31 August 2018

De Grey stands his ground

A man who (perhaps) will live forever

The correspondent of "The Attic" spoke with Aubrey de Grey, a scientist who developed his plan to defeat aging

Our hero is easy to recognize from afar: he is tall, thin, bearded and not deprived of media attention. Aubrey de Grey is probably the most famous gerontologist in the world and certainly the most famous optimist in this field. His position is simple: a little more money, a little more research and humanity will learn to live forever. Various tools of the popularizer of science are used – public lectures, texts, interviews – everything to convince a wide audience to finance scientific work. Polina Loseva talked to Di Gray to understand his struggle and find the limit to his optimism.

We are meeting with Di Gray at the Future in the city conference on the first floor of the Empire Tower in the business center of Moscow City. I immediately notice him in a crowded hall, but I'm afraid to approach him right away and look at him from afar: he looks quite severe and does not look at all like an eternally young man. Will I be able to find a common language with this strict person when his ideas seem strange to me, to put it mildly?

However, upon direct acquaintance, everything turns out to be not so scary. De Grey smiles, jokes and casually corrects grammatical errors in the speech of his companions as we walk to the elevator. The elevator takes us to the 56th floor, from where we have to climb two more flights of dark stairs. De Grey walks slowly and does not hurry to catch up with two girls in heels. Either this is the notorious English politeness, I think, or he really has nowhere to hurry – there is nowhere globally.

Run Achilles, run

In his texts and speeches, De Grey repeats that he considers aging as an engineering problem: in his picture of the world, aging is simply the accumulation of damage in the body. The young organism has few of these injuries, and the old one has a lot. Therefore, by eliminating them, it is possible to reverse aging and restore the lost youth to the body.

The list of breakdowns to be repaired, di Gray formulated a decade and a half ago. Initially, there were nine items in it, but since then there have been seven: mutations in nuclear DNA, mutations in mitochondrial DNA, accumulation of "garbage" (damaged molecules and metabolic products) inside cells, accumulation of "garbage" outside cells, formation of extra cross-links between extracellular molecules, cellular aging, and, finally, cell death.

There is nothing surprising in this list itself, all these problems have long been known to science, but how to rid a person of all at once? That's what doesn't fit in my head.

– Do I understand correctly that your idea is to repair the body piece by piece? – I begin our conversation cautiously.

– In general, yes. We already understand that the aging process consists of the accumulation of damage in the body that the body creates for itself – di Gray seems to immediately enter the usual rut and becomes a bit like a school teacher. How many times had he said those words? – The question is how we can prevent these injuries from causing diseases. Until recently, there were two approaches. The first is to wait until the damage accumulates so much that we start to get sick, and then try to stop the disease. And it certainly doesn't work. Damage continues to occur, and the benefits of this approach are gradually disappearing. The second approach is to make our body work more accurately, that is, to create damage more slowly than in normal mode. And it didn't work out either, because the body is too complicated. Therefore, almost 20 years ago, I expressed the idea that there is a third approach – to eliminate damage at a time when they have already occurred, but have not yet accumulated in such quantity as to disrupt the functioning of the body.

Aubrey.jpg
Photo: Sergey Bobylev / TASS

As a person with a biological education, it's hard for me to imagine that this approach could actually work. The human body is a system of many ambiguously interconnected elements. Therefore, trying to influence one process, we will inevitably affect many others, causing side effects. In addition, di Gray speaks of many methods as almost ready for operation or at least standing on the right path. At the same time, there is a long way from the idea of a drug, for example, new organs from stem cells to replace the old ones, to its concrete embodiment – actually grown organs. And its length is unknown, since restrictions on the use of each therapy arise as the study progresses.

– At what age should you stop hoping and start repairing yourself? – I'm trying to joke.

– In middle age. Say fifty. You can always start over," De Grey is not going to joke. – You need to have something to fix, but you don't want to do it too soon. On the other hand, if there is already so much damage that you are sick, we can still do it, get rid of the damage, and this may be enough for the pathology to stop progressing. If not, then you can turn to existing medical technologies to deal with the pathology – and in this case they will really help you, because we have already removed the damage that fueled the pathology.

This answer and its variations have been practiced by de Grey for years. The phrase clings to the phrase, and after five minutes it is impossible to remember which question he answered initially. His reasoning sounds like a fairy tale in which you don't believe a bit, but you still want to hear the continuation. I succumb to temptation:

– If your method works, will we be "frozen" at some age or will we go back to youth?

– We'll go back.

– How far can you go back?

– By the beginning of adulthood.

– Is it 15 years? 20 years?

– Let it be 20, – says de Grey. – The amount of damage can be reduced to a lower level than in 20 years, but the difference between a twenty-year-old and a one-year-old is not only in aging, but also in the level of development. We are not going to rewind anything and reverse the development processes. So let it be 20.

– Does this mean that we will be able to reproduce indefinitely?

– Reproductive functions, of course, can be restored. The ovary is the same organ as the others.

I carefully follow his intonation and can't take my eyes off his facial expressions. It's not every day you meet a person who talks about the destinies and bodies of other people from the position of an almighty deity. 

– That is, we start aging at 20, age up to 50, then come back in our twenties and age again, right? I ask, hoping that De Grey will finally be outraged and say that I misunderstood everything.

"That's right. Of course, we don't know the details yet. Perhaps some of the methods will need to be applied every ten years, and others every month or day, because they will be injections or pills.

The book in which de Grey described his approach to the final solution of the problem of aging, he called "The Abolition of aging" (Ending Aging). However, this name, if you think about it, does not quite correspond to his ideas. Di Gray plans not so much to abolish aging as to reduce its participation in our death, to neglect it. The full name of his concept – and the fund of the same name – is the strategy for achieving negligible aging by engineering methods, aka SENS (from strategies for engineered negligible senescence). Di Gray plays with this abbreviation with his inherent humor: one of his program texts is called Time to talk SENS, that is, he calls for "reasonable conversation" (talk sense is an English idiom implying a rational exchange of opinions). The scientist suggests reducing the level of aging to negligible, destroying its signs – damage to the body at the molecular level – as they accumulate.

In other words, according to his plan, while we live for 25 years, medical technologies should develop just enough to prolong our life for another 25 years, and if they continue to move at this pace, then people will be able to live forever.

And this future is closer than it seems – already our peers, as di Gray said in his speech at the TED conference in 2005, have a chance to live at least to 150 years.

However, in order for such rosy prospects not to lose their colors, progress must run at least a little ahead of our withering. Then the turtle of old age will never catch up with the Achilles of progress. But in the modern world, the roles are so far distributed the other way around. Scientists have not yet built a final rejuvenation strategy even for a mouse, and people continue to age as before.

– How optimistic are you about the problem of transferring technology from mouse to human? – I am interested. - It is known that many therapies working on mice are ineffective for humans.

"We're in a better position here than most areas of medicine," de Grey, of course, is enthusiastic about the problem. – Since we fix breakdowns, and not slow down their formation, the main thing for us is that the types of accumulated breakdowns are very similar. They are not identical in mouse and human, but are distributed in the same seven categories.

– And what do you think about another, perhaps more important problem, – I do not give up, – about the gap between the medicine created in the laboratory and the medicine on the pharmacy counter?

– There are two differences between these stages. The first is costs, and the second is government regulation. I am absolutely calm about the latter, and he really looks completely relaxed. – I think that when this therapy becomes close to becoming available, the level of public pressure will increase significantly [and society will begin to advocate for the rapid approval and entry into the market of appropriate drugs]. Now about the first one – money costs. People often say: my God, these therapies will be completely new and highly technological and therefore very expensive! But we must remember that most modern methods of treating the elderly do not work. And all we achieve [now] by spending large sums of money on the elderly is that we briefly postpone the moment when they get sick. And then we spend money to keep them alive while they are already sick, that is, we spend this money anyway.

The chicken doesn't work

I listen to De Grey and remember how one of my friends, a biologist, told me about physicists who once worked with her in the same laboratory. Physicists, she said, had great difficulty handling living objects whose behavior they were investigating, in particular chickens. When the reaction of the object did not meet their expectations at all, for example, he did not run to his mother, but stood in place in fright, they threw up their hands and said: "The chicken does not work."

– As far as we know, the damage begins to accumulate immediately after the first division of the embryo cells. Doesn't this mean that by the age of 50 it will be too late to fix anything?

"Imagine a car," De Grey doesn't smile. He is not speaking a metaphor (he literally says "Think about a car" – ed.), but a direct comparison. – The first rust appears on the very day when you get it at the sink. But for the first five years, you don't have to worry about anything, because the speed at which it grows is so small that nothing happens, no door falls off. And if you remove the rust in five years, the door will not fall off for ten years. Yes, we begin to accumulate damage long before birth, but they do not reach the limit with which the body is accustomed to cope.

The chicken pops up in my memory for a reason. Di Gray came to work with biological objects from another science. He is a mathematician and programmer by education and worked in his specialty for the first 30 years of his life. But after he married a biologist and changed his field of interest.

For 10 years, he mastered biology from books, wrote a book about mitochondrial DNA damage and received a doctorate for it. Since then, his relations with the academic community have remained strained. Di Gray criticizes the "classical" scientists for being too fundamental and slow progress, and in response they reproach him for oversimplifying and misunderstanding the nature of biological research.

– Have you ever regretted the lack of formal biological education? – I'm trying to come in from the other end.

"Actually, it was good for me that I didn't study biology from the very beginning," Di Gray answers without delay. – And I'm not unique in this, it happened often in the history of science: people started working in one field, and then switched to another. Often they ended up achieving more in the second, because the skill of research is easily transferred [from one area to another]. So at the very beginning, when I thought it over well, I brought [to the science of aging] some new way of thinking and was able to make predictions that could not be made for a long time.

– Have you ever tried to do practical, laboratory biology?

– Oh, no, no, – my interlocutor shakes his head decisively. – There are a lot of people who are already good at it. Take them and apply them.

I am overcome with envy. How many of my colleagues, and myself, are reproached for daring to draw any conclusions about the state of affairs in modern science without spending days and nights behind laminars and pipettes! And De Grey doesn't care. Or not all of them?

– Have you ever felt discriminated against or humiliated because of this in the scientific biological community? "I hope to find a fellow sufferer in him.

"It was very funny," De Grey perks up for the first time in the evening and laughs sincerely. – I went through several stages. At the first stage, when I first started studying biology, I came with my own ideas, which were an interpretation of the ideas and data of other people. At that moment, they did not contradict me, I still had no thoughts that we could live to be a thousand years old. And in the first years of my work, the fact that I came to this field in a non-standard way was rather my advantage. Leading experts in the field said, "Hmm, this guy came up with what we had to come up with, and he doesn't even have a degree in biology. How is it? He's probably terribly smart!" – here Di Gray is so fond of history that he even switches to more conversational English and for a while leaves the image of a school teacher. – Therefore, respect for me grew much faster than it could in another scenario. And then, when I started to cause inconvenience, everything changed and they started talking about me being nothing more than an amateur. But even that passed.

Here I feel offended already for the official scientific community – apparently, all their arguments are broken by di Gray's impenetrable confidence that his cause is right.

"Were they right about anything?"

- no. In fact, I was very lucky. Every idea that I put forward 10 or 15 years ago about the division of damage into seven categories or technologies to combat these categories, all of them are still alive and thriving. We haven't found any new categories, we haven't found any reasons why our approaches wouldn't work. No, I'm extremely happy with how things are going.

The most desperate optimist

My interlocutor is completely different from how I imagined a fanatical scientist. He does not try to convince me of anything, does not flash his eyes and does not go into lengthy conversations about the meaning of life. He speaks in an even tone, he is calm and peaceful. It quickly becomes clear to me that at least half of the money to his foundation was brought by his charisma. At the same time, he is completely focused on his story. We are talking in a walk-through room, around us the technical staff is preparing for the conference: someone is carrying buckets of water, someone is vacuuming carpets, someone is drilling the walls. I nervously flip the recorder from hand to hand, hoping that it won't be heard on the recording, but De Grey doesn't seem to pay attention to anything at all.

Our time is already coming to an end, and I understand that it's time to talk about the most important and dramatic:

– Have you ever felt disappointed in your ideas? Were there times when you thought the technology would never work?

– No, because everything worked, – di Gray does not give dramatic answers. – Of course, we are not moving as fast as I would like, and not even as fast as I imagined 15 years ago, but there is no scientific reason for this. The only thing that worked worse than I expected was financing.

"It's often not easy to distinguish "pure" scientific reasons from economic ones," I object. – Perhaps the result has not been achieved because not enough money has been invested in research. But it is also possible that it cannot be achieved in principle.

– You're absolutely right. Indeed, in the first five years, these reasons were difficult to distinguish. But after 15 years of work, we can show the progress we have made, and this is a very good result for the small amount of money that we had. Therefore, we can say: look, if we have advanced so much in 15 years with such a sum of money, it is logical to assume that we can advance 10 times further if we have 10 times more money.

De Grey's worldview is incredibly integral, I note to myself. He perceives not only the human body as an engineering mechanism, but also everything else: even the process of scientific knowledge in his view is likened to a car!

– Personally, I have exactly one question to your theory – I'm going all in. – Okay, if the strategy works, then it works, and if it doesn't work, then it just means that it doesn't have enough money. Is there any experiment that can be set up to make this theory refutable?

–That's a great question," De Grey nods at me and immediately walks away. – People often think, and I thought so until I came to this field... they don't understand the difference between science and technology. Science is actions aimed at a better understanding of nature, and technology is actions aimed at managing nature. Therefore, we do not test any hypothesis, we have no theories, we only have a technological project. But your question is still relevant – how do we know that this can work? Where do we get the preliminary data from?

I started by saying that we already have data obtained on cars and planes. We know how to successfully extend the healthy functioning of simple machines so that they last much longer than originally planned. Therefore, the same approach should work for complex machines like you and me.

This is the first confirmation [that we can do something]. And the second is the progress we have already made in the development of specific technologies. The most obvious example is stem cells, which were already actively studied by the time I came to this field. Therefore, we hardly do them – other people are already developing key points in this technology.

– What will you do if in 15 or 20 years your method still won't work?

– I look at what we do, not just every ten years – I look at it every week. I'm evaluating whether we're moving well or can do it better, so I'm ready for that. It's like with any new technology: you don't know what will work, you look at what is there and make decisions. But my goal here is to save lives, not to make money or become famous–and at this point, de Grey begins to sound like a very successful preacher. – Therefore, even if I have only a 50% chance of success, this is quite enough.

"The only difference is that you make promises," I remind him. – Do you often speak at your performances: "Here you may live a thousand years"…

"There's no 'maybe' in promises," De Grey cuts me off, "and I always use it." I say: I think there is a 50% chance that I will achieve this in 20 years. But this is not a promise, this is a prediction, and this is the very prediction that we are obliged to make. Perhaps my colleagues will object that I should not say this even with the caveat that this is probabilistic reasoning. But I think that in this case they are behaving irresponsibly. I think that if we do not make such predictions, then people who do not know this and are not experts will draw the wrong conclusions. And their conclusions will be super-pessimistic: they will say that we will achieve this in a thousand years. And this means that they will not be interested in spending money to make it happen faster. So I have to talk about it as it is in order to achieve it faster. Which is what I'm doing.

***

After the interview, the organizer meets me.

– How did the interview go? – she asks.

– Very interesting, thank you, – I try to reduce the outcome of our conversation to a short answer. – A lot of unexpected things.

– What was the most unexpected? Tell me.

– I was impressed by the quiet confidence with which he talks about his ideas. Usually you expect a person to push, to drill you with a look ... but no, he is very calm and relaxed.

"Of course," she says, "he's going to live forever."

"Maybe," I add to myself.

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


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