An Interview with Dr. Aubrey de Grey on Longevity and Biomedical Gerontology Research Now by Scott Jacobsen

Author(s): Scott Douglas Jacobsen

Publication (Outlet/Website): USIA Research Journal (United Sigma Intelligence Association/USIA, formerly United Sigma Korea/USK)

Publication Date (yyyy/mm/dd): 2020/02

Abstract: Dr. Aubrey de Grey is a biomedical gerontologist based in Cambridge, UK and Mountain View, California, USA, and is the Chief Science Officer of SENS Research Foundation, a California-based 501(c) (3) charity dedicated to combating the aging process. He is also Editor-in-Chief of Rejuvenation Research, the world’s highest-impact peer-reviewed journal focused on intervention in aging. He received his BA and PhD from the University of Cambridge in 1985 and 2000 respectively. His research interests encompass the characterization of all the accumulating and eventually pathogenic molecular and cellular side-effects of metabolism (“damage”) that constitute mammalian aging and the design of interventions to repair and/or obviate that damage. Dr. de Grey is a Fellow of both the Gerontological Society of America and the American Aging Association, and sits on the editorial and scientific advisory boards of numerous journals and organizations. He discusses: new research on longevity and longevity escape velocity; promising anti-aging research; research all over the place; advancing research into the Hadwiger-Nelson problem; organizations to look into; books to look into; and final feelings and thoughts on the conversation.

KEYWORDS: Aubrey de Grey, longevity, Rejuvenation Research, SENS Research Foundation.

1. Scott Douglas Jacobsen: What is new about longevity escape velocity and research into it?

Dr. Aubrey de Grey: I could spend a half-hour just talking about that question. It has been a while. Remind me, how long ago was our last interview?

Jacobsen: 2014.

de Grey: All right, things are unrecognizable now. There is a private industry in this. In 2014/2015, it was the time when we created our first spinout. We took out a project philanthropically at SENS Research Foundation. An investor found us.

Jacobsen: Is this Peter Thiel?

de Grey: No, no, another person who had been one of our donors. A guy who was our second biggest donor back then. A guy named Jason Hope. He decided that one of our projects that we had been supporting at Rice University in Texas was ready to be commercialized.

Of course, it was early in terms of becoming a project. He felt that it was far enough along to invest as a project with his own money rather than as a donation. He created a biotech company of his own. He hired our people. He gave us a percent of the company and went off and tried to do it.

He did not have the faintest clue to run a biotech company.

Jacobsen: [Laughing].

de Grey: It changed our attitude to the whole thing. Since then, our business model has been to pursue this kind of thing. It is to pursue projects that are too early to be investible. It is to be in parallel with conversations with potential investors and to identify the right point, where the thing has achieved enough proof of concept.

So, it can be spun out into a company and can receive considerable amounts of support, more than can be provided philanthropically. We have done this half a dozen times. We have been able to do this due to increasing investments at an increasing rate, including deep pocketed ones.

Something that happened 3 years ago with an investor named Jim Mellon who had made his money in a variety of other completely unrelated fields decided that he wanted to get into this. It was the next important thing to him.

He approached me. We started talking. We became very good friends, very quickly. The long of the short is he is the chair of a company called Juvenescence. Its model is basically to invest in other companies.

So, they have already put quite a bit of money into quite several start-ups. Some are spinouts of SENS. Others are closely aligned with what we do. It is transforming everything. It is fantastic. Around the same time, a guy came to us from Germany. A guy named Michael Greve who made his fortune in the early days of the German internet.

He made some of the most successful German websites. He has wanted to do this for a while. He has been investing in a variety of start-ups. The good news is most of these new investors, especially Michael Greve, have been also donating to the foundation as well as investing in companies.

That is very, very important, of course. For the near future, there will be projects that are not far enough along to really join the dots to make a profit. They will need to be funded philanthropically. We try to make the case to investors, even if they are inherently more in an investor mindset than a donor.

We try to make the case. Even if they donate a smaller amount than they are investing, they have as much of my time as they want. They will have the opportunity to have the information, so they will be the founding investor of the next startup.

For me, it is extraordinarily gratifying. I am at the nexus of all of this. Everyone comes to me, whether the investors or the founders of companies who want to find investments. I spend a ridiculous amount of my time just making introductions.

What had not changed, we are still woefully low on the money throughout the foundation. Even though, I have been able, as I say, to put some money in; and we have some money from elsewhere. Nevertheless, it is far less than we need.

I am constantly spending my time on the road and camera trying to change that. That is the biggest thing that has changed. The next thing that we are changing is the huge spike in the value of cryptocurrencies. We benefitted quite a lot from that. Several of our investors who used to be relatively penniless and had not funded us financially suddenly became rather wealthy.

They ended up with a lot of money. We had four 7-digit donations adding up to a total of 6.5 million dollars. So, obviously, this was a windfall. That we are making us of now. Only one of the donors is likely to be a repeat donor because the others decided to give away most of their fortune.

That guy created Ethereum, Vitalik Buterin. He, basically, read my book when he was 14. He is now 26.

Jacobsen: [Laughing].

de Grey: He is one of these true children of the revolution who never had to change their mind about anything. They always grew up knowing it was a sad thing and tried to fix it. So, that is cool. My life is largely the same in broad strokes, but, in the specifics, in terms of the ways in which I can bring the right money to the right people; it has improved a lot.

2. Jacobsen: As aging is numerous processes, what programs of anti-aging, given individual processes of aging, seem the most promising within your remit?

de Grey: When I talk about what is more promising and less promising, I am always looking at the research. I am looking at how SENS is moving forward. Of course, there is a big spectrum to how far along things are.

On the easy end of the spectrum, we have hardly done anything throughout our 10-year existence on stem cell research, even though it is a key area of damage repair. It is a place for others too. Almost every area of stem cell research is important for cell damage and aging, which is being done by others and not us.

While at the other end of the spectrum, things like making backup copies of Mitochondrial DNA, hardly anyone else is working on it. That is a big spectrum. But if I look at the rate of progress, it is not the same at all.

One gratifying thing is making great advances in some difficult areas over the last few years. For mitochondrial DNA, we published a paper about 2 and a half years ago that sounded like only a modest step forward.

Basically, out of the 13 protein coding genes that we need to work in the nucleus, we were able to make two of them work at the same time, in the same cell. It sounds modest, but it is a huge progression from before. With the result now, we have a paper in review, which is a huge step forward from there.

We have these genes working now. We are understanding how we are getting them working. It is not so much trial-and-error now. More of the same thing is crosslinking. So, as you know, the extracellular matrix, this lattice of proteins that gives our tissue their elasticity. It gets less elastic over time because of chemical reaction with circulating sugar.

So, in 2015, the group that we were funding in that area, at Yale University, were able to publish a paper – our first paper in Science magazine – on the huge advance in that area. The advance sounded tangential at first hearing with the structure, which is one of the structures responsible for the loss of this elasticity. We want to break it, therefore.

The advance made that was published was ways to create it, to synthesize it, from simple agents. As it turns out, there is an enabling step. It allows us to perform experiments that would be impossible with the very trace amounts of this material that would have been previously available, just making antibody tissue or finding bacterial enzymes that break it down.

That work is proceeding very much faster now, as well. That is one of the companies that we are in the process of spinning out.

3. Jacobsen: If you look at the projections of research that looked very promising, what ones were very disappointing? What ones came out of nowhere and were promising?

de Grey: Of course, they are all over the place. Some of the most important ones were the ones no one cares about. One is pluripotent stem cells created 13 years ago, and CRISPR, which was very much more recent, like 6 years ago.

We have been exploiting those advances. Same with the entire medical profession. But there are also isolated things that have been unexpected. Let us go back to mitochondrial mutations, one thing that we were kicking ourselves over. It will be talked about in the upcoming paper.

It is codon optimization. It is well-known. Mitochondrial DNA has a separate DNA. Codons code different things, different amino acids, compared to the nucleus (in the mitochondria by comparison). One thing is true, which we thought was relevant.

Out of the range of the codons that code for a given single amino acid, let us say the 4 that encode for lysine, there may be one of them used more often than others. This will affect the speed of translation of the messenger RNA among other things.

Nobody had bothered to try to optimize that for expression of these genes in the nucleus. It turns out that if you do then things go far, far better. It was a serendipitous discovery. Science, itself, is full of serendipitous discoveries.

4. Jacobsen: Also, you solved a math problem, recently. What was it?

de Grey: [Laughing] right, that was about 18 months ago. It is a problem called the Hadwiger-Nelson problem named after some mathematicians from 1950s. The question is normally stated, “How many colors do you need to color all of the points on the plane in order that no pair of points that is one inch apart is the same color?”

The answer was immediately shown back in 1950 to be somewhere between 4 and 7 inclusive. I was able to exclude the 4 case. Many, many, many mathematicians have worked on this in the interim. So, it was quite surprising that I was able to do this, as I am a recreational mathematician. I got lucky, basically.

I would describe this as a game. What you do is, you have a two-player game. The playing surface is an initial blank sheet of paper. Player 1 has a black pen. Player 2 has a bunch of colored pens. The players alternate. When player 1 makes a move. The point is to make a new dot wherever player 1 likes.

Player 2 must color the dot. He must take one of his pens and put a ring around the new dot. The only thing that player 2 is not allowed to do is to use the same color as he used for a previous dot that is exactly one inch away from the new dot.

Of course, there may be more than one dot. Player 1 wins the game if he can arrange things so that the new dot cannot be covered. All the player 2’s pens have been used for other dots that are exactly an inch away from the new dot, right?

The question is, “How many pens does player 2 need to have in order so that player 1 cannot win?”

Jacobsen: Right.

de Grey: So, if player 2 only has one pen, obviously, player 1 can win with just two dots. He puts a dot down. Player 2 uses the red pen. Player 1 puts down a second dot exactly an inch away. Player 2 cannot move. If player 2 has two pens, then player 1 can win with three dots by just placing a dot; player 2 can uses the red pen, places another dot an inch away.

Player 2 uses the blue pen. Player 1 uses third dot in the triangle with the two, so an inch away from both of them, then player 2 cannot move. So, then, it turns out. If player 2 has 3 pens, player 1 can also win. It is a little more complicated.

Player 1 needs seven dots. But again, it is not very complicated. It was already worked out back in 1950 as soon as humans started thinking about this kind of question. The natural question would be the number of dots go up in some exponential way, but player 1 can always win.

It turns out that that is not true. It turns out if player 2 has seven pens. Then player 1 can never win, no matter how many dots that he puts down. But what I was able to show, if player 2 has 4 pens, then player 1 can win, but with a lot of dots.

The solution that I found took more than 1,500 dots. It has been reduced by other people since then, but it is still over 500 is the record.

5. Jacobsen: [Laughing] if we are looking at the modern landscape, especially with the increase in funding, what organizations should individuals look to – other than your own as well?

de Grey: Things are looking good. There is a huge proliferation of investment opportunities as well, in this area. They are certainly raising money, as they are investing in more start-ups. In the non-profit world, there are plenty of organizations as well.

I should probably mention the Methuselah Foundation, which is the organization from which SENS Research Foundation arose. They are funding a bunch of research as well as doing prizes. They are choosing well and the right things to fund.

Then there is the buck institute, which is a much more traditional organization on the surface. In other words, it is mostly funded by the NIH and by relatively conservative funding sources. But! They understand the scientific situation. It has become much more acceptable to do work that is overtly translational, even if you are getting money from these types of sources.

We work closely with them. We have two ongoing projects there. We send summer interns there. We have been able to work with them on funding, in terms of bringing in new sources of funding. That is something that I would include.

In terms of the world, one important organization is called LEAF or Life Extension Advocacy Foundation. One in the UK. One in the US. One in Russia. They focus on advocacy and outreach. They are extraordinarily good and play a key role in elevating the level of debate in this whole area.

In Europe, the Healthy Life Extension Foundation was founded by two people from Belgium. They run a nice conference every year, every couple of years anyway. They have a vibrant mailing list and spread useful information about this area. They could use some more money. The list goes on now.

There are increased organizations, now, not just in this space but really know what they are doing. They know what the priorities ought to be. One thing I have always known since the beginning. No matter how good I get at outreach and advocacy. I could never do this all myself, not just for lack of time, but because different people resonate with different audiences.

So, there are people who will overall inspire. Others will not like people with beards.

Jacobsen: [Laughing].

de Grey: People may not like my act. So, there are people around now who are very capably complementing the kind of style that I have in communicating the value of this work. That is also extraordinarily important.

6. Jacobsen: Any new books that can provide a good introductory foundation into this kind of research? Also, what about advanced texts as well?

de Grey: On the introductory side, there is one guy named Jim Mellon. So, Jim, this businessperson, has a very interesting of going about his job. He preferentially gets into very emerging new sectors. What he does is, he creates his own competition.

He, essentially, writes newsletters and blogs and books about this new area whose intended audience is other investors. That is what I mean by making his own competition. The reason he does this is, basically, that when a sector is just beginning. That the faster it grows, then the better.

Essentially, it is floating all boats by increasing the buzz around something. He wrote a book based on conversations with me over the previous year or so. It is called Juvenescence, which is the same as the name as his company. It is targeted to other investors.

It is very good. I was able to help with this a fair bit with the technical part. But it is written in a style that is very, very appealing, which is not a way that I would be able to write. He has a second edition upcoming. This is one that I would highlight.

In terms of advanced texts, I would not move to texts right now. Things are moving so fast. One simply needs to read the primary literature. One needs to identify that, which is not necessarily an easy thing to do. I would point to our community’s effort.

Probably, the most important one is to fight aging in the blog done by Reason. Even though he has become one of the CEOs of our start-up companies, he is running the blog. He is extremely good at highlighting the important points of the research.

7. Jacobsen: Any final feelings or thoughts in conclusion based on the conversation today?

de Grey: I would say, “Thank you for having me on your show again,” and for the opportunity to give an update to your audience. I think, really, the conclusion that I would give is that it is extremely exciting that things are moving much faster than before. But we must not be complacent.

There is still a long way to go. My estimation for how long we must go has gone down, but it has not nearly gone down enough. We still need to be putting in every effort that we possibly can in whatever way.

8. Jacobsen: Thank you for the opportunity and your time, Dr. de Grey.

de Grey: My pleasure, Scott, thank you!

Original Source: Jacobsen, S.D. (2019, October 22). An Interview with Dr. Aubrey de Grey on Longevity and Biomedical Gerontology Research Now. In-Sight: Independent Interview-Based Journal. Retrieved from http://www.in-sightjournal.com/grey.

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