Online science dialogue in Spanish "La nanotecnología llega a la vida".

Summary:

On 26 May 2022, the Rafael del Pino Foundation organised the dialogue "Nanotechnology comes to life: how nanotechnology is transforming medicine and the future of biology", with the participation of Sonia A. Contera, professor of biological physics at the University of Oxford.

We live in a very complex universe. Reality is very complex, but, in order to survive, it is very important to understand it. It is something that living organisms, people, do. The key to survival is to have a good understanding and a good collection of relationships with the complex environment around us.

Physics is one of the most successful ways of understanding reality. It is a system that has been developed over thousands of years. Physics has a system that is very good at understanding reality. It has no method, but it has a way of looking at the world that consists of doing experiments and from them extracting intuitions about how we see reality. We rationalise these intuitions, we make a balance between intuition and reason and reason allows us to make mathematical models.

The universe is so wonderful that our mathematical models sometimes allow us to predict how a system works. That is the power of physics.

Physics is able to transform reality because it is able to extract intuitions from those logical and mathematical models that are then transformed into technology. The 19th century was totally transformed by physics and electricity and the 20th century was revolutionised by physics and its ability to transform warfare. But it also transformed all models of communication, our reality.

Most of these processes were a reductionist way of understanding the universe, that is, looking at the parts of the complex system that surrounds us, looking at its components and seeing how they interact with each other. From there a reductionist model was made. In the 20th century, the same thing was done in biology. Instead of looking at a plant, they started to look at the molecules in a plant and its genes, and tried to understand the relationship between the two.

In the 20th century we have to face the fact that complex reality cannot only be understood in a reductionist way. When systems of many particles start to interact in a very deep way, behaviours emerge that have nothing to do with the behaviour of the parts. At different scales, matter interacts in different ways and with different behaviours. The moment physics reached nanotechnology, a door was opened, the door to being able to interrogate biological complexity.

Reductionism begins in the 17th century with the invention of microscopes at Oxford. In the 20th century, X-rays and other methods of looking lead us to the atom, to quantum physics, at the beginning of the 20th century. Right after that, physicists start investigating what happens when atoms are put together and questions about life immediately arise. In 1944, Schrödinger gives a series of lectures in Dublin explaining life because what we humans are interested in is us.

The complexity of atoms gave rise to transistors which, in a very short time, made computers possible. Soon, when the atomic bomb began to be made, the first computers were already being prepared, based on Turing's ideas. They were all inspired by biology, by neurons.

At the same time, we start to become interested in energy, in how living systems use energy in a very different way to how non-living systems use energy. Here we begin to bring together intelligence, information, energy and structures, the way the universe has been able to create living structures by the use of energy and information.

When computers emerged, physicists and mathematicians began to study complex systems. So we came up with the idea of emergence, the idea that when systems of particles interact in a very close way with each other, things emerge that don't emerge on any other scale.

So as much as we may have an idea of the physics of simple, inert things, physicists have always been obsessed with intelligence and complexity. Richard Feynman predicted in the 1950s that, at some point, we would reach the nanoscale and that would transform our ways of making. That moment came in the 1980s, when chemists started making nanoparticles. But not just chemists. A mathematical physicist at MIT, who was working on DNA structures, first had the idea of using DNA to build. Thus begins the field of DNA technology.

Chemists, structural biologists and people interested in computational physics begin to think that the time has come for nanotechnology. At the same time, the microscope is invented in physics laboratories, transforming the way we see reality. The scanning microscope is the first microscope that allows us to see individual atoms and nature at the nanometre scale. These are not microscopes with light or waves, but use very fine tips to obtain images of surfaces. But they are not only images, but because they are a kind of nano-finger that you can manipulate to see surfaces, you can also manipulate them to move and create structures with atoms. That's where nanotechnology begins.

In one way or another, all the sciences started to get to the nano in the 1980s, and many scientists, in the 1990s, became interested in the mechanisms that make life possible. At the same time as we were trying to manipulate matter at the nano-scale, crystallographers were using X-rays to look at the structure of proteins, and the protein structures of life began to emerge.

We have millions of atpase proteins all over our bodies in almost all our cells. All living things have atpases. They are enzymes that generate the ATP molecule, which we need for most of the actions our molecules do. An active person moves about eighty kilos of ATP molecules a day. So these enzymes have to be very good and very fast.

How has evolution been able to create a machine that can use eighty kilos of molecules a day? By creating a molecular engine. It's a molecule that's embedded in the cell membrane, which, using electrostatics, is able to make that motor rotate. As it rotates, it traps a molecule of ATP, doubles it and catalyses the chemical reaction with almost no energy. This is the trick of biology. At the nano-scale, one can simply use the temperature of the molecules with a mechanical design like a windmill to transform the energy of the water molecules into motion. And, because it is at the nanoscale, you are able to grab a molecule and catalyse a chemical reaction. That's why life arises at the nanoscale, because at the nanoscale you can transform energy from one way to another, reducing entropy to create work.

In the 1980s, people like Hiroyuki Noji began to show that these machines worked like machines using energy to do different processes. DNA is not just a code. It's a form, it's able to sense forces, electricity and it's one of the ways our cells are able to understand what's going on outside.

When nano physicists began to use biology and to interpret proteins not as a point, information or code, but as a machine, they began to see biology differently. In the 20th century, molecular biologists and biochemists saw biology as interactions of shapeless protein networks and tried to understand biology as a complex system of communication between proteins. This is where a couple of cultures began to meet, the one that wanted to see biology as analogue machines and the one that wanted to see it as digital machines of DNA and proteins.

The beginning of nanotechnology in biology was primarily medical. Doctors tried to use nanoparticles to improve cancer treatment. But they did not change the paradigm. They simply continued the way they had been treating cancer, which was to look for proteins or DNA and make molecules that would stick to the cancer. The main problem with chemotherapy cancer treatment is that it has produced very few new drugs in the last twenty or thirty years and they are very ineffective. So they were looking for new ways of interacting with genes and proteins through nanotechnology, which would allow them to have a more direct way of attacking problems like cancer.

That's when the drugs started to appear and they started to be put in liposomes. They started to be put in nanoparticles similar to the Covid vaccines to treat cancers. This has had a rather limited effect because cancers are able to immunise themselves against these nanoparticles and our body is able to get rid of them. There are very few treatments in a traditional pharmacological way that have reached the market.

Another application of nanotechnology to medicine has been sensors. During the Covid pandemic we realised how important it is to have sensors that tell us what is going on and which molecules or viruses are attacking us. We have also seen how difficult it is, PCR is very slow, antigen sensors took a long time to come out and they are still having problems.

The sensor problem is still very complex. There have been great advances in the last five years, with new ways of creating sensors, but the pandemic has come a little early for sensors and there has not been enough investment in the field so far. The dream of many people working in this field at this time is to create like stickers of nanoparticles that we can attach to the body and they are able to measure in real time the concentrations of chemicals, for example glucose, and react by delivering insulin when the body needs it, or creating specific treatments in specific fields. We are not there yet. There are a lot of people working in this field and the pandemic is accelerating investment in these kinds of projects tremendously and there are great opportunities for countries and for investors who have a vision in this field. We want sensors that can talk to our phone and we can look at the diseases we have.

One field that is set to revolutionise nanotechnology is nanotechnology made with protein. During the pandemic, we heard the news that Google's Deep Learning was being able to predict the structure of proteins. This is not really the work of Google, but of many people, in particular David Baker, who has been working for 40 years trying to predict proteins. It's important because, at last, we have a quick method of understanding which are the nanomachines of life that are important for example for a biological process. But more interesting is that this kind of technology makes it possible to make proteins that don't exist in nature using cells. What David Baker did as soon as he was able to predict proteins was to design in a computer proteins that don't exist in nature, but that he thought a bacterium or a cell could make, and he managed to create proteins that don't exist in nature, but with atomic precision, using cells to sequence them, that could self-assemble. This is the most precise and radical nanotechnology there is, but it is not a dream.

During the pandemic, one of his students, King, quickly began designing a vaccine for Covid based on these structures and succeeded very quickly. It's in clinical trials, it's already passed phase 3 and it's going to be used in humans in South Korea. So this is the step of biology and nanotechnology. In 2016 the first results start. In 2022 we already have a vaccine on the market made with protein nanotechnology.

While nanotechnology has not improved cancer, for example, when using traditional pharmacology methods, we have seen during the pandemic that lipid nanoparticles with RNA are able to train the immune system to remove a virus, but also to remove cancer. Moderna and BioNTech were founded ten years ago. The two companies that have made Covid vaccines were founded ten years ago and used nanoparticles to remove tumours. Just as nanoparticles and traditional medicines have not been very successful in the last twenty years in treating cancer, immunotherapies are radically changing the treatment of diseases.

These immunotherapy technologies, or protein technology, are emerging technologies. They are no longer relying on a reductionist way of creating technology, of looking at atoms, putting them together and then designing, but are using the complexity of life to create new technologies. Covid's vaccines are lipid nanoparticles that have RNA inside that are able to activate the immune system to create immunity against the virus.

Moderna and BioNTech have a very different model of innovation from other companies we have had before. They are companies that are very multidisciplinary, that are looking for a very different kind of technology transfer, that are groups of scientists, financiers and people interested in business almost from the beginning, with a very clear strategy to change cancer treatment. When you talk about entrepreneurs, everyone thinks of young Silicon Valley kids in t-shirts. But in the pandemic, it was not them who came up with the idea of how to create these vaccines, but women in their fifties who had been thinking for a long time about how to create vaccines. The heroes of the pandemic are not young computer scientists, but women who have been working for a long time, for example Sarah Gilbert with the Oxford vaccine, Ozlem Tured and Ugur Sahin with the Pfizer vaccine, or Kizzmekia Corbert who found the protein that carries the RNA for vaccines, or Katalin Kariko's work realising that RNA could be used as a vaccine.

These vaccines are no longer only being pursued in injectable form, but also as cancer implants. Nanotechnology models and materials are beginning to be used not only to implant but also to repair tissues.

Another area of technology that is transforming the treatment of many tissue damage problems, through disease or accident, is regenerative medicine based on nanomaterials, from spinal cord repair, to getting neurons to talk to each other again after an accident, to organs on a chip - creating artificial organs that allow us to better understand organ biology and create medicines.

What we are starting to want is very good sensors that allow us to measure, quantitatively, in real time, what is going on in the body of a sick or healthy person. The intelligent mathematical modelling of those processes is going to be fundamental to understand all that data that we are getting from the body and that we don't know what to do. Finally, to have smart medicines that are able to talk to the body's complex system and understand all its interactions.

This of intelligent models and data leads to the relationship between biology, nanotechnology and the future of computing. Biological and medical problems are very complex and probably cannot be solved with current computational models. We are now trying to introduce artificial intelligence into almost all medical measurements. One way or another we are starting to understand that all this data that we are collecting from a lot of diseases, from a lot of processes, we need better ways to understand it.

The artificial intelligence we use now is also a process that is inspired by the order of neurons in the brain, but it has very large computational limits. The main problem with artificial intelligence is that it needs a lot of energy. It costs two million dollars to train the neural network so that the AI can identify a person and draw a picture of him or her. It takes so many connections and so many operations to be able to simulate the process of understanding that it is starting to have a lot of problems for practical use in biology.

Scientists are therefore starting to look for other ways of computing that will allow us to do fast computations without so much energy use. Biology uses a dual digital and analogue code. A plant rotates towards the sun and for that you don't need to do a computation with proteins. Simply, its shape, its physics and how proteins adapt to them, allows it to create an analogue computation that uses almost no energy. Scientists are beginning to look to biology for inspiration to create new computers that allow them, for example, to be faster at understanding medical problems. These are neuromorphic computers, or computers that can mimic a plant as it turns towards the sun. This type of neuromorphic computing is about understanding how nature is able to understand and create computations using energy and information. The idea is that these complex structures are able to change shape to understand information. Matter, organic or inorganic, at the nanometre scale, is capable of producing computations. They are analogue computations, they are not digital, and they will increasingly transform the way we process what we mean by information.

This is starting to give rise to new robots. For example, soft structures like a plastic robot that has been fitted with cells that are able to sense the light around it and the robotic toy is able to move towards the light. We are beginning to integrate, as humans have always done, all the technologies in toys, in creating what is possible, and here we begin to see the possibilities of what is coming, that is, new forms of intelligence, new forms of computation, new machines that are able to extract energy from the environment.

One of the ways scientists think we are going to be able to process all the information we are beginning to be able to gather from the environment is by using quantum computers. The idea is that in a quantum computer many operations can be performed at once. Our analogue computation as people, our intuition, our emotions, involves the idea that we have a series of superimposed states that are able to collapse at specific moments to create our consciousness. In many laboratories we are beginning to see that many biological systems are also capable of quantum computations, or whether we can learn from biology how to create quantum computations that allow us to overcome the limitations of digital computation.

The Rafael del Pino Foundation is not responsible for the comments, opinions or statements made by the people who participate in its activities and which are expressed as a result of their inalienable right to freedom of expression and under their sole responsibility. The contents included in the summary of this conference are the result of the debates held at the meeting held for this purpose at the Foundation and are the responsibility of their authors.

The Rafael del Pino Foundation is not responsible for any comments, opinions or statements made by third parties. In this respect, the FRP is not obliged to monitor the views expressed by such third parties who participate in its activities and which are expressed as a result of their inalienable right to freedom of expression and under their own responsibility. The contents included in the summary of this conference are the result of the discussions that took place during the conference organised for this purpose at the Foundation and are the sole responsibility of its authors.

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