Ideas to Innovation - Season Three
Jim Collins: My focus has primarily been on human health care. And it’s where I think synthetic biology can make a big difference in that a critical kind of decision point in most projects that I see is in what applications can biology out-compete chemistry, and in the case, particularly of human health, the design of meaningful therapeutics, the design and meaningful diagnostics, biology often wins over chemistry. And this is where we’re excited, where we think our work has had an impact and will continue to have, we hope a meaningful impact.
Intro: Ideas to Innovation. From Clarivate.
Neville Hobson: Rapid advancements in technology and science are shaping a new era with artificial intelligence and synthetic biology at the forefront.
Lauded as the technology to watch, AI’s prowess in learning from and interpreting data is unparalleled. Synthetic biology, heralded as the next big leap in science, is enabling the precise engineering of biological systems.
Synthetic biology, or syn-bio, is the design and engineering of biological systems to create and improve processes and products. It offers new ways of producing almost anything that human beings consume, from flavors and fabrics to foods and fuels. In short, the confluence or flowing together of syn-bio and AI, two of the most potent realms of science and technology today, is poised to unravel solutions to some of our most pressing challenges.
Welcome to Ideas to Innovation, a podcast from Clarivate with conversations that explore how innovation spurs people and organizations to think forward and achieve their full potential in areas such as science, business, academia, technology, sport, and more. I’m Neville Hobson.
To help us navigate this exciting but complex landscape, I’m delighted to welcome Jim Collins, a recognized trailblazer in the realms of medical engineering and biological engineering at the Massachusetts Institute of Technology, as well as the Wyss Institute and Broad Institute at Harvard.
Jim was also named a Citation Laureate 2023 for his pioneering work on synthetic gene circuits, which launched the field of synthetic biology. Each year since 2002, the Citation Laureates program from Clarivate recognizes a small group of highly cited scientists and economists whose influence is comparable to that of past and future Nobel prize recipients.
Welcome, Jim. Thanks for joining us.
Jim Collins: Thanks, Neville. Delighted to be on your show.
Neville Hobson: To start, please tell us more about your role and work at MIT and at Harvard.
Jim Collins: I’m the Termeer Professor of Medical Engineering and Science and Professor of Biological Engineering at MIT. And I’m also one of the core founding faculty members of the Wyss Institute at Harvard, as well as an institute member at the Broad Institute of MIT and Harvard.
Our lab across these three institutions is really focused in two areas. One is synthetic biology and using this idea we can engineer biology to create new classes of diagnostics. and therapeutics, as well as tools to probe the complexity of biology. And the second is a newer effort of using artificial intelligence to both discover and design new antibiotics.
Neville Hobson: The scope and scale of your work as I’ve looked into it is pretty impressive and your drive and commitment are quite evident just simply with that landscape look, if I could say. But how did you get started? That was the first curiosity point I had in my mind. What, what is the passion, if you will, that drives you forward and what kicked it off?
Jim Collins: My origin story really goes back to my youth and that I was brought up in a family of engineers and mathematicians. My dad, who’s still with us, is an electrical engineer. My mom, who passed away nine and a half years ago, was a mathematician and a mathematics teacher, and my dad worked in the aviation industry, and his team, for example, helped design the altimeter for the Apollo 11 mission.
Growing up, he’d bring home technology that his team was developing and shared it with myself and my brother and sisters. And it was really fun to see cutting-edge technology. But also when I was young, his dad, my grandfather lost his vision. And then my mom’s dad had a stroke, a series of strokes and became hemiplegic.
So on the one hand, I saw this amazing technology, my dad and his colleagues, developing to shoot stuff into the sky and shoot stuff out of the sky. And I saw absolutely nothing being done to help these two guys who I cared for very much to recover or restore function they lost due to disease and injury, and I became interested as a middle schooler in a high school, or could I help develop technologies that could address challenges in human health and so became excited about biomedical engineering before it really was a serious academic discipline.
I started my academic career in 1990 as a professor at Boston University. And at that point, primarily focused on whole body dynamics, studying how people walk, run, maintain balance. Among other things we showed you could take small amounts of noise in the form of a vibrating insole to improve the balance of an individual, both young and old.
And it was in the mid-nineties that my colleagues at Boston University encouraged me to explore getting involved in the Human Genome Project. The Human Genome Project was the story in American science at the time. And bioengineers really were playing a big role.
And my colleagues introduced me to some leaders in the project, including Eric Lander and Lee Hood, who were very excited to think a guy with my background in knowledge, dynamics, control theory, can they make a difference, and they basically encouraged me to think about getting involved in this new field of systems biology. Could we begin to reverse-engineer natural networks that have evolved in living cells?
And I looked at it and saw that there really weren’t enough data to do that meaningfully. And so sat back with one of my students, Tim Gardner, and thought about, well, young people can become engineers by taking apart the radio to see how it works, but many of us become engineers because we’re tinkerers. We put stuff together in our garage, in our attic, in our basement, create go karts, create mini radios.
And Tim Gardner and I began to think, could we be tinkerers in biology? Could we begin to put together parts of living cells into circuits that could then be used to reprogram living cells, living organisms?
And it was this thinking that helped us launch what became synthetic biology.
Neville Hobson: Well, that’s, that’s quite, uh, that’s quite radical, if I, could use that word as a lay person listening to what you’ve described that kickstarted this. Terrific perspectives, Jim, and I can see why many in science see syn-bio… is that an accepted abbreviation, by the way?
Jim Collins: It is, I use it quite frequently. Yeah.
Neville Hobson: Great. So we’re saying it, we’re saying it the right way, which is good! I can see why many in science see syn-bio as a big deal. To help our listeners understand this point more clearly, though, I wonder if you could briefly explain why synthetic biology is so important.
We’ve got a clue to the answer to that, frankly, from what you’ve described and how you got started, but what is the real-world impact you think likely to be from your work?
Jim Collins: You know, the field itself is still relatively young, a little over two decades old, and the field is really bringing together engineers with molecular biologists to use engineering principles to model design and build synthetic gene circuits and other components, and use these circuits and components to reprogram, rewire living cells and cell free systems, endowing them with novel functions for a variety of applications.
Why I think the field is important is twofold. One is, it’s the romantic notion that we can engineer and reprogram living cells. It’s really quite attractive on the idea that we really now can influence the living world in ways that we couldn’t previously. And the second is that by doing so, and endowing such systems with novel functions, we can address some of the world’s biggest challenges.
Be it in food and water, be it in environment and sustainability, be it in bio-energy, be it in human health care. My focus has primarily been on human health care. And it’s where I think synthetic biology can make a big difference in that a critical kind of decision point in most projects that I see is in what applications can biology out-compete chemistry, and in the case, particularly of human health, the design of meaningful therapeutics, the design and meaningful diagnostics, biology often wins over chemistry.
And this is where we’re excited, where we think our work has had an impact and will continue to have, we hope a meaningful impact. And this is, for example, the design of inexpensive, easy-to-program diagnostics that can be used in clinical settings and at home, as well as the development of new classes of therapeutics, be it living therapeutics that can address rare genetic metabolic disorders, inflammatory bowel disease, cancer, as well as RNA based, controllable, inducible, programmable therapeutics that can address similarly broad ranges of disease conditions.
Neville Hobson: I think you mentioned when we were discussing this conversation earlier that you were involved in the study that led to the founding of Moderna. This is related to the COVID pandemic and the development of the vaccines. What can you tell us about that?
Jim Collins: So this was a collaborative effort with Derrick Rossi, who became a founder of Moderna, and George Daley, who recently became Dean of Harvard Medical School. And our team recognized that there was an opportunity to use these modified RNA components that were developed by our colleagues at the University of Pennsylvania for stem cell reprogramming.
And this is this idea that you can introduce some number of proteins into a mature cell, say a skin cell, and induce it to become a pluripotent stem cell, a cell that now could become any other cell type of interest.
Prior to our work, this would involve using viral vectors to deliver these proteins, which can be time-consuming, somewhat problematic, and give a very low yield. We showed and said you could deliver these modified RNA directly to the cell, into the cytoplasm, express these proteins, and lead to very rapid and very highly efficient reprogramming and redifferentiation efforts.
So it became really the first biomedical application for this synthetic mRNA technology. Derrick saw the possibilities and teamed up with some of our other colleagues, Bob Langer here at MIT, Noubar Afeyan pioneering a venture creation firm. saw the opportunity to create a company around this technology, which initially was launched as Mode RNA, which then got re-pronounced as Moderna.
And so while Derrick had initial interest in stem cell engineering, I think the team there saw there was more to other therapeutic indications, including vaccines and the company was in development for over ten years with massive investment. It was very well poised to then act on their platform in the face of the pandemic.
And, you know, of course, the rest is history. It was remarkable at so many levels of what their team was able to accomplish so quickly and so effectively. So we had a small part in the origin story and our group did both the synthetic biology and systems biology aspects of that initial project.
Neville Hobson: Yeah, I think I can see why a lot of people think this is a big deal. Um, you’ve given us a good sense of this, uh, in the context of human health. Uh, that’s a huge topic in itself, but I know there’s more to this though, isn’t there?
Jim Collins: There is more to this, you know, again, it’s, it’s this differentiation of where can biology really make a difference.
And what I’m seeing in addition to just the general development of tools to enable us to better understand the complexity of living cells and living organisms – again, we have so much to discover over this next century – I think the field of synthetic biology is well poised to impact other spaces. So we’re seeing, as you alluded in your introduction, interesting efforts in food and materials and fabrics. I’m most intrigued of the contributions synthetic biology can play in climate change. Efforts… sustainability efforts, environmental efforts.
For example, in our lab, we collaborated with Ting Lu, a professor at University of Illinois, who had done a postdoc with me recently on an effort that was led by Ting, a really brilliant effort to engineer consortia bacteria that can break down and up-cycle plastics. So that you can now take plastic waste and convert it into energy sources, convert it into other high commodity materials that can be useful.
There are efforts underway to use synthetic biology to monitor ocean health. We have an effort in our lab to do this, to look at various measures in coral reefs and other aspects of health of ocean.
There’s interesting efforts now to explore to what extent synthetic biology can be used to improve the resilience of coral reefs, as well as potentially leading to biomasses that can more efficiently store long-term carbon that could be captured from the atmosphere.
So it’s a… I think it’s a very, very exciting time. The challenges are multifold. Biology is not yet an engineering discipline. And as we see so often in our lab from the really fun, cool idea we might have in my office here, when we move into the lab, the complexity of biology often gets in the way of our very best intentions and innovative options.
Neville Hobson: Yeah, I can imagine that.
Let’s explore this idea of confluence that I mentioned at the start. Artificial intelligence is a seriously hot topic these days without question and synthetic biology could almost be a perfect partnership, I think.
If we marry the power of AI with the scope of syn-bio, we could accelerate research and development and widen its scope in all the areas we’ve mentioned so far, from human health to sustainability, energy, food, and more. Or is this a rose-tinted view of a Utopia that doesn’t exist? What do you think?
Jim Collins: You know, I think it’s probably an in-between spot, meaning that I don’t think the Utopia exists yet, but I don’t think it’s very tinted in the glasses; I think we just need to actually get efforts underway. So what I find interesting is that artificial intelligence has not had a major impact yet on synthetic biology.
We’re at the precipice and really where I think artificial intelligence can make a major difference in our field is in two levels.
One is enabling us better to embrace the complexity of biology and learn and infer the design principles. I’ll put design in quotes, but the principles underline the functioning of biological systems that have evolved over millions, billions of years.
And the second is to expand our capability to effectively design and discover new parts for synthetic biology.
What I like to point out is that we’re 23 years or so into the field, and yet we’re still largely reusing only a few dozen parts. And the analogy I make is it’s if we’re expecting an Intel engineer to create a professional integrated circuit using a kid’s electronics kit you might get at the gift shop of a science museum.
Unacceptable! There’s no Intel engineer that would accept that challenge. And yet that’s what we’re expecting of our biological engineers with our current toolkit.
I think artificial intelligence, specifically deep learning approaches that are emerging broadly in technology, open up the possibility that we can discover and design hundreds, thousands, millions of components that would now broadly expand our toolbox, putting it on par with what the electrical engineers have, enabling us now to design integrated biological systems, just as you would integrate electronic circuit with multilayers of functionality that function in predictable and desired ways.
Neville Hobson: What about risks? This mini topic, if you like, pops up in my mind quite a bit when I look at what’s happening in this broad area of artificial intelligence, ranging from the stuff everyone’s familiar with ChatGPT and the like of chatbots to deeper, large language models and beyond that even.
The big debates in governments in particular, but generally, is precisely on this: guardrails. What do we do to minimize risk? Can we… what are the actual risks? What can you throw into that pot, Jim?
Jim Collins: You know, I think the risks around synthetic biology are real and need to be discussed, they need to be considered. But they need to be considered and discussed against the backdrop of reality and not of projected potential.
So, the idea of genetically modified organisms has been discussed now for decades, with some hindrances and some success. I think we need to continue to advance these and the notion that we can engineer biology, like any new technology, can be dual use.
You can envision it largely using to help humanity, but you can think of bad actors that might try to use it for ill effects, be it, of course, in bio-weaponry and or have it for untoward unexpected effects where you’ve released something in the environment and it might have had negative consequences.
In many cases with synthetic biology, the organism they’re engineering carry what’s called a fitness cost. So that is if they’re introducing the environment, they likely are at a disadvantage relative to what else is out there. Having said that, we have actually efforts underway in synthetic biology to put safeguards in. So engineer the safeguards if you have an accidental release that the organism can be very quickly eliminated.
If the patient has an adverse reaction to the engineered cell, it can be eliminated. Once the engineered cell leaves the patient’s body, you can engineer, so it can be eliminated. So we have marvelous ways now that can address these.
Against this backdrop – and I’m regularly visited from my colleagues in the CIA, the FBI, the DIA to discuss worries and synthetic biology – I like to point out that my bigger concern is what nature has in store for us versus what the bio-engineers have in store for us.
And that is, as we see climate change increasing pressures on our organisms, as we see human overpopulation effects and crowding increasing pressures, my bigger worry is of some nasty virus jumping from an animal into the human population. And it’s not again to ignore the worry about synthetic biology, but I would be worried that if we focus too much on the engineered biology at the expense of what nature has in store, we probably are miscalculating the risks that we face.
Neville Hobson: It’s a fascinating landscape, Jim. You’ve portrayed a look and feel, if I can call it that, of where we’re at in 2023. And as you mentioned, this is only the last two decades or so that we’ve been able to do the things that we’re now talking about.
What about a little look into the future, just ten years out. I know in science in particular, that’s a very short period of time. You tend to like to look longer, but things have happened fast in just 20 years. And particularly with AI, things are moving extremely fast in that area. So what about ten years from now? How do you see the landscape in 2033? How would you like to see it if that’s different? What should we be expecting in the coming decade?
Jim Collins: You know, it’s interesting. I think it’s been said that we tend to overestimate what we’re going to get done in the next year, and we underestimate what we’re going to get done in ten years.
Ten years from a science point of view is still a relatively short period of time, but I’m really quite excited at what we could see happen, given what I’m seeing is growth activity and potential in the field.
So I think broadly, very easy comment to say is that I think biology will be more of an engineering discipline ten years from now. I think our toolkit will be dramatically expanded and our ability to engineer components and re-engineer living cells will have expanded substantially with our toolkit now, including what will be easily thousands of parts.
I think we will have a number of approved synthetic biology therapeutic products in patients. I think we’ll have a number of diagnostic platforms being used at home and in the clinic. And I think we’ll see early efforts as synthetic biology products that are being used to address challenges and climate change and environmental issues, really looking to see if they can scale.
I think we’ll see synthetic biology really having a very big impact in introducing tools in a basic science standpoint, really expanding our ability to again, better understand how living cells interact.
I hope to see many more educational programs so that we can train young people at the undergrad grad level, that we see synthetic biology being introduced in the curriculum at the high school level, and maybe even the middle school, given that I think biology will really be one of the dominant themes of this century and in particular, biology as technology. And so we need to train as many folks as we can to be informed and ready to contribute to synthetic biology.
Neville Hobson: That’s excellent. This has been a great conversation, Jim. Short, though, it has been, but thank you so much for sharing your time and your insights.
Jim Collins: Well, Neville, I really enjoyed our discussion. Thanks again for having me on your show.
Neville Hobson: You’ve been listening to a conversation about the research and development of synthetic biology and its confluence with artificial intelligence with our guest, Jim Collins, Termeer Professor of Medical Engineering and Science at the Massachusetts Institute of Technology and a Citation Laureate 2023.
For information about this program, visit clarivate.com/citation laureates. To find out more about Jim Collins’ work, visit collinslab.mit.edu.
We’ll release our next episode in a few weeks. Visit clarivate.com/podcasts for information about Ideas to Innovation. And for this episode, please consider sharing it with your friends and colleagues, rating us on your favorite podcast app, or leaving a review.
Until next time, thanks for listening.
Outro: Ideas to Innovation. From Clarivate.