Who is for life and who is for death

A surprising fact is that all the proteins in our body change frequently, yet we exist as one identity from birth to death. Why do body proteins have to die for us to live? Nobel laureate Prof. Aharon Chachanover identified, together with his two award partners, the mechanism that determines which proteins will die and when they will be sentenced. This discovery paves the way for the development of new life-saving drugs and for the understanding of the control systems that watch over our bodies

A conversation with Prof. Aharon Chachanover

Some time after it was announced that he had won the Nobel Prize in Chemistry, Aharon Czahnover was invited to Portugal, to a small town 150 kilometers from Lisbon. By chance, he and his son came across a small synagogue there, which was recently renovated and renovated and is used by Jews, who had been converts for hundreds of years and only in recent years had come back to identify as Jews. When the keeper of the synagogue heard that the guests were Israelis, he excitedly invited them to a festive ceremony to be held the next day, Sunday, in the synagogue.

A ceremony in a synagogue on Sunday? Chechenover asked in bewilderment. Yes, the guard replied, this is the biggest event in the history of our synagogue. An Israeli who won a Nobel Prize is coming to town, and we are celebrating a special celebration in his honor, for us and the Jewish people.

This story, which Chechenover tells with great excitement, symbolizes the special combination he represents: a brilliant scientist, a former officer in the navy and a proud Zionist, a Jew who sees the Jewish tradition as a central pillar of his education, and a man who devotes a large part of his time to education in values ​​and the connection between science and society.

Allegedly, Aharon Chachanover deals with a tiny mechanism that resides in the solitary cell. The discovery that brought him and his two research colleagues (Abraham Hershko, his supervisor in the doctoral thesis, and Irwin Rose, their partner from the Cancer Research Institute in Philadelphia) the winning of the prestigious award appears, to the lay observer, as a technical explanation - one of many - that describes in illustrations and chemical formulas a mysterious action - also One of many - that takes place in our body. After all, modern scientists limit themselves more and more to focused and precise research, and only a few manage to understand how the results of their research communicate or affect our lives and our ability to better understand the essence of man.

But this description does not at all fit the discovery of Chechenover and his partners, and even less so - his personality and work. More than that: he actually succeeded, and continues to succeed, in connecting his discovery with understanding the way the human body functions and proves that there is a close connection between research in chemistry and the advancement of the medical profession and the development of life-saving drugs. Chechenover even insists on pointing out the connection between the education system and higher education and the values ​​of good citizenship. In his lectures, and also in the personal example he gives, he offers an integrated, interdisciplinary model, which fascinates his listeners and creates a close and impressive connection between the scientific work and the mission of the scientist and his role in society.

Although Chechenover often travels the world, the laboratory was and remains the center of his world. His office is in the heart, and doctoral students and researchers work there under his direction on the development of new research. "I believe in freedom of action and full initiative of my students", he says. "I let them jump into the deep water and drown. Only if we recognize real danger do we come to their aid. Science requires trial and error, initiative and risk-taking. I believe in hard work and mistakes that everyone makes and learns from."

You won the Nobel Prize in Chemistry, but you are a doctor and not a chemist.
Since childhood I was attracted to the field of biology, and going towards medicine was a kind of compromise. The academic reserve in the sixties allowed only medical studies, but already during my studies I realized that I wanted to connect fields. During my studies, I developed a kind of frustration regarding medicine and its ability to deal with serious diseases and epidemics, especially in regards to understanding their basic mechanisms, and I wanted - and I applied, already during my studies - to engage in research, in which I thought there was a chance to understand the mechanisms of diseases and cure them. I knew that I wanted to be in the field of chemistry of biological processes - biochemistry - which connects biology, chemistry and medicine.

Modern science is becoming more and more professional, and is becoming smaller and smaller in focused and limited areas of research. In medicine alone there is a division into dozens of types of expertise, and the result is that an expert in a certain field usually knows very little about other fields. Particle physicists, for example, are not familiar with astrophysics, and so on. The division into disciplines creates worlds where there is almost no speech or contact between them.

All the disciplinary definitions, the scientific division into separate professions, are human definitions and are not related to the reality of nature. These are artificial definitions. They were born as a result of us having difficulty understanding the overall picture and being unable to deal with too much complexity. The universities, when they were founded about nine hundred years ago, adopted this method for reasons of convenience, because it is not possible to teach otherwise. They teach according to subjects and give up - at least during the studies - the complexity that exists in nature. Smart people placed artificial dividing lines, took the field of atomic structure and associated it with physics. Then they climbed to a higher level, to molecules that have a name and an identity, and called this profession chemistry, and divided it into inorganic, which deals with the still universe, and organic. For the latter, whose occupation is the plant and animal world, when molecules become organisms and life - call biology. And when there is a disorder or malfunction in biology - you go to the garage which is the hospital, and this profession was called medicine.

All these definitions are definitions only, and they are on a continuum within which we created an arbitrary division, in my opinion, for the purpose of instruction. In practice, all of us - humans and all the inanimate, plant and living world - are made of one inseparable part. Our entire body is atoms and molecules that obey all the laws of physics and chemistry and are organized into cells and life, and within them, obviously, the human spirit is also found.

Still, science builds walls between professions and fields. Scientists specialize in increasingly narrow fields. Does this process advance the development of scientific knowledge or stop it?

We probably have no other way. Nobel laureate in physics, David Gross, said that the most important product of accumulated knowledge is further ignorance. The more we know the less we understand. We make pits. The accumulated knowledge opens up more extensive and comprehensive circles of questions. Fifty years ago it was possible to find people with comprehensive knowledge who were well versed in many fields. Today it is more and more difficult to find such people, because the amount of knowledge is so great, and the questions are so many, that it is impossible for a person to encompass everything.

On the other hand, interdisciplinary professions are also developing. Today there is a new profession called systems biology, a profession that deals with communication between different cellular systems. I call biologists who study systems of this kind, pilots. They do not work at a high resolution level, nor in penetrating the individual molecules, but in an "overview". It is understood that they pay a certain price for this, but they create new tools, which will lead to a different perspective and understanding of the complexity of the living cell. The tools that accompany this revolution are the computer and computing, which brought about a big change in the amount of accessible data and research methods. There is no doubt that the development of the ability to calculate and process data today has revolutionized our knowledge and understanding.

The cooperation and combination between the high-resolution view and the overview will advance us. The penetration will continue. We will not return to the situation of a family doctor who answers all the problems, but we will turn to specialist doctors who are knowledgeable in fields that will become even narrower in terms of their definition, but extremely broad in terms of their scope. Think what we knew about the heart 40 years ago, and what we know today. We have experts in the subfields of the heart and for every type of treatment. We have experts in electrophysiology, catheterization, valves, heart failure, birth defects, ultrasound, and the profession called cardiology is broken down into sub-specialties. The role of the family doctor who knows us personally will change. He will have powerful tools, some imaging and some chemical-molecular-genomic, with the help of which he will be able to make an initial diagnosis and refer us to the appropriate specialists. He will then compile the information. He will be the one to beat the expert orchestra, and his role will be largely different from his role today.

Certain philosophers of science, as well as some scientists, try to make a reduction of the phenomena in order to try to put them, in the end, on one basic explanation. Biology relies on chemistry, which relies on physics. Is it possible to learn about the human spirit from a small molecule? Is it possible to reduce intelligence to a small molecule or chemical activity in the brain?

Man, like any organism, living or plant, is a whole. Between all the elements that make us up there is an inseparable continuity and integration. I do not believe in reduction, in placing one phenomenon over another, but I do believe in breaking down complex phenomena into their smallest components and reassembling them in order to understand their mechanism. Nature, as I mentioned, has not heard of the separation between disciplines. Will it ever be possible to understand everything? Will it be possible to learn everything, to give one explanation for all the phenomena? At this stage the complexity is greater than our ability to understand, and we don't even have the experimental tools to analyze it. In recent years, a new discipline has been created, that of synthetic biology, which tries to create life from molecules for two purposes: to understand the process of creating life, and at the same time to try to improve it. How far the process will go and penetrate even into the complexity of human qualities - into his spirit - is difficult to know. It will be a tough nut to crack anyway. The approach, in my opinion, is correct and perhaps based on the statement of the well-known physicist Richard Feynman, according to which we can never understand what we cannot create.

There is a debate on the question of whether the human spirit, reason, is essentially different from the body and cannot be explained chemically and physically. Different people of science and spirit make a kind of separation between body and soul, matter and spirit. Can you live with such separation?

As a scientist, I tend to believe that everything is chemistry, and when I pass from this world I will no longer be here. In the cemetery I will be food for worms, and everything I carry with me will disappear. There will remain, of course, the things I wrote and recorded, the remaining films, and the ideas I taught, but I myself will not be here anymore, not even to publish. My spirit will disappear, my creativity will fade, my loves, feelings and intelligence will disappear - everything that makes up a person will be no more. This is perhaps the evidence that everything is chemistry. Once the cells and molecules become food for worms, only the past remains, which is metaphorical; The ability to create freezes at the moment of death. The task of continuing to develop ideas based on the existing ones was entrusted from that moment to the living ones, to the chemical reactions that take place in them. The torch only passes between lives.
We can save a large part of my features and ideas on the computer, and they will remain in the minds of other people, who can continue to develop them, but we cannot preserve my dynamic and responsive spirit on any computer, and it will disappear with my death. It is possible that in the future we will be able to preserve more, but at least today, this is still impossible. The main reason for this is that we do not have "blueprint” to the thinking and creative processes that we can “synthetically produce” and imitate.

What does an architect or engineer do? He draws, plans and builds according to basic plans. In human activity there are areas that we are able to understand and break down, such as the engineer's work, but there are also areas that we cannot explain, such as composing music, creating a sculpture or painting. We do not have a mechanical understanding of inspiration, creative thinking, the secret of originality, and we do not know how to produce or imitate them. We don't have, for example, a blueprint for writing symphonies like Beethoven's "Ninth". The way in which it was created is mysterious to us, because the creation is related to the human spirit and we are far from understanding. To be honest, we have no understanding even of apparently simpler processes, such as memory and even recognition.

Can we understand the spirit? Will there be a blueprint in the future that will make it possible to reconstruct and build the human spirit? I don't have an answer for that. In my heart, as a scientist, I want to believe that it is, perhaps due to my curiosity to understand the complexity of human characteristics and the complexity of its organs - the brain. We are indeed marching towards a partial understanding, and the answers to our questions at this stage come from the fields of chemistry, physics, biology, medicine, imaging, computing, and also from the field of behavioral sciences which have a chemical basis, I believe. It is a fact that with the help of drugs we can control mental properties, such as mood. We treat depression and other disorders of the so-called mind and spirit with the help of chemical substances, and sometimes with considerable success.

Scientists are constantly looking for one simple explanation that contains all the phenomena. "God doesn't play with dice", said Einstein, so he looked for a unifying theory that would explain all the phenomena of physics. Do you believe in such a possibility?

I believe that there is no end to knowledge, and that the more we know, the more knowledge we will need to understand will increase, therefore most likely there is no "final understanding". Philosophers and scientists alike have searched and are searching for the overall explanation that will give us a picture of everything. That one day we will know everything and understand everything. But knowing everything means gaining the ability to reassemble everything, to compress millions of years of evolution into a short-term experience of a few minutes, hours, days, months or a few years. It is very possible that such an explanation will not be found.

At the base of the thinking process is a mechanism. Can we decipher it? Is it all decipherable chemistry and physics? I do not know. I want to believe that it is indeed so. The attempt to decipher the process is a kind of construction of the Tower of Babel, the goal of which is to reach the "secret of creation". Although science is trying to build a tower of Babel all the time, we are still far from complete understanding. The higher we go in this Tower of Babel, the wider the structure becomes, and it turns out to be a kind of pyramid or an inverted spiral, which shows us, in fact, that this tower has no limits or end.
If we look at the classical paintings depicting the biblical Tower of Babel, it seems to have a wide base and it gets narrower towards the top. This is indeed how engineers build. But nature has built us an upside-down tower, an ever-widening spiral, where each step upwards illustrates how much the structure is expanding. This is our problem. We ascend - but the radius of the distance from the center increases.

One of the protracted debates in philosophy and science deals with the question of determinism - that is, to what extent all things are predetermined. The assumption is that if the world is deterministic there is no free will, and once we identify the principles - we can know in advance any future action. For example, when we understand the operation of the genes, we will predict all our qualities and actions.

The debate about determinism is ancient and has been dealt with by the best philosophers and thinkers: a chorus that said, "What was will be and what will be will be done", through the Aristotelian Greek philosophy to the present day. The uncertainty principle in quantum theory was supposed to remove determinism from the world, at least in its physical sense, but it didn't happen that way. Who am I, therefore, to express my opinion on the matter? I will only point out that one of the fascinating phenomena discovered in recent decades is the plasticity of the brain - the changes that take place in it during its activity, and its ability to change according to what we go through and experience. This is great news for opponents of determinism. The environment in which we grow up has a great influence on shaping us as people. If you take a child and teach him to be a cannibal, he will act like that for the rest of his life. If we take his twin brother and raise him in a moral school, he will be a completely different person from his brother. Culture, education and the society around us - all of these have a great influence on human behavior and its design. We are certainly far from determinism and from the possibility that we will reach a stage where we can decipher and predict what is expected in the future.

I want to understand the plastic mechanism of the brain, the elements that determine and influence our behavior. It is not a deterministic procedure, although it is activated by a mechanism that is mainly physico-chemical. We try to understand the mechanisms, but even if we understand them, this does not mean determinism. We are constantly changing and adapting ourselves to changes, therefore, even if the mechanism is clear to us, this does not mean that we will have the ability to predict.

The conclusion from your words is nevertheless a form of determinism. When we know all the details of the mechanism and how it works, we will know what will happen in the future.

I think that would be impossible. If we know everything that is happening around us, can we really pull out a computerized prophecy? I don't know how to say, but I don't currently see a situation where we can really know everything, mainly because of the inverted pyramid I described. Before the Human Genome Project we had no idea what awaited us after it. And here he came, and the picture only got more complicated; Many more questions arose than those we faced before its unveiling. Mainly we learned that there is not only the genome, but also the epigenome¹, and above it sits the proteome, and these are perhaps more complicated than the genome. The proteome is surely infinitely more complicated than him. Science is a polygon with infinite sides that each form an angle or a corner, and we progress from one to another, but the next corner is always waiting for us.

Take, for example, life expectancy and the development of diseases. Just a hundred years ago people died at an average age of 40 or 50 from infectious diseases. We discovered the antibiotic, improved the quality of life in other aspects and extended the life expectancy in the developed countries to 80 years. Then we reached the next barrier - cancer. People didn't die of malignant diseases earlier because they didn't live long enough to get them. Now, when we understand more about cancer, partially overcome it and continue to extend our life span, we encounter degenerative brain diseases, such as Alzheimer's and Parkinson's. At each stage of progress, with each step we climb - the problems that arise in the new stage are revealed, and we are faced with a new confrontation. When we reach an average age of 120 we may discover new problems. To me, this is an optimistic reality; It is a dynamic understanding of what is happening and what is developing. I am often asked, all your life will you study one molecule? And I reply that I wish I could succeed in all my life to finish the work on the investigation of this one molecule. The unknown about her far exceeds, even today, the known about her, and it is only growing. I think that the attempt to predict whether one day we will know everything and therefore also be able to control and direct processes, is an interesting theoretical exercise that scientists are less concerned with. They try to solve problems that can be solved experimentally, and not engage in prediction beyond them. They trust their findings and nature, which together with technological developments will take them to the next problem and its solution.

You are a doctor and a life sciences researcher. How can life be defined?

I'm a biologist, not a philosopher. To me, everything that organizes itself within a membrane and is able to exist and reproduce on its own and pass its properties on to the next generation - such as a virus or bacteria - is a living being. It is convenient for me to reduce myself to biological definitions that speak of a genetic load that can be transferred. What separates life from non-life is, apparently, the ability to reproduce (asexual or sexual) and the ability to reproduce and transmit the genetic information vertically from generation to generation.

To this day, science cannot explain the transition from inorganic matter to life, which brings us back to the issue of the absence of the blueprint. Recently they succeeded in producing a dividing cell from synthetic DNA - although one that was copied from a living natural cell, but created entirely in a laboratory. In other words, the researchers were able to mimic nature synthetically for the first time. But, as mentioned, we still don't have a blueprint for creating a new nature, better than the existing one. I, as a biologist, see life in any body that has the ability to reproduce itself, the ability to breed and preserve and improve the properties from generation to generation, but even this definition is not without problems and cracks. I guess there are different types of definitions, and there is no agreement on all of them.

We also do not know how the components of life were formed: how the first single amino acid was formed, the first single nucleotide, and in particular, how the nucleotides joined the chains that carry the genetic information - RNA and DNA. We do not understand the chemistry that created the building blocks of life. Now we hope that the new accelerator in Sarn (the Large Hydron Collider) will restore the physical materials that were created at the beginning of the universe, but even in this case it is not the beginning of life, a matter that we are still a long way from understanding.

From here on - from the moment of the creation of the primordial life, a still undeciphered moment - we understand at least the principles of the evolutionary process - that is, the biological process and the mutations that led to the development, according to the Darwinist theory, to life as we know it today. The effects of the environment on these processes are less clear to us. We keep changing all the time. Evolution does not stop for a moment.

What was the main problem that led you to the discovery of the ubiquitin system, the mechanism that enables the breakdown of proteins in our body? What questions did you ask, and did you know where you wanted to go?

In the mid-70s, the entire scientific community in the field of life sciences was engaged in deciphering the genetic code, in the vertical transfer of genetic information and its lateral translation through RNA into proteins. This topic was a charm for everyone. Only a few dealt with the genetic products, namely the proteins, and especially their breakdown. At first the researchers did not even believe that proteins were broken down at all, but when the understanding of this came in the mid-XNUMXs, they did not attach any importance to the process, because they thought that it was not specific, and all proteins are broken down by the same mechanism, like the food proteins in the digestive system. The uniqueness, they thought, lies in the creation of the proteins, which are the molecules that perform all the functions of life and their importance is enormous, but the researchers were not interested in the process by which we get rid of proteins, even though it was clear that it was taking place. There were a few signs that the process was unique and complex, such as the demand for energy that was not thermodynamically clear (why invest energy in breaking down a molecule that is high in energy), and that hinted to us that it was a specific and complex mechanism, and these signs gave us hope. We also knew about experimental systems where we could measure the process, but we had no hypotheses about the essence of the mechanism, and especially not about its complexity, as we understand it today.

Proteins are the orchestra players of the living body. There are about 25 thousand different proteins in our body. Why this number? It is not clear. There are creatures much lower in their evolutionary scale that have a greater number of proteins. Needless to talk about the importance of proteins; Every action we do is done through them. The operations are mostly done automatically, independently, without a conductor. We breathe, our heart beats - all this, without a conscious and deliberate decision. Each protein can be compared to a long word made up of hundreds of letters, with the alphabet consisting of about 20 letters - 20 different amino acids.

Our research dealt with the way in which proteins break down: why and how a certain protein breaks down at a certain time. The food proteins, which are foreign to the body's immune system, and therefore must not be exposed to it, are constantly breaking down in the digestive system, but this is a breakdown that happens all the time and is not controlled. Even in the blood stream, outside the cells, protein breakdown processes take place, which are more controlled. We were interested in what happens in the cells themselves, to the proteins inside the cell - how the breakdown is carried out, and who makes the decisions and control. When is a protein doomed to degradation, and when is it not?

It was known that the human body destroys about five percent of its proteins every day and produces new proteins under them. Once a month on average - and maybe less - we replace all the proteins in our body. The main questions that arise in view of the recognition that this kind of process takes place are, why does our body carry out turnover all the time? Who makes the exchange? What happens when there are breakdowns, and how can they be fixed when they occur?

What does spoiled protein mean?

In the living body, the protein molecules "break down" all the time. We live in a temperature of 37 degrees. This is a high temperature for proteins, whose structure is complex, and they misfold. If they had created us, let's say, at a temperature of four degrees, we would have preserved much better. But at four degrees we wouldn't be developing at the rate we are developing. If you buy, for example, steak meat from the butcher (which, of course, consists of proteins; it is muscle tissue) and leave it at room temperature, it will spoil, as we know, after a few hours. We consist of such meat, which does not spoil even at 37 degrees of heat. It lives and lasts without spoiling for about 80 years! How can we live and the steak goes bad? This is possible, because we are constantly exchanging proteins. The proteins that have deteriorated as a result of the high temperature are destroyed and replaced by new ones all the time. The steak derived from dead meat is not able to carry out the turnover process. This is an amazing phenomenon. We remain the same person all the time, but our physical structure is constantly renewed. As we speak, much of our body's proteins have been replaced. We eliminate old from new.

There is an interesting question here. If all the components of our body are replaced, who are we anyway? How are memory and talent and creativity and emotions preserved? How does it happen that even though we constantly replace the hardware, the software is preserved? It is similar to if we would replace a music player with a new one, and yet the music would be preserved; The computer is replaced, and the programs inside it were preserved despite the replacement. Our entire body changes, and the content is preserved. The memory, emotions, creativity and imagination - everything remains. When we replace a computer, we must reload everything that was on the old computer. In our body there is no need to recharge. Everything is saved and goes through sequentially.

When our hardware dies, so does the software, but when the hardware is replaced, the software is still preserved. More than that, the software is even getting better. We learn and change all the time, during the exchange process. This is an amazing and fascinating phenomenon. Also from the philosophical point of view. In the face of all these exchanges, are we the same person all the time? Who are we anyway? These are complex questions, which remain unanswered for the time being.

Isn't the breakdown of proteins and this turnover actually the phenomenon of aging? Are we falling apart with age?

Aging is different in nature from the turnover phenomenon, and is a very complex phenomenon. As I understand it, people die of disease, not old age. We still do not understand, however, why we suffer from certain diseases in old age - does it happen as a result of an accumulation of events throughout life that ripen into old age? Why are we more susceptible to diseases in old age? Why are there more diseases in old age? Why the malignancies and degenerative diseases of the brain are characteristic of the more advanced age, as well as why the results of any disease, even a relatively simple one, are more serious in the elderly. Why is the immune system weaker in old age than in young age? we do not know. At this point we only know that with age we are more sensitive to the outbreaks of certain diseases and their severity.

You discovered that there is logic in breaking down the proteins. There is order and there is planning, which determines which protein is condemned to death and which to life. that this arrangement makes life possible. What is the mechanism you uncovered?

We discovered that there is a process in the body Quality Control Fixed: a control system that checks the state of the proteins, marks those that require elimination, and performs the breakdown of the broken proteins. We identified the mechanism following some assumptions that were known before we started the research. It was known that breaking down proteins requires energy. Proteins are supposed to give us energy, not consume it. There is, apparently, a thermodynamic paradox here. If to break down a protein you need to invest energy, we have a problem. We tried to find a solution for her. We break down proteins that have broken down, but not only them: we also break down normal proteins that we no longer need, that have finished their function, and for the purpose of distinguishing between the broken and the normal, between those that are active and those that are no longer active, a control system is needed. In order to sift the broken proteins from the normal ones and the required ones from the unneeded ones, specificity is needed, and for specificity nature pays with energy. We were looking for a system that breaks down proteins and uses energy.

Without going into complicated details, I can say that our discovery was the revelation of the principles of the control process. We found out how the selection process is done and how the disassembly is carried out. We identified the process of marking the protein destined for degradation, and following it the degradation. The revolution we proposed in the way of thinking was a breakthrough because of the decomposition mechanism. We found a mechanism that allows the "scissors" that remove the proteins and "cut" them to exist in harmony inside the cell, together with the normal proteins, and not devour the proteins indiscriminately and destroy the cells. The designated prey will not be eaten or disposed of, unless it has been marked and determined as spoiled or unnecessary. This is the beauty of the mechanism we discovered. If carnivorous scissors were roaming in the cell without control - the cell could not exist.

Did your discovery open up new questions? led to new research directions?

He opened entire areas of research, and especially pushed for new understandings of the quality control mechanism in cells. Quality control means removing proteins that have gone bad, as a result of mutations, heat, oxidation or other reasons. It turned out that all neurodegenerative diseases - for example, Alzheimer's, Parkinson's and others similar to them - are caused by the accumulation of unwanted proteins that needed to be eliminated. In such diseases, the cells accumulate proteins that are supposed to break down and do not break down, therefore causing the disease. Not all of them, of course, have the flaw in the system that we discovered, but in some of them flaws in it play an important role.

As mentioned, it is not always about removing damaged proteins. Sometimes the body eliminates normal proteins that are not needed. For example, we got the flu and developed antibodies against the virus that causes it. But once the disease is over we no longer need antibodies; There is no reason for us to hang out with them. It is better to eliminate them, but keep the memory of how to produce them next time. We eliminate not only them, but also ensure the elimination of a control protein that reproduces antibodies, the disappearance of which will stop the process of their production. Therefore, the system we found knows how to eliminate even proteins that are not spoiled; The ones we just don't need anymore. This way of control, which was previously known for a few proteins, those that control cell division for example, has penetrated consciousness, and today it is known that it encompasses many proteins that control important basic processes in the cell, and that their disruption causes many diseases, including malignancies and inflammatory processes.

It should be understood that the quality control in the cabin is not similar to the quality control we do for a car every 5,000 kilometers, for example. This is "on-line", continuous quality control. It happens all the time. The body is constantly in motion and testing itself, and when the proteins break down, they are automatically replaced, while traveling. There is no need to enter the garage (that is, the hospital) for the repair; This is done all the time without us even noticing it.

Quality control is necessary, and when we understand how it works, we can create tools to deal with many diseases. Failure to remove certain proteins causes, as mentioned, brain diseases, but also liver, digestive system, heart and lung diseases. Following the discovery of our system, a cure has already been developed for certain types of cancer, and many others will be developed in the future.

The field of genetic research continues to advance, and in the morning news we hear about the decoding and identification of the role of additional genes. They are talking about the fact that in the future it will be possible to make a genetic diagnosis of people and predict the diseases they are expected to suffer. Do you foresee such a realistic possibility?

Genetics is important, and deciphering the personal genome of each and every one of us will make a very important contribution to understanding the diseases to which we are susceptible, and will be an important basis for what is today called "personalized medicine" or "personalized medicine". But our genetic load does not hold the whole secret. A large part of the explanations for diseases are epigenetic. Epigenetics is an important field of research that has developed in recent years, and many researchers are engaged in it today. It encompasses the changes that apply to the control of genes and proteins, but which are not inherited. More than ever, we know today that some of the influences we are exposed to are environmental or behavioral - that is, changes in diet, mental stress, and the like. Genetics advances our understanding considerably, but it does not provide a complete explanation or complete prediction.

We live in a dynamic world, in which phenomena occur that cannot be separated from each other. We have extended life, and our diseases have changed; The environment changes, and our diseases change. The environment inevitably affects the nature of our diseases. Among the diseases, three important groups can be distinguished: genetic, environmental (caused by air pollution or water sources, for example) and behavioral (such as smoking and obesity). The causes of environmental and behavioral diseases can, of course, be influenced by the hereditary burden - some people will be more sensitive to certain environmental diseases than other people, or their behavior pattern will be different, so the distinction is not sharp, but it is clear to us that diseases, even infectious ones, are largely influenced by the environment and the behavior and not only from the hereditary load.

How is our medicine different today from the medicine of 50 years ago, for example?

To me, the most important difference is prevention. Medical care has undergone far-reaching changes throughout history. We started out thousands of years ago, with a minimal understanding of the body's mechanisms and treatment with plant species, which sometimes had an effect and most of the time did not. For hundreds of years, people have been treated with "grandmother" medicines and with potions and herbs provided by the medicine men of the tribe. Today we live in an era of gene exchange and organ and tissue exchange. Even in an age like this, prevention is the best and most effective treatment. We prefer to understand the causes of diseases and prevent them, just as we understood the process of infection with infectious diseases and we make every effort to prevent the infection and not to be forced to treat them. A great effort - scientific and financial - is being made today in the field of prevention. Invest in preventive behavior education and encourage early testing. A large part of human diseases are preventable, and medicine has great achievements in this field.

But if we failed to prevent a disease, its future treatment will be drug-based as it is today - small molecules will gradually become "smarter", but an innovative element will be added to it, which is the replacement of damaged genes and stem cells that will replace damaged genes and cells. This is still the classic way of drug development, in which pharmaceutical companies invest a great deal of financial effort, combined with innovative ways that we did not know about until now.

In this age of new and advanced drugs, which of them are the most important, in your opinion?

Any life-saving medicine - whether immediate or long-term - is important. For example, the statins, the cholesterol-lowering drugs, which prevent not only repeated heart attacks, but possibly also other diseases, such as neurodegenerative diseases of the brain, have created a great revolution in recent years. Millions of people are taking them today around the world. Another example is aspirin, which prevents platelet aggregation (clumping and adhesion of platelets to each other; aggregation) and blood clotting, and as a result may prevent recurrent infarctions in the heart muscle. In addition, it also prevents inflammation, which may have made it an anti-cancer drug as well. Aspirin is perhaps the drug that is consumed the most in the world in the last decades. Of course, we should not forget medicines that change the quality of life, starting with Viagra and its derivatives through anti-depressants, which have a huge impact on our way of life and our ability to function.

Several periods can be seen in the history of the development of medicines. If we scan the path we took in the twentieth century, which is important in this matter, then in the first stage drugs were discovered by chance - aspirin and the antibiotic (penicillin), for example, were discovered without deliberate research and caused a huge revolution in medicine. This happened in the twenties and thirties. The second phase of drug development began in the XNUMXs and continues to this day. I call it the "non-intelligent" phase - the scanning phase of hundreds of thousands of chemical compounds, with the aim of finding one, or a few, that have the desired effect. The scanners do not know which compound will become a drug and what the mechanism of action will be. It is about trial and error. This period used the great advantage that synthetic chemistry gave us in the middle of the twentieth century, which created libraries of hundreds of thousands and more compounds, which could be tried one after the other and see which one had the desired effect.

The third period, which we are now entering, will be characterized by the "tailoring" of individually adapted medicines. This is the personal medicine revolution, which will be largely based on the genetic and epigenetic information of each of us. This is how we move from the era of pajamas that fit each person, from an era in which we treated all patients with the same disease with similar treatment, to the era of the personal suit that is adapted to each patient; For an era where every woman with breast malignancy is treated according to the genetic profile and set of mutations that characterize her disease. The personal diagnosis is made mainly on the basis of the DNA sequencing, and in a second step from the analysis of the patient's epigenome and personal history. We are still a long way from implementing this approach, and many obstacles are still ahead of us. The need to move to personalized medicine stems from the fact that the one-size-fits-all treatment method did not succeed, not all patients with the same disease (apparently, as we now know) responded to the treatment, some responded and some did not.

Isn't this medicine for the rich?

I think not. It is not a personal medicine for a particular person, but a medicine intended for a group of people - subgroups for which the medicine will be suitable. Every disease has subgroups of diseases that need to be differentiated, and then the medicine should be adapted to them. As soon as we identify to which subgroup a certain patient belongs - the right medicine will be adjusted for him. With a completely different approach and in relation to a different group of diseases, we will perform treatment not with the help of drugs, but with cellular therapy, using stem cells that will replace old, non-functioning cells. For example, insulin-secreting cells will replace those that have degenerated in diabetes. As above, cells that secrete catecholamines will replace those that have degenerated in the brain, and as a result, Parkinson's disease has developed.

You are a scientist who is often involved in education, and in your visits to different countries you meet other cultures and societies. Is there a connection between science and humanity? Between science and morality?

People are people. Every good thing can be used for evil. Any knowledge can become a destructive tool. That's why I say - first of all, education. I didn't say, first of all he knew. I didn't say, first of all education. I'm talking about an education that contains moral values, respect for others, empathy and humanity. Education is not just knowledge; He is much more than that. Unfortunately, the education system in Israel today is not at its best. she sinks When the leadership is not clear about the importance of education and investing in it, and this is what is happening today in Israel, we are in the sunset.

I cannot say that the scientific system is a moral system, but the scientific method is a method for revealing the truth, and as such, it has an educational value. She is being tested all the time. Everything a scientist says is subjected to an objective test by others - in stark contrast to what politicians do, say or feel. Science reveals nature. I did not invent the cellular control mechanism for breaking down the proteins; I just exposed it. This is a mechanism that developed over millions of years with evolution and was hidden from us, something real. The mechanism behind this "something" and the interpretation given to it can be refuted or confirmed, and as long as it is confirmed - it is the truth.

Misuse is especially easy in science, which has great power. Dynamite allows us to build and develop, but also to kill people. The choice of how to use science - for good or bad - is our choice, of humanity, and from my personal experience, I find that science in the developed free countries is an international language of sharing. It is a universal value that brings companies and people together. Science is a unifying and bringing language, a language of peace. In countries where the regime is totalitarian or in those led by religious fundamentalism, the picture is different, unfortunately: the scientific freedom given to scientists is limited, and the paths of creation are channeled by the government.

Comments

1. Epigenetics (beyond genetics) is an important field of research in biology, which deals with changing the phenotype without a corresponding change in the genotype, or, in other words, changing traits as a result of environmental influences even though there is no genetic change in the DNA.