Monthly Archives: December 2014

The International Front Interview with David Williams: Part 3


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.



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.

Core Principles and Challenges Interview with David Williams: Part 2


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.



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.

Biomaterials and Clinical Translation Interview with David Williams: Part 1


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.



New Organ: What is your background?

David Williams: I’m trained as a materials scientist, but I worked for the last 45 years as a professor of medical engineering and in various aspects of the medical industry, mostly in Liverpool, and now at Wake Forest in North Carolina. Most of my professional life, I’ve been concerned with medical technology, especially implantable devices—hip replacements, heart valves, and many others—and the materials used for them.

About 10 years ago, I transitioned to incorporate regenerative medicine. The reason for this is that we’ve been pretty successful in working with implantable devices, but we’ve had a very limited range of options and functions. We can use synthetic materials to replace parts of the body that have failed for some reason, but we can only replace mechanical or physical functions. We can’t replace biology. Therefore, we can’t address many of the really important diseases, especially degenerative conditions, where we need to restore biological or pharmacological functions. That’s where regenerative medicine comes in.

NO: Between the Wake Forest Institute for Regenerative Medicine (WFIRM), the Tissue Engineering & Regenerative Medicine International Society (TERMIS), the University of Liverpool, the journal Biomaterials, and more, you wear a lot of different hats within the regenerative medicine community.

Williams: Yes, I suppose I do. Most recently, after 40 years as an educator heading up a large research group and chairing the department at Liverpool, Dr. Anthony Atala asked me to come work with him at WFIRM as a professor of biomaterials and also as director of international affairs. So my role is to mentor and facilitate international collaborations.

In everything I’m doing, you’ll find that the words “international” and “global” figure strongly. That’s my role at both TERMIS and WFIRM. And perhaps just as importantly, it’s my role as editor-in-chief of Biomaterials, the world’s major journal in this area. I’ve taken Biomaterials to number one as a major journal, and I’ve done so internationally—encouraging, promoting, and sponsoring research work all over the world, including Asia and Africa. I think advancing this field is largely a global issue, and whether we’re doing research or educating or working in the commercial sector, we should look at it that way.

NO: I want to come back to your international work, but for the moment, let’s talk about biomaterials. What are they, and what kind of work are you doing with them?

Williams: I published a short paper recently called “The Biomaterials Conundrum in Tissue Engineering,” and to put it simply, I think we’ve mostly gotten it wrong. I’m not being too critical, because it was probably inevitable, but the early attempts at tissue engineering involved material scaffolds, and that’s where biomaterials come in. The scaffold is the form in which you’re going to develop an engineered organ, and the originators felt that they needed to get FDA approval for them. Therefore, they needed to use an FDA approved material, and although this was understandable, I think it was misguided.

The sole criteria for FDA approval for biomaterials used in implantable devices was that the material did no harm. It had to be known to be safe. You’re never going to get a scaffold or template material to function properly if all it does is play safe. You need the material to actually stimulate cells through mechanical forces or growth factor delivery, and standard synthetic polymers were never going to do this reliably and routinely.

Because of this, I think we need totally different types of materials that try to replicate or represent the micro-environment of the cell. I’ve been shouting this from the rooftops for a long time now. It can’t be an engineered fabricated structure that looks nothing like the cell micro-environment, or we’ll never be able to make the cell regenerate the tissues that we want.

We do have a number of pretty good hydrogels that do this, especially biologically-based hydrogels. That’s why decellularized extracellular matrix (ECM) is getting so popular. I don’t think we’re there yet by any means, but there are some interesting approaches around. But the key is that we have to have a different mindset regarding how we develop our biomaterials, and the regulators have to have a different mindset regarding how they regulate them. We can’t use the standard tests for safety that the FDA is saying that we still have to use, and that’s a big issue at the moment. For the most part, the regulators still want to play it too safe.

NO: Are you a voice in the wilderness on this, or are there others out there who see it the same way?

Williams: There are some very good labs that are doing what I’m suggesting, but far too many that are not. Sam Stupp in Chicago and Jeff Hubbell in Switzerland are two who are, and there are quite a few others. Steve Badylak’s work on decellularized ECM is also very good. So I’m certainly not alone. I’m just trying to make sure that the community is aware of it.

I do get frustrated sometimes. I was at a biomaterials meeting in Europe this year, and presentation after presentation and poster after poster talked about a minor modification to an old material that never worked anyway. We academics have to get over this barrier. Why spend dollars and student time working on old science that is never going to work? It’s easy to do, but it’s not going to get us anywhere.

NO: What do you see as the most promising approaches to biomaterials?

Williams: Let me first make clear that even though I’m a biomaterials scientist, I don’t believe that we will always need biomaterials as part of regenerative medicine. There are a number of different approaches and therapies out there, for which a variety of different materials may be appropriate. However, if we do want to create solid organs and achieve reasonable dimensions to tissues, they will have to have some sort of structure, and I think we can only get that by using materials that are capable of elaborating that structure.

I mentioned Sam Stupp in Chicago, who uses peptide hydrogels, and works in both the musculoskeletal and the neural areas. I think his approach is very sound. I work with some groups in China who have made good progress in peripheral nerve regeneration using a combination of materials and growth factors and other bio-molecules. The overall principle, though is that we need a systems approach. It’s not just one issue, but putting many different pieces together that gives the best opportunity for a cell to regenerate the cellular matrix and then for it to be integrated into the host.

NO: In terms of advancing state-of-the-art biomaterials science, what would you like to see happen that’s not happening? What activities would really move things forward?

Williams: One of the biggest questions now has to do with suitable models for evaluation prior to “first in human.” It’s a huge issue. We know that we can use both biomaterials-based therapy or cell therapy in mice, and we can do it in rats or in rabbits. But the first thing you notice is that you get different results in these different types of small animals, and when you go to a large animal, you get even greater variations in the results, especially in vascularity.

We need an appropriate large animal model that will be sufficiently predictive of performance in the clinic to allow regulators and funders to say, “Yes, go ahead and do it.” Without that, we’re never going to be able to commercialize, because any company involved in this will have to follow the proper regulatory rules, and those are just too burdensome at the moment.

For example, the great work that has been done to date on the bladder and the trachea by people like Tony Atala and Paolo Macchiarini has been done under regulatory approval, but not as a commercial entity. And doing these transplants as orphan procedures is not necessarily going to translate into commercial success. The companies that are making money in regenerative medicine, I think, are those that are scaling up on the cell manufacturing side, companies like Mesoblast in Australia.

So far, we don’t actually have a business model or a real clinical translation model that is going to allow for-profit companies to make their profit by treating a significant number of patients. We’ll do it one by one, but to translate that into companies actually coming in, investing, and making money at scale in the manufacturing of tissue is a huge issue. We should never forget the role that health economics plays in all of this.

NO: Do you think we’re more likely to see clinical commercialization success in other countries? In other words, are economic conditions more favorable elsewhere? And if so, will those successes increase the odds of more favorable conditions in the U.S.?

Williams: It’s too difficult to predict that at this stage. Let me give you an example. Ten years ago, when I was back in my lab in Liverpool, we worked on a tissue engineering approach to treating diabetic foot ulcers. We were working with a company and we had a system that was looking pretty good. But it was costing 20,000 euros to develop one product for one person, and that was just never, ever going to work.

From a health insurance point of view, the answer is, “We’ll just put a new bandage on every week. You can have a band-aid.” And I’m not diminishing the impact of diabetic foot ulcers, but that was not the life-threatening issue that New Organ is trying to deal with. That’s why here in the U.S., I think we’ve got huge problems. It’s not simply ObamaCare or the Affordable Care Act. It’s the way in which the insurance provider is now in charge. I think it’s going to be very difficult as long as their priorities are focused on short-term benefits. As far as I can see, long-term solutions are not really in the best interests of many insurers right now, and so the overall health economics in the U.S. are working against us rather than for us at the moment.

In order to change that reality, we have to persuade real decision makers that “Yes, there really is a future in this.” And there are very significant early costs required in order to get to that point. Pre-clinically, for example, we’re nearly there now in the treatment of patients with acute myocardial infarction (heart attack). There are some good cell therapies, as well as some tissue engineering approaches that look as though they may work.

I can also give you a couple of examples from the medical technology area. You may remember the artificial heart, and especially the heart assist devices? They can certainly be successful, but when the hardware and the first-year costs of these treatments amount to almost $500,000, and it saves one life for a year or two, that’s obviously a big health economics issue. It’s the same when you look at the treatment of peripheral vascular disease (when a patient has clotted arteries in the leg). To avoid an amputation, we can put in vascular grafts, and I work with Peter Zilla in South Africa who developed a technology 10 years ago to seed those vascular grafts with endothelial cells from the patient. This improved the performance significantly, and he published paper after paper showing the improved patency rate (i.e., freedom from obstruction). He believes that this is the first type of tissue engineering, which I think it really was, and it improved patients’ lives enormously. But it was just too expensive for any hospital to take it up. You had to take the patient in, harvest her endothelial cells, and then grow them in the graft for several weeks. It just wasn’t going to happen.

Examples like these lead me to conclude that health economics presents a very significant immediate barrier to what we’re trying to do. It’s still unclear to me what a successful business model in regenerative medicine is going to look like.