Recent news reports have announced the successful transplantation of pig kidneys and a heart into humans. Similar work is being done to use pig livers in humans. A number of members have asked me about this swine parts business so this will be a bit of background and my thoughts about the future for this strategy.
Rejection of a transplanted organ by the immune system is the great barrier here and taming that response has been the key to human organ transplants. It is much harder to use parts of another species as the immune system can kill foreign tissue in minutes to hours. The secret, make a pig look more like a human at the cell level, a really hard thing to do.
One of the greatest achievements in medicine was the development of the Crisper-CAS 9 gene editing tools. it gives us the ability to directly edit the DNA of the cell. It is truly a god like capability giving us the ability to directly modify the fundamental code of life. There are interesting ethical questions about this but that is for another time.
To use pig tissue in a human a lot of things need to be fixed. There are 62 known retro viruses that have been incorporated in pig DNA. Those must be eliminated. Pig cells have a carbohydrate on their surface that triggers the human immune system to attack instantly and must be removed. There are 3 pig genes that increase human immune response which need to be silenced. The pig heart will grow to be too big for a human so half the growth genes must be removed to keep it human size. There are 6 currently identified human genes that the immune system needs so those must be inserted. There are no doubt more things that will need to be done, but amazingly all of these steps have been accomplished and the first trial kidney and heart transplants have been done. Remarkable!
I imagine that both of the recent transplants will fail. The kidneys were put in a brain dead person as the first proof of concept but the heart was given to a living man. He was terminal and not a candidate for a human heart so it was a last chance choice for him but a logical next step. The docs will learn important new information from this step but for the rest of the patient community it is a glimpse of a possible future.
A liver transplant is a miraculous gift but for most patients who may need one it is a dream that is out of reach. We do about 8,000 liver transplant a year and each is an incredible gift to the person who receives it. However, about 35,000 people die of liver disease each year and most are not even entered in the transplant lottery. For most it is like a kid living in poverty, standing on the cold sidewalk, looking in the windows of a giant department store and wishing, knowing that all that is beyond the glass is denied. We speak about equity a lot these days but when it comes to transplants equity is largely out to lunch and luck more often steers the ship.
Pig parts and the magic of Crisper offer us a solution. Success would solve the supply problem and offer an open door to those currently stranded out in the cold but the current vision would likely crash on the reef of cost and expensive dreams. The cost of drugs to manage the transplants at volume over the years would be difficult to manage so we would still probably be faced with the death panel gauntlet of organ allocation.
My vision of the future is more expansive. Scientific knowledge is exploding. We have no way to predict how far it can go but I think it will be possible to create a transplant organ that requires little ongoing drug support. Crisper has the ability to rewrite biology. I imagine a time when there will be a foundational pig variety raised to provide human ready organs but with Crisper we go one step further and take stem cells from me and create an organ that contains those things that allow my immune system to ignore the new liver.
As we think about the future there will be tremendous conflict between the science teams and the safety oversight and ethics groups. Science is moving faster than our institutions and the rules about patient safety have been hard won and it is vital that we retain that focus. However, as I think about my situation, should I reach a point where my liver is failing me and a transplant isn't in the cards, I would choose to participate in this kind of research rather than go quietly to hospice.
I believe many would join me in that but there will be very strong resistance to that approach. Legal risk driven by greedy lawyers has put us in a place where it is better for institutions to allow people to die than to accelerate transformational research.
The tsunami of liver disease is nearly upon us and one possible solution is custom parts. We should encourage this process. Curing liver failure with a one time surgery rather than life long drug support should be a cost effective strategy.
The Fatty Liver Foundation has launched a public private partnership fund with the long-term goal of screening a million asymptomatic, undiagnosed individuals a year for nonalcoholic fatty liver disease (NAFLD). The SUNN Study was the pilot for that effort. The next step is SUNN-2 with a goal of screening 20,000 people
If you would like more information click the image below.
This fund will provide a mechanism for public and private funders to join together in common cause with the patient community. By joining together we can work with local communities in finding ways to engage this threat at the only truly effective level, that of the patient within the life that they lead and the reality of their community.
We hope you are happy and safe.