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Mehmood Khan on Aging Policy and Collaboration


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#1 Steve H

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Posted 03 December 2024 - 04:56 PM


I first met Dr. Mehmood Khan in 2022 at the inaugural Longevity Summit Dublin, where organizers Aubrey de Grey and Martin O’Dea made a bold decision to include policy and advocacy discussions alongside the traditional focus on longevity research. Like many others in the audience, I was captivated by the forceful, engaging, and compelling one-man show that Khan delivered with apparent ease. “This is how public persuasion is done,” I remember thinking. “We need more people like him on our side.”

Khan had already enjoyed an illustrious career before joining the longevity movement, holding high-profile roles such as Vice Chairman and Chief Scientific Officer of Global Research and Development at PepsiCo and President of Global R&D at Takeda Pharmaceuticals. However, Khan is not just a high-profile bureaucrat. He has a solid background in science and healthcare, having served as Chief of the Endocrine Division at Hennepin County Medical Center in Minnesota and later as a faculty member in endocrinology at the Mayo Clinic and Medical School.

It’s this rare combination of qualifications and interests that led him to his current role as CEO of Hevolution, the world’s best-funded healthspan-focused non-profit, created by, no less, a royal Saudi decree. Despite being a relatively new player in the field, Hevolution has swiftly established itself as a dominant force, leveraging its overflowing war chest both boldly and strategically.

Hevolution is the largest sponsor of the $100-million-plus XPRIZE Healthspan and supports dozens of researchers in the fundamental biology of aging across the globe. It has also begun investing in longevity startups. With so much happening, an interview with Mehmood Khan was long overdue. We sat down to discuss Hevolution’s vision, its progress, and his thoughts on the future of the field.

Let’s start with your personal journey to the longevity field. I know it’s an unusual one.

Unlike most experts, I haven’t been in the field long directly. Indirectly, it’s been my whole career. I was an endocrinologist, practiced at the Mayo Clinic and the University of Minnesota, saw a lot of patients with diabetes, metabolic disease, obesity. Much of my early research, if you go back 25 years or so, was around metabolic disease and obesity, and this was before aging was itself considered a discipline.

My career has progressed from being focused in a specific subject area to being fascinated by how you can impact health at a large scale, which is what bridged my interest from medicine to food. I had a faculty appointment in food science as well as in medicine because I trained in food science at the College of Food Science and Agriculture. This was 35 years ago, and that progressed to thinking about global challenges, whether it’s food supply, water, or the carbon footprint of large industries like PepsiCo.

The chance to converge all of this together crystallized with the whole field of healthspan. When I started looking at this field, everyone was still primarily talking about longevity. And it was clear to me that longevity is not the target here – healthspan is. What we’ve spent the last years doing, and it’s been my privilege to lead the team, is to focus Hevolution much more on healthspan than longevity.

This distinction between healthspan and longevity seems important to you. Yes, we have seen increases in longevity but not in healthspan in recent decades, which isn’t good, but do we really have to uncouple these terms to such an extent?

I think sometimes you have to uncouple it because it’s the vocabulary that you use that gets the traction with policymakers. I’ve spoken to a lot of health ministers, finance ministers, and several heads of state over the last few years. If we make this purely about getting people to live longer, it becomes interpreted as more dependency – more people to take care of, bigger pension bills, bigger health bills for Medicare, National Health Service in the UK, Japan, China, wherever you go.

If you talk about longevity, you end up with not a lot of interest at the very senior policymaker level. Health ministers, yes, but they’re not the ones holding the purse strings. You’ve got to convince the finance ministers, the labor ministers, the economy ministers that this is of national interest. It isn’t about people living longer for the sake of living longer, but about productivity.

If you talk to individuals (and we’ve surveyed them), and you ask, “Do you want to live longer?” – that won’t be their number one priority. But if you ask, “Do you want to live healthy as long as possible?” – yes, almost unanimously. So, as scientists, we may not uncouple it, but the average person on the street understands those two things differently.

More importantly, policymakers view these as two different things. I think it’s important for us as leaders in the field to say that our primary goal is to keep populations healthy as long as possible. The secondary benefit of that might be that people live longer. But if we start with the argument that we want people to live longer, that’s not going very far. It hasn’t gone for decades.

If you focus on life extension, you inevitably get sucked into debates such as “Is this against God (if you’re religious) or nature?” You get into all other kinds of ethical debates. But the minute you say, “I want people to live healthy for as long as possible,” there’s no disagreement about that.

Yes, that makes a lot of sense. Let’s now talk about Hevolution, which emerged in the field just a couple of years ago and has since become a major player.

Hevolution was created by a royal order from the King. It is chaired by His Royal Highness, Prince Muhammad, the Crown Prince and Prime Minister. It was the vision to take on a global challenge that would benefit as many people on the planet as possible. Healthy aging touches every human being. It’s a global challenge that affects every country, including the kingdom, so it’s very relevant locally across the Gulf, but globally as well.

It was set up as a nonprofit because the primary driver was to fund the science to move the field forward, accelerate the science into the marketplace with patient capital willing to take risks, and put it under a nonprofit umbrella. So, the incentives are aligned – we want our venture capital arm to succeed, attract other investors, and grow the size of the pie.

One part of that mission statement was particularly important to us: to extend healthy lifespan for the benefit of all. That’s something that is uniquely possible under the umbrella of a nonprofit. We want to democratize everything we do. We put that lens on everything we evaluate. Whatever we do, we look at it through the scalability lens. We’re not interested in technologies that might touch a few privileged people in the world, even though that may be where it starts. We look at it and ask ourselves, “How does this scale? Is there a path?”

Naturally, we care about another important issue: the bioethics of healthspan extension. It’s not just asking the question “Can it be done?” but also “Should it be done?”, and that shouldn’t be left just to the scientists. I am a scientist, and I should not be the one leading that conversation. I’m a strong believer that this should be something that experts in ethics are engaging with from day one.

Before we funded a single science grant, we put together a global ethics team, and that, to my knowledge, is the first time global bioethicists have been convened around the field of aging and asked to guide us and hold us accountable. Arthur Caplan, who is at the helm, is a world expert on ethics. He’s the chair of bioethics at NYU, previously Johns Hopkins, New Orleans. Julian Savulescu, founding chair of bioethics at Oxford, is another example.

This is a very interesting aspect of Hevolution I admit I’ve never heard of. I think many aging researchers don’t really want bioethicists around – they see them mostly as a nuisance. Can you name some of the insights this team has come up with?

There are a couple of things that they’ve started to push us to think about. One is, “How do you make this inclusive?” Not only the output, but the research. Initially, like everybody else, we were looking at the world and saying, let’s fund North America, the UK, but usually absent at the research table are people from the African subcontinent, South America, Latin America. Our bioethicists asked us why.

If you’re really going to address global aging, you have to understand aging in the context of the world. The continent that’s going to have the most elderly people in the world in the next 50 years is Africa, and yet, you almost never see people from Africa at aging meetings. It was a good push. We went to the WHO to explore possible collaborations: they’ve got a much better footprint there than we do. How do we collaborate with them? I don’t have an answer yet, but we’re working on it.

Another example is how we think about aging as a process in terms of when we would intervene versus not intervene. When is the earliest you should intervene? If you ask biologists, they’ll tell you that aging as a process starts around 14 days after conception. Should you intervene in an embryo? Should you intervene in a child?

I had the privilege of giving a couple of lectures at Yale Law School three or four years ago on the distinction between law and ethics in business. Something you learn when you look at this as a scientist (the lawyers already know that) is that the law is only a memorialization of a society’s ethics. Then, isn’t it our job as scientists to help convene that ethics discussion and move it forward alongside the scientific field rather than have it follow?

What’s your philosophy in choosing projects?

First, we want to fund the underlying science in the biology of aging. That’s our primary target. We don’t want to just fund another research study on Alzheimer’s, diabetes, dementia, osteoporosis. There’s lots of research going on and lots that’s been done. Most of it has come from working backwards from the end case. They say, now you’ve got osteoporosis, what can I do to increase your bone mineral density? If you have dementia, what can I do to slow it down? Not what can I do to prevent it.

So, understanding the biology is the key. The second thing is understanding how and when to intervene. When you start asking those questions, one thing that will surface is that we still don’t really know how to measure aging as a biological process. Yes, there’s DNA methylation, there’s this and that. Every six months you’ll hear of a new biomarker, then another, but most of them come from relatively small studies correlated with one or two variables. We have A-glycohemoglobin (HbA1c) for diabetes, but not its equivalent for aging. We know what cardiovascular risk profiling looks like based on biomarkers – LDL, HDL – but we don’t have the same for aging.

So, one bucket is how do you measure aging? This has to be predictive and correlate with treatment. Ideally, a good biomarker will reverse with treatment. This is why we funded the global meeting on biomarkers of aging at Cold Spring Harbor earlier this year. We brought together the world’s experts, both clinicians and biomarker experts and regulators, to start a series of discussions.

I strongly believe that we should fund this research and facilitate this debate. For instance, we should think about how we make biomarkers of aging open source. You know, if LDL cholesterol had been patented, we probably wouldn’t have statins.

Right now, we’ve got about 150 labs and 200 principal investigators around the world that are funded by us. We’re also funding partnerships where we’re a partner in the scientific grants. Basically, just like the NIH, we say, send us your best idea. We then send it to independent review; we don’t like to review the grants ourselves. I don’t need to take phone calls saying, “Hey, Mehmood, I just submitted this grant. What do you think?” I wouldn’t even know what you’re talking about because it goes to an independent panel.

I’ll give you an example. We’re interested in proteostasis at the cellular and tissue level. How do we bring the best minds together? In this case, we went to Richard Morimoto at Northwestern, one of the world’s academic leaders in proteostasis, and said, if you would put your dream team together and develop a series of research plans around that, we’ll fund you. And he did. It’s almost 30 million dollars. That’s an example of a partnership where we targeted the area, found the world expert, and asked that PI to put together a multi-center team.

The value of that is he’s going to collaborate with people who might have been competing with him for grants in the past. Now he can say, “Listen, we can get funding together if we come together.” That’s the catalyst role that we play as Hevolution. We’re catalyzing the field by catalyzing collaboration.

Another way you’ve been catalyzing the field is through XPRIZE Healthspan, where Hevolution is the lead and single-largest funder. Can you tell me more about this collaboration? In particular, since you talked about biomarkers, what do you think about their idea of reversal of age-related loss of function as the endpoint?

It’s very exciting to see how they’re incentivizing the world. They’ve done this successfully in other fields, putting the best minds, ideas, and resources to answer the question. This is the moonshot, this is the challenge: show us 10 years of reversal (of loss of function). Let’s go!

Evidence shows that in prizing mechanisms such as XPRIZE, the multiplier is about 8 to 10. For every dollar of the prize money, the collective investment brought in by the competitors is eight to ten times that. For a chance to win 80 million I’m going to put in two million, three million from grants or investors. This scenario repeats itself a hundred times over, everybody’s competing, and finally, the 80-million prize draws 800 million into that field.

That’s the beauty of this model. The reason we support it is that, in the back of my mind, a hundred-million-dollar prize means a billion dollars will potentially be mobilized. That’s the leverage. Every team that’s competing is going to either find investors, or government funding, or donors.

Regarding the specific biomarkers, when we went to the table, I said that nobody from Hevolution or any sponsor should be involved in defining the endpoints or sit on the judging committee. We helped find independent judges, we helped put together the endpoint committee to come up with the definition, but that was the limit of our involvement.

I was delighted when Professor Patrick Maxwell accepted. He’s the Dean of the Medical School at the University of Cambridge – a world-class researcher. Ironically, some of the people we approached turned us down for a very interesting reason. When they learned about the details of the prize, they said they couldn’t do it because they now wanted to compete. We still counted that as a win.

Tell me about the upcoming second Hevolution Summit. What is special about this particular longevity conference?

Actually, we did a small regional one early in 2023 in partnership with the National Academy of Medicine, and that one was focused on the Gulf area. So, it’s our third event of this type but the second Healthspan Summit.

At the first Healthspan Summit, we brought a lot of people together – it was bigger than anybody expected. We had people with subject matter expertise and people who were there because they were curious. The delightful part is we had people travel from all over the world, and we didn’t pay anybody to speak – no honorarium. We said, if you want to come and speak, it’s a privilege, and we’ve held that bar.

People loved the fact that we convened experts from different disciplines. We had regulators talking with investors, talking with scientists. People also appreciated the depth of the discussion on all the topics.

For the second summit, we’re taking the best of what we did and making it better. Now we have a chance to tell the world what we’ve accomplished since the first one. We can showcase research programs we’ve funded, partnerships – not ourselves, but we get the experts, the funded scientists to stand up and talk about their field.

We’ve now announced three companies we’ve invested in. We can showcase not only what those investments are but why we’ve invested in them. By then we may have announced more as well. We look to bring investors and these startups even closer together for matchmaking.

We’ll have updates from the XPRIZE – by then, we’ll be able to show the world how many teams there are, where they’re located, what types of fields they’re involved in, what science they’re interested in. The second summit is about the proof points.

The challenge I have right now is focus. Think about what I just shared with you: 2000 grants reviewed, 200 PIs funded, three companies announced, potentially five partnerships. I can’t put everybody on stage. It’s a good problem to have, but I think the world wants to hear from these people. They don’t want to hear from me.

The last piece, which I think will be the most exciting in the future, is matchmaking between our ecosystem of scientists. One thing we can do better than any government funding agency is cross borders. We can fund teams across borders much more easily than the NIH or the MRC because their priorities lie first and foremost within their own borders. We’re trying to cross these borders.

I have heard you on several occasions talking about the need to work across the entire ecosystem, including with public opinion and decision makers. However, I understand that Hevolution hasn’t funded any projects in that particular field. Why is that?

We’re very careful. We see ourselves as advocating for the field, convening different experts, but we’re not a lobby. We can’t legally lobby, nor do we want to.

However, we’ve had several policymakers, ministers, former ministers, attending our meetings – in the UK, in the US, in the Middle East. We’ve had very senior people from industry: Jon Symonds, Chairman of GlaxoSmithKline, was there as an example. Numerous CEOs from big pharma, small pharma, all engaging.

This means we have a chance to bring these parties together and hope that will shape the discourse around policy. We’re seeing early signs of that traction. Recently, I had a meeting right here in Riyadh with a former health minister. He was on a formal visit, but he asked his staff to arrange a private lunch meeting with me. That tells us that people like him are looking to Hevolution as a credible source, they are interested.

I was delighted to hear that when ARPA-H was announced by President Biden, one of the pillars this year was going to be aging. That’s a huge win for the field. Nobody’s going to be able to put in the sort of resources that the U.S. federal government can: the NIH’s budget is 44-plus billion dollars. Put 10 percent of that toward aging, and you’ve made a massive impact on the field’s progress.

How optimistic are you about the near future of our field?

I’m quite optimistic for several reasons. One, it’s a public health imperative. Two, it’s an economic imperative. Three, the science is now optimistically telling us that something can be done about it. You can have the first two, but if nothing can be done about it, so what?

The fourth reason is your field – the media. Today, I see three bodies in the media. One is mostly about the throw-away terms, the sound bites, those are people who don’t do their homework. Whatever the latest vitamin cure is, they’ll push it. That hurts our field. The second is the outlets that not only understand the science but find a way to communicate it to the readers who might not have a scientific background. The third is core science – the fact that Nature now has Nature Aging is huge. One of the top two journals in the world having a whole series on aging tells you something.

What then frustrates you? What bottlenecks do you see that you’d love to change in terms of public opinion, regulation, the scientific environment?

I see two major things. One is that sometimes, people in this field get over-enthusiastic and ahead of their own data. While I love passion and energy, the challenge is the risk to credibility. If you suddenly start making statements like, “In my lifetime, you’re going to live to be 150,” it sets an expectation and that hurts the field. Let’s not get ahead of ourselves. That frustrates me. Let’s stick with the evidence. Let the data push this field forward.

The old African proverb we often quote is “If you want to go fast, go alone. If you want to go far, take everybody with you.” Sometimes people in our field forget this wisdom. This is going to take a village. It’s a team sport. It’s going to take multiple players in different scientific and non-scientific disciplines. We’ve got to bring them together.

Just trying to create likes on social media in the short term gets a lot of publicity, sometimes gets you stardom, but that’s usually short-lived. Sometimes in that process, one forgets that it’s about the field, not oneself. I’ve been a CEO for a long time. I’ve been running large organizations and small organizations. One of the things you learn as a senior executive, whether at organizations as big as PepsiCo or as small as a biotech company, is that it’s always about the field, the business, the enterprise, not oneself. And if you remember that, you can move mountains.

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