David Leigh | Exploring the possibilities of nanotechnology

Beatrice Erkers: Hello everyone! I am not Allison, as you may notice. My name is Beatrice and I will be conducting this interview today with David, while Allison is traveling. With that said, welcome to the Existential Hope group this Friday! We are here today with David Leigh, who is a scientist working with molecular machines. He designs and synthesizes molecular models and machines, and he works at the University of Manchester. He has made a lot of contributions to the field, and I have heard that he is truly someone supporting a lot of junior scientists in the community. He is basically a pioneer in the field of Nanotech. 

I also understand that he won the Feynman Prize in 2007 from the Foresight Institute. I am truly excited to hear from David regarding how the work he is doing with nanotech can create futures of existential hope. Hopefully this interview can help inspire more people to get curious about what's happening in the field of nanotechnology, as well as the potential and possibilities of this science. I know that David is doing a lot of work to popularize and explain the field already. Let’s get started! Thank you so much for coming. What are you working on? What got you started in the field?

David Leigh: Thank you Beatrice and welcome everyone! I am a synthetic chemist at the University of Manchester in the UK. We work trying to make artificial molecular machines. The reason that we know that an artificial molecular nanotechnology is possible is because there is already a working molecular nanotechnology called biology. That is one of the reasons why scientists of the 21st century have an interest in trying to make molecular machines, because biology uses molecular machines for every conceivable biological process. This includes the way that energy is harvested from the sun, the way it is stored in the cell, the way that we can think, the way we can move, the way you can process what I am saying, and so forth. All of these depend on controlled molecular motion and molecular machinery. In contrast, human kind at the start of the 21st century, despite our myriad of molecular technologies, don’t use molecular machines for anything at all. So every catalyst, every radiant, every polymer, every pharmaceutical, and every material just relies on the static properties of the materials for their functions. 

Biology hasn’t evolved over 2.5 billion years to use molecular nanotechnology for everything for no good reason. As such, when we learn how to do the same and control molecular movement, I am convinced it will change every aspect of functional molecule material design. It will make things today look like a Harry Potter film. Essentially, I got into this area by chance when I was working on something else about 25 years ago. We were trying to make molecules that would bind to carbon dioxide, that captured sequestered carbon dioxide from the atmosphere. One of the molecules that we were making was a ring-type molecule, with the idea that it would bind CO₂ in the cavity. However, when we tried to make it, we couldn’t get a single ring at all and ended up with two rings interlocked together because of the quirkiness of the chemistry. 

We recognized, by following some of the earlier pioneers in the field, that having these interlocked architectures could be used to make molecular machines. If we controlled the movement of the components in that, we could use the large amplitude motions of the nanoscale to make these machines. The big problem in the area of trying to do this is that you cannot string engineering concepts of the big world down to the very small one because the way matter behaves is just very different. For instance, my mobile phone will just sit on the desk in front of me because it is a big object with inertia. It will not move, unless I give it some kinetic energy. However, if this is a molecular sized object it would be constantly moving through random thermal motions. Basically, you have to design molecular machines in a completely different way to how you design machines in the big world. What we really do is learn how to do molecular engineering. 

Beatrice Erkers: That is extremely fascinating to hear. You told us it could be like Harry Potter and one thing we are really trying to do with this podcast is inspire young people to think about what is possible. With that, could you tell us a bit more about what some of the specific possibilities of nanotechnology are?

David Leigh: Yes, similar to Harry Potter, just take a look at the possibilities with materials. I think we will have active matter going forward. For instance, things like clothes will not just be made out of fabrics that just have one shape and one size. Instead, you will be able to make active clothes that shrink to fit every wearer, or surface properties could change to repel viruses, be sticky, change color, and so forth. One day you will be able to go into your kids bedroom, see clothes all over the floor, and be able to flick a switch or something. From there, the active materials will know where to jump back onto their hangers, after getting rid of the dirt and sweat on themselves. 

I mean these are just trivial examples using fabrics. Really, I think we are at the start of synthetic molecular machinery and molecular engineering. It is a little bit like being at the start when stone age man and woman just invented the wheel to grind corn or something. They couldn't foresee that putting two wheels on an axel would enable you to control movement and transport things easier. So it is a little bit like we are right at the start of this process, but what we have that the stone age man didn’t have is a technology that we can work towards. We have a working molecular nanotechnology called biology, so we can see all the absolutely amazing things that it is able to create using just 20 building blocks, the amino acids. We have the whole periodic table, as well as years of chemistry and physics development. When we apply all of these things in ways that nature doesn’t do, things will develop to be unimaginably different. I truly believe that, but it will take a bit of time and it won’t be immediate. It’s really hard to predict exactly what that future is going to be, but that is precisely why we want to invent it.

Beatrice Erkers: Yes, I am curious as well. Nanotechnology does not seem like it has not been around for that long. Since you entered the field, what has the development been? Have there been any shifts or changes?

David Leigh: Of course, nanotechnology means a lot of different things to different people. To talk about my particular area of synthetic molecular machinery, it is actually something that Fyneman touched upon in his famous lecture, “There’s Plenty of Room at the Bottom,” where he talked about the possibility of little molecular robots being able to assemble objects by moving atoms around. I think that it was difficult for people to move in that direction of thought for a long time. I think the way to do it is by mimicking the way biology does engineering, as opposed to shrinking down macroscopic engineering concepts. We already know how biology does things, and I think being able to mimic those processes using chemistry and physics makes an awful lot more sense to me as a practicing synthetic scientist. 

So the big developments to come were in the start of the nineties when a lot of these pioneers realized we could maybe start to make molecular machinery. They mainly made switches, and they were awarded the Nobel Prize in chemistry for this pioneering work in 2016. Also, serendipitously all the first synthetic molecular motors didn’t really explain how other sorts of motors and machines could be made. It was sort of really a fancy switch. So, our contributions and those of others coming after the pioneers has been to recognize how to take other factors of what biology does and take the next step to make more sophisticated machines. I think that those early works were extremely important and exciting. Also, other advances in theoretical physics showed us how we can actually make mechanisms that could be then applied to molecules, to where people like myself could make much more advanced systems than before.

Beatrice Erkers: Amazing! Is there anything that you currently think is being undervalued in the field?

David Leigh: Yes, science is always like that, you know? Things usually take time before they are recognized. I think the most important way to advance in science is to take discoveries in one area and apply them to completely different areas. Those things take time to have that kind of crossover because it is not easy to recognize why something, or some discovery, in one area can be applied in another. This is because languages in science are just so different, so it is not always so easy to cross over these complex concepts. For instance, theoretical physicists noticed random thermal movements from Brownian particles that could be directionally controlled. We then realized that because molecules are also undergoing random thermal movement, that if we just took the idea that physicists applied to Brownian particles and applied them to molecular machine design, it would be a way of making motors. In fact, it turns out that it is even more profound than the applications of those mechanisms on molecular machinery. I think it is actually the key of how chemistry becomes biology and how the inanimate becomes animate. So this is going to become a very strong area in the next few years as people show how chemistry can translate to biology. Biology is quite complex because of how evolution works, and I think that it does not have to be.

Beatrice Erkers: Yes, that is very interesting to hear. I was also hoping that you would be able to provide some light on what it is like to be a specialist in your field, as we hope to inspire young people to follow similar paths. 

David Leigh: The field is extremely exciting. There are plenty of discoveries to be made. It is a bit like being an explorer in the 1500s, knowing that there are so many possibilities, such as Columbus sitting there in Spain. He knew that he wanted to go towards India, but it was a long way around to go east, so he went to the west in fear of losing sight of the shore. He knows that there is this vision of something great there, but he discovered something even better along the way by accident. If you are willing to lose sight of the shore, and go off to explore things, then there are all sorts of exciting things to discover. It is not a mature field, so there are a lot of upcoming things to do. 

I think one of the nice things about my job is that each day is a bit different. Today I am speaking to you from beautiful British Columbia, as I am on a lecture tour. Normally, I go into the laboratory to see my group about once a week when I am back home. I tend to work from home the rest of the time because I am writing or responding to emails. However, when I am in the lab, we start off with our group meeting. I give the latest updates to everyone in our team, about 25-30 people. Then, there are different meetings with other members of the group and we have project updates. Another luxury of what I am able to do is thinking, because I need to prioritize the efforts of our group. We also are actively trying to find aspects from other fields that we can translate to ours to make our machines better. 

Beatrice Erkers: You’re making it sound like a very exciting field to get into. I wanted to continue on this slightly philosophical lens. The premise of this whole group is to think about what direction we want to take this in. A bit like the Columbus metaphor you were speaking on, we have to think about what we want for our society and what we don’t want. So, we think about existential hope, what the future can look like, and how we can make that a good place. I wanted to ask you if you have a vision of existential hope, rather than existential angst, for the future?

David Leigh: Yes, I am definitely an optimist for the future. I see how technology and society has advanced for the better during my lifetime. Obviously, we take a longer route, but I think the quality of life for most of us in the west is way better than it was when I was a young boy. My vision of the future in terms of science helping society is that miniaturization of technology has always advanced technology dramatically. It has inherent, amazing advantages. Miniaturization means you need less materials to build whatever you are building, less waste produced, less energy is required to run it, and it allows you to have new applications that are not possible on macro scales. These factors address sustainability and technological desires of society directly. 

I feel as though they are really key to our future where we don’t need as much energy, or it is used more wisely. The miniaturization of technology is just an inherent good for society. Of course, things can always be used for bad. For instance, if you’ve seen the latest James Bond film, he has a few problems with nanobots. However, we should not let these things worry us. Technology can always be used for bad or for good, but the increase of knowledge and the miniaturization of technology is certainly an inherent good.

Beatrice Erkers: Of course. Also, one of the questions we usually ask revolves around the idea that it is very difficult for people to envision positive scenarios. Envisioning dystopias seems easier as there are so many ways that something can go wrong, whereas thinking of a utopia is much more challenging. We may also have a harder time agreeing on what we want, versus what we do not want. Is there anything you think we can do to change this outlook?

David Leigh: I don’t think it is my role. I don't claim to have a great vision of these sorts of things. There definitely could be a lot of societal and political questions revolving around how we want to live with the possible advantages nanotechnology will give us. However, my vision is to try and get there as quickly as possible, because I believe that it would provide a lot of these advantages for sustainability, less waste, efficient energy, technological advancements, and so forth. It can be hard to think of what all of these possibilities could be, and especially what that would mean for people when there is a lot more time on their hands, due to increased automation. My views on that though are not as well informed as I am regarding the potential of nanotechnology altogether. 

Beatrice Erkers: From your vantage point, are there any undervalued risks you feel we should get around to solving?

David Leigh: Well, I certainly don’t think self-replicating, gray goo, or anything like that is any kind of problem. Dangers in that realm come from synthetic biology, which is sort of taking existing biological pieces and using techniques like CRISPR to chop them up and manipulate organisms. I’m sure in the wrong hands, these powerful technologies and efforts could be used for bad. Nevertheless, these are sort of removed from my focus. I feel as though chances of gray goo based on synthetic molecular machinery is infinitely smaller than the possible advantages.

Beatrice Erkers: I have heard of the concept of gray goo, but do you want to touch upon it briefly?

David Leigh: Gray goo is this hypothetical catastrophic scenario. For instance, Eric Drexler came up with this interesting idea of molecular assemblance. These are things that people in my group sort of work closely on, and we call it molecular robotics. Essentially, these are molecules that can be programmed to build other molecules. They cannot build anything sophisticated or replicate themselves, nothing like that. Nevertheless, we are in the early stages of being able to do that. That is also how biology works as well. There are things called super enzyme complexes that actually pass building blocks from active site to active site to build molecules. So those sorts of things with synthetic molecular machinery have good analogies with biology. 

However, when Eric came up with the concept, the idea of gray goo came up, in which you would have self-replicating nanobots that would be able to pluck the building blocks they needed from almost any kind of matter and make more and more of themselves. Essentially, they would be able to feed off of anything. It led to popular works, such as a Crichton novel and those sorts of things. But those are not serious risks in the field of nanotechnology, not for the current timeframe of the science at least. Whereas there are real existential risks in other kinds of synthetic biology if they are used for ill, which need to be taken care of.

Beatrice Erkers: It is reassuring to know that the gray goo scenario isn't a very likely one, even though there are other areas to worry about. If we go back to envisioning positive scenarios, are there any specific breakthroughs, say in a 5 year time frame, that would tell you we are on track to getting to this more advanced place?

David Leigh: It is hard to say what will happen in 5 or 10 years time that will really change our lives. Who would’ve thought that when Facebook came out that it would be so persuasive? It is really hard to know how discoveries will be received by science and what the next factors to change society could be. What I can say is that the first application of synthetic molecular machines would likely be things like smart surfaces that can do stuff. These could add real value to conventional materials. The reason I am saying surfaces is because they only require very small amounts of substances to be made. Whereas if you wanted to make molecular factories that were making large amounts of something, you would need an awful lot of resources to do that, which is limited with our current technologies. There are examples of very simple molecular nanotechnologies already going into products. Some phone screens are strengthened by the sort of mechanical interlocking structures I was talking about that we discovered a while ago. Those are already being used to improve the properties of conventional materials, but it will take a bit more time before these concepts are sophisticated enough that they can do something of a greater magnitude. 

Beatrice Erkers: If you were thinking of someone interested in entering the field, is there a focus in particular that you would recommend they specialize in?

David Leigh: I would say look into application. The concept that made molecular machines into motors is actually being able to use energy to perform some task. This isn’t limited to just molecular machinery. It could be used for materials, such as light energy, chemical energy, or molecular energy, to do active things. These active properties could simply be materials sensing things and responding to that. This is an area that people have just started to look into so it is much less developed. So these concepts can be applied elsewhere, and I think that it would definitely have very exciting consequences. 

It would stop materials from just being stuck to fixed objects, allowing them to be responsive in ways that are hard to even imagine now. Imagine my shirt being like a computer, and being able to respond to its environment, sense things, and develop protection. For instance, if it sensed viruses, it could put out antiviral bits on the surface or close the distance between the fibers to stop penetration. All of these sorts of things could happen autonomously through active materials, and I think that is an area people can get into now since it is right at the start. 

Beatrice Erkers: Let’s hope it happens soon. It sounds possible and exciting. Again, for someone coming into this field - Is there anything in particular you recommend reading, listening to, or watching? It can be any genre really.

David Leigh: This podcast series is the way to go! I am not sure though to be honest. If it is a scientist thinking what can I do to contribute to this area, I would say research. It is good to be a specialist in something, so you can offer this to others. At the same time, if you are a specialist, it is crucial to have a broad awareness of what other fields are doing. That can tell you where your expertise could be applied outside your area. You could specialize in chemistry, physics, or molecular biology. Do something that gives you the skill of expertise. In my group, our expertise is that we can build molecules, which gives us a big advantage over say physicists. They may know more than me about how to design molecular machines, but they cannot build them because they do not have that skill set. As for me, my advantage over synthetic chemists in my field is that I am also aware of what those physicists know. I am not an expert in it, but I am able to understand and appreciate the things going on in that field, using them in things that I want to design and make. 

I think in my own career, this idea has benefited me very well. Be an expert in something, while broadly aware of everything else. As for what people should read, they should look into everything. Go for topics of nature, science, scientists, popular findings, magazines, and so forth. This compilation of topics would help give a broad overview of breakthroughs in many areas so that you can better apply these into your area of interest. It is a huge skill. What distinguishes great scientists from the ordinary is the ability to come up with a problem that is important enough to work on, but difficult enough that no one has solved it already. Then, you need to have the uncanny ability to know when the time is right. The problem then becomes tractable and you can apply these breakthroughs from different areas. And you have to be lucky as well!

Beatrice Erkers: That sounds like very wise advice. Thank you so much. I am going to take us on a bit of a turn. In every one of these episodes, we ask for an example of a eucatastrophe. I am unsure if you are familiar with the term. It was coined by Owen Cotton-Barratt and Toby Ord at the Future of Humanity Institute. They defined the term as an event that causes much more expected value after the event than before it. It is basically the opposite of a catastrophe. We like to think of that term and play with it in terms of helping people envision these positive futures. Do you have any suggestions of a eucatastrophe?

David Leigh: Yes, this could be many things. Let’s look at the huge energy crisis at the moment throughout the world, even without taking the war in Ukraine into account. The way we have been using energy is catastrophic. I think something that would be a good eucatastrophe could be biology actually using chemical fuels. It harvests the energy from the sun, but all of the molecular machines in your body work through chemical molecules. They use ATP converted to ADP and use the energy from that to do things. 

Similarly, I think a real breakthrough would be to find a way to use chemical energy effectively and interface it with our current technologies so we do not have to rely on more conventional fuel. It would be a completely new way of harvesting energy. I have no idea how people would be able to do that, but that would be something that could solve all of our energy problems. Of course, other ways, such as a breakthrough in fusion, could solve the world’s energy problems as well. There are many other problems we face as well, but I think that would be an interesting one.

Beatrice Erkers: I love it! It is very specific. What we do is ask an artist to interpret this and create an art piece from this prompt. Also, we are aware the term is a bit of a confusing one, because people are quick to think it sounds like catastrophe. We did have a bounty out where we were asking for better terms. I believe the winner was “effervescence.” If you have any better suggestions, we are open to hearing them. 

David Leigh: No, that sounds great to me!

Beatrice Erkers: Yeah, it is a beautiful one. I think I will ask you two more questions and then we can go to the audience for any more questions. You have already given a lot of really good advice, but do you have one piece of advice that stands out? What is the best piece of advice you feel you have received?

David Leigh: The best advice I ever got was that the cheapest way to pay for something is with money. The most valuable thing for many of us is our time. When I have had a big problem and I have made a mess of things, the easiest and cheapest way out of it is to pay and get it done. Governments could learn from this as well. Science is the key driver of success in all economies. All the time, they try to avoid funding it. If they just invest properly, they will find that they will get their money back and far more. Again, it is up to people like me to convince both politicians and the general public who vote for these people, that it is a good use of their tax dollars.

Beatrice Erkers: Yes, that sounds like good, concrete advice that can be applied on a small and large scale. Thank you. I will focus on the audience's questions now. The first says that most of biology seems to work with a small number of elements. What potential does the rest of the periodic table have for building molecular machines?

David Leigh: That is a great point and one of the most important ones as well. The reason that biological machines are so huge is because biology only has 20 building blocks - the amino acids - which are used to build everything. However, we have the whole periodic table, so we can make things much simpler and more effective by using different elements. That is just chemistry. The whole field of chemistry is about using different elements, chemistries, and conditions to achieve different outcomes. Different elements allow you to do things that just cannot be done with carbon. We can choose things in a much more effective way than biology can, by taking inspiration from how it does things and incorporating simpler ways of our own.

Beatrice Erkers: Wonderful. Another audience question is how would you deliver energy to the smart fabric you mentioned earlier?

David Leigh: It could be light, electricity, or chemical energy in some sort of way. Any of those sorts of things could be used in principle. 

Beatrice Erkers: Interesting. Another question is do you see any value in design rules that let engineers make design shapes out of protein blocks?

David Leigh: It’s always interesting. It is hard to know what new ideas or concepts are going to be useful. However, just the ability to do that sounds to me like it would be extremely interesting. It is like controlling the quaternary structure of proteins. You have the primary, secondary, and tertiary structure. The quaternary structure is how they stick together to form a larger object. It sounds to me like the question is finding a new way to control the quaternary structure of proteins, which I am sure could be useful for function. It certainly is in biology. 

Beatrice Erkers: I trust you on this. Another question is can nanobots be used for atomic precision in construction of novel materials?

David Leigh: Ultimately, I think yes. That is some of the work we focus on, which is making these first programmable, synthetic molecular robots that can do simple, chemical reactions. As that becomes more and more sophisticated, we will be able to build more and more complicated structures. We need to be able to make more complicated systems and molecularly engineer those components together. That is how complex machinery is made. You cannot just use these concepts in the big world, so we have to invent our own ways of doing that. The great thing is that we can learn from biology and use our own imagination to find those rules ourselves.

Beatrice Erkers: Yes, it has been very interesting to hear your points. You are great at making these metaphors and this has been a wonderful introduction in molecular machines. Is there anything else you would like to share?

David Leigh: You covered everything so well Beatrice. Thank you for giving me the opportunity to speak to the group and asking such nice questions. 

Beatrice Erkers: Thank you! We actually just received one last question, if that is okay. Might nanobots lead the way from the bottom in exploring emergent phenomena in foundational physics?

David Leigh: Yes, so just as we have learned from physics to design our molecules, what we do can feed back into physics to help make better theories. Physics normally treats things as points or spheres, so it is very simplistic in those sorts of interpretations. Whereas we work with real molecules that have real shapes, limits, bond lengths, and things like that. In turn, that gives us insight by knowing how those things we design behave according to the physics theory. They allow us to say to physicists things like, “You know the particle with an unsymmetrical surface? You can also achieve the same thing by having an unsymmetrical particle on a symmetrical surface.” That is something you would not necessarily think about in physics. So these collaborations can create great insights. It is definitely a two way street.

Beatrice Erkers: Yes, of course. I am happy we got that last question in. This sort of collaboration between fields is something we are currently trying to do at Foresight as well. Again, thank you so much David. It has been really interesting. Thank you to everyone else who joined in as well. 

David Leigh: Thanks for having me. Bye all! Take care and stay safe.

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