Crystal ball gazing is a risky hobby at best - but it is hard to think of an area where the uncertainties are greater than in the realm of medicine.

Just a generation ago, who would have predicted that surgeons would someday take out gallbladders without making big incisions, that genetic manipulation would be a routine source of useful drugs, that pills would lower cholesterol, grow hair and improve sexual performance? ``We are doing things now that we wouldn't have dreamed of even 10 years ago,'' muses Dr. Robert O. Bonow, a heart specialist at Northwestern University. ``A lot of this is unimaginable.'' Some research directions are set and some goals are clear, and the Associated Press asked experts in several medical specialties to make their best guesses about what we can expect in the next 25 or 30 years. Here are their answers: - CANCER: Optimism for screening, therapy - DR. ROBERT MAYER, chief of the Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston. I'm very optimistic that we're going to make great inroads into cancer prevention. Developing a vaccine against the hepatitis C virus will be critically important in preventing liver cancer. The abolition of tobacco will reduce cancer enormously, as will the use of prophylactic compounds such as tamoxifen for breast cancer or aspirin and folic acid for colon cancer. Screening technology will also undergo a revolution. Virtual colonoscopy, a very elegant computerized x-ray technique to simulate the appearance of the colon, will very likely improve patient ease and compliance with this very important test. Mammography for breast cancer will likely improve through computerized technology, and better and more specific blood tests will make screening for prostate cancer more effective. We will be able to identify and counsel individuals with strong family histories of malignancy far better. I hope we will be able to refine gene therapy by either replacing an abnormal gene or turning it off. Gene therapy may also focus on stimulating the body's own immune response to selectively destroy the tumor, or take advantage of the unique genetic pattern in malignant cells to target biological treatments to those cells. I hope newer forms of systemic treatment will be more specific, making them far less toxic and far better tolerated. - TRANSPLANTS: Educating the immune system - DR. J. RICHARD THISTLETHWAITE, chief of transplant surgery, University of Chicago. First, new surgical techniques will make it far easier for living donors to give organs or parts of organs to those in need. The donor shortage has created a lottery where the winners get transplants and the losers die. The government and the transplant community are trying to devise schemes to provide equal access. In time, human organ donation will be replaced by transplantation of animal organs. Herds of genetically mutated pigs are being developed to provide organs for transplant on demand. Second, new medicines will let us educate the immune system to look at a transplanted organ as ``self'' rather than ``nonself.'' Medicines today that prevent organ rejection are expensive and dangerous. They suppress all immune responses and must be continued for life. Transplant patients are trading one disease for another - organ failure for immunosuppression. We are close to being able to use short-term therapy to achieve immune tolerance so that we can stop all medications. Finally, we will be able to change organs themselves by transplanting genes to help prevent organ failure and organ rejection. Cell transplants, like nerve cells, rather than organs, will be used to treat illnesses like diabetes and Parkinson's or Alzheimer's disease. And then the ultimate science fiction dream that will become reality will be the ability to clone entire new organs from single cells. Ultimately, we should be able to actually grow new kidneys, new hearts - any organ or tissue. - MENTAL HEALTH: Brain scans will aid diagnosis - DR. STEVEN E. HYMAN, director, National Institute of Mental Health. I think changes in our approach to mental illness will be among the most revolutionary, compared to other areas of medicine. Right now, diagnoses, while they can be made with relative certainty for illnesses such as depression and schizophrenia, still remain anchored in symptoms and behavior. Thirty years from now we're going to have diagnoses based on brain scans, or brain scans plus genetic tests. That will provide a great deal more certainty. The second thing is, within the next decade, we will have discovered many genes that create vulnerability to mood disorders, to schizophrenia, to autism and to several other mental disorders. These discoveries will play out so that by 30 years from now, we will have treatments that will really make an enormous difference in these illnesses. Advances in science will really drain the stigma out of mental illness. It is still unfortunately true that many people who suffer depression are made to feel in some way that it's their fault, or if they were just trying hard enough, they could shake it off. I think the science will help the public understand broadly that these are real disorders of an organ, the brain, just as coronary artery disease is a disease of another organ, the heart, and that these conditions have nothing to do with moral weakness, or in no way reflect something that can just be shaken off without treatment. - GENETICS: Tools for targeting treatment - DR. DAVID R. COX, professor of genetics and pediatrics, Stanford University. Genetics is like fire. It can burn you, or it can cook your dinner. It holds great promise in the next 10 years ... It won't fundamentally change medicine. It's more information, another piece of the puzzle. By mapping the human genome, to say that you know how it all works is silly beyond belief. That's like saying if I spread all the parts of a car on the garage floor, I can understand each of them and how they cause a car to run. So how will it be practical? Today we go to the doctor and describe a variety of symptoms. The physician considers a variety of ailments and narrows down what it could be. Genetic medicine will be much more targeted because it will be tied to how your cells work. We'll know that a gene makes some protein product. But there are minor changes from one person to another. That means that in maybe one out of five patients, the genetic treatment will work. Genetic medicine will be more targeted because it will be evidence-based, rather than medicine based on expert opinion. What about the other 80 percent? This will be a new region where research and clinical practice will overlap. Large numbers of people will be enrolled in clinical trials. The public will be an active participant in medicine, and research and clinical practice will be close to one in the same. So genetic medicine has tremendous potential for improving people's lives. We'll need an ethical framework to guide us as the research moves forward. We'll be in a real mess if we don't do that. - HEART DISEASE: Better drugs, virtual operating rooms - DR. ROBERT O. BONOW, chief of cardiology, Northwestern University We will have much better drug therapy for various forms of heart disease. Heart failure will be more easily treated by rapid, early administration of drugs to people with heart attacks. These will not just open the arteries but also allow the heart to withstand damage better. We will also have new and ingenious ways of preventing blood clots in arteries, so there will be fewer heart attacks. We will be much better at getting devices into arteries to open them up. Surgical techniques will undoubtedly be robotic. In a virtual operating room, a surgeon will sit and operate on the heart of a patient who is in a different place. Gene therapy will be well understood. Right now, we are at the early stages and don't know the risk involved of inserting genes in various places. Hopefully in 25 years, we will be at a point where we can treat the genetic abnormalities in heart disease by inserting the right genes and removing the wrong ones. This could prevent the development of atherosclerosis, keep arteries from developing blood clots and generate heart muscle when tissue dies. Our diagnostic imaging techniques clearly will be a lot better. What we do now will seem old-fashioned and laughable in 10 or 20 years. We will have much more information about the function of the heart, have images of the blood vessels themselves and have three-dimensional pictures so we can look at the heart from the inside out, all without penetrating the body. I hope some of the most important things we will be doing then are not in the high-tech realm but merely better implementation of what we now already know about smoking cessation, diet and exercise as a means to reduce heart disease and stroke. - MEDICAL ETHICS: Designed babies, brain implants - ARTHUR L. CAPLAN, director of the Center for Bioethics, University of Pennsylvania. It's going to become very uncommon that you wouldn't want to know your genetic makeup. Few women today over 35 would think of having a baby without getting an amniocentesis (a test for certain fetal abnormalities). It just became part of what a responsible person does. Just take out the genetic discrimination part of the insurance problem, then people won't be afraid of other types of genetic testing. I think we'll also be watching another heated debate about assisted suicide, not a debate about what to do if you're terminally ill, but a debate about what to do if you're demented. Do you have the right to end your life? I think there will be a debate about whether to use scientific knowledge to design babies, not by changing their genes, but by at least screening embryos, testing embryos for their traits. There will be some discussion about whether eugenics is a good thing to try to improve your kid. I think we'll see more artificial organs, man-made parts. I think we will see the first effort to use implants into the human brain to repair things, so someone might get an implant to boost their memory or to help their dyslexia. I think we'll also see strong pressure to identify children in school who might be at risk or encounter problems through this kind of forensic study of the brain. I think in 25 years someone will have made the first artificial life form, a virus or a bacteria in the lab, using gene mapping. - STROKE: Strides in prevention, nerve restoration - DR. ANTHONY J. FURLAN, medical director, Cerebrovascular Center, Cleveland Clinic. New risk factors for stroke are constantly being identified. Most excitingly, new genetic markers of atherosclerosis may allow us to identify persons at risk for stroke at an early age. Once the genes involved are identified, their activity can possibly be modified. New pills to prevent stroke will be much more potent inhibitors than aspirin of cells called platelets that trigger blood clotting. An exploding area is a procedure called endovascular therapy to prevent and treat stroke, where we dilate the carotid artery using angioplasty balloons and metal scaffolds called stents. New catheters will allow us to access and repair small brain arteries that are blocked by clots or that are leaking due to an aneurysm. Some novel devices under study allow us to remove clots from blocked brain arteries within seconds, limiting damage. There is hope that the treatment window will be opened beyond the current three hours. Newer, more powerful and safer clot-dissolving drugs will be combined with drugs that limit the damage the blocked artery causes to brain cells. Other strategies, such as extreme body cooling, will also slow down stroke damage in the brain. Lastly, the field of restorative neurology will lead to novel stroke recovery therapies, such as brain cell transplants. - AGING AND LONGEVITY: Lowering risk factors for Alzheimer's, others - DR. CALEB E. FINCH, director of biogerontology program, University of Southern California. Who the heck knows? Science moves so fast and so unpredictably. The human lifespan has been increasing steadily for at least 100 years. We have no way of knowing if this powerful trend will hit its ceiling or continue to increase as improved public health measures and medical technology become more widely available. One thing is clear: A number of unhealthy behaviors, including heavy smoking, exposure to toxins in the environment, foods that lead to chronic elevations in blood sugar, and lack of exercise, can lead to shortened lifespan. Whether changing these will truly change the underlying pattern of human aging is unknown. We will know a lot about genetic risk factors for diseases. Already, there are four or five strong candidates each for Alzheimer's disease, heart disease, cancer and diabetes. Relatively early in life, it will be possible for most people to know if they have any major genetic risk factors. There will be specific recommendations and guidelines for how to minimize those risks. A major opportunity will emerge in organ replacement, as genetic engineering of stem cells progresses. In principle, it should be possible to take a skin cell and grow any type of cell that is needed. It may not be too fantastic to imagine regrowing whole bones and joints and hearts and kidneys. The scientific problem is to discover how to regulate the genes we all have in our adult cells. I'm highly optimistic that human lifespan will include increasing duration of health. I look to the remarkable example of Jeanne Calment, who died at 122, having lived almost all of her adult life in excellent physical health and capacity for social interactions. - INFECTIOUS DISEASES: Pandemic likely, but also disease eradication - DR. JAMES HUGHES, director of CDC's National Center for Infectious Diseases. Infectious diseases currently are the leading cause of death worldwide and the third-leading cause of death in the United States. When I'm asked what do I worry about over the next 25 or 30 years, it's obviously hard to predict. We know we're going to be surprised. We're going to see increases in this problem of antimicrobial resistance. That is a major problem. Think about the need to use antimicrobials appropriately. We're going to continue to see large regional and national and even international foodborne-disease outbreaks, with this globalization of the food supply that has occurred. More widespread use of food irradiation could reduce the risk. We can't help but notice the number of diseases transmitted from animals to people, most recently the West Nile-like virus infections in New York City, transmitted by mosquitoes. The Nipah virus in Malaysia and Singapore that spread from pigs to people, causing encephalitis with a very high mortality rate. The avian influenza episode in Hong Kong, providing the reminder that we are constantly threatened by the next flu pandemic. Within the next 25 to 30 years we should just assume we will have an influenza pandemic. We are overdue. Will some diseases be eradicated? We certainly hope so. WHO targets the end of 2000 for the global eradication of polio. The Guinea worm eradication program is proceeding. Measles is a future candidate. The development of new generations of safer, more effective, easier-to-administer vaccines will undoubtedly help us greatly. That leads you to the need to strengthen the public health system. Progress can be made.

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