Leading Cardiothoracic and Vascular Surgeon in AIIMS New Delhi, Doctor devgaurau velayoudamtalk to , Padma Rao Sundarji For The Times of Online, on the recent pig-to-human heart transplantation in the United States, and on the future of xenotransplantation in India.
Q: Earlier this month, doctors at a US hospital transplanted a pig’s heart into a human for the first time in history. Opinion is divided between biotechnologists and surgeons. Some are apprehensive, others excited. How are you?
A: I see it both ways. On the one hand, this is a real milestone in science. There is always a shortage of human organs. So, this achievement by the Maryland medical team is a major breakthrough in terms of science and what it can accomplish. His process began with genetic engineering. He genetically modified a pig. In simple words, they had to deal with ten genes in the pig. They removed four, modified one to stop the pig’s heart from growing, and added six genes. They did this to reduce human reactions and prevent pig hearts from growing after transplantation. The only doubt that prevails is the fact that since this is just a beginning, there is no certainty. Even in a human-to-human heart transplant, which should ideally be accepted by the recipient’s body, an immune response can occur. Over time there can be either extreme rejection, or chronic rejection. So even for such transfers, we need immunosuppression. Only in the long run will we know how the American transplant is working, how the patient has taken to pig hearts, whether doctors will be able to deal with immunosuppression in his case, and so on.
Q: It’s been almost two weeks since the transplant and the patient is still alive, so what qualifies as ‘long term’ for you?
A: In case of implants, we consider the terms of existence of one year, five years or ten years. The ten-year survival rate is currently touching 90%. So we should be targeting that figure in the long term, even a . also for pig heart transplant, This means that currently, 90 out of 100 people who receive a human heart transplant live at least ten years. In the case of the US patient, we would like to see and wait for at least a year. Even if he lives that long, it will be a big milestone. Then, we would be able to assess how similar or different this was for human-to-human transplants, which immunosuppressants to use and in what doses, how they work, etc. Many of these questions will be answered over time.
Q: Are other pig organs also considered suitable for xenotransplantation?
a. The main advantage of using pigs is that they become adults within a short period of time. Also, the heart of a pig is like the heart of a human. A pig kidney has been transplanted to a human before, but since it was done on a patient who was brain dead, it was an experiment to see if it worked. And it did.
Q: Do you envisage animal organ transplantation, or xenotransplantation, anytime in India?
A: Look, there is a tremendous cost involved for R&D, because there is genetic engineering involved. America has been fortunate to have both public and private funding. Of course, in India also we have the Department of Biotechnology (DBT) and other sources, which help us in research in genetic engineering. DBT also has collaborations with the United States. They allow fellowships, researchers, and all kinds of other exchanges in this area of genetic engineering. With time things can get better.
Question: What is the situation in India as far as the availability of human organs is concerned? Is this very important, or is it improving?
A: Human organ donation is much more rare in India than anywhere else in the world. According to global data, India’s position may be better than some other countries, but human organ donation is not as high as it is in Spain. Even within India, donations vary between northern and southern India. Perhaps because of the level of awareness there, most donations take place in the South, while in the North, there is still a divide. Maybe we have to transcend the urgency and push for greater awareness here in the answer as well. Because all that said and done, we are still decades away from xenotransplantation. That’s why we should put all our efforts in creating awareness about organ donation.
Q You have indicated cost as a factor. But is organ donation in India low, that too due to religious or moral issues?
A: I think religious issues are secondary. We’ve been using porcine tissue valves and bovine pericardial valves for decades – they’re made from pigs and cattle, respectively. I have never seen any patient refuse till date. When it comes to life and death, I think people choose life over religion.”
Q:U.S. doctors may be allowed to use pig hearts almost immediately. In India, we have Human Organ Transplantation Act 1994, but it does not mention animal transplantation even in extreme emergency. Surely India needs to start enacting new laws to accommodate the future of animal organ transplants as well?
A legislation will certainly evolve over time. Take the case of vaccines. It used to take us a decade to make a vaccine. Now, we are making vaccines within a year and passing them on in emergency situations. I am sure things will develop; I don’t think law will be a big issue.
Q: Still, it cannot be denied that public health has been poor so far. So has R&D: India has lost a lot in the “brain drain” phenomenon. The pandemic has been a boon in disguise as it made India realize those shortcomings. Can you comment on both the aspects?
A: We have very good scientific and engineering institutes. Also, biomedical engineering is available as a course in many private institutes and government colleges. I think we will see a boom. People have now seen what it was like with vaccines, so there will be better brains, more people join these courses. You hit the nail on the head with the pandemic. People have realized how important it is to invest money in health and infrastructure. Fortunately, we had good private hospitals, so we were able to overcome the first wave and to an extent the second wave of the epidemic with their help. Wave 3 will also be better managed now. The government is serious about health facilities. They were worried before, but the way the pandemic spread has shown us how far we are behind the western world. But, please remember: the Western world was also found to be lacking in the management of the pandemic, as it is a once in 100 years event. Therefore, any preparation made by any country can only fail. Still, it has made us realize what is important in life and that health is paramount.
Question: In 1997, a cardiac surgeon from Assam, Dhaniram Barua, transplanted the heart of a pig into a human patient. The patient survived for seven days, but the doctor was imprisoned and later, his professional reputation was under attack. What do you think about that initial transplant?
A: Perhaps Dr. Barua was ahead of his time. Also, at that time there was no regulatory body to oversee such transplants. Furthermore, the pig used by Dr. Barua was not genetically engineered, so his procedure was different. But please note: few people know that even in the United States, there is no law that allows xenotransplantation. Animal organ transplantation is not approved anywhere in the world. American doctors had to seek Food and Drug Administration (FDA) approval on an emergency basis, as the patient had no other option. He was not a candidate for a human heart transplant. Perhaps there were no donors available. Maybe he was already on prosthetic support and was losing time. Doctors had to set up committees to prove that no other therapy like a ventricular assist device (VAD) could be used on it. This is how he achieved this position.
Q: Earlier this month, doctors at a US hospital transplanted a pig’s heart into a human for the first time in history. Opinion is divided between biotechnologists and surgeons. Some are apprehensive, others excited. How are you?
A: I see it both ways. On the one hand, this is a real milestone in science. There is always a shortage of human organs. So, this achievement by the Maryland medical team is a major breakthrough in terms of science and what it can accomplish. His process began with genetic engineering. He genetically modified a pig. In simple words, they had to deal with ten genes in the pig. They removed four, modified one to stop the pig’s heart from growing, and added six genes. They did this to reduce human reactions and prevent pig hearts from growing after transplantation. The only doubt that prevails is the fact that since this is just a beginning, there is no certainty. Even in a human-to-human heart transplant, which should ideally be accepted by the recipient’s body, an immune response can occur. Over time there can be either extreme rejection, or chronic rejection. So even for such transfers, we need immunosuppression. Only in the long run will we know how the American transplant is working, how the patient has taken to pig hearts, whether doctors will be able to deal with immunosuppression in his case, and so on.
Q: It’s been almost two weeks since the transplant and the patient is still alive, so what qualifies as ‘long term’ for you?
A: In case of implants, we consider the terms of existence of one year, five years or ten years. The ten-year survival rate is currently touching 90%. So we should be targeting that figure in the long term, even a . also for pig heart transplant, This means that currently, 90 out of 100 people who receive a human heart transplant live at least ten years. In the case of the US patient, we would like to see and wait for at least a year. Even if he lives that long, it will be a big milestone. Then, we would be able to assess how similar or different this was for human-to-human transplants, which immunosuppressants to use and in what doses, how they work, etc. Many of these questions will be answered over time.
Q: Are other pig organs also considered suitable for xenotransplantation?
a. The main advantage of using pigs is that they become adults within a short period of time. Also, the heart of a pig is like the heart of a human. A pig kidney has been transplanted to a human before, but since it was done on a patient who was brain dead, it was an experiment to see if it worked. And it did.
Q: Do you envisage animal organ transplantation, or xenotransplantation, anytime in India?
A: Look, there is a tremendous cost involved for R&D, because there is genetic engineering involved. America has been fortunate to have both public and private funding. Of course, in India also we have the Department of Biotechnology (DBT) and other sources, which help us in research in genetic engineering. DBT also has collaborations with the United States. They allow fellowships, researchers, and all kinds of other exchanges in this area of genetic engineering. With time things can get better.
Question: What is the situation in India as far as the availability of human organs is concerned? Is this very important, or is it improving?
A: Human organ donation is much more rare in India than anywhere else in the world. According to global data, India’s position may be better than some other countries, but human organ donation is not as high as it is in Spain. Even within India, donations vary between northern and southern India. Perhaps because of the level of awareness there, most donations take place in the South, while in the North, there is still a divide. Maybe we have to transcend the urgency and push for greater awareness here in the answer as well. Because all that said and done, we are still decades away from xenotransplantation. That’s why we should put all our efforts in creating awareness about organ donation.
Q You have indicated cost as a factor. But is organ donation in India low, that too due to religious or moral issues?
A: I think religious issues are secondary. We’ve been using porcine tissue valves and bovine pericardial valves for decades – they’re made from pigs and cattle, respectively. I have never seen any patient refuse till date. When it comes to life and death, I think people choose life over religion.”
Q:U.S. doctors may be allowed to use pig hearts almost immediately. In India, we have Human Organ Transplantation Act 1994, but it does not mention animal transplantation even in extreme emergency. Surely India needs to start enacting new laws to accommodate the future of animal organ transplants as well?
A legislation will certainly evolve over time. Take the case of vaccines. It used to take us a decade to make a vaccine. Now, we are making vaccines within a year and passing them on in emergency situations. I am sure things will develop; I don’t think law will be a big issue.
Q: Still, it cannot be denied that public health has been poor so far. So has R&D: India has lost a lot in the “brain drain” phenomenon. The pandemic has been a boon in disguise as it made India realize those shortcomings. Can you comment on both the aspects?
A: We have very good scientific and engineering institutes. Also, biomedical engineering is available as a course in many private institutes and government colleges. I think we will see a boom. People have now seen what it was like with vaccines, so there will be better brains, more people join these courses. You hit the nail on the head with the pandemic. People have realized how important it is to invest money in health and infrastructure. Fortunately, we had good private hospitals, so we were able to overcome the first wave and to an extent the second wave of the epidemic with their help. Wave 3 will also be better managed now. The government is serious about health facilities. They were worried before, but the way the pandemic spread has shown us how far we are behind the western world. But, please remember: the Western world was also found to be lacking in the management of the pandemic, as it is a once in 100 years event. Therefore, any preparation made by any country can only fail. Still, it has made us realize what is important in life and that health is paramount.
Question: In 1997, a cardiac surgeon from Assam, Dhaniram Barua, transplanted the heart of a pig into a human patient. The patient survived for seven days, but the doctor was imprisoned and later, his professional reputation was under attack. What do you think about that initial transplant?
A: Perhaps Dr. Barua was ahead of his time. Also, at that time there was no regulatory body to oversee such transplants. Furthermore, the pig used by Dr. Barua was not genetically engineered, so his procedure was different. But please note: few people know that even in the United States, there is no law that allows xenotransplantation. Animal organ transplantation is not approved anywhere in the world. American doctors had to seek Food and Drug Administration (FDA) approval on an emergency basis, as the patient had no other option. He was not a candidate for a human heart transplant. Perhaps there were no donors available. Maybe he was already on prosthetic support and was losing time. Doctors had to set up committees to prove that no other therapy like a ventricular assist device (VAD) could be used on it. This is how he achieved this position.
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