Transplant cells, not organs : Susan Lim
So I was privileged to train in transplantation under two great surgical pioneers: Thomas Starzl, who
performed the world's first successful liver transplant in 1967, and Sir Roy Calne, who performed the first
liver transplant in the U.K. in the following year. I returned to Singapore and, in 1990, performed Asia's first
successful cadaveric liver transplant procedure, but against all odds. Now when I look back, the transplant
was actually the easiest part. Next, raising the money to fund the procedure. But perhaps the most
challenging part was to convince the regulators -- a matter which was debated in the parliament -- that a
young female surgeon be allowed the opportunity to pioneer for her country. But 20 years on, my patient,
Surinder, is Asia's longest surviving cadaveric liver transplant to date. (Applause) And perhaps more
important, I am the proud godmother to her 14 year-old son.
(Applause)
But not all patients on the transplant wait list are so fortunate. The truth is, there are just simply not enough
donor organs to go around. As the demand for donor organs continues to rise, in large part due to the aging
population, the supply has remained relatively constant. In the United States alone, 100,000 men, women
and children are on the waiting list for donor organs, and more than a dozen die each day because of a lack
of donor organs. The transplant community has actively campaigned in organ donation. And the gift of
life has been extended from brain-dead donors to living, related donors -- relatives who might donate an
organ or a part of an organ, like a split liver graft, to a relative or loved one.
But as there was still a dire shortage of donor organs, the gift of life was then extended from living, related
donors to now living, unrelated donors. And this then has given rise to unprecedented and unexpected moral
controversy. How can one distinguish a donation that is voluntary and altruistic from one that is forced or
coerced from, for example, a submissive spouse, an in-law, a servant, a slave, an employee? Where and
how can we draw the line? In my part of the world, too many people live below the poverty line. And in some
areas, the commercial gifting of an organ in exchange for monetary reward has led to a flourishing trade in
living, unrelated donors.
Shortly after I performed the first liver transplant, I received my next assignment, and that was to go to the
prisons to harvest organs from executed prisoners. I was also pregnant at the time. Pregnancies are
meant to be happy and fulfilling moments in any woman's life. But my joyful period was marred by solemn
and morbid thoughts --thoughts of walking through the prison's high-security death row, as this was the only
route to take me to the makeshift operating room. And at each time, I would feel the chilling stares of
condemned prisoners' eyes follow me. And for two years, I struggled with the dilemma of waking up at 4:30
am on a Friday morning, driving to the prison, getting down, gloved and scrubbed, ready to receive the
body of an executed prisoner, remove the organs and then transport these organs to the recipient
hospital and then graft the gift of life to a recipient the same afternoon. No doubt, I was informed, the
consent had been obtained.
But in my life, the one fulfilling skill that I had was now invoking feelings of conflict -- conflict ranging from
extreme sorrow and doubt at dawn to celebratory joy at engrafting the gift of life at dusk . In my team, the
lives of one or two of my colleagues were tainted by this experience. Some of us may have been
sublimated, but really none of us remained the same. I was troubled that the retrieval of organs from
executed prisoners was at least as morally controversial as the harvesting of stem cells from human
embryos. And in my mind, I realized as a surgical pioneer that the purpose of my position of influence was
surely to speak up for those who have no influence. It made me wonder if there could be a better way -- a
way to circumvent death and yet deliver the gift of life that might exponentially impact millions of patients
worldwide.
Now just about that time, the practice of surgery evolved from big to small, from wide open incisions to
keyhole procedures, tiny incisions. And in transplantation, concepts shifted from whole organs to cells. In
1988, at the University of Minnesota, I participated in a small series of whole organ pancreas transplants. I
witnessed the technical difficulty. And this inspired in my mind a shift from transplanting whole organs to
perhaps transplanting cells. I thought to myself, why not take the individual cells out of the pancreas -- the
cells that secrete insulin to cure diabetes -- and transplant these cells? -- technically a much simpler
procedure than having to grapple with the complexities of transplanting a whole organ.
And at that time, stem cell research had gained momentum, following the isolation of the world's first human
embryonic stem cells in the 1990's.The observation that stem cells, as master cells, could give rise to a
whole variety of different cell types -- heart cells, liver cells, pancreatic islet cells -- captured the attention of
the media and the imagination of the public. I too was fascinated by this new and disruptive cell
technology, and this inspired a shift in my mindset, from transplanting whole organs to transplanting
cells. And I focused my research on stem cells as a possible source for cell transplants.
Today we realize that there are many different types of stem cells. Embryonic stem cells have occupied
center stage, chiefly because of their pluripotency -- that is their ease in differentiating into a variety of
different cell types. But the moral controversy surrounding embryonic stem cells --the fact that these cells
are derived from five-day old human embryos -- has encouraged research into other types of stem cells.
Now to the ridicule of my colleagues, I inspired my lab to focus on what I thought was the most noncontroversial source of stem cells, adipose tissue, or fat, yes fat -- nowadays available in abundant supply -you and I, I think, would be very happy to get rid of anyway. Fat-derived stem cells are adult stem cells. And
adult stem cells are found in you and me -- in our blood, in our bone marrow, in our fat, our skin and other
organs. And as it turns out, fat is one of the best sources of adult stem cells. But adult stem cells are not
embryonic stem cells. And here is the limitation: adult stem cells are mature cells, and, like mature human
beings, these cells are more restricted in their thought and more restricted in their behavior and are unable
to give rise to the wide variety of specialized cell types, as embryonic stem cells.
But in 2007, two remarkable individuals, Shinya Yamanaka of Japan and Jamie Thompson of the United
States, made an astounding discovery. They discovered that adult cells, taken from you and me, could be
reprogrammed back into embryonic-like cells, which they termed IPS cells, or induced pluripotent stem
cells. And so guess what, scientists around the world and in the labs are racing to convert aging adult cells -aging adult cells from you and me -- they are racing to reprogram these cells back into more useful IPS
cells. And in our lab, we are focused on taking fat and reprogramming mounds of fat into fountains of
youthful cells -- cells that we may use to then form other, more specialized, cells, which one day may be
used as cell transplants. If this research is successful, it may then reduce the need to research and
sacrifice human embryos.
Indeed, there is a lot of hype, but also hope that the promise of stem cells will one day provide cures for a
whole range of conditions. Heart disease, stroke, diabetes, spinal cord injury, muscular dystrophy, retinal
eye diseases -- are any of these conditions relevant personally to you?
In May 2006, something horrible happened to me. I was about to start a robotic operation, but stepping out
of the elevator into the bright and glaring lights of the operating room, I realized that my left visual field was
fast collapsing into darkness. Earlier that week, I had taken a rather hard knock during late spring skiing -yes, I fell. And I started to see floaters and stars, which I casually dismissed as too much high-altitude sun
exposure. What happened to me might have been catastrophic, if not for the fact that I was in reach of good
surgical access. And I had my vision restored, but not before a prolonged period of convalescence --three
months -- in a head down position. This experience taught me to empathize more with my patients, and
especially those with retinal diseases.
37 million people worldwide are blind, and 127 million more suffer from impaired vision. Stem cell-derived
retinal transplants, now in a research phase, may one day restore vision, or part vision, to millions of
patients with retinal diseases worldwide. Indeed, we live in both challenging as well as exciting times. As the
world population ages, scientists are racing to discover new ways to enhance the power of the body to heal
itself through stem cells.
It is a fact that when our organs or tissues are injured, our bone marrow releases stem cells into our
circulation. And these stem cells then float in the bloodstream and home in to damaged organs to release
growth factors to repair the damaged tissue. Stem cells may be used as building blocks to repair damaged
scaffolds within our body, or to provide new liver cells to repair damaged liver. As we speak, there are 117 or
so clinical trials researching the use of stem cells for liver diseases.
What lies ahead? Heart disease is the leading cause of death worldwide. 1.1 million Americans suffer heart
attacks yearly. 4.8 million suffer cardiac failure. Stem cells may be used to deliver growth factors to repair
damaged heart muscle or be differentiated into heart muscle cells to restore heart function. There are 170
clinical trials investigating the role of stem cells in heart disease. While still in a research phase, stem cells
may one day herald a quantum leap in the field of cardiology.
Stem cells provide hope for new beginnings --small, incremental steps, cells rather than organs, repair
rather than replacement. Stem cell therapies may one day reduce the need for donor organs. Powerful new
technologies always present enigmas. As we speak, the world's first human embryonic stem cell trial for
spinal cord injury is currently underway following the USFDA approval. And in the U.K., neural stem cells to
treat stroke are being investigated in a phase one trial.
The research success that we celebrate today has been made possible by the curiosity and contribution and
commitment of individual scientists and medical pioneers. Each one has his story. My story has been about
my journey from organs to cells -- a journey through controversy, inspired by hope -- hope that, as we
age, you and I may one day celebrate longevity with an improved quality of life.
Thank you.