William Haseltine has an active career in both science and business. He was a professor at Harvard Medical School from 1976-1993 where he was the chair of two academic research departments. He is well known for his pioneering work on cancer and HIV/AIDS. He is the Founder of Human Genome Sciences, Inc and served as the Chairman and CEO of the Company until 2004. He is also the founder of seven other successful biotechnology companies. He serves as an advisor to CMEA, a venture capital company, and to several biotechnology and pharmaceutical companies.
The following transcript of William Haseltine’s presentation at the free symposium entitled Aging: The Disease, The Cure, The Implications has not been approved by the speaker. Video is also available.
The Growing Field of Regenerative Medicine
It is a great pleasure to be addressing a general audience. I hope as the evening progresses, you are able to ask us questions either from the floor or over dinner. It is one of the great pleasures to hear what people who are outside of the scientific disciplines think about what it is that we are doing.
The basic problem that we all have is that we know that we are born, we grow, we live, we die. The first three of those is fine; the last we would like to avoid. Is it possible? In that statement “we are born, we grow, we live, we die,” is a paradox. That is that every generation renews itself. A 35 year-old couple will have a zero year-old baby. The fundamental nature of life is regeneration through generations. It is immortality. What we have come to understand about life is that it is based on a molecule, DNA, that contains the information that specifies what we are to become—whether a human, a tree or an insect.
Over time the ideas that have been deduced about the nature of DNA, how ancient it is, how it is related in one organism to another, have become clarified with great specificity. We can now say with great assurance something that was only speculated some time ago, that the DNA molecule that is in you, me and all living things is a living fossil that is about three and a half to four billion years-old. It is a single molecule that has reproduced itself through time in what is near immortality.
Certainly as we look at our own lifespan, three and a half to four billion years is closer to immortality than we can even contemplate. It is that fundamental nature of life, its ability to reproduce itself over time, to renew itself from generation to generation, that gives us confidence that it will eventually be possible to attach an individual life to that fundamental immortality of our DNA.
Many of us have been working in this field for a number of years. About ten years ago I coined a term—regenerative medicine. The concept was a relatively simple one. What collection of medical technologies existing today can we imagine in the future would allow us to attach our individual self to the immortality of our DNA? There were many that were possible. Some were beginning to come into view as realities.
Let me give you one of the breakthroughs that gave us some hope at that time. That was the advent of human stem cell cloning. As you have read, and as you know living here in California, we are now able to, from a single cell which can be propagated and grown, to create the essence of our reproductive immortality. That is, a seed of a human being that has the potential to be all of our cells.
It was that breakthrough that gave most of us hope that someday we would be able to take those cells and replace our parts, one by one. We know that we have the capacity for many years to renew our bodies. All of us in this room have renewed the cells of our bodies several times over. The very material that you are made of is not the material that was with you ten or fifteen years ago. It is entirely different chemicals and it is mostly different cells.
We do renew ourselves. As Aubrey pointed out, something goes amiss over time. We are beginning to have many specific ideas about what that is. We can begin to measure those processes, but to measure those processes is not necessarily to change them. What can change them is replacement of those regenerative cells.
Ten years ago, when we began thinking about this field in much more detail, assembling pretty much the group you see here on the stage and others, we had several major problems ahead of us. We knew that somehow you could take an old nucleus, the cells and DNA from an older person, put it into an egg, and something in that environment would reset its genetic clock. This is just as when the sperm combines with the egg, the genetic clock is reset, and a zero year-old child is born from an older person.
It was clear at that time that with enough effort, we would be able to do that at will—to take any of our cells, and with the right genetic manipulation, reset its clock. We could begin to use our own cells for that purpose. What was not clear ten years ago was how long that process would take. Today I am very pleased to tell you that we now have that ability.
About a year and a half ago it was discovered that a very simple procedure can take any one of your cells–possibly any cell in your body–do a minor manipulation, and turn that into the equivalent of a zero year-old fertilized egg. If you do it in a mouse, you know it has that capacity, because you can do that manipulation on a single cell in a mouse, implant it in the uterus of an animal, and a functional, long-lived normal animal will result. That means we truly have the ability to create your individual stem cells without going through the process of embryonic cloning.
That is step one. What is also clear is that although there was the potential to take an egglike cell, and it could on its own assemble a complete animal and probably a complete human being, we had no idea of how to get it to do it on our command to build a precursor for a skin cell, to build a precursor for a muscle cell. It was very much left to chance. That too is changing very rapidly.
The confidence that we have gotten from the simple observation that you can take a normal cell, even an aged cell, and reset its genetic clock, has given us the confidence to say that we can now reach into any cell and change it at will to the program that we want. We can take one of these cells–learning about what a heart muscle cell does, about what a pancreatic cell that produces insulin does–reach in and change that in such a way that we can use it to rebuild our own bodies.
Again, just in the last year, there have been fundamental breakthroughs in that area. That is not to say that you will be able to go to your doctor tomorrow… but it means that some of the most fundamental problems of regenerative medicine have been addressed in the mere ten years since that word was coined. Making individual stem cells that allow your own cells to be used for your own regeneration, breakthroughs that tell us it is very likely going to be possible to make any type of cell in any stage that we want. The first ones will be cells for one of the major diseases—it turns out that 8% of Americans suffer from diabetes. In some cities, 20% of the entire population suffers from diabetes. That is surely going to be one of the first targets, but it will not be the only target.
What do we do until we get to the time when we can replace with young, healthy cells those of our cells that are injured or damaged? That is where the other aspect of regenerative medicine comes in. The initial concept was that regenerative medicine could replace any part of our body that is injured by trauma, damaged by disease, or warn by time.
In the end, what we care about is function, not how that function is achieved. If it is achieved by some painless injection of a cell that finds its way in the body and starts producing young and healthy tissues, we will be very happy. If it is achieved by replacing a major joint with a piece of plastic or metal, so that we can walk when we could not… if it is replaced by a bit of electronics that allow us to see when we could not… if it is replaced by electrodes that sense our intension and cause our limbs to move when they could not… we will be much happier than we were before.
It is again in this field that the tremendous advances of modern science have come to bear. It is in the field of nanoprosthetics. It is in the field of being able to use a variety of different materials to replace our own materials. The one demonstration of where this is headed that you may have seen—we saw early prototypes in some of our early regenerative medicine meetings, but they are now much more advanced—is the implantation of sensing electrodes in the brains of monkeys that allow them to manipulate robotic arms with great facility. (Monkeys can be trained to play videogames, and would beat every single person in this room, by the way. The hand-eye coordination of a monkey who plays a videogame is really something to see. Eventually, your kids may be playing monkeys.)
In fact, what they have done is trained these monkeys with these implants to manipulate these robotic arms. They then restrain the monkeys’ own arms, and he learns to play the game and get his reward with the electronic arm. Eventually the brain adapts and the monkey can learn to use all three arms for whatever he wishes to do–play electronic games, feed himself, or reach across a continent to create an effect which he wants, through electronics. There are people here in Los Angeles trying to connect those electronic signals directly to muscle stimulation for paraplegics. Those are the kinds of advances that are being made, and must be made until we have the ability to regenerate the spinal column.
There is one other field that was referred to also in Aubrey’s excellent introduction. That was reaching into your metabolism and changing its speed. Now, why do we think that will work? You may have read about a whole series of studies in many different species, including mammals now, that caloric restriction extends life. In some cases it can double or even triple a lifespan. Modern genetics, the ability to understand the internal workings of cells, has allowed us to begin to pinpoint those key switches and begin to play with them with various drugs. The one that many of you may have heard of is the substance that is found in red wines, and now has synthetic analogs that are far more potent. We can reach in and begin to slow down the genetic clock, hopefully without the pain of severe dietary restriction.
All of this has happened in the last ten years. I am personally an optimist. In my career as a scientist working in the career of medicine, I have seen what appear to be miracles. In my days as a cancer researcher, I saw the survival of head and neck cancers change from 15% to 85%. It took us twenty years to do it, but it is a fact today. In my career as an AIDS researcher, I saw the disease go from one that was virtually fatal regardless of intervention to one that is manageable as a chronic disease today, if properly treated—another virtual miracle. I have seen that with systematic efforts, we have gone from the knowledge of a few hundred genes to all the genes of our species and the genes now of some one thousand additional species. We can do great things when we put our minds to it.
Progress over the past ten years in regenerative medicine and longevity has been truly remarkable. The next ten years, which most of us in this room will experience, is going to be more remarkable still.