Instant Genius - Sonia Contera: How will nanotechnology revolutionise medicine?

Episode Date: May 11, 2020

This week we talk to one of the world’s leading pioneers in the field of nanotechnology, Sonia Contera. Nanotechnology is the application of science at a truly nano scale. To put that in perspective, if a nanometre were the size of a cup of tea, a meter would cover the diameter of the whole Earth. Being able to control the world at such an intricate level has the potential to revolutionise medicine - enabling us to target cancer cells, deliver drugs and fight antibiotic resistance – but how do we create technology to that size? Sonia talks to our editorial assistant Amy Barret about how her work in nanotechnology began, building proteins unknown to nature, and why going nano is nothing like in the movies. Her book Nano Comes To Life (£22, Princeton University Press), is out now. Read the full transcription [this will open in a new window] Let us know what you think of the episode with a review or a comment wherever you listen to your podcasts. Subscribe to the Science Focus Podcast on these services: Acast, iTunes, Stitcher, RSS, Overcast Listen to more episodes of the Science Focus Podcast: Sandro Galea: What is the difference between health and medicine? Jim Al-Khalili: Why should we care about science and scientists? Gordon Wallace: Is an implantable electronic device the future of medicine? Professor Catharina Svanborg: Is the cure for cancer hiding in human breast milk? Nessa Carey: Is gene editing inspiring or terrifying? Dr Lucy Rogers: What makes a robot a robot? Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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Hello, I'm Alexander Matt Namara, and this week we talk to one of the world's leading pioneers in the field of nanotechnology, Sonia Contera. Nanotechnology is the application of science at a truly nanoscale. To put that into perspective, if a nanometer were the size of a cup of A meter would cover the diameter of the whole earth. Being able to control the world at such an intricate level has the potential to revolutionize medicine, enabling us to target cancer cells, deliver drugs and fight antibiotic resistance. But how do we create technology to that size? Sonia talks to our editorial assistant Amy Barrett about how her work in nanotechnology began,

building proteins unknown to nature, and why going nano is nothing like in the movies. I studied physics in Madrid. After I studied physics, I move abroad. I first went to China and eventually I was interested at the time in the beginning of nanotechnology. When I was a university in Spain, I got familiar with the new tools that they were being developed that were enabled people to see atoms and nanomatter for the first time. And I was also interested in how Japan became like the second world economy through technology. So I eventually did a PhD in Japan that was based mainly on nanotechnology and physics at the nanoscale. And when I was doing that, I started to become interested in biology because biology, we are made of nanostructures. So the main biomolecules that make our body, which are proteins and DNA and, and other biomolecules are nanosized,

and they produce the most amazing movements and activities that make life possible. So I became interested in using the tools of nanotechnology to study biology. From then on, I progressively worked in both fields. So I used the tools of nanotech to learn biology and to develop tools so we could study biology from first the sort of engineering point of view

and then from a physics point of view, understanding the main principles that make life possible in the universe, if you want. And also, I got interested in learning biology so we could apply the building principles of nature to create new materials, to create nanotechnology. So I'm between both disciplines, materials science, nanotech and biology and physics.

And can you put the term nano into perspective for us? How small is that? Yeah. So normal optical microscopes cannot go down to the nanometer scale. The nanometer, so a normal microscope can see a bacterium, for example, which is a micron in size, which is a thousand times. smaller than a millimeter. So if you go through orders of magnitude, that is a thousand times smaller than a micron, that is a nanometer. So to put it into perspective, a nanometer is to a meter

the same as a, I don't know, a cup of tea or a tennis ball it is to the diameter of the earth. And this is the scale of biology. This is the scale of biomolecules. This is the scale that gave life to, gave rise to life on Earth. So it's a very special scale. It's not only, and that's the reason why material scientists are also interested in nanotechnology, is because you can do things at that size that you cannot do on any other size. And they are important for medicine, for materials, and indeed to understand life on Earth. And how do you work with things on such a small scale?

Yeah, so the kilo of nanotechnology, which started to be developed in the 19-18. 80s is the creation of the first tools that allow you to see and manipulate matter at that scale. So for me, a crucial moment was the discovery of the scanning tunneling microscope, and then the scanning probe microscopes, which I am a specialist of, which allow you to see matter, not by light, but in a way it's a bit like touching with a nanofinger the surfaces of things and figuring out with that movements of that nanofinger, the structures of things. That's an atomic force microscope, explained in a very simple way. But these microscopes because they operate by interactions of a small, tiny, tip, a small,

a small nanofinger and a sample, they allow you also to manipulate matter at the nanoscale. So with this microscope, nanoscale matter became visible. there were other tools of nanotechnology that were developed by the time that were starting to make people able to interact with matter at the nanometer scale. Chemists that also became, they became good at making nanometer scale materials on the 1990s, but the key, I think, to the development of nanotechnology was the development of scanning tunneling microscopes and scanning probe microscopes. And actually the first nanotechnology centers in the world were created,

from labs that were BC with these microscopes. I indeed come from that field. And yeah, many of us went on to apply them and to learn nanoscale physics and nanoscale materials and nanoscale biology from that moment. And when we talk about nanotechnology as a term, what actually comes under that term? What is the definition of nanotechnology?

Nanotechnology is the capacity to visualize, manipulate or fabricate matter at the nanometer scale. Basically, it can be many things. From fabricating a small nanoparticle to create structures made of DNA as a building block or even, I would argue, creating new proteins or structures with new proteins, or creating devices to look at things at the nanoscale.

So basically, nanotechnology is, is a very broad term that takes into account a lot of things. Basically, yeah, what happens at the nanoscale. You said creating new proteins, do you mean proteins that don't exist in nature? Correct. So for the last, I would argue, I mean, 70 years, if you want or even more, scientists have been interested in understanding about the building blocks of life, which is proteins. We are made of collagen, for example.

Collagen is a string-like protein, which is nanometer in diameter, and constitute the scaffold in which the cells of our bodies give us shape. Or proteins are responsible for seeing. There are little nanocensors in your eyes that detect. light of different colors. They're responsible for producing the energy of your body. They're producing for all at the basic level. They're responsible for, or at least behind most of our actions. So for a long time, they're also the target of medicine. So drugs function mainly by targeting proteins. Some drugs target DNA, but most proteins target, sorry, most drugs target,

proteins. So it's been a big effort of the scientific community since the 1950s or even before that to understand the structure of proteins and for many uses. But in the last 10 years, there's been massive breakthroughs in the science of understanding protein structure. People are starting to be able to predicting the computer a protein structure even without doing the experiments just by knowing the sequence of the structure or the sequence of the protein. And this had led people to think about designing proteins that don't exist in nature. So the protein is designing the computer and you work in reverse as you want as biology. Then you can create a DNA or an RNA molecule that coats for that protein.

And then you put that inside a living cell that you use as a living factory, could be proteins or yeast. And then you get nature to produce your nanoscale materials. by designing then first in the computer as a protein and then going back in reverse to the cells so the cell produces for you the protein you design in the computer. This is, if you want a radical new way of doing science, people are not doing technology. People are thinking of using this as drugs,

but also as building materials of the future because the proteins you design in the computer, they are designed with atomic precision. and you can design them to assemble into the structures you want. Of course, this is still early days and only a limited amount of proteins with the specific characteristics can be made in this way. But it's a radical point, I think, if you pour nanotechnology, because we are not building nanostructures top down with our devices,

nanoscale devices, we're actually using biology to create our nanostructures. So we are increasingly merging with the capacity of nature to build materials. So is it just proteins that can be used to make these kind of nanostructures? No, people use DNA. Actually, the first biological material that was used to make nanostructures was DNA because DNA is made of four building blocks. a bit like Lego. And this building blocks can stick to each other in very precise way.

So people thought from the 1980s, Nadrian Seaman, that you could use DNA as Lego for building any structure you wanted. It took some time. But in the early 2000s and now, basically, you can build any shape you like with DNA. You can go to the computer, design your shape. order the pieces of DNA online and then put them in a test tube, hit them up, shake them up a bit, and things will assemble in the structure you want.

The main challenges, though, is that you build very small structures, which is unclear how you connect with them to make something useful, which is one of the challenges right now of these technologies. But I think everything goes because it's such multidisciplinary, area so people immediately start thinking of applications for all these structures and mixing with other structures that they're already in nature. So yeah, we're starting to construct in a very different way. You say we're still very early days, but how far away are we actually from using this technology in medicine? What could it do for me in my lifetime? Well, I'm not sure with that far away.

I don't think in your lifetime, we will start probably have the first drugs that are based on artificial proteins or DNA nanostructures. Actually, there's starting to be DNA structures that, for example, are specifically designed, not just as a small little drug, but as a bigger structure that, for example, matches a whole virus and sort of grabs the whole virus. So a little bit mimicking what your body does also when it's trying to get rid of infections. Our immune cells sometimes are able to explode themselves. And so they explode the DNA they have inside of their nucleus.

And the body uses the DNA of the immune system cells to actually trap bacteria and trap pathogens. So maybe we're starting to learn these tricks that we already have in the body and create structures that trap pathogens or that are useful for detecting them is work in progress. Drug delivery is a very complicated problem to find a specific place in the body that you want to target with a medicine or with a drug. That's the reason why actually pharmaceutical companies are having such a hard time in the last years to produce new drugs, new effective drugs. But I think it will be, we will learn more. Together, we will learn more biology.

We will have better models of how the, better mathematical models about the body and how the body actually brings drugs to tumors or brings drugs to focus of infection. And I think the breakthroughs will not come just from a single field. It's just the convergence of fields in a specific problems will bring. the breakthroughs. I think one of the most important things that nanotechnology has facilitated is to bring, for example, physicists and engineers to medical problems. So we applied much more of the capacity of humans to do science to complex problems. So we apply maths, physics, materials, computation to tackle the biggest medical or indeed material challenges of our time.

I don't think we can solve either the medical problems or the materials problems we have in the world, materials in the sense of constructing or building our living environment without the convergence of sciences. Because when you think about DNA, when we talk about DNA or proteins, for me, that always seems like it's the realm of biologists. What role does physics play in ourselves and in our DNA? The thing is up to the, yeah, the 1980s, 1990s, there was no enough information for doing physics of proteins or DNA. Because basically, proteins and DNA live in salty water at the nanoscale and at warm temperatures inside our body. That's the real wet. That's when they are working.

But up to the 1990s, there was no tools that we could see them in their living environment. So physics could not do physics of life because we didn't have enough information to actually make models of how they work. Because what is physics? Physics is about getting information about the external world, planets, financial markets or proteins. And trying to extract what are the basic principles of whatever is happening that you're studying. And then try to abstract it into a mathematical. model. That's the magic of physics or of the magic of science that you can interpret reality through mathematics. So up to now, we couldn't do it in biology because we didn't have the

tool to observe and we didn't even have the mathematical tools to model biological complexity. But what has happened in the last 20 years is that we're starting to build the tools to see and interrogate biology as a physicist. For example, with my microscopes, I cannot only observe the proteins. I can push them. I can pull them. And then I can start understanding so what does it make it work? So in the case of a protein, for example, they can perform the most amazing tasks.

They are able to rotate. They are able to walk. They are able to. The biology is not chemistry. Chemistry is just chemistry. The chemistry in biology is always controlled. by mechanical movements. So for example, you have proteins that rotate and the rotation of the protein as it binds to a molecule, bends the molecule, and is able to catalyze a chemical reaction

through mechanics. And the reason they can do that is because they extract energy from the environment, from the temperature of your body to be able to create these amazing movements at the nanoscale. So as physicists, what we try to do is to understand how do they use temperature, how do they use the matter around them to create these amazing movements, why the universe actually created life on earth using, which means increasing the order of the universe. We all know and we have heard that entropy grows in the universe, but yet we are built for in the opposite.

We're building from reducing entropy for becoming complex. So this is what physicists are trying to understand. What are the principles of the universe in salty water with these little nanomachines that make life possible? But it born a very fundamental point of view. Whereas biologists and biochemists and molecular cell biologists from most of the 20th century, they have just been working really hard to identify the building blocks. But they could not study the mechanisms by which these building blocks work, or they assemble together, or they create complex mechanisms.

movements. What physicists and engineers in biology do is to try to bring all these tools, mathematical tools, engineering tools, physics tools, to understand how they move, how they assemble. Why are we so complex? Why do we need to store information? Why do we have the capacity of computing, if you want, or thinking? So all these questions are now converging into biology. Computer scientists are also interested in biology to try to understand how we think, how we build a better machine learning algorithms, the better algorithms of the future. So what is happening right now is a convergence of science in biology, because it's for the first time in history that we can actually tackle or try to understand biological complexity. And so with all these cross-disciplinary people working on nanotechnology, what is the next big challenge that needs to be overcome in the field?

Well, there are many challenges. I mean, mainly we don't work as nanotechnologies. We don't call ourselves nanotechnology. Only when we build some devices or we work at the nanoscale. We are biological physicists or material sciences that, or we, The problem is that basically the boundaries between disciplines are blurring very much. So the biggest challenges, of course, remain to create better tools, to image and to create more data, to create more mathematics, better mathematical models that allows us to understand what is going on.

There are many challenges because there are challenges of all the sciences that converge in biology. Perhaps the biggest challenge is the convergence itself. So science is very conservative by nature. A generation of scientists is always usually chosen by the previous generation of scientists, so things don't change very much. So the previous generation of scientists can keep doing the things they used to do. So the biggest challenges come from the very structure of science, whereas I think as a scientist we can see many of us what is the path forward.

You cannot do it because you can still measure by your output or research output with the rules that used to be used to measure research many years ago. So in a way, the biggest challenges are always social, the social structure of science. But that's always been the same. And how do you see this moving into medicine and where, you know, is this going to be something that in the future we, everyone has access to nanomedicine? I'm wondering, you know, it sounds like it must cost a fortune. Is there a danger that nanomedic could be a treatment reserved for just the super rich? I think, I think the one of the nice thing of nanotech is that I can actually make treatments hopefully cheaper.

And this is also something that scientists, when we do our research, most of us, take a lot of care. So you choose topics of research that actually improve the life of people and as many people as possible. One such example would be, for example, better biosensing. So nanotechnology is also very important for detecting chemicals in your body or detecting diseases. Right now, detecting tumors such as, for example, pancreatic tumors or tumors that you cannot touch, that you cannot feel is very difficult. And people actually become terminally ill almost just as they arrive to the clinic. So, for example, nanotech, from the beginning of nanotech has been a huge effort of the community and the multidisciplinary teams that are foremost for creating biosensors, basically, that they're a very important. can you can just put a drop of blood on a little device and it will detect if you're having a tumor

or if you have diseases very quickly. This has been a bigger challenge than everybody anticipated in the 1990s. As usual, scientists try to overestimate the complexity of biology, which is one of the reasons, again, as I said at the beginning, that drug discovery has got stuck in many cases. But actually the breakthroughs are starting to come through. So at the beginning is always the hype. You have the hype with the technologies promise a lot and then nothing comes out of it, apart from some bad stories that come out in the press of people that overpromise something and never happens. But for example, two weeks or three weeks ago very quietly, I think it was Hitachi or another Japanese company, released a biosensor that is actually able to

detect a lot of tumors with a drop of blood and quite cheaply. I think they were talking about a hundred pounds per test. So if you could do one of this test every two years to detect a tumor, it could definitely reduce the cost of healthcare because you could detect the tumors much early. So I think if there is a will of the scientific community and the healthcare communities, is we can use their technologies to improve and make the treatment and detection of diseases cheaper. But of course, this is a very complicated problem. Again, many of these technologies are disruptive. They are disruptive of the way we do medicine right now, especially in the West.

We have a lot of big medical conglomerates that not necessarily good for them, that we make things cheaper, for example. So we will see changes. I think the fact that some of the main players in these new fields are South Korea, Japan, China will change the way we do things. Because, yeah, I mean, by the very nature of the multidisciplinaryity of the research and the potentiality it has, it can be very disruptive. I just wanted to ask about that blood test that you were very new.

How exactly would that work? How does that detect tumors? I mean, I haven't looked at, this is just very recent news. There are many ways in which people are trying to detect chemicals in the body or molecules in the body or proteins in the body. Some ways can be electrical, optical. So usually you have a protein that will bind an antibody, another protein that you design and you put in your device. And that would trigger a kind of signal that you can mention. It can be a change in optical properties. It can be a change in electrical properties. And then ideally, you want to make a device that you can measure some signal out cheaply and simply. For

example, I myself, I'm working with a group of Japanese scientists trying to develop a graphing electric device for detecting viruses. When you have an infection, for example, remember Ebola and things like this, is important to know if the fever you have is caused by bacteria or a virus. So we, for example, require better tests. So we, I mean, there are many people working on this. I think we're starting to see the first breakthroughs. After the first, after the big hype we had in the early 2000s about biosensing, quietly things have been, work has been getting on.

And I think in the next 10 years, we really probably will see much better diagnostic tools in the clinic and much cheaper, hopefully. So would that then, if we can better determine whether it's a bacteria or a virus, would that then eventually help with antibiotic resistance? Of course, because many of the problems we have right now is that when you are very ill, they don't give you antibiotics because it might be a virus. or might not be. But if we can definitely tell you have a bacterial infection, and then you need antibiotics, and you need to have their right antibiotic, we can be much more targeted.

Yes, absolutely. I mean, detecting better the diseases and it is very important for the administration of drugs. And it might even also be a case that if we are better to administer drugs, we will design better treatments. And again, we can reduce the cost. Is there anything that we don't yet know or understand about the nanow world and the nanoscale? Everything, you know, the origin of life, right, is something that happened at the nanoscale.

We still very poor are fabricating artificial structure at the nanoscale. Only very few of them can be done with atomic precision. That's why we're going back to biology to do it. And I think one of the lessons we are learning not only in material science and in computing is that we are progressively abandoning the way we used to do science in the 20th century, which was basically we learned the building blocks of things. And then we tried to get the relationships from then and have a very top-down approach in which we design every single step of the process. one of the interesting things we're doing right now is we're merging much more with nature. So, yeah, so we use the building power of nature. We use the computing power of nature.

We mimic more the way nature works. I think it's a conceptual departure from science in the 20th century, in which biology was in a way almost separated from nature. We were just studying genes, and we didn't, genes and DNA, which was not enough, and it's not enough to explain life. And now what we are learning in the lab is that, and indeed from there, we emerge, life on earth emerged from the environment entangled with the environment. Our biologists entangled with the environment. Our materials are entangled with the environment. So we are maybe reconnecting with something we disconnected ourselves from nature for very long time.

And we have seen the consequences, if you want, in global warming. And also in the way some technologies did not progress anymore. And now we are learning, becoming maybe more humble and learning to construct more with biology, with nature. So there's a lot we need to learn. There's a lot because of the, basically, I think, global warming, the existential crisis we are facing now is changing the way we think about ourselves and the environment and the way we do technology. And I think understanding biology and matter at the nanoscale and understand how we emerge from nature might also be important if humans are going to. to survive the 21st century. And it's interesting because if, you know, before we spoke,

I was thinking about my own views on nanomedicine. And you always kind of imagine, you know, there's films, there's TV shows where they kind of, they shrink people down and they put them in these really kind of mechanical-looking, fancy cars and then they put them into the bloodstream. And that's not really the nanomedicine that you're describing. It's very natural. It's, you know, nature's Lego building blocks.

Yeah, it cannot be built. Basically, I don't think humans have the capacity to build a nanomachine that can rotate or that can walk or that can bite to a virus just with atoms. We can't do it. We don't have the capacity because what we are learning in biological physics is that the complexity that you need. basically the nanomachines that run our bodies have been created by billions of years of evolution on earth, of life on earth. It's not just physics, it's not just chemistry, is how the early organisms in Earth started to change the landscape of Earth so that more complex organisms could come. And we inherit all this history of evolution of life on earth. And that, all these billions of years of evolution have been trying and designing our building blocks, the incredible capacities of our proteins, not only to create these tasks at the nanoscale, but to assemble into cells and the cells into bodies that can think and can do

mathematics. I don't think we can build, um, I don't think we can build, um, proteins. as clever as nature does. But we can learn how nature does it and we can try to work with nature to improve our technologies. I definitely think this is the way forward. A case, for example,

if you can think of agriculture, for much of the 20th century, we thought we could dominate agriculture with chemicals, that we didn't need to take into account the environment around it. And now we know that we deplete the soils, that the soils, the ecosystem, the bacteria, everything is related.

We are all interconnected. The same in biology. We were just looking at the genes for a long time. Now we know that for every disease, there are thousands of genes involved. The DNA is a much more wonderful, complicated machine that links physics, the history of life on Earth, that links us to the environment, that the environment can do things on our DNA. And also, for example, now we're looking at the microbiome. We are ourselves an ecosystem.

We're full of bacteria. We depend on this bacteria for activating the immune system. We are re-encountering ourselves with something I think we knew from the beginning of civilizations, which is that we emerge from nature. We are entangled with nature. And the future of us as humans is entangled with the future of, of the planet. And I think we are not only learning that from the environmental crisis,

we are learning that also in the lab, when we're trying to do medicine, where we're trying to do new materials. We need to learn from nature how to create our next generation of our future technology. That was Sonia Cantera talking about nanotechnology. Her book, Nano Comes to Life, is out now. If you haven't already, make sure you look back through podcast feed and listen to our special news series where we get world-renowned scientists to answer your

questions. Just look for everything you wanted to know about physics with Professor Jim Al-Kalili and prepare to have your mind blown with some amazing science all about the Big Bang, multiple worlds and time travel. Let us know what you think with a rating and a review, and subscribe to make sure you get the latest episodes as soon as they are released. The new issue of BBC Science Focus magazine is out now. So if you want a copy delivered to your door, head over to ScienceFocus.com forward slash subscribe for the latest offers. Thank you for listening to the Science Focus podcast from the BBC Science Focus magazine team. With the UK's best-selling science and technology monthly, available in print and in several

digital formats throughout the world. Find out more at sciencefocus.com or look out for us in your app store. This podcast is sponsored by name, audio and focal. The texture and emotional depth of music can be lost through digital sources or poor sources. Signal, Name Audio believes you can have digital precision with analog warmth. Alongside French acoustic specialist vocal, Name creates high-end audio systems, combining innovation with craftsmanship, so you can listen to music, just as the artist intended. Discover more at name audio.com. In a place like Los Angeles, people don't stop being who they are.

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