Celebrating 100 Years of Innovation: Maria Siemionow, MD, PhD

Podcast Transcript

Will Morris, MD:

Hello, this is Will Morris Executive Medical Director of Cleveland Clinic Innovations, and welcome to another Health Amplified, a Cleveland Clinic podcast. Today we have a phenomenal guest. In celebration of our 100th year and our Centennial, we wanted to look back at those key events in our history that really establish the synergy of research, cutting edge policy and changes in the way we view patient care. And three is surgical technique in innovations around that. And so it's absolute honor to have Dr. Maria Siemionow. She is currently the Professor of Orthopedics and Director of Microsurgery Research at University of Illinois, Chicago. She is famously known for performing the first, with a team allograph near-total face transplant in 2008. What you won't know or might not know is the years of work, the years of research in the IRB, that was the first in the world to go ahead and approve this groundbreaking surgical technique. And we'd love to kind of explore that. And so Dr Siemionow, it's an absolute pleasure to have you here.

Maria Siemionow, MD:

Well, thank you very much for the invitation. And also it's an honor to be a part of the Centennial Celebration. I'm very happy that I will be able to share the years of preparation to the first face transplantation performed in the United States. And at that time, the... I would say the largest face transplantation and the years which were of course counted, I always compare it to the fact that the surgery was taking over 20 hours, but the preparation was taking over 20 years. And by preparation to the surgery, I mean, different experimental work performed in the laboratory. And there was also a lot of logistics in preparing the team, but most important as you have mentioned was achieving and getting approval from the Institutional Review Board, IRB, at Cleveland Clinic. And that took a long time.

Will Morris, MD:

And so, for those in the audience, can you explain a little bit about the function of the IRB and how did you navigate this? Because being a world's first and an innovator requires risk, trust and the ability to kind of articulate that vision. So take us back to before 2004, when you got the approval, what did that take?

Maria Siemionow, MD:

Well, although it took one year to get that approval, however, the protocol which I submitted... first protocol which I submitted to IRB was about 20 pages long, and the final one was 120 pages long. So you can imagine that this 100 pages extra were just related to the answers to the IRB committee. The IRB is the committee of both experts in the medical field. So like a transplant surgeons, reconstructive surgeons, but also physicians, general medicine specialist, kidney transplant experts, and also lay people and just from the streets, I would say, who can ask the question, lawyers. So, it was pretty challenging for the first time to send in front of IRB committee and I was alone and the room was full of people who were asking you are going to do what. And, yeah, face transplant was really unheard of at that time.

Maria Siemionow, MD:

And this was really amazing to see how the IRB committee got involved and understood over the time when we have a meeting almost every month for a year. When I was explaining and responding to all questions which were asked for, about, well, this technically how does it relate to the identity of the patients, identity of the donor?

Maria Siemionow, MD:

And whenever they asked the question, I was coming already with the response, which was coming from experimental work performed in my laboratory in Cleveland Clinic, or we have even done additional other studies in anatomy lab to show that the identity of the patients will not change after receiving a face transplant from another donor. There was a lot of discussion with, I think some people were afraid that when you will actually donate your organs, people will take your faces. So, that there was a lot debate also in the media and outside of our institution where some of the ethics expert was saying, Oh, you help people will be tearing their driver's license. They will be not donating organs. So it was challenging, but I think very rewarding because I was patiently responding to all questions asked by IRB.

Will Morris, MD:

Yeah, I think that's, and I reflect while you were commenting, I think with the pandemic and the vaccination, the speed in which we actually now have an effective vaccination, I think there is a general misunderstanding that the development of an mRNA vaccine took seven months, and what you don't see is the years, the decades of dedication, research, bench top work, surgical techniques, logistics, and it seems, and I love how you articulated a 20 hour surgery which is monumental as a humble internist, but the 20 years that you don't see that went in is absolutely inspired.

Maria Siemionow, MD:

Sure. And I would say that of course, that this is always a team effort. I have to mention that it was very important to get support of Cleveland Clinic leadership as well as Department of Plastic Surgery, leadership with Frank Papacy being the major promoter of this procedure. So at the very end, when I actually went through all these steps and answer all the questions at one of the last meeting, I said, Frank, you have to go with me just to stand with, and that's what's happened. And I think what was perceived by IRB was that I was not offended by any of the questions and some of them could be offending, I would say, but he was trying to understand where the people are coming from, because now not everybody was what was the expert in surgery or medicine. And I think that was very appreciated.

Will Morris, MD:

Yeah, and I think the public and the scientific community as a whole benefited by your diligence, your patience, and, you're detail oriented because it... and again I don't know if this was occupying your mind, but this surgery wasn't necessarily just about that specific surgery, but really is the Keystone to future, you know, either face transplants or other advances in the space. And so did you feel that kind of pressure? Did you kind of comprehend that?-

Maria Siemionow, MD:

I think it's that became another surgery, but philosophy and ethical issue. And I have to also just to share with you that before IRB approval, I have published with my team over 60 peer review publications, not only in surgical journals, but also in ethics and psychology journals. So I think that that was very important to share with the public, to prompt the public something is coming. It's not like the Arctic freezing conditions we are getting one day unexpected as it is happening right now in Chicago. But this was more like they are talking about face transplant, they're doing it in the lab, oh, they are presenting it at the conference, aha they are now telling us that actually ethics is starting to approve it.

Maria Siemionow, MD:

So that was this all preparatory work, which was involved even before I went to IRB with defense protocol, written protocol. And by collaborating and discussing with different faculty members and team members in Cleveland Clinic, but also with friends and colleagues outside of the institution during the national and international meetings, I could see that there is a lot of support and approval for something like a next step, something should happen. That was never done before, but it's feasible because the solid organ transplantation of course has a very long history. So why not to come to the new fields of what is now known as a Vascularized composite allotransplantation.

Will Morris, MD:

And, how do you feel that the attention and certainly the media followed this intensely because of the complexity, both the surgical technique, the management of the patient with a complex immunotherapy afterwards, but then also the policy, how has that played with the importance of just organ donation as a whole? Were there conversations with Life bank and others to kind of figure out how can this also push the dialogue of the importance of people being organ donors?

Maria Siemionow, MD:

Well, that's a very good question. That was a challenge, I would say. Just for the historical record, we received the IRB in 2004, but it took again another year before the Organ Procurement Organizations approved face transplantation as a potential organ. And technically, it was not only talking to Life bank in Cleveland, but also I will say taking a couple of trips outside of the region and actually going with Dr. John Funk, driving to Pittsburgh to another organ procurement organization to present them the case, and even the patient, in terms of sort of PowerPoint presentation what we are going to do. Also to Michigan, and this was very challenging because everybody was kind of looking into that they were discussing, they were looking how it will affect their donor pool. They will present it to the potential donors of families of the loved ones. We just... it takes brevity of someone who will accept that the... after passing of their loved ones, they would still agree to face transplantation.

Will Morris, MD:

Yeah. And then fast forward with just the groundbreaking journal work with National Geographic and their chronicling Katie's story and journey, how has that kind of continued to shape the field and create awareness and conversations?

Maria Siemionow, MD:

Sure. I think the important part of the being able to show the... I would say late public with all respect, that they are just normal people who at one point in life being very young, they turned a life from being great to life being miserable. And this National Geographic of course, piece was I think very well respected by international of course in Cleveland Clinic as well. And to present that you can accomplish something, that you have family involved, that you have a team involved, that the patients are not alone. If you lose something in your life so important as your face, or maybe just your kidney. You have the team of physicians who are always behind you. And for me, the most important is just to share that as any other patient, of course, you almost remember probably most of your patients, but transplantation are for life.

Maria Siemionow, MD:

That as long as they are alive, they... you see them. You see them for the follow up. And, as a hand surgeon, I will say, when you have a little fingertip injury and you fix it, and in a week the patient is coming and it's healed, then you don't see the patient, okay. The patient is fixed, but when it comes to transplantation field and face transplantation specifically, which is a very novel procedure for the field, then you see the patient as conical. She was first of course for several months in Cleveland Clinic. But also then she was coming to every couple of weeks, then every couple of months, then every half a year and then at least several times per year, just for the follow-up visit.

Maria Siemionow, MD:

And we are always on the phone and her daughter, Alicia, and sometimes was texting the picture, "Oh, my mom has some redness on the face, is it the rejection?" Then I would say, well, not sure just recurring. So it's emotionally engaging care. And, it's very important that the audience will understand that we are not just doing something for being famous or just doing it fast, but it's changing the humanity.

Will Morris, MD:

Yeah. So, fast forward to, now tell us a little bit about your work. What gets you excited? What are the breakthroughs? The next breakthroughs that you're working on that you feel can again, contribute to the amazing impact in this field?

Maria Siemionow, MD:

Sure. So, just now at University of Illinois, I also opened program for Penn Transplantation, just to mention about face transplant program, I think it's fair to emphasize that the two face transplant patients out of three performed in Cleveland Clinic were supported by my Department of Defense Grant of the Forest Institute for Regenerative Medicine. So it would not be possible without the financial support from DOD of several million dollars. That's when the question comes about the future. So where we will have money to support and finance the expensive procedures of transplantation such as face which are still not considered standard of care. So which Standard of care like a kidney transplant you can consider and have a support from insurance companies but we are fighting. That's the next step we are fighting now for just approval of the face transplantation, the hand transplantation as a standard of care.

Maria Siemionow, MD:

So insurance companies wouldn't be supporting that. This brings us to Chicago or where I opened the Hand Transplant Program. I opened one also in Cleveland Clinic at that time. So, hopefully you will perform at some point another innovative surgery, but I think the future of this new field of Vascularized composite allotransplantation, including face transplantation and hand transplantation and abdominal wall transplant and even Penile transplant.

Maria Siemionow, MD:

All these new organs, I would say the future I think we'll be the regenerative medicine. And a lot of work done in my lab right now is towards creating the combination of the scaffold, which are based on, for example, Seychelles scaffold, which will be covered with the stem cells, which will be kind of a growing organs. That's one of the options. And the second one I think the more important in terms of future of the entire field of transplantation, is the work which I started in Cleveland Clinic and then continue here at the university of Illinois at Chicago is all in tolerance inducing strategies in transplantation. And you may be interested as general medicine, especially is that we are performing a fusion between the cells of the donor and recipient coming from Bone-Marrow.

Maria Siemionow, MD:

And we are creating a chimera chimeric cells with Jack Donald recipient chimeric cells and are supporting transplantation of the experimental lab of let's say face with the cells will represent donor and recipient. And we are getting tolerance, which is very important for the solid organ transplantation, but also just to not be bored. I brought this chimeric cell therapy towards the field of muscular dystrophy specifically for Chengdu muscular dystrophy. And we are creating now dystrophy in expressing chimeric cells for application in Chengdu and talking about innovation. So we have Spinoff company based of the license and here at UIC for this chimeric cells audition. And this is actually in preclinical stage. We have talked already to FDA, we're talking to EMA the European Medicine Agency, and we are preparing certain human chimeric cells. So which will be representing the father, who is a normal donor and the father... biopsy of the father muscle, they will be giving us the Bio glass from the donor and then from the recipient and the chimera we'll be bringing to the shared patients, the regenerative medicine potential.

Will Morris, MD:

That is beyond exciting. I mean, what I love hearing this and, we are up on time, but I think it actually is a perfect culmination of... you exude intellectual curiosity in passion and advocacy for impacting a patient's life, whether be a face, whether be a hand, Cheyenne's muscular dystrophy, but I love, it's all based on hardcore science, relentless work, unbelievable hours I'm sure in the lab researching at seminars, working with colleagues. And I think that to me is the ethos of the 100 year celebration is, it's a celebration of our sheer intellectual curiosity, ability to convene others and relentlessly pursue avenues even when they shut down. And it just sounds like this is not ended and I want to come back maybe in a year or so, and hear about the chimeric cells, because I think that is absolutely phenomenal and fascinating and just such a fascinating output. Someone who is so renowned in microsurgery and research.

Maria Siemionow, MD:

Well, thank you very much. I would just say at the end that there are certain places when you can achieve success, and Cleveland Clinic definitely promoting science, research and innovation was the place that this was possible. I'm not sure if it will be possible in some other places. So, at this Centennial, I think that's also support of the Cleveland Clinic as an institution and a major difference.

Will Morris, MD:

Well, we wish you all the best at the University of Illinois, Chicago, but you can consider yourself... you're always family back here in Cleveland. We're a little bit warmer too than Chicago right now. So I'm just saying that. But thank you, Dr. [crosstalk 00:24:58] yeah. Thank you so much Dr. Siemionow for this time, your impact on and in the lives of many, your leadership, your passion, your vision, and we're excited to read the next chapter. Thank you so much. This is Will Morris with a Health Amplified, a Cleveland Clinic podcast.