Ann Giudici Fettner, a Washington science writer, is author of The Truth About AIDS, published by Holt, Rinehart & Winston.
One idea we never let go, holding to it in the face of all evidence to the contrary, is that someone, someday, somehow, is going to find something to let us stay young and live forever. This yearning for eternal youth is an ancient fantasy. The myth of Shangri-La comes from the Greek tale of the Hyperboreans who, after living 1,000 years, simply plunged into the sea. The promise of gold wasn't the Spaniards' only quest in the New World: they genuinely thought they'd find the Fountain of Youth on these shores. Had the Spaniards recognized the ritual paintings of snakes drawn by the Incas and Aztecs as symbols of rebirth, it would have tipped them off: The Indians werelooking, too.
Despite the occasional exaggerated claim of great age, no life of longer than 115 or so years has ever been documented. If something never happens, it probably means it isn't possible. So "forever" is out: would you settle for living 90 or so years in great good health and dying, as writer Dr. Lewis Thomas suggests is ideal, as "a healthy old creature" all of whose "bubbles" burst at once? Says Thomas, "What a way to go!"
THAT'S A DISTINCT possibility in the near future. Researchers are beginning to get a fix on the central reasons for the downhill slide of health that begins in middle age. Much of it hinges on the immune system, and biochemist Allan Goldstein has an important part of that puzzle in hand.
"To me the tragedy of life is that we spend so many years trying to get wise and by the time we're able to put it all together, our bodies fall apart," Goldstein says. The researcher has spent the last 20 years working to develop a way to avoid this grim eventu- ality. His focus is the immune system, what he calls "the bubble that protects us from a dangerous, hostile environment."
At 46, Goldstein exudes satisfaction. He is chairman of the Department of Biochemistry at George Washington University; he is working to develop his own Institute for Advanced Studies in Immunology and Aging; and he has a beautiful second wife, Linda, a 4-year-old son, Adam, and an important scientific discovery behind him. Ahead, if all works as it should, is the application of a simple substance, "thymosin," that will help us to live out the years to which we are genetically entitled -- in health.
The dialogue this night takes place in Goldstein's Cleveland Park home. The conversation, part science, part philosophy, part speculation, keeps coming to the possibility of enhancing the number of healthy years one can live.
Goldstein's soft, insistent voice dominates the hard-edged, science part of the talk. His colleague, researcher Nick Hall, young and British, focuses on the way people behave and what it means in terms of their health. "Nick watches rats and mice," jests Goldstein, ignoring his own lifelong preoccupation with cells, microbes and other squiggles. Their research is headed in the same direction. Says Hall: "We aren't simply going to be working with diseased people to see what has caused them to become ill. We want to define healthy individuals, people who don't get sick, to see what there is about them that keeps them healthy." A nice difference in approach: look at health instead of diseased organs.
What they have reason to believe they'll find is that the immune systems of extrahealthy people, regardless of age, are unusually effective. They want to identify what it is these people are and do that makes the happy difference. Then, they will formulate a "stay healthy" pill. "It will be taken once a day like a vitamin supplement," Goldstein says of the promising potential use of thymosin.
"We don't have any idea that we will be able to extend life expectancy more than a dozen or so years," he then cautions. "What we do think, however, is that thymosin can stave off the chronic decline in health that occurs with age."
TWENTY YEARS AGO, as his first independent research project, under Dr. Abraham White of Albert Einstein College of Medicine in New York, Goldstein undertook a "needle- in-a-haystack" research to discover whether the thymus gland secreted a hormonelike substance. It did, and he found it. Scientific opinion of the time maintained that the thymus gland, a smallish cluster of pink cells nestled under the breastbone, was useless after adolescence. We now know better. Goldstein emphasizes the gland's importance with a brief chronology of the thymus and the lymphocytes (white blood cells) for which it is responsible. n the first three months of life infants have fragile, incomplete immune systems. But their thymus glands are busy producing a supply of T-cells that will be able to mount defenses against infection. At the end of infancy the thymus weighs about 370 grams; in the elderly it [weights] around three grams." This disappearing act begins at adolescence and accelerates during early middle age.
The thymus processes white blood cells to create T-cells. These can live as long as 25 years and have a multitude of vital activities. T-cell interaction with the other class of lymphocytes, B cells, creates the immune system. This is usually defined in terms of self and other. Self is just that: the tissues of the self, each cell of which carries a unique genetic pattern, the famous DNA. Self is okay. In the body anything recognized as self is allowed to go about its business.
Other is a different story; a virus, fungus, something to which one is allergic, a novel bacterium, cancer cells and organ transplants -- these are strangers to be eliminated. In youth and in health the immune system does just that with fury and dispatch. But when the immune system isn't working well we are open to immediate danger from almost anything with which we come into contact and from miscoded cells of our own bodies.
Goldstein's first clinical success with thymosin was a child named Heather who was born with a rare condition that resulted in a complete lack of functioning T-cells. Her first five years had been a constant battle against infections and the little girl was dying. Thymosin saved her life and maintenance doses have kept her healthy enough to be, now, a junior high school cheerleader.
Heather was the first child t have ever been successfully treated with a thymic hormone, so a good bit of news was generated. When Goldstein came to George Washington University in 1976 his arrival was noted by political figures interested in aging. "My first real introduction to D.C. was a telephone call from Sen. Alan Cranston's [D-Calif.] office asking me to attend a Sunday morning meeting," Goldstein recalls, still incredulous: "It never occurred to me that senators worked on weekends!"
For the entire day, the invited scientists worked with Cranston, who Goldstein thinks has done as much as anyone on the Hill to advance the cause of the sciences. "It's a shame the TV camera can't capture Alan's great vitality and youth," Goldstein says, referring to Cranston's failed bid for the presidency, "because he's such a vigorous man. His gaunt appearance is a result of his lifelong marathon running."
Goldstein was dazzled by his first brushes with Capitolower people like Cranston and Robert Dole and former senator Birch Bayh. His growing up in New York and the years spent working in Texas didn't prepare him for the power trip in Washington. But, of course, New York wasn't the ideal launch-pad for Texas either.
"Dr. White was horrified when I said I was going to Texas," recalls Goldstein, "but I felt I had to fly on my own. They [the University of Texas] made me a 'godfather' offer, and at the age of 34, I had the opportunity to head a discipline, a big division of biochemistry -- with an unlimited budget to pursue my research." Goldstein feels he was helpful in building the department, but eventually he became frustrated at "the mentality of some of the administrators down there."
For Goldstein, getting to Washington "was a breath of fresh air, a more civilized world," he says. And being here has allowed him to work along with the top people in his own field of interest.
Thymosin is being used in close to 200 research programs around the world. "One of the things we can do with it already is to reverse the immunosuppressive effects of steroids [often taken to treat severe arthritis conditions] and of the chemotherapy being used in cancer treatment," Goldstein explains. "One of the major applications of thymosin at present is combining it with radiation therapy for some lung cancers. Radiation may knock out tumors, but it also causes profound suppression of the immune system -- because when you irradiate that part of the body, you're getting the thymus, too." And when you "get the thymus," the patient is liable to contract a multitude of "opportunistic" infections as well as having fewer cells left to deal with the cancer.
Dr. Richard Schulof at George Washington University Hospital treated 42 lung cancer patients with a combination of thymosin and radiation. On the basis of the positive results, the National Cancer Institute is sponsoring large confirmatory trials with thymosin in 300 patients with this kind of tumor at 20 centers throughout the country. The drug is also being given to patients with multiple sclerosis at a number of hospitals. Multiple sclerosis, lupus and rheumatoid arthritis are among many autoimmune diseases that thymosin is likely to help.
Goldstein, with Drs. Schulof, Craig Kessler and Gary Simons, has been treating patients at risk for AIDS with what appears to be considerable success. Although these patients have antibodies (showing they have been exposed) to the HTLV virus thought to cause the deadly disease, and though many have other early signs of AIDS, thus far, in over a year, none receiving high-dose thymosin have gone on to the killing infections characteristic of the immune deficiency disease. "Thymosin is no cure for AIDS," Goldstein emphasizes, "but it appears to stimulate the immune systems of these patients and may ward off the opportunistic infections from which AIDS patients do not recover."
The first trial of thymosin specifically for older people is to use the substance with shots of flu vaccine. Flu epidemics can be lethal for the elderly and infants, but vaccination programs haven't lived up to expectations. Goldstein says this is because, to eliminate a virus, the immune system has to be able to respond with active T-cells. Older people and infants often simply don't have them available for a vaccine to call up.
The treatment of disease and as a help in cancer therapy are only the first, tentative uses of the drug. "We hope to spend a lot of time developing immune profiles that will tell us about why healthy people are healthy. The profiles will include aspects of people's environments, cise. But, look!" says Goldstein, "it may all be mental!"
WHEN YOU FEEL GOOD, many think, you get healthy. Writer Norman Cousins swears he laughed his way back from the brink of death (with Marx Brothers movies). And take the notion a step further into a common hospital scene.
"I can't stand it!" wails a young nurse, "lovely Mrs. Harris is dying and that old stinker in 604 is going to be going home soon. It just isn't fair." The experienced charge nurse replies, "No, but you might as well get used to it; it happens all the time." Nick Hall says, "The patients who antagonize the doctors and nurses usually recover. Those whom everyone likes seem to take forever to recover -- and often succumb."
"This is a form of aggressive behavior described [in animals] by Lorentz and Tinnbergen," Hall explains. "However, instead of the body defending against predaronment, it's coping with a microbial environment. And why shouldn't both systems be under the same control?" Many facts support his thesis: the same hormone levels that appear to go along with various kinds of aggressive behavior, such as the sex hormones, are the nes for which there are markers on the cells of the immune system. These hormones are known to influence the functioning of the immune system.
Perhaps there is a given personality that determines how external events will be perceived and handled through life. Mothers with several children say they can feel the difference between their newborns from the very start. There clearly seems to be something special about the psychologies of "survivors." An important research question is whether a corresponding difference is reflected in the cells of their bodies as well.
One aspect of the question is how different personality types respond to "stress." There's much interest in Washington about stress and how it may alter the performance of people in space, in "submarines, even on the Hill.
We can assume that stress is anything that pushes an individual's mind or body beyond an ordinary neutral state. Disease does, strenuous exercise, sex, something perceived as hilariously funny or deeply depressing, the changes of age, the pimples of adolescence, a lousy haircut, a sick child, falling in or out of love. Life's events, in other words.
Those who experience, respond and act in aggressive ways -- and aggressive doesn't necessarily mean ugly, more like active -- clearly seem less likely to become helplessly stressed . . . and ill. By evaluating stress' im pact on the individuals involved and comparing blood cell changes to those taken in health, Goldstein and Hall expect to be able to draw chemical profiles of immune system functions under various stresses. One of the most important measures will be that of the thymosin levels.
THERE'S CERTAINLY little pleasure in aging. All the talk about the "golden" and "leisure" years, the smiling, wrinkled faces in condominium ads, are a pure shuck. The young person trapped unbelieving inside the aging body faces a daily insult in the mirror. But maybe if Goldstein and his group can do what they are convinced they can, things will be better. Knowing you could avoid the chronic, crippling disabilities of age would make a mighty difference.
Allan Goldstein says it's not only possible, but imminent. He's getting along himself, and he isn't wasting any time. "If we can be as successful at fund-raising as we have been with treatment -- well, we should see some pretty dramatic results in only a few years."
Goldstein and Hall, and the remarkable group they've assembled as directors of their embryonic institute (Cranston, Jonas Salk, Mary Lasker, Nobel laureate Julius Axelrod and others) need funding. They are going about it in a straightforward way, to the usual sources. But a major source is closed to them because the NIH doesn't fund interdisciplinary programs. Like his exciting AIDS study -- which won't receive needed federal funds for another year or so -- the institute for the study of aging may also have to wait. There's a lot of talk about prevention, but precious little money for creative thinking in the area of aging. Goldstein is marginally sanguine, having had to fool around with money people many times before. But he's frustrated. You get a good thing like thymosin, and good ideas like the ones they're working with now, and "you just hate to think of the people who could be helped if the money was there."