You can get vaccinated against old age

Why Harvard Medical School geneticist Leonid Peshkin considers death a mistake of nature

Ivan Branitsky, Forbes, 08/27/2020

For several years, the specialists of the Harvard Medical School laboratory, led by Leonid Peshkin, PhD, have been working on creating a new platform for classifying the effects of substances on life expectancy. A few years ago, Professor Peshkin and his parents gave their genome to science for use as a single standard in laboratories around the world. The project was called the "Genome in a Bottle" and in Leonardo da Vinci's terms could be called the "golden section" of the human genome. 

Forbes Life talked with Leonid Peshkin about the longevity industry, the effectiveness of new methods of prolonging life and solving the mystery of immortality. And, of course, about the pandemic and new vaccines.

– The first question on the topic of the day. If you look at the COVID-19 pandemic through the eyes of a geneticist, have you learned anything new in these few months?

- Yes. I learned to what extent humanity is irrational. Especially when it comes to risk assessment. I often have to get into arguments with others about "why live like this at all if nothing is possible...". Today, the ways of COVID-19 spread are well understood, and with the observance of security measures, the danger is minimal. This summer, I'm more afraid of a shark bite in the sea or a brain-eating amoeba in a warm lake. Both are rather unlikely, but not impossible.

The past months have hurt my scientific work, the laboratory, and the entire Harvard Medical School were closed. It will take many more months before we return to the experiments that we actively conducted a year ago. 

At the same time, without any pandemic, about 200,000 people die every day on the planet. Most of them are from old age. However, there is no panic about the fact that the population of the planet is mortally hurt by "aging". People do not think about the fact that life is a one–way street, and do not realize that "normally" the same thing will happen to them as with other "normal people", namely, death from old age.

The pandemic will pass sooner or later, and aging will torment us for a long time. Of course, during the months of the pandemic, it was impossible not to delve into the topic of viruses, the immune response. The most interesting thing for me is the sharp age dependence of mortality on the virus. There are few examples of other diseases where the outcome is so dependent on age. 

We are not yet used to thinking of aging as a widespread but curable disease. Meanwhile, this is quite a reasonable approach. It is well known that with age, the immune system is undermined. But one of the most interesting directions in the fight against aging is the idea of "inciting" the immune system against old, unnecessary and often harmful ballast cells, the so–called senescent cells.

I think it's time for humanity to seriously think about a vaccine against old age right now. It would be worth spending a lot more resources on this than thrown into the fight against COVID-19, which we will sooner or later forget about, as we forgot about SARS and other viruses.

– As for COVID-19 vaccines, how do you assess the effectiveness of a new type of RNA vaccines? Is it possible to talk about some kind of scientific breakthrough? 

– I emphasize that I am not an immunologist and cannot competently talk about the advantages and disadvantages of RNA vaccines. The idea of RNA vaccines seemed to be a breakthrough when it first appeared about 10 years ago (the RNA vaccine is not a solution of weakened viruses and not their proteins, but pure, but artificially created genetic material of the pathogen - its RNA. – Forbes Life), but since then no such vaccine has been widely used. But who knows, maybe COVID-19 will be the first success. I think the main task is to prove that it does not cause severe complications. Finding an acceptable balance between efficiency and safety will take some more time. And, apparently, it will reflect the national character of individual countries. We will find out who are hot-headed daredevils and who are cautious reinsurers, we will compare the reaction with established stereotypes about the national character.  

– If you believe the statistics, COVID-19 infects selectively, is it possible to look for an explanation for this in epigenetics, that is, not hereditary, but acquired changes? Have the directions of scientific research changed under the influence of the pandemic?

– In order to explain the heterogeneous picture of infections and without genetics with epigenetics, there are many much simpler answers. The process of infection depends on age, general health, lifestyle, for example, whether you smoke. Some interlocutors tend to spray saliva in an argument, others do not. Does the infectivity depend on individual genetics? Of course! But so far, as far as I know, there have been no extreme examples of exclusively genetic variants. Like, for example, "elite controllers" who, having contracted the HIV virus, live with it without contracting AIDS, due to the presence of a successful variant in the genome or similar genetic resistance to intestinal flu caused by norovirus. But, perhaps, while we were talking, an article was published in which the authors found such a protective genetic variant from COVID-19 somewhere in the inhabitants of Easter Island or the tribes of Brazil. 

– As for the genetic material. You and your family have given your DNA as a single standard for genetic research. The project was called "Genome in a bottle". Why did you do this and what risks are possible in these experiments, because your genetic information is now publicly available? 

– When George Church started collecting data on genomes in order to put them together with information about the health and characteristics of people in free access for research, he made informed consent a mandatory part of the process. It scared someone off, but not me and my parents.

Later, the organizers of the Personal Genome project turned to our family with a new request: to participate in the federal government's project to develop a standard for genetic sequencing. People like to set standards. For example, a platinum-iridium alloy cylinder is located in a basement in the UK, providing a reference weight. A genomic standard was also needed. By an amazing coincidence, it was my genome that became it. Dozens of laboratories are currently working with him in the "Genome in a Bottle" project of the American National Institute of Standards and Technology. In 2017, data related to the "Genome in a Bottle" samples were uploaded to approximately 15,000 computers in laboratories around the world. But it's not just data, it's also cell lines created from my skin and blood cells, including stem cells. When deciding to participate in this phase of the project, of course, I was thinking about the possible "consequences". For example, theoretically, you can make my clone out of my cells. I fantasized a little, but then I agreed anyway. 

I think death is senseless and illogical, but it is even more stupid to burn or bury a body in the ground. The best thing we can do so far is to bequeath our body to science. Although it is worth admitting that most of the scientific activity is also a waste of time. But science is the best we have until we have corrected the mistakes of nature and defeated death.

– You said that the creation of a "vaccine against old age" is as natural as for other diseases. And what, in your opinion, is the real effectiveness of existing methods to combat aging? From genome sequencing to the use of stem cells. 

– Unfortunately, today there is no generally accepted scientifically-based method of combating aging in humans. There are many interesting ideas, promising areas, there is an active commercial activity that boils down to the same recipes as under the ancient Egyptian pharaohs – hygiene and a healthy lifestyle.  

– Can such methods as the project proposed by geneticist Craig Venter to create a global database of human genomes and its subsequent analysis become a trigger for new discoveries and the fight against diseases associated with old age?

– The charm and curse of biology today is the abundance of data, the fashion for Big Data. Unfortunately, such data can be useful only if the data is collected with scrupulous quality. But in reality, we are not observing this yet. So projects were created to read thousands of genomes. In fact, so far no one has literally read the genome. Take, for example, the case of the famous genome decoding company 23andme.

How does the so-called sequencing work? If you imagine that your genome is the text of a cookbook that exists in a million copies, then you can pass all this million copies through a shredder, cut into scraps, then take a bunch of scraps and try to put recipes back together from them using coincidences in the text, as in a cookbook. In some places, the pieces will not add up at all, paragraphs are formed somewhere, fragments of phrases somewhere. For example, "finely chop the onion and fry", but a full functional recipe for a pie or soup in most cases will not work out without a huge expenditure of materials and time.

As we have already mentioned, my own genome is the most qualitatively read and assembled, the most well–characterized genome on earth. What can I now testify not as a scientist, but as a "guinea pig"? Hundreds of scientists in dozens of scientific groups around the world have been understanding my genome for many years and there is no end in sight yet. They use my genome precisely as a quality standard, that is, they set the task to restore the "text" extremely accurately from the shards, scraps and scraps that we can read. There is no question of deciphering what this text is yet. Many parts of my genome have not been read. The situation is standard: in a cheap genetic test, there is less information from the original than in a school essay from "War and Peace". 

But back to Venter. The idea itself – to collect a lot of human genomes and compare, to look for meaning in genomic texts using comparative analysis – is wonderful. Venter is probably the most qualified specialist of those who could be at the head of this project. Just don't count on quick success. 

– Does this mean that so far there have been no breakthroughs in the fight against aging, and an increase in average life expectancy is just a "side effect" of the treatment of concomitant diseases? 

– Unfortunately, the field of anti-aging suffers from premature attempts at commercialization, and therefore from an environment of secrecy, exaggerations, marketing slogans. In my opinion, one of the biggest obstacles on the way to discovering the secret of rejuvenation is a blind belief in the "invisible hand of the market", that if there is demand, supply will appear, whether it is teleportation or resurrection from the ashes. 

One of the main obstacles to the search for the "immortality pill" at the moment is the lack of a single standard for classification, assessment and analysis of the effects of substances on the life expectancy and health status of experimental creatures. Experiments on mice, frogs and worms are either too expensive or not representative of humans due to the huge difference in the structure of the organism, the genome and the doses of drugs used. There is simply no single method of evaluating drugs today. 

– If you believe the media, in recent years you have been working on creating such a platform – a system for testing the effect of various substances on life expectancy. Tell us about it. 

– There is a long overdue need for a single representative platform with the use of artificial intelligence methods, where you can compare the results of drug exposure.

Specialists of our laboratory create a classification system for laboratory experiments and the effects of substances on the lifespan of organisms using planktonic crustaceans, daphnia. For us, Daphnia is like a tiny person whose motor, cognitive, cardiac, and immune systems can be characterized. Our compatriot Ilya Mechnikov discovered the immune system and received the Nobel Prize for it in 1908 in experiments on daphnia. We are creating a platform using artificial intelligence, where you can test many different drugs on these organisms. There is no other such platform in the world. 

This work can only be done in an environment like Harvard, not in a startup. I'm trying to have time to reverse aging. Their aging and the aging of their loved ones. Many of my colleagues forget about this when they get involved in the commercial activities of companies. They sort of say: "We no longer hope to live to see the success of the fight against aging, but at least we will earn."  

– I noticed that here at Harvard, scientists dealing with the problems of longevity look suspiciously young for their age. Do you already have some secret knowledge?

– David Sinclair is often asked why he looks so young, to which he usually answers: "I am sending my old photos to journalists." Being specialists and enthusiasts, we mostly lead a healthy lifestyle, eat a variety of harmless food, and monitor minimal physical activity. Our secret is not to accelerate aging unnecessarily, as many do. I'm 50, and they say I look younger than my years. But if you look at the photos of my father at the age of 50, just when I was born (my father died two years ago, before he lived a week to 97), and how my mother is jumping on boulders and playing tennis today, you will understand that my secret is the right genes. 

– But do you have your own hypotheses, where to look for clues to immortality or longevity?

– Of course there is. This is a completely different story. Everything we've discussed so far has been about figuring out how to compare the effectiveness of new methods. But it did not concern the question of where the secret of immortality lies. This is the second chapter of our journey. Let's take a deep breath and forget about daphne for a while.

In my opinion, at the moment the greatest achievements of biological science, which have become commonplace, are primarily painkillers. Something got sick, ate a pill and go for a walk. Antibiotics. We remember how tuberculosis was a death sentence in the recent past. Vaccines. We have practically defeated infectious diseases, including COVID-19. Genome editing. Now there is a revolution in therapy.
These examples prove that people have not invented anything from scratch. All inventions belong to evolution, to nature. We noticed something and learned how to use it in a new context.
Antibiotics were known in ancient Egypt. They knew that if you take a moldy cake and rub it on a fresh wound, the wound tightens faster – the mold does not allow bacteria to multiply on the blood. 

There is evidence that the idea of vaccination has been familiar to nomadic Arabs since the Middle Ages. They deliberately infected children from smallpox ulcers, as they noticed that they then do not get sick or carry infections more easily. In all these cases, observant people have transferred what nature has created from one context to another. And they took advantage of it. The same will happen with rejuvenation. 

After a few hundred years, someone will say from the stage: "Imagine, until the 21st century it was considered the norm to get sick, get senile and die before the age of 80," the audience will laugh in embarrassment.

The secret of immortality has long been found. He is known to us by nature. It's an everyday miracle that we just don't notice. This "something" happens every time a new life is created. Think about it: in the body of a sexually mature woman there is a cell that has already spent, say, 30 years in the body. Suddenly, this cell meets a sperm, which has practically no age restrictions at all. Cells consist of material that has been in the body for many years, they have been subjected to oxidation, metabolic stress, ionizing radiation rays. And these, in fact, old cells merge, and a child is born who is zero years old. At some point before that, regeneration somehow occurs with the cells. The miracle of rejuvenation is happening. The miracle of rejuvenation is repeated every time a new life arises. How? We don't understand. 

There is a theory, which I do not adhere to, that this is just a selection. Nothing comes out of most of the old cells, but some are accidentally saved. There is another idea that everyone has garbage, but it does not harm. The garbage is diluted at the moment of division and growth and leaves. However, there is evidence, and in particular in my work on frog embryology, that this is not the case. We have shown that the materials, proteins in the egg are actively used further. If a damaged cargo came, it would affect the next generation, each next generation would live less and less until all living things died out. Therefore, not only me, but also other scientists say: there is a clear reset, zeroing. Purification, the mechanism of which is recorded in DNA. It's just that this mechanism does not start in the adult body. If you find this mechanism and run it in the tissues of an adult body, it will lead to rejuvenation. Like in a fairy tale: the key to life and death lies in the egg. This hypothesis I'm working on using two organisms, a frog and a daphnia.

Why, if everything is so simple, didn't all the scientists rush and figure it out? Both George Church and David Sinclair know about this direction, I have consulted with them more than once, they wished me good luck. 

– Maybe it's about money? Until recently, all anti–aging programs were funded from government grants - these are expensive studies. But it seems that private funding has finally come to fundamental science. In particular, Leonard Blavatnik gave Harvard Medical School $200 million. Will this affect your research? 

– I would say that no one finances anti-aging programs. It sounds paradoxical, but it's a fact. NIA, the National Institute on Aging, many people jokingly call the National Institute for Alzheimer's, because they replaced the topic of aging with the topic of diseases manifested in old age. Like, for example, Alzheimer's disease, and the lion's share of grants goes to finance traditional programs to find cures for diseases, and not for research and treatment of old age itself.

And Blavatnik's money will not go to the problems of aging and not to fundamental science, because they came with limitations.

– What restrictions did Blavatnik's money come with? Do you mean certain targeted studies?

– It's better to ask the management about this. Many scientists at Harvard have become much worse from this "gift", because most will not get anything. And now, when we ask for money for our specific research, we are told: "Well, you have become arrogant, Blavatnik has just "paid off" $200 million to you, and you still need it," and it has become much more difficult to find financing. How the target capital industry is developing is a separate topic of a big conversation. (The endowment of Harvard University is more than $32 billion. – Forbes Life.)

– Who else from the business is actively investing in this area?

– Google, as you know, has opened a whole Calico institute, but I have not heard about grants from them. I am familiar with many scientists who have moved to work there. However, their research is developing according to the scheme as in a pharmaceutical company: in an atmosphere of strict secrecy, with a minimum of contacts with fundamental science, which at this stage of knowledge about the mechanisms of aging promises failure.

It seems that successful businessmen have become skeptical about promises to prolong youth, but they are not averse to investing money in hyped topics and making money on the naivety of the general public. It never ceases to amaze me this lack of faith in science and the irrational thirst for profit by people who will never spend their billions.

This direction does not require investments, but deposits, the dividends for which will be expressed in additional years of healthy life. This simple truth, it turns out, is very difficult to convey to wealthy people who, on the one hand, are used to taking risks for the sake of super profits, but at the same time believe that "fundamental science, far from commercial use, should exist on the money of the state." We, scientists, find ourselves in the inter-fund space. When I say "we", I mean a team of like–minded people who are making an audacious attempt to master another and probably the greatest miracle prepared for us by nature - to prolong health, restore youth, literally step into the future. 

Portal "Eternal youth" http://vechnayamolodost.ru