COMMENTARY

Face Transplant Doc: Challenges in Repairing Destroyed Faces

Arthur L. Caplan, PhD; Eduardo D. Rodriguez, MD, DDS

Disclosures

March 07, 2014

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A Winding Road to Wounded Warriors

Arthur L. Caplan, PhD: Welcome to Close-Up With Art Caplan. I am privileged today to have a guest whom I think you are going to find exciting; informative; and in some ways, probably amazing in terms of the cutting-edge work that he is doing.

Dr. Eduardo Rodriguez is at New York University (NYU). He recently came here from the University of Maryland and Johns Hopkins University. He is one of the world leaders in face transplantation, and I asked him to join us to talk today about some of the ethical, social, and medical issues involved with face transplants. Thank you very much for coming.

Eduardo D. Rodriguez, MD, DDS: Thank you very much for the invitation, Dr. Caplan.

Dr. Caplan: Let's jump to the medical part first. Many people are wondering how you became interested or made the move into a field such as face transplantation. What background brought you to this? Why did you decide to get into this particular cutting-edge area?

Dr. Rodriguez: It was a combination of events, starting with my education and training. I began as a dentist and continued my training and education in oral and maxillofacial surgery. At that point, I proceeded into medical school and general surgery.

Dr. Caplan: So you are one of those "MD, DDS" guys?

Dr. Rodriguez: Yes. As I pursued my training to try to solve a clinical problem, I figured out that there were some issues that we couldn't solve with conventional medicine or surgery.

If we fast-forward the clock to 2003-2004, I began to work as an adjunct faculty member, doing my clinical work. At that time, we were also faced with the wars in Iraq and Afghanistan, so I was asked to assist in the treatment of soldiers at Walter Reed Medical Center and National Naval Medical Center in Bethesda. And we were faced with significant problems.

At around that same time, I was asked to participate in a research project, which was funded by the Office of Naval Research, for management of the wounded warrior. Putting all of those elements together, it was only practical that the next logical step was to pursue research in facial transplantation with human subjects for care of the wounded veteran.

30 Successful Face Transplants

Dr. Caplan: When I first heard about face transplantation being considered in the early 2000s, something that concerned me from an ethics point of view was that there didn't seem to be a lot of animal research going on with face transplants. Do you use many of the same techniques that you learned in reconstructive surgery? Are these techniques just being applied more fully with a face transplant? Did the field sort of evolve with a good scientific foundation?

Dr. Rodriguez: That's a great question. The first transplant was done in 2005 by the group in Amiens and Lyon, and before that, there was no research. The only group that was performing animal research was at the Cleveland Clinic. That was a small animal model (a rodent), and we decided to move forward with a larger animal and thought that it would be important to be able to translate that information to human subjects. And sure enough, we worked on the basic foundation of research for approximately 10 years before we went ahead with the clinical transplant.

That was pivotal, and we found some important things from a scientific standpoint that could be translated to human clinical trials. But of course, the technical components were modifications of advanced or conventional surgery.

Dr. Caplan: I don't want to alienate our more surgically oriented audience, although I know that a lot of folks out there are wondering about the obvious emotional and psychological issues. We will come to those in a second.

I do want to ask, for those interested in the technical side, what are the biggest challenges in doing face transplants? What is most difficult as opposed to trying to do a reconstruction of an injury of the face, for example? Are there difficulties in trying to get nerves to function again, trying to get the eyes to function? What is the most challenging?

Dr. Rodriguez: One of the biggest challenges is functional return. The first transplant was performed in 2005. To date, we are up to 30 transplants. The difficult part is in the recipient; you have to remove all of the elements that have defined this person post-injury, so you actually have to recreate the defect. That is a big challenge. You want to get to healthy, virgin tissue.

The second thing is the procurement of the facial allograft from the donor. You want to ensure that you are taking all the elements that will restore normalcy. Once you procure the face, it is preserved in a cold solution for about 3 hours. We don't know the determinants of longevity in solution and whether that is going to work when we transplant the face.

So, functional return has been a big issue. Are our patients going to animate normally? Are they going to speak normally? The return of function from a nerve standpoint is questionable.

What we have seen so far in about 30 patients is that this has yet to be a problem.

Patients Want to Eat and Speak

Dr. Caplan: What brings patients to you? Do they say it is appearance, 'breathing, emotional signaling, socialization? What do they say makes them even consider a face transplant?

Dr. Rodriguez: That's a great question. It is a combination of factors. You would think that the obvious factor would be appearance, but for most of them, the most important factor is function. There is no question about it; specifically, the issues are with speech and eating. Those are the biggest factors.

Without getting into specifics of vision or eyelids, a big problem is, how can they interact socially? Of course, when people look at them, there are a lot of curious individuals who ask questions, such as how did this happen? These people try to avoid social contact. They conceal themselves in their homes. They avoid social interaction. They don't have employment.

So, it is a combination of functional and social concerns. They want to become members of society, and the last component -- an important one -- is their appearance.

Dr. Caplan: Let me ask this a slightly different way. When someone has been severely injured, is a face transplant a kind of suicide prevention technique?

Dr. Rodriguez: You might think that is the case; we do see patients who have self-inflicted wounds -- there is no question about that. When we look at the central facial injury -- which is what we focused on, because it was a similar type of injury to what the wounded veterans experienced as a result of improvised explosive device blasts -- we felt that this would be a good target of patients to try to reconstruct. But they would have to prove to us or confirm that they were psychologically stable, and there is a very rigorous psychological or psychiatric evaluation and assessment before we move forward. We would not consider most of these individuals to have suicidal ideation concerns.

Dr. Caplan: When somebody suffers a horrendous facial injury beyond what reconstruction can handle, are they more likely to want to end their lives? Put another way, do you think face transplant is in part a technique of suicide prevention?

Dr. Rodriguez: I hadn't thought about it that way before. When you have an individual -- for example, a serviceman or servicewoman -- who has an injury that is facially disfiguring, those individuals are definitely more prone to suicide. But the individuals who attempt some form of self-inflicted injury don't actually proceed to suicide. It is quite unusual, and no one has really studied it.

Dr. Caplan: Interesting. It is counterintuitive. The reason I asked you about suicide prevention is that one of the ethical issues that came up in the early days of face transplant (not that it is so old), in thinking about whether it was ethical to try it, was that the patient would have to take immunosuppression. We don't know how long the transplanted face is going to work, so some people questioned the risk/benefit ratio of putting people on immunosuppression -- saying that it is one thing to give them a heart or a liver and save their lives and deal with the risks of the drugs, but is it worth it if you are repairing their appearance? You mentioned that function is restored, but maybe saving a life might be part of the rationale for taking that risk?

Dr. Rodriguez: Of course.

Dr. Caplan: How bad is the immunosuppressive challenge?

Dr. Rodriguez: It is the same as for solid-organ transplant patients. The quality of the medications has improved dramatically since the inception of solid-organ transplantation. We are finding that the number of medications that they have to take is not as high as previously. When patients enroll in these trials, the number of medications within the first 6 months is quite extensive, and then the number starts tapering down, because at the beginning, the patient is in immune suppression. We use a very strong lymphodepleting agent in the operating room; we have to protect these patients from developing any kind of bacterial or viral infections, so we add several medications just for that protection.

Dr. Caplan: You are always in that balance of rejection vs infection.

Dr. Rodriguez: It is a very tough balance at the beginning, but once we pass those first 6 months, it may come down to 1-3 medications daily. So it's not as demanding, but the patient must take that medication every day.

Donor Procurement: Can You Cross Genders?

Dr. Caplan: Let me jump into the donor side for a second. I think people are fascinated with this. When someone needs a face, where do you turn? Where do you look for a potential donor? How do you identify someone and say, that might be a donor for us?

Dr. Rodriguez: There are a couple of criteria that we look at, and we partner very closely with the Organ Donor Network. It is an organized system of organ procurement, and every state has one. There is a universal governing body, which is labeled UNOS (the United Network for Organ Sharing). We partner with our state institutions and organizations, and they help us define the types of patients.

There are specific things that we look for. We look for blood-type match; antibody match; and also specific characteristics that relate to the face, such as skin-color match and skeletal morphometry.

Dr. Caplan: Would you cross gender?

Dr. Rodriguez: I would, and that is one of the interesting questions that we are looking at now. When we look at the pool of patients available as matches for a specific patient, that pool is very small. If you look at Richard Norris, for example, our patient from Maryland -- he had about a 14% chance of a match, looking at the statistics of patients in the state of Maryland. One of the ways we thought of to broaden that donor pool was to go to female donors -- and sure enough, when we looked at female donors, we were able to increase the donor pool.

Dr. Caplan: Let me stop there for a second. Either men or women might wind up brain-dead and on life support. That is the place where I am going to be a facial donor. Are you going to talk to my family? Is the organ procurement organization going to talk to my family? Do they care whether I have signed a donor card?

Dr. Rodriguez: That is another great question. Surgeons are not allowed to communicate with families, and it is probably the right way to perform this mechanism. Surgeons do not communicate with a family in a time of great need. The organ procurement organization is responsible for that communication, and they broker that relationship.

There are specific occasions when the families do wish to talk to a surgeon. Those are limited instances with respect to consent of organs. I feel that it is very important to our regulatory process for us to separate facial donation from solid-organ donation.

Dr. Caplan: Is that because of the emotional significance? There are not a lot of poems written about people's pancreases, but faces seem to have a different status.

Dr. Rodriguez: Families should be aware in this tremendous time of need and difficulty that we would like to procure the face, and they should understand and be willing to make that informed decision.

Dr. Caplan: So you almost set up an extra hurdle.

Dr. Rodriguez: Exactly.

Dr. Caplan: We want to hear that they are okay with this, even if they were okay with donating a kidney. When a face transplant happens, some donor families are going to want to be in contact with the recipients, and the recipient's family. Historically, we haven't allowed that for various reasons. There are worries about too much intrusion emotionally, and issues come up about whether they are going to try and get compensation under the table. Should they be in contact? Do they ask about being in contact?

Can the Donor's Face Be Recognized?

Dr. Rodriguez: That is a very common question, and rightfully so. In looking at the scientific publications that we have seen, on the basis of cadaver work, there are some resemblances between the donor and the recipient patient, but they are subtle resemblances. You can't say that you are going to see your loved one walking down the street. There is no question that there are subtleties, such as nasal appearance, or lips, depending on the tissues that are transplanted.

Dr. Caplan: Do you think a family could recognize that face?

Dr. Rodriguez: I don't think so, but I would not want to argue with a loved one -- and in our situation with our patient in Maryland, the mother, who had an opportunity to meet the recipient, did say that he looked like her son.

Dr. Caplan: Interesting.

Dr. Rodriguez: I am not going to get involved in that dilemma, but certainly there are some subtleties, especially if the recipient and donor had resemblances before the injury. There is no question about it. But that is a difficult question to ascertain. The donors sometimes do want to meet the recipients. The recipients sometimes want to thank the donors; how do we accommodate that?

Dr. Caplan: Historically, in the solid-organ world, we try to preserve anonymity, partly out of fear of intrusion into the person's life, partly for fear that some might look for reward or payment or compensation down the road. In this area, with the face being so visible, it seems even harder to say that we are going to keep things anonymous, particularly given all the publicity that currently surrounds it. They are going to see a face transplant on TV and know who the recipient is, most likely.

Dr. Rodriguez: Of course. And that is a great point that you bring up, with the publicity and media coverage. It is appropriate that we notify the families that this will be occurring. We cannot communicate directly with the families, but the organ procurement organizations communicate with the donor families that this is happening.

Dr. Caplan: So they are brokering again.

Dr. Rodriguez: Yes.

What Does a Face Transplant Cost?

Dr. Caplan: Speaking of brokering, before I get into some of the recipient issues, what does this cost and how is it going to be paid for? To be blunt, do we have a good future here? I know it is expensive.

Dr. Rodriguez: We look at the history of solid-organ transplantation, and we focus specifically on liver transplantation -- which is somewhat of a similar dilemma, where a large number of patients undergo liver transplantation for either self-created disease or an organic disease process. Face transplant is very similar. At the beginning of liver transplantation, many of those patients were not able to survive the operation.

Dr. Caplan: There were dozens of deaths in the early days.

Dr. Rodriguez: Exactly. If we had talked to the pioneers at that time, they would have said that they did not feel that it was going to move forward, but sure enough today, large numbers of liver transplants are being performed.

Dr. Caplan: They probably cost a quarter of a million dollars and up. They are not cheap.

Dr. Rodriguez: Exactly. We compared prices, and we looked at the budget at Maryland. Now that we are creating a business proposal here at NYU, what we have come up with is roughly half a million dollars. That does not include the surgery itself, because it is experimental. It includes prescreening, all of the elements before the operation, the entire surgical procedure, and the hospital care -- and also, since we are at the beginning of this new field, we are including essentially 3 months of hospital stay, just to be safe.

Dr. Caplan: One of the toughest issues is payment. How do you negotiate with such payers as the Department of Defense or insurance companies? What convinces them? What can you tell them that would make them say, "This works; we are going to cover that"?

Dr. Rodriguez: The Department of Defense has played a large role, and they have been incredibly generous in contributing to this innovative field, but their goal is to ultimately translate this into some form of standard of care and transition out from research. From our protocols, the way we have defined it, with 3 months of initial care (which is a good amount of care), we ensure that every patient who is enrolled in our regulatory process has some form of third-party support and that the third-party payer will contribute to the medical care.

Dr. Caplan: When thinking about access, let's move over to the recipients. Sadly, there are many different types of individuals who suffer horrendous facial injuries, probably beyond anything that can be satisfactorily reconstructed, so to speak. How do you pick? How you decide? You have people who have tried to injure themselves; you have people who have been in accidents. I have seen people get transplants who have been mauled by animals, and people who have been assaulted by a domestic partner. There is the issue of children vs adults. How do you decide who is going to get this?

Dr. Rodriguez: It is a pretty interesting process. Initially, patients come to me or our surgical team with a deformity, and we evaluate them. We try to define at least an anatomical deformity that cannot be satisfactorily reconstructed.

Once we feel that the patient has a deformity that cannot be reconstructed, then we proceed and we enlist them in the consent process. At that point, they get evaluated very closely by a participant selection committee, which is made up of psychiatrists, clinical psychologists, social workers, transplant surgeons, and immunologists -- a whole slew of medical professionals and ancillary personnel who will be involved in deciding whether this individual is a good candidate. It has to be objective enough beyond my control.

Dr. Caplan: Can I be considered if I am a smoker?

Dr. Rodriguez: We will evaluate you, but one of the recommendations from our standpoint is that you have to cease smoking before you are enlisted in this protocol, and we check nicotine levels.

Are Face Transplants for Children Viable?

Dr. Caplan: How about children vs adults? Does growth pose a challenge?

Dr. Rodriguez: Growth is a challenge, and it is a great question. We are beginning to consider attempts at evaluating children. It is a big process. It relates to informed consent; someone like you can help us address that question.

Dr. Caplan: The child is going to be going through quite a run, and we don't know how long the transplant is going to last.

Dr. Rodriguez: Correct. And now you put the informed consent process on the family, but you also have to look at the potential psychological dilemma of children living with severe disfigurement until they reach an age at which they can make an informed decision. But we haven't really touched on that yet.

Dr. Caplan: Has anybody? Is this something that the field is talking about?

Dr. Rodriguez: The field is definitely talking about it, and there are specific children's centers; NYU is one of them, because we have been dealing with craniofacial deformities for such a long time.

Dr. Caplan: NYU has a long history of dealing with that.

Dr. Rodriguez: Families are beginning to talk to us about this. How does it work? What are the medications? What is the longevity? It is something that at some point we will have to tackle, but for right now we are being careful.

Dr. Caplan: Whether it is a child or an adult, do you think that we are good at providing the kind of emotional follow-up to families of people who receive transplants? They clearly are going to be participants in this kind of current experiment or innovative surgery. Is that an area that you worry about?

Dr. Rodriguez: Very much so, and more so with facial transplantation than I would with solid organs, because we are not just looking at function, but also at psychosocial adaptation. We are looking at cultural integration. There are so many factors involved.

Dr. Caplan: Do you find different cultures being more wary or less wary?

Dr. Rodriguez: You see it within the family dynamics. Everyone is a little different in how they look at this deformity. One of the benefits here at our new location in New York is that we have a comprehensive center, and probably the biggest aspect is that we all think that the surgical part -- the technical part -- is challenging. But once we get past that, everything else is psychosocial involvement, assessment, and integration into society. These patients are going to be ours for life, to ensure that they don't encounter any major hurdles; we don't know when that will come about, but we are getting better at assessing that.

What if the Donor Face Is Rejected?

Dr. Caplan: Something that I worry about with face transplants is, what if things go wrong? What if there is acute rejection? What if there is, even worse, chronic rejection?

Dr. Rodriguez: What we have seen so far in the historical experience is that all patients who undergo facial transplantation do have acute rejection episodes. Now, we can treat rejection. Rejection is treated with medication, and we supplement that and that has not been a problem.

Chronic rejection is a bigger problem, and to date, there is one patient in the Amiens/Lyon group who is chronically rejecting the face. The face does not completely fall off. It is a slow resolution, loss of function, a scarring process, and fibrosis -- not an immediate process. But what is interesting with that patient is that he does not want to give up the face. They are considering removing the face and relisting him, but he does not want to give up his face.

Dr. Caplan: Is that technically possible?

Dr. Rodriguez: It is technically possible, and if that were to be considered he would be the first patient who would undergo a reprocurement of a second face.

Dr. Caplan: That is fascinating.

Dr. Rodriguez: But that patient does not want to give up the face. So chronic rejection is a big problem, and we don't know how we are going to handle it. That is probably the thing that keeps me up the most at night. What will we do if this presents itself? And now we have a patient who has been exposed to greater numbers of antibodies, making it more difficult to find a match; every time we introduce foreign antibodies into a patient, we are reducing the potential matches with another patient.

Dr. Caplan: Thank you for this interview. I feel that the procedure is in great hands, given your thoughtfulness and willingness to put up with questions from the likes of me and others who worry about the ethical and social side. I know that you are really thoughtful in trying to pay attention to the entire spectrum of issues. That speaks well to where this might go, so thank you for being with me today.

I am Art Caplan. Thanks for watching.

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