Dr. Ratner: I'm Lloyd Ratner, Professor of Surgery at Columbia University, and I'm the Director of Renal and Pancreatic Transplantation at Columbia University/New York Presbyterian Hospital, in New York City.
Dr. Peters: I'm Tom Peters, Historian for the American Society of Transplant Surgeons. Tell us about your early days: college, medical school, interests?
Dr. Ratner: Yes, I did go to college and medical school. I went to college at State University of New York in Buffalo, where I majored in biology, and I then went on to medical school at Hahnemann University, which is now part of Drexel in Philadelphia.
And during college and medical school I had the opportunity to spend my summers working in the cell biology laboratory of Gunter Blobel, who actually went on to win the Nobel Prize for the work that he was doing while I worked in his lab. So I had an outstanding academic mentor at that point in time. Basically the most important thing I think I learned while working in that lab was there’s no reason to settle for mediocrity.
I then went on to do my residency at Long Island Jewish Medical Center in New York. I initially started out thinking that I would be a general surgeon in practice in the community, and found that I thought I would be bored by that over a 35-year or 40-year career. And Lew Teperman, who was my chief resident, got me interested in transplant. When he finished the residency, he went on to do a fellowship at Pittsburgh.
I was influenced by my chair of surgery, Leslie Wise, who had been trained and had been on the faculty of Washington University, and I did my fellowship at Washington University. I had the opportunity to work in the laboratory of T. Mohanakumar, who ran the tissue typing laboratory and who was a fantastic mentor and a prince of a guy who taught me a number of very important lessons, particularly about science, in terms of knowing how to ask the right questions, not being limited by what you know. He found more people are actually limited by what they know than what they don't know, and that techniques are merely tools, if you ask the right questions and you go to find the tools you need to answer them.
Dr. Peters: Let's talk a little bit about the early attending years. How did you get to Hopkins from your Washington University fellowship?
Dr. Ratner: Right. So when I was getting out of my fellowship, my wife and I decided that we wanted to be closer to family, we wanted to come back to the East Coast. An opportunity opened up at John Hopkins Bayview Medical Center, which is sort of their satellite program which did about 20 kidney transplants a year. I came out of my fellowship to be the program director at Johns Hopkins Bayview and attended on the transplant service a couple of months a year at the Johns Hopkins main hospital.
The great thing about that position was it gave me a fair amount of autonomy to be able to do new things—I didn't realize this at the time, but in actuality that's what happened—so that I could do new things without having a lot of hierarchy telling me I couldn't.
And so I finished my fellowship in December 1990 after spending some extra time in the lab. Went to Johns Hopkins Bayview in January of 1991 and I was trying to establish a lab with my background in immunology and cell biology. I was looking at the chronic effects of acute ischemia on kidneys in a very simple renal artery cross-cramp model. And then a couple of years in, in 1993, I had sort of an epiphanal moment that came out of taking care of a patient.
There was a young woman about 28 years old. She was highly sensitized, and she had been on the waiting list for about 6 years at a time when most people waited about 2 years. And a kidney became available for her that she didn’t have any antibodies against; she was negative cross-match, but it was from a 77-year-old donor. And I quickly calculated that the donor’s creatinine clearance would sort of be sub-optimal for her. And I said to her, “Look, we have this kidney for you; I know you have been waiting a long time. I advise you against it, but if you want it I'm willing to do the transplant.”
She said something to me that really resonated, that I had never really thought about before. She said, “Well, you know, these last 6 years should have been the best years of my life, but they’ve been the worst.” She says, “I could never live with myself if I turn this kidney down not knowing what would have happened.” And I said, okay, we’ll do the transplant. Then I calculated the GFR of the donor was about 70; that's pretty good, but for one kidney it would be 35. If she had some rejection or some ischemia reperfusion injury, she would be down to 30 or 25, and it’s almost an end stage kidney at that point. I said to myself, I wonder if anyone is using the other kidney? No one was, and I wound up doing what was the first dual renal transplant to try and maximize renal function for her.
She left the hospital with a creatinine of 1.8 which we thought was pretty good; she was doing fine. About two weeks later she came back with a bad rejection and we treated it, and then she came back two weeks later with another bad rejection and we treated her with OKT3. And then she came back two weeks after that with a post-transplant lymphoproliferative disease and we had to take the kidneys out.
Mel Williams was the chief of transplant at Hopkins at the time. He liked the idea of the dual renal transplant so much that a few weeks after that, he did a dual renal transplant and unfortunately one of the kidneys thrombosed. And so our first two forays into dual renal transplant weren't successful, but across town Steve Bartlett at the University of Maryland had heard about the dual renal transplant, and they started doing them. And actually Lynt Johnson, who was at the University of Maryland at the time, published the first paper on dual renal transplantation and was nice enough to include me as one of the co-authors on that.
So that really sort of the changed the focus of my career to trying to look at access to transplantation. And so around the same time in 1993, we were interviewing for a new chief of urology at Johns Hopkins Bayview. It was a one-person department, and the person that came and interviewed was someone who I had known from Wash U, Lou Kavoussi. We were fellows at the same time at Wash U, he in urology and me in transplantation. I knew him, and he had worked with Ralph Clayman, who was the first person to do a laparoscopic nephrectomy for disease.
I go off to take my first job as an attending at Johns Hopkins Bayview. Lou Kavoussi comes to interview for the chief of urology, and he says, we have done an animal series of laparoscopic donor nephrectomies; here’s a preprint, and the kidney worked afterwards. And I said, okay when you come here to Baltimore we’ll think about it. And I said, let me watch you do a few nephrectomies for disease, which I did, and I saw that this was doable to do it as a donor nephrectomy. We decided we wanted to get the right donor and recipient pair, and it took us two years to find the right patients for this.
And we went to the animal lab, did a couple of pigs. Interestingly, the director of the IRB was a nephrologist, and his office was across the hall from mine. I saw him in the hall and I say, “Gary, this is what we want to do, do we need an IRB?” And he said, “Well, you’re applying an already used procedure to a different application, and if you’re not doing a formal study, you don't need an IRB. Go ahead and do it.”
So in February of 1995 we did the first laparoscopic donor nephrectomy. The first donor went home on the first post-operative day; he came back a week later and said, “I’d like to go back to work.” We said, “What do you do?” He said, “Well, I'm a welder.” We said, “That sounds like a pretty physical activity; you can't go back yet.” And then the second week, he came back and said, “I don't care what you say, I feel fine. I'm going back to work.” And he went back to work as a welder within two weeks of the donor nephrectomy. His sister was the recipient; she went home on about the fifth post-operative day, which was not unusual in those days, with a creatinine of 0.8. And we said, “Boy, this is great; let's write the paper.” We quickly wrote up the paper and submitted it, and it got promptly rejected. And the critique basically said you would never be able to prove that this will be as safe as an open donor nephrectomy, and the stakes are too high, and basically you shouldn't do this, and we are not going to publish the paper.
I was mad because I thought it was a ridiculous review, and I wrote a nasty letter back to the editor saying that this obviously is going to be a controversial topic. We are not trying to say that it's equivalently safe, but we are trying to say that it's technically feasible, describe the operation, and also to say that it may have benefits in terms of decreased pain, quicker recuperation, and that this might encourage more people to donate. And furthermore, I said if you don't want to make it look like the journal is endorsing this procedure, then write an editorial but don't nix the paper.
So it went from being outright rejected to accepted with zero revisions. And I'm happy to say, although it was basically a case report, at this point in time it's now been cited over a thousand times. So that feels good.
But as we predicted, we started to see the number of people willing to donate increase dramatically. And at the same time, we were writing a bunch of papers showing that it was safe, writing papers about the learning curve, writing papers about the recipient, that the recipient wasn't hurt in any way. So it was a busy and interesting time.
The other thing that fueled the adoption of the laparoscopic donor nephrectomy was that our crosstown rivals, University of Maryland’s team led by Steve Bartlett, picked up on it really quick and also started publishing series. I think that competition actually aided the development of the procedure and the adoption of the procedure.
The next thing that happened was that we saw that as our numbers went up, we started seeing more and more patients that had willing and medically suitable donors but they were either positive cross-match or ABO incompatible. And so what had seemed like a small problem at the time before that now seemed like a much bigger problem, and we decided to sink our teeth into that. Given my background having worked in a tissue typing lab for research at Wash U and my background in immunology, we started looking at all the issues related to desensitization and ABO incompatibility.
Around the same time, we had treated a couple of patients who had antibody-mediated rejection, and we used plasmapheresis to remove antibody, and we had also given high dose IVIg to try and down-regulate the antibody response. And lo and behold, these patients were successfully treated for antibody-mediated rejection. So we said, if that's the worst case scenario, while they’re actively rejecting, why can't we do that up front? And I went to our pheresis people and I said, well what could you do? And the reason they had a finite number of pheresis treatments was because they got too coagulopathic if they did more treatments. So I said, how could we minimize the coagulopathy? And they said that's easy, just space the treatments out to every other day. And then we came up with our protocol to desensitize patients, and it was the first time that we had a pretty near universally successful desensitization protocol. So then, we started the whole desensitization program and expanded it to ABO-incompatible transplants at Hopkins. And by that point, because our program had grown so much at Bayview, the satellite program, we were starting to parasitize the main program at Johns Hopkins Hospital. So the powers that be shut down the Bayview program and moved me and one of my nephrologists over to Johns Hopkins to run the program there.
So we then started doing ABO-incompatible transplants, the program was growing, our desensitization program was growing. And we started thinking about other ways to overcome incompatibilities. There had been a paper written in 1985 by Felix Rapaport who described the idea of a swap to overcome incompatibility. And I said, “Gee, this is a good idea, why don't we do this?” And we went to the legal department at Johns Hopkins and asked them how we accomplish this. Do we get the patients to sign contracts so that no one backs out? And they said, no, you can't contractually obligate someone to donate a kidney, so what you have to do is put them all to sleep at the same time.
And so we did what we thought was the first swap in the United States. There had been some done in South Korea. It turned out, unbeknownst to us at the time, that a group in Boston had beaten us by a few months.
Then we started with the help of MedImmune—this is where industry partnership comes in. They sponsored a number of meetings of what we called the antibody working group, a very informal society, to talk about issues like this in terms of desensitization, and then ultimately swaps to overcome incompatibility, and that's really when the whole thing started to take off. So that sort of launched kidney paired donation.
Dr. Peters: And then the move to Philadelphia.
Dr. Ratner: I moved to Philadelphia; I saw my wife was unhappy in Baltimore. I felt also that there wasn't sufficient room for me to move up in the world at Johns Hopkins. The opportunity came up to move to Thomas Jefferson in Philadelphia, and you know, I didn't understand how much culture means in an institution at the time. I thought I could remake the kind of environment that we had at Johns Hopkins and was ultimately unsuccessful in that. We grew the program, we improved the program quite a bit during my tenure there, but the chair of surgery who had recruited me left and I followed shortly thereafter. After three years in Philadelphia, I went to Columbia University in New York. So my wife was very happy we were back in our hometown with all our family.
New York had sort of been an underperforming area for renal transplantation, and we went there with a five-year business plan to go from 100 kidneys a year to 200 a year. And we hit 200 in year one, we hit 250 in year two, and by year three they told me I was behind budget. I said, how could that possibly be? And they said, well we budgeted for you to do 325 this year. And I said, where did you get that number from? And they said, we made it up. I said, have you given me any of the resources I asked for to get to 200? They said, well no, you obviously didn't need it.
So that's kind of how the administrators think. But we have sort of changed the face of transplantation in New York, built a really strong, solid, vibrant program, and now I'm happy to say that there are about four programs that are doing 200-plus kidneys a year in New York.
Dr. Peters: You mentioned your wife, and you have a daughter.
Dr. Ratner: So we moved to New York. My daughter was going into her junior year of high school, and she was happy to move to New York; she enjoyed being in New York. My wife has been thrilled about being back in New York; she's a New Yorker through and through. And she is actually a nurse who got a job working in a group where she is basically a study monitor for cardiac assist device trials, and she's really enjoyed doing that.
And my daughter continues on at school, and she's interested in statistics and would like to be a bio-statistician at some point.
Dr. Peters: Let’s chat about laparoscopic donor nephrectomy and related safety issues.
Dr. Ratner: One of the things that I think was necessary to demonstrate in the success of laparoscopic donor nephrectomy was to show warts and all, so that people would believe our good data as well as our bad data, and we became very interested early on in patient safety issues. And somewhere around 2004, Amy Friedman and you noted that there were patients dying from hemostatic clips falling off the renal artery. You each had been asked to serve as expert witnesses in lawsuits, and I had also been asked to serve as an expert witness in a lawsuit. So, we decided to look at the issues regarding vascular control in donor nephrectomies.
And we did a survey of the membership of the ASTS with the help of a colleague of mine from Hopkins who was in the school of public health, Dr. Ebony Boulware. And we were able to demonstrate that there were real safety issues regarding the use of non-transfixion techniques in control of the renal vessels.
This is one of the things that I was very proud of, because it was an issue that was flying under the radar, and I think this was also one of the first times in the surgical literature that looked at near misses as well as the actual events. We were able to show this association that the non-transfixion techniques in control of the renal vessels were unsafe, and it ultimately resulted in both the FDA and the manufacturer of the hemostatic clips issuing a contraindication for their use.
The sad part of the story is that people continued to use the clips after the publication and after the contraindication; a number of living kidney donors both in the United States and also internationally have died as a consequence of that. We have spent a lot of effort, particularly Amy and Tom, trying to make the rest of the world aware of this problem. And we got European colleagues involved in this. I think that's been very gratifying, too, because when I was a fellow at Washington University we actually had a living donor death from a pulmonary embolism, and I can remember the anguish that it caused both the patient and the families, and the center, and the program itself. No one should ever have to experience that, and the safety of living donors should always be paramount.
Dr. Peters: Your years with the ASTS.
Dr. Ratner: My mentor for the ASTS was Avi Shaked, who encouraged me to get on the Council. Fortunately, I was put on the slate and won the election; six people were on the slate, three people were elected. It was the first year that there was a competitive election for Council. And then when I was finishing the Council, I decided I was enjoying this and I was getting things done. The treasurer position was open, and I was nominated. And it was the first year that there was a competitive election for the treasurer position as well, and I won that.
So I think I'm the first person who's won two competitive elections that will then ascend to the presidency of the ASTS. I really enjoyed the work with the ASTS, and I'm looking forward to a few more good years before I become a dead president.
Dr. Peters: And twenty million dollars?
Dr. Ratner: The goal was set in, I guess, 2004 to get to 20 million dollars by 2020. And I'm happy to say that we hit it while I was treasurer, although I didn't have that much to do with it, in 2017. Now we are starting to take a 360-degree look at how we invest the money, how we spend the money, and re-plan now that we've hit that 20 million dollar goal. So I'm looking forward to that process because I think that will add a lot of legs in terms of the legacy of my own tenure in the Society and also for the Society itself.
Dr. Peters: Is the 20 million viewed kind of like an endowment?
Dr. Ratner: The idea was a fear that since the ASTS was living primarily off pharma support, that pharma support was decreasing and would eventually go away, and that the ASTS needed to have an endowment to spin off about a million dollars a year to pay for operating expenses.
The world has changed since 2004 when that goal was set. So number one, pharma support hasn't gone away; it's reduced, but we've also developed other revenue streams. But we've also increased our activity, so a million dollars isn't really enough to run the whole shebang now.
Dr. Peters: A million dollars isn't a million dollars anymore.
Dr. Ratner: That's very true. [Laughs] Yeah, that's very true.
So anyway we are relooking at our targets. In talks with financial analysts, they said that if a not-for-profit gets to about 25 million, that puts them in a whole different league in terms of what kind of investments they could do, what kind of strategies they could have. So we're starting to think about that now, and hopefully in the next 6 months or so we will have a little bit more of a concrete plan on how to move forward.
Dr. Peters: Look a little bit into the future; you're the inventor guy.
Dr. Ratner: I think when we look in the past, the obstacles to transplantation, to getting people successfully transplanted, were very different. In the early days it was immunology, immunology, immunology. Now there are things like process, policy, organizational infrastructure, finances, as well as immunology.
So I think that the Society is expanding, and what I would like to see it do is expand the scope of training opportunities and professional development throughout the whole course of a surgical career to meet demands that we now face that weren't that relevant previously.
And I think ultimately someday, but I don't think in my professional lifetime, we will see bio-engineering, and maybe bio-engineered xeno-transplantation, and who knows what great things. But I think that as we develop those biological approaches, we're going to also be opening up a whole new Pandora's box of other challenges. But I think right now we need to work on the organizational policy and financial aspects of both training and clinical care.