Reflections on the Future of Medicine

 

Recently, I traveled through China. I climbed mountains, hiked through forests, crossed deep valleys. I visited cities of every size. I floated across lakes and traveled beautiful shorelines churning with life. As a man of a certain age, I began to compare the permanence of the timeless landscape with the evanescence of my own existence. Yet, as a scientist, I knew these reflections were flawed.

Scientists are trained to think in terms of aeons, millenia, and lifetimes. Consider the paradox. Is it the solid mountain or fragile the forest that is permanent? Is it the massive shoreline cliffs or the teeming shore life that survives the relentless churning of our continents? The answer is not intuitive. Over time the mountain will crumble, the sea will flow to the hollow, the mountain will rise again. Wherever there is a mountain, a forest will flourish. Wherever there is a sea, life will abound. It is not the rock and water that are everlasting. It is life that abides. Life is immortal.

Each one of us is a direct, living descendent of the first living forms that arose four billion years ago, when our planet was still being shaped by bombardment from the heavens. Inheritance is a fundamental characteristic of life. One cell divides into two. Those two cells give rise to others. The DNA molecule within each cell drives cell duplication, dividing and replicating to form nearly identical versions of itself. The molecule resides in each and every one of our cells. It is the cumulative consequence of imperfections in the duplication that account for the marvelous diversity of living forms. All life springs from a single source. All are united by a common inheritance of this four billion year old molecule, the immortal molecule. We are but transient vessels of the passing of the immortal molecule from generation to generation.

The question we ask today is, can we tie our transient existence to the immortality of the molecule that defines us? Need we vanish with time if the fundamental essence of our being is itself immortal? This is a central quest of regenerative medicine. It is becoming more of a possibility each year.

When I first created the term regenerative medicine in a lecture in 1999, I was explaining the impact of what were then new fields of medicine, tissue engineering and stem cell biology. I asked, "How is it that the DNA in cells of a forty year old provide the code rise for babies that are zero years old?" I went on to state that there must be substances in the fertilized human egg that resets the genetic clock and that one day we would discover those substances and finally hold the key to extended life.

That was 1999. Seven years later, that key, a combination of substances found in the fertilized egg, was discovered in Japan by Shinya Yamanaka. Those substances, applied to normal cells of even older adults, can turn back the genetic clock of the cells of each person. We can reverse both the process by which the single fertilized egg gave rise to the diverse cells and the aging of the DNA in that cell. We can return almost any cell in the body back to its origin, the equivalent of the first fertilized egg that has the capability of producing an entire human, complete with the original DNA.

Will that person be philosophically you? Certainly not. But it will be genetically you--and in that genetic identity lies the power of self regeneration. That primordial cell, derived from your own cell, can be coaxed into producing the full variety of the many different cells that make up a human body. We are now acquiring the knowledge and techniques to reseed your body with younger cells, to build and replace failing tissues and organs with younger, healthier versions. That is the promise of regenerative medicine: to reset your genetic clock; to find at last a fountain of youth.

In more specific terms, regenerative medicine is a set of medical interventions that restore the body to youthful functioning, whether it is damaged by trauma, injured by disease, or worn by time. The most powerful medicine is a younger form of yourself. We have made enormous progress in understanding how to take the newly created embryo like cells and develop them step by step into adult tissues. We are now close to producing cells that can restore muscle function to damaged hearts, neurons that can replace parts of the brain damage by stroke or age, and cells that allow the growth of new cells to repair injured eyes. In theory these cells can be induced to recreate almost any cell in your body. The cells of your body may be replaced by your younger self. This is aging in reverse.

The promise of regenerative medicine is developing more slowly that I had hoped seventeen years ago. I certainly would like to see the full flowering of regenerative medicine in my lifetime. I imagine the pleasant dissonance of looking in the mirror to find a person whose youth and vigor is at odds with my advanced actual age. I would like my physical self to be that self. Whether that happens in my lifetime, or my children's lifetime, or my grandchildren's lifetime, this is a promise science can fulfill.

The central breakthrough was the ability to reset DNA, to move a cell backward, step by step, until it becomes the precursor of any aging cell in your body. What we lack is the medical science that allows those fresh cells to be implanted into our tissues. An enormous amount of work remains to be done to understand the signals that direct a specific tissue to become what it is. In this we are underinvested. Any country could become the world leader in this field. If I could recommend a single area for investment for the future of mankind and the future of science, this would be it, the fusion of cell biology and transplantation medicine.

Let us consider another philosophical concept. Our bodies are stardust, at one with all matter in the universe. Our common birthplace is an exploding supernova. We know that in the beginning the universe was composed mostly of hydrogen. Exploded, compacted hydrogen created all the other elements. The atoms of the earth derive from the cycle of birth and death of stars over the past fourteen billon years. These are the selfsame atoms of our body. The identity of our material with that of the universe means that the laws of physics that govern all matter apply equally to our organs, tissues, and cells. As we learn more about the physical universe, we in turn learn more about the universe of our bodies.

A key aspect of what we call precision medicine is the intersection of physics and personal biology. To me, the miracle of a modern diagnostic laboratory is not the blood test but rather the magnetic resonance imaging and other noninvasive ways of imaging the deepest recesses of our bodies. We now have the physical tools to unveil the invisible within our bodies. We can see not only the organs, not only the tissues, not only the cells, but tiny structures deep within each cell in real time. We can detect and understand what is amiss with ever increasing precision. Understanding the medical problems in detail is the key to precision medicine, a precise joining of specific diagnosis with specific treatment.

These new technologies open new insights into the last great unknown frontier of science and medicine, understanding the human brain in health and disease. Neuroscience is progressing at warp speed, thanks to new technologies. If I were a young man again, the beneficiary of fully developed regenerative medicine, I would use these new tools to understand our brain. We now have much of what we need to solve one of the great unsolved mysteries, how we think, how we remember, how we feel, at the level of individual neurons in real time. If you think this is fantasy, visit your nearest advanced neurosciences lab.

I recently had the great pleasure of having a private seminar with ten of the best neuroscientists at the New York University Langone Medical Center in New York. They gave me an astounding introduction to the forefront of neuroscience. For example, New York University scientists have developed little membranes that can lie directly on a brain and record the real time activity of individual neurons. We can activate individual neurons and neural pathways deep within the brain. We can begin to observe how signals from the eye or ear bounce around the human brain to become our memories, feelings, emotions, and thoughts. The journey to understanding our brain is nowhere near complete, but just as for regenerative medicine, I am convinced we are well on our way.

That our bodies and cells follow the same physical rules as all other matter means that we can begin to fuse our living bodies with tiny mechanical devices that interact with, and in some cases mimic, the function of our living self. Familiar examples are hearing aids that physically and electronically amplify sound, and lenses that bend light so we may see better. Cochlear ear implants, small electrodes that fit inside the inner ear, stimulate the auditory nerves allowing those with defective outer ears to hear. It is now possible to restore hearing to those who have no connection between the ear and the brain. Microchips implanted in the lower brain connected to external microphones can send signals directly to the brain that are interpreted as sound.

This is not in the future. This is now. The communications revolution now touches our brain directly. If that is happening today, think of the advances that microelectronic sensor communication and electronic neural communication might bring. Direct fusion of our brain to the internet? Conceivable. It is a brilliant and, to some, perhaps troubling vision of the future.

We are now unleashing the power of the immune system for medicine. As a very young scientist I elected to move from my studies at the Massachusetts Institute of Technology to a new cancer hospital and research center, Harvard University's Dana Farber Cancer Institute. I applied molecular biology to the field of cancer research and later to the field of HIV/AIDS research. The main thrust of research of the Institute then, in the early 1970s, was not chemotherapy but rather the new field of cancer immunology. That was more than forty years ago. Cancer immunotherapy was a dream at the time. Today, through their work and the work of thousands of scientists around the world, cancer immunotherapy is rapidly becoming a reality. I was pleased that a company I founded in the late 1990s, Denderon, developed the first immunotherapy approved for treatment of cancer. Effective immune therapy for cancer is still in its early stages. In my opinion, the breakthrough we had always hoped for may occur in cancer treatment. The breakthrough that will allow almost everyone to survive cancers. It will not happen tomorrow, but as with other therapies, we are well on our way.

How long will it be before the full promise of immune therapy is realized? The past may be a guide to the future. Emil Frei was a pioneer of one of the first successful systematic chemotherapies for leukemia. In the 1950s, he began with the idea that a couple types of drugs could kill white blood cells. One of them was a poison derived from mustard gas used in World War I. The first results were promising, but most leukemias eventually returned. When they did, they were resistant to further treatment by those same drugs. Frei and his team continued searching for answers and, along the way, realized that some survivors develop cancers induced by the therapy itself. That issue is still being addressed today, more than sixty years on. Getting it right takes a long time. Immune therapies are where we were fifty years ago with chemotherapy. We have a long way to go but the future looks bright.

Our understanding of the natural world from cosmology to physics combined with our understanding of our own biology and our own genetic makeup give us a deep understanding of who and what we are. We are now beginning to understand how we can repair and restore our flagging and diseased bodily functions. It can even allow us to peer into how we think and how we feel. We are on the cusp of another great revolution in the understanding of ourselves.

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