or more accurately in his words, “a cold tolerant elephant”. He elaborated that “I thought the mammoth was a good one because it’s not a carnivore, so you won’t have Jurassic Park, at least not right away, and it’s extremely closely related to another animal, the Asian elephant, but it looks very different. And then there are certain ecological arguments, which, as far as I know, there’s no opposition to them (but I’m willing to reconsider)…they are capable of improving albedo (the reflecting of light) by altering vegetation, and preserving the tundra in its frozen state which is advantageous to the ecosystem because it traps two times the carbon as the rest of all the forests in the world.” Dr. Church also pointed out the huge potential for science to inspire others. “There’s also a gee whiz factor (in de-extinction). Why was it necessary to put a human footprint on the moon? I think the fact is that the footprint on the moon inspired a whole generation to become scientists and engineers.”

 However, despite sensationalized media claims about bringing back Neanderthals as part of de-extinction, Dr. Church stated that, “I would probably say not…it’s going to cause a backlash because we’re not ready for any kind of cloning now. That’s not to say never, but I would say at this point it’s too contentious, there are many more significant things to do. But we should certainly discuss these sorts of things, controversy is not something you run away from. It’s good to teach people that science is not something that you get out of the book and it’s all settled and there’s nothing to be discussed.”

Lastly, coming back to the Aldous Huxley book from which this event drew its name, Dr. Church was asked, “Should people design new people?” His response: “Brave New World was in the midst of the eugenics movement, but eugenics was radically different. Back then, government would sterilize people without their permission or in other ways influence their genetics. Today, it’s more like, ‘If I want to change my genome, as an adult, am I fit to do that?’ It’s a completely different ethical problem. Instead of the government coming into my home and injecting my genes, can I alter my children’s chances of getting a good job or getting medical care? I think that’s a fundamentally different thing, I’m not saying that I know the answer to the “should”, it’s something that we should continue to discuss as it develops…I think it’s fairly inevitable, hopefully it will be done very thoughtfully.”

Thanks again to Dr. Church for an outstanding event, and to all the packed audience at Armenise Amphitheater for their participation and questions!