Sonia Contera: Okay, so um, I studied physics in Madrid. After I studied physics, I moved abroad. I first went to China and eventually I was interested at a time in the beginning of nanotechnology. I was, when I was at university in Spain I got familiar with a new tools that they were being developed that enable people to see atoms and nanomatter for the first time. And I was also interested in, 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 or physics of the nanoscale.
And when I was doing that, I started to become interested in biology, because biology we are made out of nanostructures. So the main biomolecules that make our body, which are proteins, and DNA and other biomolecules, are nano sized, 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 a, first a 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, material science, nanotech, and biology and physics.
Amy Barrett: And can you put the term nano into perspective for us? How small is that?
SC: 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 1,000 times smaller than a millimetre.
So, if you go three orders of magnitude that is 1,000 times smaller than a micron, that is a nanometer. So, to put it into perspective, a nanometer is to a metre, 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 this way about molecules. 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 at any other size and, and they are important for medicine, for materials and indeed to understand life on Earth.
AB: And how do you work with things on such a small scale?
SC: Yeah, so they key of nanotechnology, which has started to be developed in the 1980s 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 tunnelling microscope, and then the scanning probe microscope, 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 nano finger, the surfaces of things and figuring out with movements of that nano finger 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 nano finger and the sample, they allow you also to manipulate matter at the nano scale. So, with this microscope, nano scale matter became visible. There were other tools of nanotechnology that were developed by the time that we’re starting to make people able to interact with matter at the nanometer scale.
Chemists they also became, they became good at making nanometer scale materials in the 1990s, but 80s but they key I think, to the developing of nanotechnology was the developing, the development of a scanning tunnelling microscopes and scanning probe microscopes, and actually the first nanotechnology centres in the world were created from labs that were bc with this microscopy, I am indeed come from 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.
AB: And when we talk about nanotechnology, the term what actually comes under that term. What’s the definition of nanotechnology?
SC: Nanotechnology is the capacity to visualise, 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, so, or creating devices to look at things at the nano scale.
So basically, nanotechnology is a very broad term that, that takes into account a lot of things. Basically, yeah, what happens at the nanoscale.
AB: You say creating new proteins, do you mean proteins that don’t exist in nature?
SC: 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. W e are made of. collagen for example, colaghen is a string like protein which is nanometer in diameter, and constitute in the scaffolding which our the cells of our bodies give a shape. Or proteins are responsible for seeing their little nano sensors in your eyes that detect light of different colours. They are responsible for producing the energy of your body, they’re producing for all at the basic level that 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. Not 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 predict in 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 has led people to think about designing proteins that don’t exist in nature.
So the protein is designed in the computer and you work in reverse as you want as biology then you, you can create a DNA or, or an RNA molecule that codes 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 you get nature to produce your nanoscale materials by designing them first in the computer as a protein, and then going back in reverse to the cell. 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 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’re 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 a specific characteristics can be made in this way. But it’s a radical point, I think if, for nanotechnology, because we are not building nanostructures top down with our devices, nanoscale devices, we’re actually using biology to create our nano structures.
So, we are increasingly merging with the capacity of nature to build materials.
AB: So is it just proteins that can be used to make these kind of nano structures?
SC: No, people use DNA actually, the first biological material that was used to make nano structures was DNA, because DNA is is made of four building blocks, a bit like Lego, and these building blocks can stick to each other in very precise ways.
So people thought from the 1980s, 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 in a test tube, heat them up, shake them up a bit, and things will assemble in the structure.
One of 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, that because it’s such a multidisciplinary area, so people immediately start thinking of applications for all this is structures and mixing with other structures that are alreadyin nature. So yeah, we’re starting to construct in a very different way.
AB: You say we’re still very early days, but how far away are we actually from using this technology in medicine? Like, what could it do for me in my lifetime?
SC: Well, I’m not sure we’re 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, or or DNA nanostructures. Actually, this is starting to be DNA structures that, for example, are specifically designed not just as a small little drug, but as a bigger, of 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, when, 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 this, 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 a structure that trap pathogens, or that are useful for detecting them. Is work 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 mathematical models about the body and how the body actually brings drugs to tumours or brings drugs to focus of infection. And I think the breakthroughs will not come just from a single field, is just the convergence of fields in a specific problem will bring the breakthroughs.
I think one of the most important things that nanotechnology has facilitated is the move 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 applied 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 or, or, or yeah, or building our living environment without the convergence of sciences.
AB: Because when you think about DNA, and we talk about DNA or proteins for me that that always seems like it’s the realm of biologists. What role does physics play in ourselves and in our DNA?
SC: Biologists, the thing is up to the, the 1980s, 1990s there was not 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 way, is when they are working. But up to the 1990s, there was no tools that we could see them in their living environment.
So physicists 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.
So, for example, with my microscopes, I cannot only observe the proteins, I can push them I can pull them and can 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 I mean, it’s just chemistry is, 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, is able to catalyse a chemical reaction through mechanics. And the reason they can do that is because the extract energy from the environment from the temperature of your body to be able to create this amazing movements are the nanoscale.
So as physicists what we tried to do is to understand how do they use temperature? How do they use the matter around them to create these amazing movements? How why the Universe actually created life on Earth, using, which means reducing the or increasing the order of the Universe. We all know when 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 nano machines that make life possible? But it born a very fundamental point of view. Whereas biologist and biochemist 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 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, 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, 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.
AB: And so with all these new cross disciplinary people working on nanotechnology, what, what is the next big challenge that needs to be overcome in the field?
SC: Well, there are many challenges. I mean, mainly, we don’t work as nanotechnologies. We don’t call ourselves nanotechnologists. Only when we build some devices or we work at the nanoscale. We are biological physicists or material scientists, 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, to image and to create more data to create more mathematics, better mathematical models, that allows us to understand what’s going on. There are many challenges because there are challenges of all the sciences that converge in biology.
But 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 are 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 you still measured by your output, your research output with with the, with the rules that are 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.
AB: And how do you see this moving into to medicine and where you know, is this going to be something that in the future, we, everyone has access to nano medicine? I’m wondering, it sounds like it must cost a fortune. Is there a danger that nano medicine could be a treatment reserved for just the super rich?
SC: I think, I think that 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 tumours such as, for example, pancreatic tumours or tumours that there you cannot touch that you cannot feel is very difficult, and people actually become terminally ill almost just before as they arrive to the clinic.
So, for example, nanotech from the beginning of nanotech has been a huge effort of the community and other multidisciplinary teams that are formed is for creating biosensors, basically that can, you can just put a drop of blood on, on, on a little device and it will detect if you’re having a tumour if you have any diseases very quickly.
This has been a biggest, bigger channel, 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 gotten 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 promised a lot, and then nothing comes out of it apart from some bad stories that come out in the press of people that over promise 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 sensor that is actually able to detect a lot of tumours with a drop of blood and quite cheaply. I think they were talking about £100 per test. So if you could do one of these tests every two years to detect a tumour, it could definitely reduce the costs of healthcare, because you could detect the tumours much earlier.
So I think, if there is a will of the scientific community and the health care communities, we can use 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 the many, some of the main players in this new fields are South Korea, Japan, China, will change the way we do things.
Because yeah, I mean by the very nature of the multidisciplinarity of the of the research and the potentiality it has, it can be very disruptive.
AB: I just wanted to ask about that blood test that you were referring to, how exactly would that work? How does that detect tumours?
SC: I mean, I haven’t 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 will trigger a kind of signal that you can measure. It can be a change in 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 they 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 happening, work has been getting on, and I think in the next 10, 5, 10 years, we would really probably will see much better diagnostic tools in the clinic and much cheaper, hopefully.
AB: So with that, then if we can, you know, better determine whether it’s a bacteria or a virus, would that then eventually help with antibiotic resistance?
SC: Of course, because many of the problems we have right now is that when when you have your very ill they don’t give you antibiotics because it means might be a virus or might not be, but we can definitely tell you have a bacterial infection, and then you need antibiotics, and you need to have them, the right antibiotic, we can be much more targeted.
Yes, absolutely, I mean detecting better the diseases and it is very important for the, 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.
AB: Is there anything that we we don’t yet know or understand about the nano world and the nano scale?
SC: Everything you know, the origin of life, right, is something that has a nano scale. We, we still very poor at fabricating artificial structures at the nanoscale, only very few of them can be done with atomic precision.
That’s why we go in 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 learn the building blocks of things, and then we try 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 and just when 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. We, 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. We didn’t. Genes and DNA which was not enough and it’s not enough to explain life and now, then what we are learning in the lab is that, and indeed from there, we emerged life, and life on Earth emerged from the environment entangled with the environment, our biology is entangled with the environment, our materials are entangled with the environment.
So we are maybe reconnecting with, with something we, we disconnected ourselves from nature for a very long time. And we have seen the consequences if you want in global warming and also in the, in the, in the way, some technologies did not progress anymore. And now we’re learning, becoming maybe more humble and learning to construct more with, with biology, with nature. So there’s a lot we need to learn this a lot because of the basically, I think, global warming, the existential crisis we’re 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 understanding how we emerged from nature might also be important if humans are going to survive the 21st Century.
AB: 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 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.
SC: 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 come bind 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 nano machines 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, 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 are to not only to create these tasks at the nano scale, but to assemble into cells and the cells into bodies that can think and can do mathematics.
I don’t think we can build proteins as clever 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 think 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 this soil is 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’s thousands of genes involved. 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 so, and also, for example, now we’re looking at the microbiome. We are ourselves an ecosystem. We’re full of bacteria, we depend on these bacteria for activating the immune system. We are reencountering ourselves with something I think we knew from the beginning of civilisation, 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 the planet.
And I think we are not only learning that from the environmental crisis, we are learning that also in the lab in when we’re trying to do medicine, when we’re trying to do new materials. We need to learn from nature how to create our next generation of our our future technology.
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