The International Front

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.