Episode 006 – Could Cryopreservation for Human Organs Save 700,000 – 900,000 Lives a Year?

 

Transplanting Organs

Join us on this episode of the Methuselah 300 Podcast as we interview Sebastian Eriksson Giwa; founder and CEO of Sylvatica Biotech, and co-founder and chairman of the Organ Preservation Alliance.  Dr. Giwa will discuss how Cryopreservation could ​transform and ​revolutionize transplantation.  Currently at least 1 in 5 people on the organ waiting list die due to the inability of keeping organs viable for transport, resulting in 700,000 deaths a year by some estimates.  Dr Giwa and his team want to change that…

The Defense Department, National Science Foundation and even the White House ​are beginning to recognize the need and potential of this scientific frontier , and scientists from around the world to an increasing decree are tackling the remaining challenges.  ​

Will you join us?  You can find out how to become a foundation supporter at  Mfoundation.org.

We thank you for your support now and in the future!

Sincerely,

Methuselah Foundation

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Could a New Approach to Alzheimer’s Move Us Closer to a Cure?

 

PRESS RELEASEDecember 16th, 2015

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Leucadia Therapeutics and the Methuselah Foundation Announce a Partnership to Cure Alzheimer’s Disease

Leucadia Therapeutics LLC, a biotechnology company focused on treating and preventing Alzheimer’s disease, and Methuselah Foundation, a public charity incentivizing innovation in regenerative medicine, today announced a joint partnership to develop a novel therapeutic strategy to treat Alzheimer’s disease. Alzheimer’s disease is the most common cause of dementia in the elderly, affecting over 5 million people in the USA. Affected individuals have difficulty creating new memories, and problems with language, mood and reasoning.  As the disease progresses, patients become withdrawn and bodily functions decline, leading to death within 3-9 years of diagnosis. No current drugs or treatments slow or halt the relentless progression of Alzheimer’s disease.

Leucadia Therapeutics LLC was founded with the idea of taking a new approach to curing Alzheimer’s disease, using patent-pending technology to correct the cause of the disease rather than its effects.  The company will use this investment to accelerate development of novel therapy with the goal of beginning clinical trials in 2018. Leucadia Therapeutics Chief Scientific Officer, Douglas Ethell, Ph.D., said, “This is an exciting event for LT as it frees us from fundraising and allows us to focus our efforts on getting into the clinic as soon as possible.”

Under this agreement, the Methuselah Foundation has made an equity investment in Leucadia Therapeutics LLC.  Over the next 3-5 years, Leucadia will develop and test a novel therapeutic device to treat the underlying cause of Alzheimer’s disease.

Will you join us?  You can find out how to become a foundation supporter at Mfoundation.org.

We thank you for your support now and in the future!

Sincerely,

Methuselah Foundation

Episode 005 with Dr John Geibel; Yale University How Yale's Team of Researchers are Moving Toward 3-D Printable Organs

 

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John Giebel, Director of Surgical Research, Yale University

On this week’s podcast, join us as we talk with Dr John Geibel, Director of Surgical Research and Professor of Department of Cellular and Molecular Physiology at Yale University.  Discover how his team is working hard to develop the first iterations of 3-D printable organs, a goal that will revolutionize the medical organ industry and save thousands upon thousands of lives.

To keep up with the latest developments, join our newsletter HERE

To find out how you can be a part of the Methuselah Foundation and support our work, go to Mfoundation.org or click HERE

Methuselah 300 Podcast Episode 004: Is a Synthetic Liver on the Horizon? With Dr Bryon Petersen A Synthetic Liver Could Bridge the Gap Between Now and the Development of an Real Tissue New Organ

Could this device bridge the gap to new organs?

Join us on this week’s podcast as we interview Dr. Bryon Petersen, who is researching and developing a new device that could bridge the gap for those awaiting a new liver so that those in need can have a quality of life impossible for them now.  You’ll here about where he is in the stage of development, and what timeline he is working toward.

To keep up with the latest developments, join our newsletter HERE

To find out how you can be a part of the Methuselah Foundation and support our work, go to Mfoundation.org or click HERE

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Episode 003 Interview with Founder Dave Gobel Part #2 Interview with founder Dave Gobel Part #2

 

In this Episode of the Methuselah 300 Podcast, we’ll continue our interview with founder Dave Gobel as he explains more of the specific areas of regenerative medicine the foundation is working toward, some new partnerships and backers including NASA, and how he believes future life will be impacted in the near and mid term by exciting progress currently being made in medical research.

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Episode 002 of the Methuselah 300 Podcast The Podcast keeping you in tune with the Methuselah Foundation's latest Progress

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In this Episode of the Methuselah 300 Podcast, we’ll interview founder Dave Gobel and learn what planted the seed for the idea that would grow into the Methuselah Foundation. You’ll also learn the specifics of what innovations the foundation is working hard to create.

For more information visit Mfoundation.org

Episode 001 of the Methuselah 300 Podcast An Introduction to a new way of staying in touch with the the Foundation's work

 

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In this episode, you’ll learn what the podcast will be about and what you can expect to see in the future.

For more information and to see how you can help make a difference in the future of medicine, visit MFoundation.org

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A Banner Year at Methuselah Winter 2014 / 2015 Newsletter

Dear Friends,

2014 was a year to remember. With a $10,000 Methuselah Prize awarded to Dr. Huber Warner of the National Institute on Aging’s Interventions Testing Program, the first six teams officially announced for the New Organ Liver Prize, and our first Organovo 3D printer awarded to the Yale School of Medicine, we’ve certainly been keeping busy.

Thanks to all of you, and especially to the passionate support of our many generous donors, we’re also looking forward to an impactful 2015. We’re still gathering more teams for the Liver Prize, exploring a possible New Organ Vasculature Challenge with federal agency partners, looking forward to the inaugural Organ Banking Summit in February, and much more.

We closed out last year by taking part in a successful $150,000 fundraiser for the SENS Research Foundation, and we’re ringing in the new one with a founding investment in Oisin Biotechnology (see below). We also look forward to sharing more illuminating conversations with you from around the world of tissue engineering and regenerative medicine on our blog, “The Bristlecone.” (In case you missed it, our most recent dialogue, with David Williams of TERMIS and the Wake Forest Institute of Regenerative Medicine, was a fascinating three-part excursion (part 1, part 2, part 3) through a wide range of key issues.)

Read on for more Methuselah news from the last quarter of 2014, and please don’t hesitate to stay in touch.

Warm wishes for a prosperous year ahead,

Dave Gobel

CEO

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BACKING OISIN BIOTECHNOLOGY

The Methuselah Foundation has become a founding investor in Oisin Biotechnology, Inc, an early-stage company that aims to provide targeted biological solutions to degenerative aging conditions. We are also now represented on Oisin’s Board of Directors.

Initial research and development at Oisin will focus on controlled removal of senescent cells that underlie certain degenerative aging conditions. Both proprietary treatment protocols as well as proprietary methods for delivery of biologics to affected cells will be employed. Oisin is currently performing in vitro studies to confirm the expected mode of action of its therapy.

“We invested in Oisin,” Methuselah CEO Dave Gobel explained, “because of the promise of their highly targeted approach to removing senescent cells without causing collateral damage or side effects. To put it more colloquially, I like to think of this as ‘getting the crud out’—one of our key themes at Methuselah.”

We hope this founding investment will enable Oisin to establish proof of principle (does it work in vitro or not?). If it does work, we believe that Oisin will become extremely important in the field of longevity science—and provide us with a mission-aligned solution that is industrializable by harnessing infotech, biotech, and the body’s own systems. We’ll keep you posted.

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NEW FEDERAL GRANT PROGRAMS FOR ORGAN CRYOBANKING

We’re excited to announce that the Organ Preservation Alliance, one of New Organ’s partner organizations, has informed the development of three new federal grant programs by the Department of Defense targeting complex tissue and organ cryobanking for transplantation.

These three unique but complimentary “Small Business Innovation Research” (SBIR) grants, the first of their kind, will launch on January 15, 2015. Together, they could fund research for 20 or more U.S. teams, with strong candidates potentially receiving $3-$3.5 million across phase one and phase two awards.

Congratulations to the Organ Preservation Alliance for its critical role in this landmark moment for the undervalued field of cryopreservation.

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BOWHEAD WHALE STUDY PUBLISHED

We’ve seen great news coverage recently of the bowhead whale research we funded at the University of Liverpool, and the full paper by Dr. Joao Pedro de Magelhaes and his team is being published in the journal Cell Reports.

According to Magelhaes, “The bowhead whale is the longest-lived mammal, possibly capable of living over 200 years. Thanks to generous support from the Methuselah Foundation, we sequenced the bowhead genome and transcriptome and performed a comparative analysis with other cetaceans and mammals. We found that changes in bowhead genes related to cell cycle, DNA repair, cancer, and ageing could all be biologically relevant.”

Next up for Magelhaes? Sequencing the genes of the Capuchin monkey….

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EXPLORING c60oo AND CANCER GROWTH

Ichor Therapeutics, Inc. (LaFayette, NY), an exciting pre-clinical biotechnology company funded in part by Methuselah donors, is preparing to commence pilot studies to investigate the effects of c60oo administration on human cancer proliferation in vivo.

It has been theorized that c60oo may be a potent inhibitor of primary tumor growth or metastasis. Data about human leukemia growth rates in the presence and absence of c60oo is expected to pave the way for additional studies of c60oo’s effects on a variety of tumor models.

“We are grateful to the Methuselah Foundation,” Ichor CEO Kelsey Moody said recently, “for providing much of the necessary funding for this project, without which this important research could not be completed.”

Thanks, Kelsey. We look forward to seeing your results!

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The International Front Interview with David Williams: Part 3

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David Williams is the current President of TERMIS. He is a Professor and Director of International Affairs at the Wake Forest Institute of Regenerative Medicine, Chairman of the South African medical technology company Strait Access Technologies Pty and a Master of the DeTao Academy in China.

The New Organ Initiative is hosted by the Methuselah Foundation.

Click here for part 1 and part 2 of this interview.

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New Organ: Let’s return to the international arena. Why are you so focused internationally?

David Williams: It’s pretty clear that the United States, and a few countries in Europe, and one or two elsewhere, are at the forefront of developments in these medical technologies in regenerative medicine. But they can’t do everything. We have to recognize that there are very good academic, clinical, and commercial entities all around the world. And I think it is appropriate that we interact with them in order to get the best of everything.

Also, when you look at issues of commercialization and clinical translation, we know that here in the U.S., there are—sometimes understandably—many limitations and barriers to how far and how fast we can go. And there are opportunities in other parts of the world where there are different formats and different styles. Part of my rationale is to try to get the best of all possible commercial, clinical, and academic opportunities in different parts of the world.

For instance, I’ve spent a fair a bit of time in China. Ten years ago, when I started going there, I don’t think they were doing very good work, but they’ve now put money and people into some very interesting developments. Now, I’d say that they are almost as good as any other country. In Biomaterials, I publish more papers from China than I do from the United States. I also know the regulators well in all of these countries, and they are not trying to move things faster or do things cheaper or less rigorously, but they have very different sets of principles than both the FDA and the European Union do.

The FDA is risk averse for understandable reasons, because they’ve got Congress looking over their shoulder and they have to be as sure as possible to get things right. If that means delaying or stopping new developments, then so be it. China, Japan, Korea, and Taiwan, on the other hand, have a somewhat different attitude. I work with those regulators and some of the key labs in Beijing, Shanghai and Singapore, and it’s pretty clear that the progression of translation is likely to be faster there. And at this stage, although we obviously have to keep a close eye on it, I don’t think that this will happen by sacrificing any issues of safety.

NO: In terms of international collaboration, what’s missing that you’re working to achieve?

Williams: One of the key issues is for there to be clear and transparent collaboration between the best in the U.S. and the best in Asia. There’s going to be some good competition there, and that’s just fine. But in key issues, I believe that it is better to be working in collaboration and in joint ventures. Most American companies now have activities in China and in Korea, and some of them have major research offices there. I’m also involved in a couple of cases where a Chinese company would like to have American representation on its Board in order to validate its work; and therefore, to move together to get both Chinese and American regulators on site. To me, this kind of collaboration is a win-win for everyone.

NO: How does your work with the Tissue Engineering & Regenerative Medicine International Society (TERMIS) play into all this?

Williams: TERMIS is about 10 years old now. The first meeting was held in Shanghai, and its purpose was to facilitate not just international collaboration on particular projects, but to shepherd the formation of a growing family of colleagues in regenerative medicine. I think that was a good idea, and I give a lot of credit to the people that started it, like Alan Russell, Bob Nerem, and Hai-Bang Lee. Back then, I was the director of the UK Centre for Tissue Engineering, and saw myself having some role to play in the development of the community. So I went to that first meeting in Shanghai.

There are now three continental chapters of TERMIS, all of which are successful to varying degrees. TERMIS America is now a solid organization. Europe is a bit more disparate, but there was a very good meeting this year, and they’re getting their act together as well. Asia, which is where I spent a lot of time, is more difficult, because there are many different cultures with totally different customs and approaches to things.

When Steve Badylak’s term as president was up, a lot of people suggested that I should run, because of all the people in the world, I probably knew all three continents together better than anybody else. So I did. It’s a three-year position, and my manifesto was, “Let’s try to consolidate TERMIS globally.”

As president, I’ve outlined two basic principles. One was to ensure that regenerative medicine is growing not just in the big countries, but all over the world, because a lot of the smaller countries have a lot to offer this process as well. Part of the subtext for this was that medical tourism, i.e. stem cell therapies, were being carried out in places like Mumbai and Moscow and so on without any evidence whatsoever. That’s a massive danger to us if they get it wrong, and of course, they are getting it wrong. So the idea is that if we can consolidate the academic and clinical communities around the world into one solid organization, that might help to address some of these unfortunate side effects.

The second principle, which I am working very hard at, is to allow TERMIS to become more than just an organization that conducts conferences. We have a World Congress every three years, and in the intervening two years there are three continental chapter conferences. That’s fine, and they bring together those communities, but TERMIS has no other role. I’d like to see us take on more of an educational role, to look at best practices and how we teach tissue engineering, cell therapy, and regenerative medicine, and help to develop a more well-educated workforce. I’d also like to see TERMIS become the voice internationally for regenerative medicine, so that when organizations such as the WHO or the US Congress or the European Parliament want to go somewhere for an authoritative statement, they’d come to us. We’re not there yet, but I’m working to try to get us in that position.

NO: Tell me more about that role, and what kind of impact it could have.

Williams: I’m really talking less about the scientific base here and more about the infrastructure in which regenerative medicine has to operate. And in that space, I think there are a number of different factors that are hugely important in controlling the way regenerative medicine will progress. That includes ethical issues. It includes health economics. It includes the perceptions of the public, all of which I think are immensely important. Public perception is one area where we have to be extraordinarily careful. And it also includes regulation and the regulatory bodies. For all of these areas, if we get them aligned, then things become easier. If we make mistakes, then it becomes more difficult.

We also have to be extremely careful about not overstating or over-hyping what is possible. There’s a natural tendency to do it, especially if you have a camera or a microphone in front of you. I’ve been guilty of that myself. You want to give a positive spin on things. We all do. But there is a danger there when we begin to over-promise. When we look at some of the advances in regenerative medicine, we have to put them in perspective. There have been some tremendous advances in organ tissue engineering, like what Tony Atala has been doing here at Wake Forest, and Paolo Macchiarini in Europe. But we should not expect too much too soon from these developments.

When Tony Atala was working on the bladder, for example, he did roughly one patient a year, and followed them each very, very carefully. That’s the way you have to do it. Similarly with Paolo, with his trachea and lung. He’s actually had difficulties with that, because expectations rose, and he’s gotten pressure from either individual patients or patient support groups saying, “We need this now. My child has this disease and it needs to be treated now.”

We can make big errors that way. In fact, we’ve seen it happen in medical technology in the past. Even with the best will in the world, trying to get things to patients too quickly can result in real problems. It can end projects, in fact.

In today’s climate, we’ve just got to be careful. For example, you’ll find significant arguments in the literature about work with tracheal tissue engineering, where concerns have been expressed about the clinical translation of some of the concepts. We just have to be mindful of the impression we’re giving to the world. If we have major advances, let’s put them into perspective and make sure we don’t say “We’re going to be doing this in clinics tomorrow.”

The news media do not particularly like that, because they want to tell exciting stories. That’s why we need to make sure to keep things in perspective. So having the ear of important agencies around the world and keeping them informed about what we’re doing will help. Getting more involved in patient support groups will also help. Whether it’s in macular degeneration or Type I diabetes, where there are good patient advocacy organizations, they need to know what we’re doing and what it might deliver, as well as to have a realistic understanding of expected time frames.

NO: Now that you mention patient advocacy, I wanted to ask you about your thoughts on the state of public and patient advocacy as well, in relation to regenerative medicine.

Williams: I think it’s probably average. There are certainly some advocacy programs out there, but I’m not sure they’re pushing us forward that much. What the public hear are the news items, and they tend to be sensational. Sometimes, that’s for good reason—we’ve seen major breakthroughs in recent years, like many of the ones we’ve been talking about. But I don’t often see stories about big breakthroughs in regenerative medicine being channeled through the lens of patient advocacy. I don’t see much related to Parkinson’s or Alzheimer’s, for example.

Maybe it’s there and I just miss it. It’s a little bit like looking at support groups in cancer. When you have a lot of money coming in from charitable organizations and advocacy groups, you tend to go either towards patient treatment management counseling or towards basic research. Sometimes, that dichotomy doesn’t help. You can see this with Alzheimer’s, too. I think we’re so far from a “cure” that most people are far more concerned about how we’re actually going to treat the millions of people who do have Alzheimer’s, and going down that particular route where care is very important. So I think advocacy groups could probably do more. I’m not an expert on this, but that’s my impression.

NO: We talked with David Green of Harvard Apparatus Regenerative Technology, and he commented on how we could use an organization like the Juvenile Diabetes Research Foundation that was focused on the intersection of tissue engineering, regenerative medicine, and organ transplantation. There does seem to be a lack of patient advocacy at the intersection of these areas, and I don’t really understand why.

Williams: Neither do I. Maybe it’s that these organizations are wary of giving false hope to patients who have these diseases? If so, I agree with that. Perhaps it’s a question of balance. Of giving hope by showing how some patients who were blind from macular degeneration can now actually see a little bit, but emphasizing at the same time that we know it’s going to be decades before that becomes widely available. I think many of these organizations are understandably worried about over-hyping good science or good early-stage clinical work.

NO: That makes sense. I have one more question for you, and that’s about the pros and cons of putting forward some kind of “Grand Challenge” initiative surrounding tissue engineering and regenerative medicine in the United States. The Office of Science and Technology Policy, for example, has set up an office dedicated to Grand Challenges, and they’ve been coordinating efforts like the BRAIN Initiative and others in the U.S. Do you think that it would be valuable to see some kind of Grand Challenge Initiative for tissue engineering and regenerative medicine? Do you have any views on how to focus such an effort?

Williams: Yes. Again, a good question. Since I haven’t been in the U.S. that long, I’m not familiar with the process of formulating Grand Challenges. But as I’ve been implying, I think regenerative medicine in all its ramifications is an entirely appropriate area for such a thing. Perhaps the main reason I say this is that regenerative medicine is both interdisciplinary and multidisciplinary in nature, and you need the benefit of scale to be able to tackle these issues.

When I was back in Europe, I headed a major European program known as “STEPS,” which was essentially a systems engineering approach to tissue engineering. It was a five-year program funded by the European Commission, and it involved 27 organizations in 15 different countries working through various systemic issues. We had health economists, regulators, scientists, modelers, manufacturers, and more all working to coordinate solutions to very specific tissue engineering processes and challenges.

This field is enormously complex, and I don’t think we’ll actually get where we need to go without that benefit of scale. So I think the Grand Challenge direction is a great idea. In the end, the STEPS program was too big and complex to achieve finality in anything, but it enabled us to build a very good infrastructure in Europe, and that infrastructure has now led to a number of other networks across Europe that are all flourishing pretty well after I left.

NO: That’s an encouraging outcome. Thanks so much for taking the time to talk with us. I’ve admired the unique role that you play in this space for some time now, and appreciate the chance to learn more about your work and better understand where you’re coming from. In shaping programs like New Organ, the systems approach you’re describing very much resonates with what we’re trying to do.

Williams: I appreciate that.

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Core Principles and Challenges Interview with David Williams: Part 2

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David Williams is the current President of TERMIS. He is a Professor and Director of International Affairs at the Wake Forest Institute of Regenerative Medicine, Chairman of the South African medical technology company Strait Access Technologies Pty and a Master of the DeTao Academy in China.

The New Organ Initiative is hosted by the Methuselah Foundation.

Click here to read part 1 of this interview.

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New Organ: How would you express the core values or principles that guide your aspirations for regenerative medicine?

David Williams: I could talk about the importance of honesty and so on, but I think the critical piece is that we make sure that the products of science and technology are translated for the benefit of humankind. That is fundamental.

Of course, as I’m sure you’re aware, there are some dangers in overstating things, and perhaps in underestimating the difficulties. But my core principle is to address in an honest way—initially scientifically, but also from an infrastructure point of view—those issues which we can’t ignore if we want to get to successful clinical translation.

You cannot translate bad science. You also cannot translate no science. If we honestly want to address unmet clinical needs, we have to have the appropriate science, whether that’s stem cell, or biomaterials, or bioreactors, or immunology. We have to put all these areas together to give us the best chance of succeeding. So my core value is this: Let’s take fundamental principles and work to develop them for the benefit of patients for whom there is no existing successful treatment.

NO: Absolutely. But here’s another question: Your values are probably shared by most of your colleagues, and yet people often operate within environments that make it difficult for their values to be expressed. If you agree with that view, what’s getting in the way?

Williams: Yes, I do. That’s a hugely important point, and I have a lot of sympathy, especially for young scientists who share these core values. I mentor them. I teach them. And they’re seeing significant barriers to their own progress.

We know about the difficulties with the NIH in getting grant funding. There’s also the whole incentive structure with rewards based upon metrics and not necessarily on alignment with core values. By this, I mean building up CVs for the sake of CVs. This is something I’ve been very focused on. You see it time and time again if you’re the editor of a journal—the rationale motivating people who want to be published in your top journal, and who are being forced down this route because they’re putting in a grant and have to be able to quote three good papers in order to get to the next level, or need at least five papers of a certain impact factor on their CV to get promoted from assistant to associate professor.

The metrics are driving things, and we’re all to blame here. But the grant-giving bodies and the select panels at universities are far too driven by metrics and ticking boxes and far too little concerned with the core values of how good a person’s science is and how good his or her philosophy is. I think even at its best, it’s very tough for young scientists. It takes a brave man or woman to stand in the way of these rules.

NO: A related concern is that if tissue engineering and regenerative medicine are built upon the existing bedrock of healthcare economics without significant improvements to that bedrock itself, it’s going to leave a tremendous amount to be desired. We have the opportunity to influence the initial conditions by which the frontier-to-industry transition happens for this field. We want to be working to optimize that transition for maximum societal benefit.

Williams: I agree. Broadly speaking, I think there are two different levels to consider. First, as I said before, you can’t translate bad science or no science, so we still need a big effort on the science side, especially in the handling of cells and their ability to express new tissue. We don’t fully understand that yet, and everything has to flow from there.

Then from a higher vantage point, even if we get to the place where it looks like we are getting the science right, we still need to tackle all the problems of translation through manufacturing. I know a few big companies are making progress—like Mesoblast, as I mentioned—but there are still a number of confounding issues to deal with. One is the communication between regulators and the scientific commissions. I’ve got a lot of sympathy with the regulators, but at the moment, they are serving as more of a barrier rather than being of assistance. Secondly, as I also mentioned, it’s still unclear how regenerative medicine is going to be profitable. Is it a product? Is it a service? Who’s going to pay for it? Is the payer here in the U.S. the insurance companies? Private pockets? Who is it?

NO: All great questions.

Williams: One of the things that has struck me over the last couple years is that research funding in the U.S., especially through the NIH, is in a diabolical situation. I’m not sure I have an answer for that. The NIH has a big budget, and maybe we’re just trying to spread it too thinly. I don’t know. But when you have a success rate of 10% or less, that gives rise to circumstances that are very difficult and inefficient. For the amount of time that professors have to spend writing grants, a 10% chance of success is a pretty desperate situation.

At the same time, put that alongside the fact that for most of the large hospitals with medical schools, the last few years have not been kind to them in terms of their own economies. They’re making their academic doctors do more clinical work just to pay the bills, and so they have less and less time for research. I’ve known several senior clinicians who have recently decided to retire because they were, even at very high levels of seniority, being forced to go on call and spend all their time in the clinic with no time whatsoever to even think about research. So I think these things together are working against us.

The other issue is that if this area is eventually to become commercially successful, then you might reasonably expect to see investment from big companies, and right now, most companies in the medical technology sector are more or less closed to R&D. None of the big companies—Medtronic, Boston Scientific, Johnson & Johnson, St. Jude’s—do R&D any more, or hardly any.

They used to. Good medical technology discoveries were funded by the big companies, either in their own labs or extramurally, and that funding came out of revenue from their existing products. Now, companies have stopped doing that, and in the regenerative medicine area, of course, there are no revenues. What they’re doing these days is more or less sitting back and waiting till they see a discovery being developed in a small university startup, and then going in and buying it. But the startups in universities have their own set of problems. They have no revenues, and this area is expensive, and the investors putting money in want their rewards sooner rather than later. It’s a huge trap.

NO: It’s definitely indicative of a general problem that’s been going on for a while. We just don’t have that many Bell Labs or Xerox PARCs around the U.S. anymore.

Williams: Exactly.

NO: And we’ve been seeing multiple valleys of death (i.e. funding gaps in translating research into the market) emerge over time, in different areas. How do you think we might get a handle on this funding conundrum?

Williams: Well, there’s been a lot of discussion about NIH funding, and there was a significant increase in NIH funding for research for a period of time, but it’s leveled out again. Personally, I think there is good funding here in the U.S., but it’s being spread too thin. When you have a hot topic like tissue engineering and regenerative medicine, a great many universities and medical schools wish to get into that space, and therefore the number of proposals coming in has increased. In turn, people are without a doubt having greater difficulty in finding funding.

Without naming names, I’ve talked to some really good people in this area over the last few weeks who are no longer getting support, and they used to be just two or three years ago. Once you get down to a 10% or 12% funding level in any study section in the NIH or NSF, then issues other than basic science or clinical outcomes become important, which means politics. That’s where regenerative medicine is right now. It’s difficult, and probably will get more difficult, and I don’t think the national politics are going to help over the next few years.

NO: If you were master of the universe for a little while, how would you change funding allocations to better advance the field?

Williams: That’s a very good question. One important angle to mention is that the Department of Defense has been a major funder of research in the U.S., primarily aimed at servicemen and women and veterans who have been very seriously injured. That’s been a huge issue. As you know, the Armed Forces Institute of Regenerative Medicine (AFIRM), which is now spread out across the whole country, is a coordinated effort to look at regeneration in areas of large-volume muscle loss and craniofacial issues and so on.

That program is still there, but there is a decrease in need now with the scaling down of wars in Iraq, Afghanistan, and elsewhere. And this does allow the U.S. to broaden its focus. I’ve made this point before: the areas of “unmet clinical need” are changing. Right now, I believe the U.S. has a good opportunity to say, “We still should invest heavily in regenerative medicine, but where are we going to get the best value in areas, such as Alzheimer’s and Parkinson’s? How about macular degeneration and diabetes Type I?”

Those areas where we don’t really have good therapies are where I think we need to concentrate. In my view that means the whole of the nervous system. Interestingly, I just saw on the news a major breakthrough in the UK and Poland on stem cell therapy and spinal cord injury. I believe the U.S. should look at that and say, “We’re pretty good at that. Maybe we should see if we could invest more here in the U.S. on those main areas where there is literally no treatment at the moment.”

NO: How about the challenges on the science side? What would you say are the key technical hurdles that still need to be overcome in order to specifically create new solid organs, which many see as one of the holy grails of regenerative medicine?

Williams: That’s another good question. I’m not sure whether there is any one single scientific issue. Again, I go back to the need for a systems approach. Bear in mind that what we’re trying to do is to take a group of cells and persuade them to do something they don’t want to do. That is, to express new extracellular matrix that can then be organized into the structure and function of an organ.

I think many of the different scientific principles are in place. We’ve made big progress already, and to me, the key issue is in putting everything together such that we can develop the structures that function as organs do. We know how to do the little bits, but we still have to explore the complex functioning of the whole.

Another thing we haven’t talked about yet is imaging and diagnostics, and these are both hugely important for regenerative medicine. If you look at Parkinson’s, for example, by the time a patient knows they have Parkinson’s, probably from the tremors somewhere, they’ve already lost 95% of their dopamine-producing function, and it’s too late. So treatment for Parkinson’s is going in the direction of personalized medicine, with better imaging and screening and biomarkers. This is a hugely important step, but like a lot of what we’ve been talking about, it’s also going to be a massive problem as far as the economics are concerned.

NO: One of the scientific rate limiters that we heard a lot about in our work developing the New Organ Liver Prize was vascularization. What are your thoughts on vascularization as a major clinical hurdle that still needs to be overcome, particularly in the context of the heart, liver, kidney, lung, and pancreas?

Williams: Yes, that is still one of the most important issues. There has been a fair bit of progress made in vascularization, especially in using some small molecules and certain growth factors to encourage newer vascularization. So there are encouraging signs in this area, but it does remain one of the bigger challenges.

NO: How would you define the major benchmarks or milestones in overcoming that particular hurdle?

Williams: I’m not sure, but it generally goes back to a point I made before about having a suitable animal model. I think we have to demonstrate sufficient vascularization within a suitable animal model first, and I’ve got a feeling that means we’re going to have to show significant vital vascularity over a period of time in one or more non-human primates. We’re going to have to do that before we get into humans, I think, and that’s going to be very difficult to do.

Overall, I think that scientific progress has been good. There are still some key scientific issues that have to be addressed. But again, more than solving any particular issue, I believe it’s the integration of individual projects that is the most important and most difficult challenge.

Take muscle tissue engineering, for example. It’s already possible to regenerate small amounts of muscle, but the integration of that into a functional muscle regenerative project is much, much harder. We need to address the integration issues more than anything, and we need to start doing it for the areas where our current therapies are weakest. We had to start somewhere, and so skin, cartilage, and bone were good starting points. In most all of these areas, we’ve now had some degree of clinical success in alternative treatment modalities. Where we don’t have good therapies at the moment is in areas like degenerative disease, especially neurodegeneration and musculo-skeletal regeneration, and I’d like to see more effort being addressed in those areas.