Well, now, Doctor, just in confidence I’m going to tell you something that may strike you as funny, but I believe that foxes’ lungs are fine for asthma, and T.B. too. I told that to a Sioux City pulmonary specialist one time and he laughed at me—said it wasn’t scientific—and I said to him, “Hell! Scientific!” I said, “I don’t know if it’s the latest fad or wrinkle in science or not,” I said, “but I get results and that’s what I’m looking fir’s results!” I said.
—SINCLAIR LEWIS, ARROWSMITH (1925)
One way to wrap your head around the gulf between today’s brand of commercial, antiaging medicine and the world of academic longevity science is to look at the graphics to the left. The first, entitled “The Six Stages of the Life Course,” comes from a university textbook, The Molecular Biology of Human Aging; it represents the classic, humanistic impulse of modern gerontology to define various stages in the aging process and vest them with some meaning. The second—a pair of original illustrations—was inspired by drawings found in a book by a man named Georges Debled, almost unknown to American doctors but who, for some time, dominated the popular European discussion of male aging and the use of testosterone. The two are not even in the same universe.
It was easy to come by the first graphic, reflecting as it does our modern neoclassical ideas about aging—that it is “natural” and “inevitable.” It was difficult to come by the second. It was only after traveling for some time in the world of hormones and antiaging medicine that it came to my attention. As a male, it held special appeal. Not that I am that fat, but that, at the age of fifty-three, I had a testosterone problem; I didn’t have any. It had taken a while to discover that, and to find out why. I had suffered a moderate concussion in a horseback riding accident a few years ago, and, ever since, I had displayed all the signs of an aging man: extreme grumpiness, becoming overly startled at sudden noises, becoming easily overwhelmed, a decline in libido, and an overall loss of energy. Not for nothing has hypogonadism been dubbed a form of accelerated aging; and not surprising is the fact that, if you search the catalog of the National Library of Medicine with the words “testosterone” and “aging,” you get some of the few journal articles in existence with the word “grumpiness” as a medical term. Mainstream endocrinology recognizes the syndrome and cites it as one reason all concussion patients should get tested for hormone levels. Yet in all the top-flight, big university med school consultations that followed my case, no one—no one—ever suggested, let alone prescribed, such a test. I was left wondering if I would be a proto-senior forever. Hormone replacement, the single most powerful element in the modern antiaging apothecary, loomed. What was it all about?
“Rich guys playing with their hormones,” said Dr. Fran Kaufman, one of the foremost endocrinologists in the United States. “You know, basically, that’s what you’re talking about.” Kaufman and her husband, Dr. Neal Kaufman, and I were sitting in a West Los Angeles Starbucks on a rainy Sunday afternoon, talking hormones, aging, and health. Fran Kaufman had agreed to look over some PowerPoint presentations that I had been given by Dr. Ron Rothenberg, a prominent antiaging physician; I had interviewed Kaufman before on a number of articles and had come to appreciate her depth of knowledge, openness to new ideas, and worldly sense of humor. And so we had flicked through the PowerPoints, one on testosterone, one on human growth hormone, and one on estrogen. As I tapped the computer pad, I noted, out of the corner of my eye, something odd. Fran Kaufman, usually hyperattentive, seemed, frankly … a little bored.
I pointed out the data supporting hormone supplementation. She didn’t rise to it. I asked her if I should try it. Ho-hum. What about growth hormone?
Neal, a respected clinician and one of L.A.’s more agile thinkers about health care, jumped in. He had his own ideas about hormone supplementation. “No one talks about the fact that perhaps nature—or evolution, whatever—intended for humans to have low hormones as they age. Think about it: low estrogen and low sex drive after giving birth makes sense for women; their priorities and role in life have changed. The same with growth hormone; once we are past the time of life when we grow, physiologically … well, how much do you need? And testosterone—you know, that has a huge cancer risk, and—”
“But Neal, that’s not true,” Fran broke in.
“It’s not?”
“No, not testosterone. That’s not the big issue with that. You can give it to guys who want it, as long as you have the right monitoring and lab tests. It can be a huge help, too. The issue there is almost like giving thyroid—the issue is, can they stand it? A lot of guys get it and don’t like the way it feels, at least until a week or so after the injection. And frankly, if it helps them, how much should we care about what evolution intended?”
“Well,” Neal said, taking a sip of his coffee. “I’m still not sure. I wouldn’t prescribe.”
We laughed. Neal’s penchant to consider the vast complexity of health care is the subject of endless discussion, and Fran often gibes him about it. “Yes, I know, but when would you ever prescribe anything!” We all laughed again.
Driving home, back up through the rain-soaked Sepulveda Pass, I began to wonder: Was hormone supplementation for me?
Once upon a time, hormones—from the Greek hormao, meaning “impetus”—held a place of pride in American medicine, both for specific disease treatment and for longevity enhancement. Testosterone provides the perfect example. The principal male sex hormone, T, as it is abbreviated, is made in the testes after it is stimulated by follicle stimulating hormone, or FSH, itself made in the pituitary. Its origin in the pituitary, a small, saddle-shaped gland that sits behind the base of the brain, explains its connection to concussion; if you’re out long enough, or get hit hard enough, you get impaired secretion of FSH, and, consequently, low testosterone. (This is why football players and boxers always seem so grumpy.) That’s what happened to me, but to a less dramatic degree it is what happens to all men after the age of about forty.
Since the late nineteenth century, medicine has been trying to find a way to “top off” lowered T in fellows like me. In 1889, the Harvard professor Charles-Édouard Brown-Séquard reported his “rejuvenating” injections of dog and guinea pig testicle extract in the Lancet. His experiments were not easily replicable, and when they were, the treatment was found to be weak and transient at best. There followed two decades of what might be called circus medicine—testicles from corpses sewn into the thighs of prisoners, which produced very crabby prisoners but little else; extracts of racehorse balls and tinctures of monkey pee, which lightened the pockets of the nation, but did little else; and any number of strange and bizarre testes transplants in chickens, roosters, pigs, goats, horses, and, of course, mice and rats. The consequence of this oft-misguided research was predictable, especially in America, where commercial medical science seems only to have an “on” and an “off” button. Brown-Séquard died in ridicule, as did any reputable research on male sex hormones; that is, until the 1930s, when two things happened.
One was that the basic physiology of hormones got worked out by the young field of endocrinology. It goes like this: Specific chemical messengers secreted by specific glands are carried by the blood to “targets” or receptors on cell surfaces. The messages then get transcribed by the inner cell, which in turn sends a reverse signal to the originating gland, telling it to stop secretion. Such is the essence of the now well-established endocrine concept of a negative feedback loop. The other breakthrough came in manufacturing, as large pharmaceutical companies developed methods for cheaply converting cow cholesterol into chemical testosterone. (A parallel process of the era succeeded in deriving estrogen and progesterone from wild yams and soybeans.) The first wave of therapeutic use, in the 1940s and 1950s, was followed by scandal, as the chemical methyl-testosterone was found to be responsible for a number of cancers. The consequence—played out in the realms of other hormones as well—was reluctance by clinicians to prescribe it, even long after safe versions of T came on market. Robert Butler, the dean of modern gerontology and no friend of today’s antiaging medical crowd, recalls trying, with no success, to get the NIH to sponsor clinical trials of testosterone therapy on older men. “They were just too frightened of the cancer risk.”
Bubbling underneath the medical establishment, however, two powerful trends were unfolding that were less driven by fear and more driven by opportunity. The first was the rebirth, phoenixlike, of the traditional compounding pharmacy—the kind once depicted in Norman Rockwell paintings. In an era of Walmart and mail-order prescriptions, it is hard to believe that pharmacy compounding, the on-site mixing of raw chemicals in accord with a written prescription from a physician, had been the norm, worldwide, until the 1940s, when large drug companies began to standardize doses, usually in tablet or capsule form. By the 1980s, 99 percent of retail pharmacies simply counted out prepackaged doses into little containers. The art of compounding—and, frankly, some of its inexactitudes—was lost, but so was the ability of modern medicine to respond, simply, to the vast range of dosage variances inherent in as diverse a population as that of the United States.
Then something happened. That something was about “hardons,” says John Grasela, now one of the leading compounders in the United States. Or, rather, “the inability of older men to get sex-enhancing drugs out of the traditional drug system.” I had met Grasela at the annual convention of the American Academy of Anti-Aging Medicine (A4M), where his pharmacy, University Compounding Pharmacy (UCP), was sponsoring a session entitled “How to Turn Your Practice into a Cash-Based Anti-aging Business Now!” His booth was mobbed, and when I asked for an interview, he suggested I drive down to San Diego to talk to him the next week. “I can’t get loose now!” I took him up on it and met up with him at UCP headquarters, a low-slung commercial building just on the outskirts of downtown San Diego.
Grasela is a tall, somewhat taciturn-looking man in his early fifties, with the demeanor of a small businessman—all purpose—and a tan. Over a cup of hazelnut coffee and his “daily dose” of some twenty vitamins and supplements, he gave me a look at “the future” of the pharmacy in America. “This is for when your dick gets crooked,” he explained, gesturing to a tube of ointment for a compound that had been discontinued by one of the large drug companies some time ago. “And this is where we mix the testosterone cream,” he said, tapping on a big metal bowl and mixer. “We can do five pounds at a time!” Trained as a pharmacist at Wayne State, Grasela and his partner sold off their first business venture, a chain of drugstores in Detroit in the late 1980s and went west. “We basically took the money and ran,” he says of the midlife career move. “We had a license in California and we worked our way down the coast, looking for an opportunity. We bought our first store in San Diego and we realized what we’d walked into was an aging population. These were people who came here during World War II and worked in the naval yards and retired.” These were also people who wanted to keep screwing. Grasela started getting calls for “stuff” the drug companies had dropped because of low sales, like paparavine, a vasodilator that could be used “for hard-ons,” as Grasela puts it. Then there was pentolamine, another hard-o-nergic blood pressure med also dropped for low sales. “It was a great opportunity to get started in compounding, and it got me interested in aging.” He then went to one of a small number of antiaging physicians in the area for a personal consultation. There, he recalls, he got the hormone gospel: “It was a revelation. I’d never thought about aging, and about replacing only what your body needs. That made sense to me.” Soon, he was on a full regimen of hormones and vitamins. He felt fantastic— “leaner, with more energy, and that’s not to even mention the creative juices!”
But why, he kept thinking, weren’t more physicians practicing antiaging medicine? The short answer was that hormones are complicated, they didn’t always work as intended, and to prescribe them responsibly required a physician to order a lot of detailed blood tests, for which insurance companies and managed care did not want to pay. It was a stalemate. Then Grasela got a brainstorm. Fuck the insurance companies! (It was a sentiment, shall we say, that was shared by many.) The real issue was education. If you could educate average clinicians about how to diagnose, treat, and monitor hormonal deficiencies in older people, and find a way to standardize the lab tests to ensure people did not get sick and sue you, you could transform your practice into a cash practice. Patients—the right ones—would pay cash for antiaging medicine. Patients. Cash. Antiaging.
So Grasela did what many pharmaceutical companies do when they want to prepare the way for an expensive new drug. He recruited “thought leaders,” or experts, in various fields of hormone replacement to give paid workshops on the subject. He advertised in trade publications and underwrote health shows on cable TV. The workshops were an instant hit. “The physicians are basically being driven into it by their patients, who are very motivated patients, cash patients,” he says. “And that allows the physicians to reinvent their practice and gets them out of the pharmaceutical corner. They like it for another reason too. It is fun medicine.” Fun? “Fun in that it is not about trying to get a guy to diet and exercise.” He cited a recent Las Vegas workshop as an example of “how mainstream” hormones have become. “Of the 270 doctors there, 80 percent were rookies to a hormone workshop.” His own business has been transformed as well. At his state-of-the-art compounding operation alone, Grasela now has twenty-eight full-time pharmacists; he fills more than five hundred prescriptions a day. “But I have not lost sight that this is a fun business,” he says. “This is not about keeping people from dying. We want to leave at five thirty every day. It’s quality of life.”
The offices of Dr. Ron Rothenberg, one of Grasela’s thought leaders, sits off the San Diego freeway, not far from the famed Scripps Medical Center. Rothenberg had agreed to speak to me about antiaging medicine, and to treat my hypogonadism. I had heard him talk at an antiaging medical convention on the topic and had read his book Forever Ageless. He seemed sane, if, to my mind, a bit overoptimistic. His offices, which are modern, spacious but not particularly lavish, conjured a slightly oceanic feeling, with pastel colors and paintings of fish all around. Despite this, I did not hate Rothenberg. I found him to be a pleasantly engaged fellow with a refreshingly nebbische surfische sensibility—one underscored by the red, white, and blue surfboard hanging on his office wall, and the Hawaiian shirt under his clinician whites.
Coming out of a traditional medical education, Rothenberg, like a number of antiaging physicians, originally specialized in emergency medicine. “It made sense for a guy like me, who has a kind of hands-on approach to life in general,” he said. When he got a little older—and started seeing the signs of aging in himself—he started asking questions. Mainly about hormones. “Why hadn’t we been educated about them more?” he says. He began reading the various theories of aging and, in the not-unreasonable amalgam of understanding that he calls “the ongoing search for the truth as a moving target,” came to believe that the underlying cause of aging is hormonal. “We age because our hormones decline, not vice versa,” he likes to say. Although there are deep, deep problems with this statement—what, for example, causes the thymus to wither, the pituitary to stop making growth hormone, or the adrenals to stop making cortisol?—it is not off the grid either; the Stanford evolutionary biologist Robert Sapolsky has advocated something similar in many of the most respected journals in the world. Testosterone decline—apart from regular age-related drops in testosterone—is also hot among epidemiologists, with one large study showing that a sixty-five-year-old in 2002 had lower testosterone levels than a sixty-five-year-old in 1987. No one knows why, but the highly flaccid chart illustrating that drop …
… is one of Rothenberg’s favorite talking points.
What separates Rothenberg from the academics is his willingness to prescribe hormonal replacement for levels that the establishment deems “within the reference range,” or normal, or even “low normal.” “What is low normal—what is that?” he says with a Shecky Greene shrug. “Using that philosophy, do you only give a person who is nearsighted glasses that make them see as they might have at forty, rather than at twenty? What is that?” Applied to hormones, in my case testosterone, that means bringing my low-normal score of 350 (the range is 300-1000) up to youthful levels. He looks at my lab tests and then looks over at me, eyes sparkling, and chuckles. “Oh, you are going to feel so much better!”
And, truth be told, poorer. For if anything, the cost of the lab tests ($500, cash, to be repeated at least twice a year) presages the other most notable difference between Rothenberg and my usual family physician: the utterance of the word “money.” When Rothenberg’s office first received my lab tests, his assistant was on the phone, asking me if I wanted the basic lifestyle plan ($3,000) or the advanced antiaging plan ($12,000). A lot of this depended upon which hormones I decided to take, but there’s an interesting social contract at work as well, one usually not articulated in traditional clinical medicine. It is this: You pay me x per month, or I will not approve the refill of your prescription. Not surprisingly, I took the minimum—Rothenberg insisted that I take a thyroid extract as well as T because I was “low normal” on that—and I aggressively refused the lifestyle consultations on food and exercise.
Nevertheless, the “sell” of supplements—Rothenberg says, and I believe, he does not make money off the items but rather offers them at his wholesale price—can be off-putting. As I was waiting for him to perform a physical, two female assistants came into the examination room to give me samples of some kind of “acacia blueberry antioxidant” drink. I asked them to leave. They looked … hurt. Later, the same pair loaded me up with free samples of various blender drink supplements. They gave me a long lecture about the right time of the morning to drink this concoction. One of them then gave me a cursory lecture about warning signs from the testosterone cream I would be getting—from, of course, University Compounding. “Basically,” she said, “you can’t use too much of this stuff. But if your nipples start to tingle, dis … con … tin. … ue! And, oh yeah, don’t smear it on your testicles.” Put it on your arms, thighs, or chest. Oh … yeah.
The money, combined with the nontraditional yet scientifically fortified presentation, would be off-putting to anyone, but I wondered how off-putting much of traditional medical treatment for chronic disease would sound if the terms were stated just as baldly, instead of hidden behind the baloney boilerplate of HMO-speak. (Prozac as “first line treatment for clinical depression” might be translated as “we will pay for Prozac because Lilly will give us a good deal for buying it in bulk, but not for therapy, because your therapist will not work for $5 an hour.”) I decided to cut Rothenberg a break on that matter—there are plenty of ethics police out there already, there you go boys; go get ‘em!—and simply adopt a pragmatic attitude: Would it work? Clearly there were some measurable ways to assess this antiaging regimen. My cholesterol was high—and had remained so despite an energetic lifestyle and a reasonable, regular Mediterranean diet, albeit one supplemented with cookies and milk. We could check that in six months and $500 or so. My blood sugar and insulin were OK by conventional measures, but Rothenberg thought they could be a lot better. “You’re flirting with diabetes.” We could measure that, too. And, of course, there were the persistent unmeasureables that had pushed me toward treatment in the first place: the jumpiness, the lack of energy, and what I called “cognitive swamping.” Would I get better? We’d see.
Before leaving, Rothenberg asked me in for one more mini-consult. “You know,” he said, “your growth hormone levels are low, too—you qualify for supplementation of HGH, you know.” But isn’t that dangerous? “Are you kidding?” he said. “That’s just the official line. If you go over there to Scripps and ask the big shots about it, they’ll all tell you, ‘don’t do it, it might cause cancer,’ and all that. But let me tell you—half of them are on it themselves, just like me. And they love it.”
HGH—short for human growth hormone—is the second force that freed vast swaths of clinical medicine from its anti-hormone bias. In short: it was just too good not to try it.
Growth hormone, made by the pituitary, has often been called the master hormone. Its effects on the human body run broad and deep. A protein comprised of 191 amino acids, its main job is to signal the liver and other organs to produce insulin-like growth factor 1, or IGF-1, the bogeyman molecule that Paul McGlothlin at the CR Society hates so much. As its name suggests, IGF-1 is responsible for growth and maturation of bones, muscles, and cartilage. IGF-1 is also a potent anti-infection hormone; it repairs and replaces destroyed cell tissues, and it protects the heart. Just how HGH makes IGF-I, and how IGF-1 functions both on the whole body and on its individual parts, may be one of the most complex single investigations in all of medical science today. No one knows exactly how the pathway works, though there are a number of good beginnings.
This relative dearth of science, of course, never stopped anyone from, as you might guess, grinding up the pituitaries of dead people and injecting said pituitaries into children with growth hormone deficiencies. Perhaps the only thing that prevented mass grave robberies was the singular invention, by Genentech in 1981, of a way to synthesize vast quantities of HGH using modern recombinant DNA technologies. By 1985, somatropin was on the market, approved by the FDA for use only on children with documented deficits in growth hormone. Lilly, Pfizer, and the rest followed with their own versions. Of course, everyone over forty or so runs low on growth hormone; as Neal Kaufman alluded, evolutionary biologists long believed this was an adaption to long life spans—lack of growth hormone might be an evolutionary check on cancer, a form of unhealthy growth that happens more and more frequently as people live longer. Although that theory has been broadly challenged in recent years, it was one reason that many clinicians were wary of using the hormone, even when clearly warranted in borderline dwarf children.
Then, in 1990, a physician and medical researcher at the University of Minnesota, Daniel Rudman, had a breakthrough. Rudman was interested in how elderly men, displaying all the signs of normal aging, might respond to HGH therapy. It was not a theoretical pursuit. Rudman had a long and abiding interest in how frailty in the elderly could be treated, or, better, prevented. For six months, three times a week, he had twelve “overly healthy” (not fat and not too skinny) men aged sixty to eighty years inject themselves with the hormone; these men, like an estimated one-third of all men in that age group, had less than 350 U/liter of blood of IGF-1, indicating a substantial lack of growth hormone. (Healthy men between twenty and forty average somewhere between 500 and 1500 U.) Nine other subjects in the control group received nothing. All followed the same diet.
After six months, the results were striking. Although there was no substantial weight gain in either group, the men in Group One experienced two profound changes: an 8.8 percent increase in lean body mass, and a 14.4 percent loss of adipose tissue—exactly the opposite trend displayed in almost all aging human bodies. Shrinking livers and kidneys got bigger. The men also registered substantial thickening of their aged skin, and small but important gains in bone mass. Although Rudman had many reservations about the intervention, he could not help but phrase the findings in a way that would be … noted. “The effects of six months of human growth hormone on lean body mass and adipose-tissue mass,” he wrote, “were equivalent in magnitude to the changes incurred during 10 to 20 years of aging.”
Here we pause for a test on American medical culture. Finish the following sentence:
“Quickly the findings were seized upon by (choose one) …”
(a) the gerontology community, which tried to convince the government to conduct wider trials in hopes of adding something to the thin pharmacopeia for dealing with frailty, a growing cause of death among the aged.
(b) the AMA, which was concerned, as the population aged, that there existed no good way to deal with sarcopenia, the muscle wasting that accompanies old age and which is responsible for many deaths that result from falls by the elderly.
(c) pharmaceutical companies, which, seeing that there were not enough dwarves around anymore to buy their HGH, decided to hype the findings.
(d) two “bone doctors” from Chicago, one of whom held the Guinness Book world record for one-armed push-ups and handstands, who wrote a best-selling book promising that HGH could “stop the clock” on aging.
Bone doctors, or osteopaths, have been discriminated against for decades in the United States, although, like compounding pharmacists, they once held considerable sway. The problem is that osteopaths are largely practitioners of holistic medicine, and in a society that demands scientific evidence to justify a treatment, theirs has been a vocation of faith—faith with a few footnotes. Nevertheless, their numbers have begun to climb back up in recent years, fueled in no small part by older Americans who’ve had a gut full of modern medicine and pharmaceuticals. DOs now occupy a fast-evolving niche of medicine, fast because they tend to be more experimental than their brethren MDs.
In the 1980s, few were more enterprising than Robert Goldman and Ronald Klatz, two Chicago bone doctors with an interest in sports medicine. Goldman, a weight lifter with broad shoulders, a trim waist, and curly hair, was fascinated with steroids; Klatz, the Poindexter of the pair, was an inventor, constantly coming up with new patents for brain-cooling devices and bladder catheters. They both eventually specialized in sports medicine. After Klatz suffered a bad car accident in 1991, the pair gravitated toward the subject of aging, and in meetings, first informal, later more organized, they began to talk about aging as a disease. “It was very exciting, because, here we all were, in the middle of careers, and we began seeing things differently,” recalls Vincent Giampapa, a plastic surgeon who hung out with the pair. “The idea that aging was a disease, and not something that was the natural course of things, was radical, but we saw the connections.” Convening a like-minded group in the global medical science capital of Cancun, Mexico, in 1992, they formed the American Academy of Anti-Aging Medicine, often shortened as A4M. They bought a large, neo-Gothic mansion in Chicago for headquarters.
Right from the beginning, growth hormone promotion loomed large in A4M’s evolution. As Klatz tells the story, “Also present at the [Cancun] conference was another group of people, who were not part of the scientific crowd. They were a striking bunch, trim, muscular, sexy, energetic, upbeat, with the vibrant look of good health. Yet these were people in their fifties, sixties, even seventies. They talked about changes they had undergone—melting away of fat, increased muscle tone even in the absence of exercise, a vastly increased sense of well-being.” They were in Cancun because it was the only place they could get treatment with growth hormone. “Then a strange thing happened,” Klatz recalled. “The doctors and researchers who had assembled to form this organization devoted to aging were suddenly on the defensive. Could these claims be true? Had these people truly stepped back in time, or were they suffering a mass delusion? ‘My God,’ said one of the scientists, ‘we’re all talking about the possibility of reversing the aging process and here these people are actually doing it.’” Within a few years, Klatz and Goldman were HGH converts. The FDA had by then been persuaded to broaden the definition of who could be prescribed HGH. In 1996, the pair published Stopping the Clock: Dramatic Breakthroughs in Anti-Aging and Age Reversal Techniques; the next year, Klatz published Grow Young with HGH.
Should you take it? The claims in both books were largely based on anecdotal case reports and small studies of people with severely abnormal growth hormone deficiencies, not the moderate deficits experienced by most aging people. But long-term studies would be several years in coming, Klatz argued. And even then, who knew how long it would take the medical establishment to sign on to HGH replacement? It had taken forever for them to adopt estrogen and progesterone replacement for women. “We believe the consequences of not acting are far worse than the consequences of acting,” he wrote. Every day that goes by, the aging process is eroding vital capacities “in every cell in our bodies.” Deciding whether or not to go on HGH could have life or death consequences for all. Waiting for definitive studies was not worth it. It was time to act.
There was one other extremely controversial claim. It was this: that growth hormone and other replacement therapies would add thirty years to maximum life span.
Now everyone was interested in HGH. Sales soared. Celebrities endorsed it. The visage of Dr. Jeffry Life, the sixty-eight-year-old proponent of hormone replacement for antiaging, graced the pages of the nation’s toniest magazines. “Only replace what you lose naturally”—the great Grasela’s maxim—rang though the land, especially in retirement communities. It “just made sense.”
The illustrations on the office walls of Andrzej Bartke—one of a mouse, one of a sunflower that Bartke drew himself, and one showing mortality curves of mice put on caloric restriction—suggest the kind of grand, expansive, and eccentric world that all great naturalists seem to crave. One thinks of Darwin or Huxley, perhaps even Linnaeus, the great classifier of species, or Gesner, the Renaissance master of zoology. It is a world of complexity, nuance, doubt, wonder—and more doubt. It is not, to put it mildly, the kind of world that embraces ideas like “only replace what you lose naturally” because it “just makes sense.” This is exactly why Andrzej Bartke, a courtly, Krakow-born endocrinologist with a fondness for zoology, has become public enemy number one to many in today’s commercial antiaging medicine community. “Has the guy ever treated a patient?”—the ultimate put-down in that go-ahead world—is how Ron Rothenberg described him and other critics. Bartke’s sin is that he has dared to demonstrate two deeply troubling physiological facts in mice: one, that continuous, high levels of human growth hormone accelerate aging, and two, that low levels of it may extend maximum life span. In describing the results of his work, he is fond of one qualifying caveat: “in mice.” Or, as he uncharacteristically emphasized in his normally emotion-free e-mails to me: “IN MICE!” Yet despite his persistent caveats, Bartke’s work nevertheless has made it into all kinds of public forums about human aging. In 2007, Bartke’s research was even entered into congressional testimony about HGH use by professional baseball players, who are not mice.
As Bartke, a professor at Southern Illinois University School of Medicine, tells it, he got into the subject almost accidentally. Until the early 1990s, his work centered on a completely different hormone system, that of prolactin, a stress hormone that Bartke discovered played an important role in fertility. He studied it in two strains of mutant, dwarf mice—the Snell and the Ames—that carry a mutated pituitary gland, and, hence, little or none of the hormones signaled by that gland. “It was kind of an endocrinologist’s dream,” he said in his mild-mannered, almost monkish way of discoursing, head bowed, holding his brow with one hand. “I mean, you had one condition, and you had one hormone that could treat the condition.” It was a dream because things endocrinological—the endless systems of signals, negative feedback loops, and cell surface receptors that go into hormonal science—just did not unwind that way very often. So Bartke burrowed in further. He was on to something.
But while Bartke, in test after test, cautiously characterized the role of prolactin in mice, his fellows at other institutions were onto a much sexier pursuit—genetically engineering human growth hormone into cows, pigs, mice, and other animals. Much of the work was funded by the government, with an eye, ultimately, on increasing meat production in cows and pigs. One of Bartke’s friends and mentors, Tom Wagner, at Ohio State, succeeded in developing a strain of transgenic, or TG, mice that overexpressed growth hormone. The result was remarkable, if, in retrospect, predictable: animals that were twice to three times as large as normal mice, promptly dubbed “giant mice.” Wagner and others were just as interested in the scientific technique—at the time, introducing a foreign gene to an organism by using an activating third gene—but an unforeseen threat to the giants’ ability to reproduce brought them Bartke’s way. The giants—they were infertile.
Fairly quickly, Bartke figured out what was in play. The overexpression of growth hormone had tweaked other hormonal systems, in particular that of prolactin. “We knew we could fix that by giving the mice prolactin,” he says. “But the thing that got all of our attention”—meaning his colleagues Holly and Kurt Brown-Borg and himself— “was the condition of the animals. They looked awful, like they were falling apart. You could see it when you compared them to normal mice—the TG mice had the humped-up back, the fur loss, all of it—and they tended to die off sooner. That got our attention. When we dissected, they had aged kidneys and other glands. What could it be?” Eventually, Holly Brown-Borg put up a counterquestion. “Well,” she said to Bartke, “you worked with the dwarves”—the Snells and the Ames mutants that had the opposite problem, little or no growth hormone— “how long do they live?” As was the case with McCay and his rats sixty years before, the answer was “I don’t know,” Bartke says. “We had always euthanized when the experiment was done.” For the next three years, the trio ran experiments comparing normal and Ames dwarf mice, which lack the pituitary gene known as Piti. It was difficult getting funding, “because everyone was on the growth hormone track and really did not want to hear about it, everybody was talking about Rudman.” Eventually a small grant came, tellingly, from the USDA.
The results of the Bartke trial, published in Nature in 1996, were clear and unequivocating: The dwarf mice lived 50 percent longer than normal mice. Not only that, they, much like CR mice, had far lower rates of almost all diseases, including cancer. They also showed delayed aging of the brain and arteries—fewer inflammogens, plaques, and glycation products. The theoretical implications were far-reaching; for the first time, a single gene mutation in a mouse could be shown to extend life span, thus placing the mouse and mammals in the same arena of life-extending genes as the fruit fly, the worm, and yeast. All showed major life span extensions when IGF-1, the hormone generated by growth hormone, was down-regulated, or reduced. As Richard Miller, of the University of Michigan Geriatrics Center and one of the world’s foremost scholars on mice and aging, noted, “this was a remarkable piece of work.” It held the promise of fundamentally changing our understanding of how mammalian aging—and by some extension, human life span—were controlled by specific genes. Predictably, leaders in the antiaging community were incensed. “They wrote this incredibly detailed, passionate letter to the editors of Nature,” Bartke recalled. “It was … disturbing in that it basically said how dare someone imply that low growth hormone and reduced IGF-1 is good.” He gently spread his arms, smiled, and shrugged. What can you do?
But the accusation, and the barrage of data that the anti-aging proponents of HGH submitted to support their case, got Bartke’s attention. He noted that almost everything Goldman, Klatz, and others had written referred to “more than 2,000” studies that proved their case, that HGH was a bona fide anti-aging agent. Bartke began checking their data, and what he found disturbed him. “Almost every one of these supposedly solid studies was based on case studies of patients who were middle aged, and who had vastly abnormal growth hormone levels, not elderly people with normal levels, which you might have expected since they were saying that HGH was an anti-aging drug for the elderly.”
Bartke and his colleagues went on, as did Masoro and Walford, to parse and refine their own results. What was it about reduced—but not completely blocked—growth hormone and IGF-1 that extended life span? He put Snell and Ames dwarves, which make little or no growth hormone—or thyroid, for that matter, because of their pituitary mutation—on caloric restriction. The result was further increased life span. He then tried CR on a mouse with a different mutation, one that generated its own growth hormone, but which lacks a complete receptor for it on the cell surface, leading to completely blocked IGF-1 action. That mouse, named GHRKO for growth hormone receptor knock out, showed no further life span extension from CR. To Bartke, that just showed how complex the hormonal connection to life span extension could be. There were other hormones involved, he saw, and growth hormone itself was probably doing other things in the body that we do not understand. And IGF-I, undoubtedly important to heart and bone and metabolic health, was likely being autonomously generated by other organs, like the heart and brain. “And remember,” he likes to say, “this is in mice that we are showing this, not people, although it would be very unusual for a trait that seems preserved in everything from yeast to mouse not to have some bearing on humans and human aging.”
But there was an important corollary to CR humans: the dwarf mice were infertile and cold, the GHRKO mice were not. All of this implied some complicated connection to metabolism, reproduction, and multiple hormones—not just ones that you could easily “top off.” As Masoro had noted years before, it all seemed to connect to the way fuel was used in the body, the way it was partitioned. The dwarves and the GHRKO seemed to partition fuel to be used for maintenance and repair of the body, the giants seemed to partition it to favor rapid and excessive growth, and the normal mice somewhere in between. The implications for aging grew clearer, especially if you believed, as do many gerontologists, that a huge part of the underlying aging process is the loss of the ability to repair damage to cells.
There was something else. In almost all of Bartke’s scenarios of extended life span, on the one hand, and shortened life span, on the other, the great constant was insulin sensitivity. The dwarves maintain it to the end, as do mice on CR; the giants, while they have it early on, rapidly begin to lose insulin sensitivity, leading to diabetes and accelerated aging. Why the disparity? One emerging thesis is fat cell patterning. Dwarf mice are obese, but almost all of their fat is the more beneficial subcutaneous fat. Subcutaneous fat cells are smaller, and secrete tons of a hormone called adiponectin, which raises insulin sensitivity as well as anti-inflammatory and anti-atherogenic factors. Bartke wonders at the consistency: “What strikes me about all this is that what we are seeing in these long-lived mice is the opposite of metabolic syndrome,” the obesity-related conflux of high blood pressure, insulin resistance, and high cholesterol seen in a growing percentage of the population. “Having an opposite syndrome is a huge advantage.”
I asked Bartke if this was his way of saying that enhanced insulin sensitivity, rather than stress resistance, ought to be the Holy Grail of life extension study. He smiled beneficently. We had been talking about the exciting work emerging from the laboratories of Leonard Guarente and David Sinclair, the resveratrol proponents whose work on sirtuins has tended to emphasize stress resistance to oxidative damage as its main life-span-extending effect. We had also been talking about how the oxidative damage theory of aging had not exactly been faring well in recent years, with a number of studies showing that, in terms of aging, oxidative damage may be a relatively minor player. Sinclair, after all, had sold his company to Glaxo for $750 million last year, mainly because early clinical tests demonstrated that his compound had potential as a diabetes drug; a later study of resveratrol in normal, as opposed to high-fat-eating mice, showed it had no life-span-extending properties. Bartke seemed to have anticipated that himself a few years ago when, upon concluding one article, he wrote, “We suspect that research efforts to develop ‘CR mimetics’ for pharmaceutical intervention in the aging process may be more effective if they focus on targets in the GH/IGF-1/insulin signaling axis.”
What are you trying to say? I asked again. He sheepishly handed me a piece of paper. On it was a flowchart that detailed various theories of aging and how they intertwined. At its core loomed the words “decreased growth hormone.” From that box flowed all manner of boxes and arrows, from “decreased cancer incidence” to “increased stress resistance.” The only point on this map that had three distinct intersecting lines was a little bubble marked with the words “increased insulin sensitivity.”
“That’s what I’m trying to say,” Bartke said, nodding gently at the diagram. He smiled even more beneficently. “In mice!”
If Bartke has been slow to extrapolate his results to humans, a vocal core of scholars in the gerontology establishment—Big G—has not. The gerontologist Jay Olshansky, from the University of Chicago’s School of Public Health, took a leading role in the anti-growth-hormone crusade in mid-2005, proffering Bartke’s work as his standby. Olshansky, a big, bearish man, and his friend, the quieter Dr. Thomas Perls, who oversees the New England Centenarian Study, were so convinced that all antiaging medicine was quackery that they began saying so in a variety of scholarly forums, which led to their being sued for libel by Klatz and Goldman. The case was later settled, but it left both scholars even more vigorously opposed to growth hormone. Perls took the case to Congress, citing Bartke’s work—something one of his peers told me was “intellectually dishonest,” and another characterized as “unproductive and, let’s face it, where does it end when you start censoring people for their views?” (I later had the chance to ask Perls if he regretted the campaign, to which he replied, “I only wish we could get a prosecutor who would be willing to pursue a RICO case against these guys!”) Olshansky managed to marshal a broad group of scholars to issue a “consensus statement” on the “fallacy” of antiaging medicine. When I finally got a chance to ask Olshansky exactly what it was that he found so objectionable, he sat me down and lectured me. “That anyone can sit there and actually use the words ‘antiaging’ and ‘science’ is beyond me,” he said. “Anyone who runs one of those clinics will be in jail in five years. They will all be shut down. You heard it here first!” I asked him what it was that got him so motivated. “I wouldn’t have anything against it if it were not for the fact that the chief source of information about this for the public seems to be some TV celebrity,” referring to Suzanne Somers, who wrote two lucrative best sellers on the subject.
Meanwhile, the actual scientific data about humans, longevity, health, and human growth hormone—be it pro or con—has remained puzzling, murky, tainted with agendaism and strange gaps of basic research. Perhaps the most negative and influential piece of scholarship about HGH and humans came out of Stanford University in 2007. It was not a clinical trial but rather a review of older works. The conclusion: “Claims that growth hormone enhances physical performance are not supported by the scientific literature. Although the limited available evidence suggests that growth hormone increases lean body mass, it may not improve strength; in addition, it may worsen exercise capacity and increase adverse events. More research is needed to conclusively determine the effects of growth hormone on athletic performance.” But just as Bartke noted that Klatz and Goldman’s pro-HGH studies were mainly based on treatment of middle-aged patients with very low levels of GH, much of Stanford’s study looked at superhigh, or supraphysiological, doses in professional athletes, not older people taking low-dose HGH, as is the norm in antiaging practices. One widely circulated anti-HGH study showed an increase in type 2 diabetes in users of HGH, but that was in morbidly obese users who were administered large doses. Those given low, frequent dosing did not experience the complication. Similarly, the legitimate fear of cancer—cancer, after all, is unchecked growth, and growth hormone can fuel it—has yet to be sussed out with hard data. Standard protocol in antiaging practices—and one reason it costs so much—is for tests that monitor early cancer indications.
Epidemiologically, there are huge gaps. Acromegaly—which results in facial disfiguring and a range of physiological problems—is the best-established disease consequent of too-high levels of growth hormone, but its rate of occurrence has remained constant over the twenty years since HGH was introduced. Similarly, the few studies looking at growth hormone expression in centenarians have been troubled by methodological problems. A much-vaunted study of 384 Ashkenazy centenarians indicated that only nine carried a gene for disrupted growth hormone transmission—the human equivalent of the GHRKO mouse. That minuscule result has left even anti-HGH scholars scratching their heads. “How did that ever get published?” more than one told me.
One reason for the rush-to-negative judgment is that, in a nation where health care is increasingly a consumer product, driven by ads on TV, perhaps a default that errs on the side of caution is a good thing. (It would be even better if the same ethos applied to almost all chronic disease drugs.) It might be different if the antiaging profession stepped up to the plate and did its own oversight of adverse events, what the FDA calls pharmaco vigilance. But every time I mentioned this prospect—to everyone from Grasela to the head of the International Pharmacy Compounding Association—I was told that it would be impractical and expensive. That leaves the debate in the hands of static interests—vested economic interests in the case of the antiaging industry, and vested intellectual, cultural, and political interests in the case of the academics.
“There is a huge and legitimate scientific debate that everyone is just dancing around on this,” says Steven Austad, an evolutionary biologist studying aging at the University of Texas Health Science Center, and one of the scholars who signed one of Olshansky’s anti-antiaging salvos. “The fact is that growth hormone serves a much broader and deeper purpose in humans than it does in mice and flies and worms. It serves heart and brain health. And, whether anyone out there studying human dwarves and centenarians likes to admit it or not, humans with low growth hormone do not do well. They are prone to all kinds of medical problems. I wonder sometimes how miserable they are. On the other hand, there is no data that HGH taken from [a needle] is going to extend your maximum life span, and the cancer risk is still unclear.”
I decided to goad Rothenberg on this point, and because I was due for a six-month checkup of my testosterone and thyroid replacement, drove down to his offices in Encinitas. I asked him: How long does an average client stay on growth hormone? This is an important, basic question, tracked relentlessly in other drugs by pharma because it is the best single initial indicator of patient satisfaction and the drug’s effectiveness; if the patient is not experiencing benefits, the patient does not renew the prescription. With HGH running upward of $1,000 a month, that one piece of data might tell us a lot. Rothenberg hemmed and hawed. He didn’t want to make generalizations. What about himself? “I’m back on it—like a lot of people, I go off and on as I feel the need,” he said. So what is really the controlling factor? “Let’s face it,” he said. “For a lot of people, it is the money. It’s expensive. For some the effects are modest. So a lot of it is about how much money you want to spend on modest improvements.” But what about life span extension, the great claim by Klatz and Goldman? “We have to face it—antiaging has a name problem. That’s why I have that name, and not antiaging, on my door.”
Before I left, we reviewed my own hormone supplementation. I had discontinued the thyroid because it made me feel nauseous and agitated, but I had kept up with the testosterone. I felt a small elevation of my spirits; I could cut back on my dreaded antidepressants, and my waist had shrunk by at least an inch. But Rothenberg had a surprise. With a twinkle in his eye, he pulled out my most recent lab tests. For the first time in my adult life my cholesterol, which runs high despite a good diet and exercise, was almost acceptable—a total just above 200. Previously it had always run between 240 and 270—Lipitor country. Although my blood sugar has always been decent, my new tests showed that it, too, had improved. It was enough to make me suspend judgment just a little longer and wonder about what Bartke wondered: What about all those other hormones? How did they affect aging, and will supplementation slow it down?
If you wanted to find out about hormones and their place in the contemporary antiaging firmament, you’d want to go to the annual conference of the American Association of Anti-Aging Medicine, A4M, held each year at the opulently tacky Venetian Hotel in Las Vegas. It is, of course, a circus; one wishes for a Twain or a Mencken, or perhaps even a David Sedaris, to vet its quintessentially American nature. The A4M public relations people, sensing the barrel of fish they have as a client, severely restrict press access, but with a little patience, they can be convinced that you will give their fish an even break. Once in the barrel, it is difficult to do so. Here, laid out on a ballroom floor the size of the Gator Bowl, with a good size sprinkling of “demo girls,” “pavilion hostesses,” and, let’s face it, outright working girls just to make it really resemble an AMA convention, clamor purveyors of every known antiaging product under the sun.
A sampler might include the Sunetics Corporation’s “Laser Hair Brush,” about which the company touts: “Fact: the FDA cleared the first Laser Hair Therapy device to grow hair in January 2007,” although one wondered what happened in February. There was LivOn Laboratories’ Lypo-Spheric AGE Blocker, “the most powerful oral nutrient delivery system in the world,” competing, apparently, with the human mouth. There was the “Barefoot connections” antiaging device sold by Earthing Solutions, which helps the earth’s electric field “transfer easily to the body,” as if it had problems doing so in the first place. One physician panelist who had her own booth gave consultations about “how to get over the guilt of having a cash-only practice.” There was not a long line. There was also the Energy Enhancement System, a computer monitor that hooks up to one’s body and “regenerates life on a cellular level;” a company selling “cutting-edge saliva hormone testing to detect your biological age;” a pavilion selling “colon hydrotherapy stations” that can “complement your business (No Messy Leaks!! NO Messy Blowouts!! NO ODOR!!);” a German—surprise—outfit selling “fresh thymus extract;” another offering a full body-immersion unit called Cardio Cor that floods the body with infrared light and hence lets you “ride … reduce … rejuvenate;” a BioBanc system that lets you store your own white blood cells so that you can be prepared for tomorrow’s medical miracles; a supplement called “Pee-Nuts,” for “prostate health in a bottle;” a product called H4O, water with hydrogen gas dissolved in it for reducing bullshit oxidative damage; and, my favorite, a natural herbal lubricant called, perfectly, “Virgin Again.”
As entertaining as the floor show is, the main medical-science core of A4M revolves around hormones, and if there is a prince of the contemporary hormone world, it is Thierry Hertoghe, the Billy Graham of Thyroid. I first met Hertoghe at an evening session, where his presentation was billed as “Diagnosing Hormone Deficiencies—A Live Consultation.” All day long I had heard about him, and I was encouraged to get there early. (“He is so popular people chase him into the bathroom after he speaks!”) Turning up a few minutes late, I found the session in full swing, the ballroom packed with rapt physicians—MDs, DOs, homeopaths, and naturopaths. Up on the stage, microphone in hand, dressed in a pink blazer and beige pants and green tie (“testosterone zhust makes everything so veevid!”) was Hertoghe, a youngish, handsome Belgian doctor with the flopsy hair of a 1970s French movie star. Next to him, his back turned to the audience, stood a middle-aged Asian man. Hertoghe was using him as an example of how to “read” the clinical signs of hormone deficiency on the human body, rather than rely solely on lab tests.
First, he assessed the man’s overall appearance. “I guarantee you that if you take HGH, you will definitely stand up taller,” Hertoghe said. He then had the man raise first one, then the other of his bare feet, which he tapped with his fingers. “I see some discoloration, some yeast there,” Hertoghe said. “Do you eat a lot of sweets?” The man nodded. Hertoghe went on. “Hmmm, and I see some edema in your buttocks.” There were laughs from the audience. Hertoghe’s pointer was on the man’s calves. “Oh, sorry, I mean your calves, that’s right. That’s DHEA deficiency. Now look at his belly—there is bloating, he eats too much and too fast. Now, what should he do?” The audience was still. “One thing is easy. He needs thyroid. I would also give HGH—that would straighten your face out. And maybe some testosterone?”
Next up was a sixty-year-old Asian woman named Cindy, who complained that “I have too many food allergies.” Hertoghe immediately pointed out that her hair was rough and dry—“maybe some thyroid deficiency”—that she had no eyebrows—“thyroid and possibly growth hormone”—and that “your face could look firmer—that would get better with growth hormone.” He went on. “Your inside hands have a brown pigmentation—that’s cortisol. Your palms are wet—cortisol also. And look at your fingers, so bloated! You’ve been thyroid deficient since childhood!” He also told the woman about her own personality. “You tend to get dispirited when you fail. That’s cortisol too.” He then turned to the audience and made his diagnosis: “So, the whole body type is thyroid deficient since childhood, and then HGH and cortisol. I would supply them all at low doses. And I would have her cut out grains and milk.” He stopped and looked at Cindy and shrugged. “I bet zee food is bad too, right? Zee way you eat?”
After the session, I lined up with a number of people who wanted to talk to Hertoghe. One man had him look at his eyes. Another at his upper back. It was an amazing display, almost virtuoso, although I could not tell what kind of virtuoso—legit or not. Was he practicing endocrinology or hormonal mesmerism? In a way, it all felt very Old World, perhaps the way medical men assessed people before the era of blood tests and X-rays and CAT scans and MRIs. I had asked sober Fran Kaufman, my endocrine reality check, about the use of such clinical signs. “We used to call them endocrine pearls,” she said in her usual equable fashion. “And they have some basis, but they can be very wrong and misleading without the lab tests. I mean, I saw a friend I had not seen for a while the other evening, and, if I were purely ‘reading’ his physiognomy, I’d have to say he was insulin resistant, maybe testosterone deficient. But then again, maybe he is just chubby. You don’t know without the labs.” When I came to the head of the line, I asked Hertoghe about it. “You are right,” he said, before conveniently tacking the question in his own direction. “You can have access to all the hormones you want but you’ve got to have the skill to really look at the body. It is an art. A lost art.” Then, as a line of men and women tried to follow Hertoghe to the bathroom, he was gone.
But where and when, I wondered, was “it” lost?
Hertoghe, as it turns out, is more multidimensional than his presentation suggests, and when I began sketching out his biography, I found he had left a memorable legal trail, both in his native Belgium and in the United Kingdom. In 2007, he prevailed in a defamation lawsuit against the Belgian National Medical Board; Hertoghe had been running for an office on the prestigious organization when his ensconced opponents issued a booklet saying, in essence, that all antiaging physicians were quacks. The Belgian courts sided with Hertoghe and, in 2007, condemned the National Medical Board for calumny—a wonderful Old World sin—and falsifying elections. He prevailed in a separate case in the United Kingdom as well, where his testimony won exoneration for a London physician accused of being too free to hand out thyroid. When I finally caught up to him, he was exhausted. Where he’d felt “branded” as a quack before, now he was experiencing le fugue d’victor. “In Brussels there has been a lot of almost paranoia about me, like ‘Don’t say andropause, or Hertoghe will sue you.’ But the fact is that I have the stomach to straighten out people who libel antiaging doctors, unlike Goldman and Klatz.” He jerked his head, Jean Claude Belmondo style, at one of Klatz’s posters. “They didn’t have the stomach.”
I asked him why established medical folks seemed so quick to judge the field of hormone replacement and anti-aging. He acknowledged the usual: the up-and-down history of hormones, gerontology, and nontraditional medicine—yes, it was a problem. So was nomenclature; it might be better to get rid of the antiaging label and instead use, say, “longevity medicine.” But he also detected something else. “Many MDs have a sense of shame—that there is this huge world of hormones that they were never taught about—and it is a shock to hear about how much they don’t know. I mean, let’s face it, there are 5 to 6 billion people out there who are prematurely aging. They can’t do anything about it.” He stopped, perhaps to let me digest the fact that, to Hertoghe, everyone in the world is aging too rapidly, then went on to speak about his mission to slow down the aging process, and how he has had “mystical experiences” related to aging. He talked a bit about the purely technical medical issues—about how the reference ranges for determining what constitutes a “normal” versus “treatable” hormone level should be narrowed, thereby giving physicians more elbow room in prescribing hormones—but the more Hertoghe talked, the more one subject dominated: his family history, and the early twentieth century.
Hertoghe hails from a long and illustrious line of Belgian physicians credited with making pivotal contributions to the field of mainstream endocrinology. His great-grandfather, Eugene Hertoghe, was one of the first modern medical men to diagnose and treat myxedema—thyroid deficiency—in the late nineteenth century. Eugene Hertoghe’s breakthrough was in deciphering that people with shortened eyebrows (now known in medical literature as Hertoghe’s sign) or none often had a serious thyroid deficiency, which could be cured via an oral thyroid extract. In other conditions, such as cretinism, it could be prevented or cured with iodine supplements, which we now get through table salt. In the early twentieth century, Eugene garnered a sizable American following, often doing live consultations at medical conferences. In 1914, in New York, he spoke before a huge audience at the annual International Surgical Conference, many of whom were concerned with the debilitating aftereffects of goiter surgery—the removal of a chronically swollen thyroid gland. Eugene Hertoghe described one such case, cured with thyroid extract, in almost magical terms:
She had the drawling voice, the sluggish attitude of body, the thinned hair and eyebrows, the swollen mucous membranes, and the difficulty in swallowing. Her tongue appeared too large for her mouth, the floor of which was swollen and raised till it suggested a double ranula [cyst]. Even her ocular conjunctiva was edematous and prolapsed while her complexion was amber-yellow with patches of red on the cheeks. She had also the low temperature with subjective sensations of cold—but indeed Mme. X. presented all the symptoms described in post-operative myxedema and if so she must suffer from spontaneous myxedema.
As my last diagnosis was made, M. X. was too polite to say that he did not believe me, though his face plainly showed his incredulity, but he followed my instructions to the letter.
The result exceeded my hopes. After three weeks treatment the bodily and mental transformation was so complete that she would no longer have been recognised as the same woman. The edema of the tongue, of the lips, and of the eyelids disappeared as if by enchantment and the face assumed an intelligent expression.
So did Eugene Hertoghe set the stage for the family destiny: hormonal medicine. His son, Thierry’s grandfather, and his son, Thierry’s father, both followed the elder Hertoghe’s course, with Thierry’s pere credited with discovering and characterizing one of the key adrenal hormones. By the time young Hertoghe—tall, handsome, perhaps a little cocky—began to contemplate a career, the “incredulity” and “enchantment” of it all had worn thin. “I actually never meant to be a doctor because my father was so passionate about it all the time.” He instead became a psychiatrist. “But then I thought I was having hallucinations—because everywhere I looked, it seemed I saw hormone deficiencies.” What followed was a kind of medico-spiritual odyssey. Hertoghe went to London to meet Katrina Dalton, who had pioneered the diagnosis of premenstrual syndrome and its treatment with progesterone as a counter to estrogen. He took her ideas back home. “At the time, estrogen was only given at menopause, but I saw that there was a cat-a-strophic shortage earlier in life,” he recalls. “I began giving it to a forty-five-year-old woman, with progesterone, and I began seeing that the aging in her face was curtailed. With others, I began to understand that a woman who’s just had a baby looks like a mother—but what she really looks like is an older woman. If you supplement with estrogen, she looks young and happy again. She’s a ‘sexy lady.’”
Hertoghe also wondered about the other sex hormone—testosterone. He struck up a friendship with Georges Debled, who had been popularizing testosterone therapy in France (and whose illustrations of “le silhouette de l’homme regressif/ progressif” inspire the drawings that begin this chapter). “He sat me down and drew these pictures for me, of what happened when both men and women were supplemented with T, and it was a revelation to me.” Debled sent him to another pioneer, Jens Müller, in Denmark, who popularized a theory of cardiovascular disease and hormone insufficiency. “He didn’t want to see me at first when I went to see him—I literally had to stick my foot in the door—because he thought I was too good-looking and not what a doctor should look like, but we eventually became friends.”
With all of these insights accumulating, and young Thierry’s chatter about it in family circles escalating, it wasn’t long before Hertoghe’s father, who had continued the “live consultations” pioneered by old Eugene, asked the son to fill in for him. “It was completely ‘on the spot,’ and I had to rely on my learning very quickly,” Hertoghe recalls. “But it was clear I had some gift too. I hate to say it that way, but right from the beginning, when a boy came up from the audience for an exam, I could immediately detect specific thyroid deficiencies.” He took his presentation to the United States in the early 1990s, where he floundered for an audience, until he met John Grasela, then just getting his San Diego compounding empire off the ground. Grasela recalls that “Hertoghe had maybe fifteen people at a session in Florida I remember, and I recall thinking, ‘This guy is great, but he knows nothing about business and marketing himself.’” Grasela took care of that. Hertoghe’s audiences exploded in size, evangelist style.
A month or so after our talk, I attended one of Grasela’s “transform your practice into an all-cash business” workshops in, where else, Las Vegas. For three days, about 250 physicians, who had paid $950 each, sat and took detailed notes. There were presentations from a number of established antiaging practitioners. Hertoghe, clad in a vivid pink sport coat and beige cargo pants and cream shoes, was the star. Systematically, he went through each hormone and its clinical manifestations—how they show up on the body. “And remember,” he said as he began. “You cannot do a good hormone assessment without touching the patient, and I know that can be a problem here in the United States.”
One thing was utterly telling: Many of the slides were not new—they were from great-grandpa Eugene’s time. Here was a goiter. Here was a cretin. Why was that? We don’t have goiters and cretins now—we have table salt, I wanted to say. What about the great “in between,” the untreated low hormone levels that Hertoghe had championed so much, the ones that accelerate the aging process and, if treated properly, can make the ladies sexy again? There were some minor cases, but what soon slid to the surface was Hertoghe’s aesthetics. To wit: modest hormone deficiencies being too difficult for most physicians to spot, perhaps it is best simply to show “the ideal body.” Everything that departed from that, the assumption went, must be a hormonal deficiency. “We have to see the extremes to see where our patients should be.” He paused and looked at us. “So what is an example of a hormonally adequate body?” The slide on the screen changed. It was Michelangelo’s David. “See?” he said. “There’s a firm face. Have we all forgotten what a good firm face looks like? If not a firm face, then he’s not in good health. The same with the behind. It has to be firm, too.” He flashed a photo of a fashion model. “So you have to have them take off their underwear and look.” He went on to estrogen deficiencies. Again, more models, although whether he meant them as an ideal or as an example of deficiency was unclear.
Everyone is prematurely aging? Everyone should be on hormones? If one doesn’t have the David’s “tone,” then one is an estrogen case? All of this began to make me feel the way I’d felt with Paul McGlothin. Had Hertoghe played too much soccer with his head? Or had I? Everyone else was busy writing down everything he said; next to me was a Yale-trained MD, scribbling like a Boston lawyer.
Before I could completely digest all of this, Hertoghe moved on to my favorite hormone, testosterone. He showed slides of the key clinical signs: a flat hair line with no temple wings, pale skin, flabby breasts, a fatigued overall countenance. “This is a person who is slowly but certainly being castrated by time.” He paused for effect. “Castrated by time!” As if on cue, the guy next to me put his hands over his crotch. Hertoghe pointed to the man on the slide. “This person suffers. Remember, we are not made to age. We are made to be healthy.” He went through the signs of growth hormone deficiency, then on to the adrenals.
The adrenals are the next big thing in antiaging hormone replacement, probably because many of its manifestations—browner skin, a hollow face—resemble stereotypical aging. Hertoghe related some of the less obvious signs of cortisone deficiency. “I see them all the time, and I can almost tell you what their personality is going to be like just by looking at the hands. To them, the whole world is unjust, nothing is ever right, everyone else is unfair to them.”
To say that this approach has a few scientific problems, let alone some basic issues of sensitivity, is like saying that perhaps the air in Beijing occasionally might need some improvement. But let’s say, for the sake of argument, that Hertoghe himself is gifted, that by dint of family history, experience, inclination, and experiment, he really can spot the deficiencies and treat them. How would his observations help novice doctors do the same? I spoke with him again and he clarified: One would still need lab tests, but the clinical signs were a way to sensitize physicians to the hormonal aspect of health, which to Hertoghe is everything. If one dug in and really thought about such signs, “you will never look at yourself the same way in the mirror again,” he said. “Instead, you will see your destiny.” I then asked him about my destiny, telling him that the thyroid and testosterone had hardly cured my sluggishness. “Then your food is bad,” he said. “Cut out all grains and you’ll see improvement in twenty-four hours.” He was, in short, simply a hot version of McGlothin; he wanted me to treat my body like a test tube.
Just as I was considering never looking in the mirror again, I remembered something. I had brought with me a picture of Alvise Cornaro, a photocopy of the Tintoretto painting that hangs in Florence’s Pitti Palace. I showed it to Hertoghe. “Oh, my God, he has all the hormonal deficiencies,” he said. “The hair, the eyes, that’s estrogen deficient. The caved cheeks and that wispy beard—probably adrenal and growth hormone deficient. He was probably not sometimes such a nice fellow.”
From all of these discussions, I drew a few reasonable semiconclusions: Growth hormone likely does not expand maximum human life span, but if the antiagers and their foes can ever take their heads out of their vested interests, it may turn out to be a way to ameliorate the misery of aging. Simply “topping off” hormones—replacing “only what one loses naturally”—ultimately turns into a medical money decision, where one replaces reliance on pharmaceuticals with reliance on lab tests and physician “monitoring” fees. And replacing everything early on—a la Hertoghe—turns one into a bottomless test tube, hopefully with a bottomless wallet. It seemed that there were two models in the commercial antiaging game: Either one had a bunch of science and had paired it with a product that really did not perform, or one had a product that performed but for which the science was inconclusive at best. It all began to sound a lot like the traditional pharmaceutical industry’s profile for chronic disease products—think Lipitor for kids, which, as of this writing, Pfizer is.
I had met Jonathan Wright, considered by many the elder statesman of hormone replacement in the United States, at John Grasela’s hormone cashfest in Las Vegas. I had also heard about him from one sober-minded scientist, James Duke, one of the nation’s foremost medicinal botanists. Although he is no friend of traditional pharma, Duke extends his tough-mindedness into the vast realm of natural and alternative medicine as well, and so I was surprised, when I mentioned Wright, when Duke wrote, “Generally speaking, I find that Wright usually is … right, especially on the subject of bioidentical hormones.” You might not agree with all of Wright’s social-political commentary—he’s an ardent Libertarian with utter disdain for the FDA, which once raided his offices for prescribing vitamin B6—but Wright has something substantial, if not completely proven, in his arsenal. It is this, as he put it himself: “Natural molecules are better than extraterrestrial molecules.”
In his signature Paul Lynde-meets-Marcus Welby style, Wright means that drugs made from botanicals and minerals that molecularly mirror human hormones, rather than, say, mare’s urine, generally work better, with fewer side effects and adverse events. These he calls bioidentical hormones, many of which derive from soy and yam; they are not—repeat not—products such as the ubiquitous yam and soy creams sold on the Internet, but pharmaceutically processed plant molecules that are recognized, for the most part, by the FDA and the standards-setting U.S. Pharmacopeia board. They can be obtained only by prescription. If you look at a molecular diagram of, say, estrogen made from mare’s urine, Premarin (the “prem” in Prempro), and USP estrogen derived from wild yam, and then compare it to progesterone as made by the human ovaries, the USP progesterone diagram will more closely resemble the human hormone; hence, Wright’s use of the word “bioidentical.” It is not a term recognized by the FDA, and so, from time to time, Wright and his followers clash with the agency.
When I met him at his spacious offices in his Tahoma Clinic in Renton, Washington, Wright had just come off a jag of publicity surrounding a full-page ad he had placed in the New York Times. In it he ridiculed the FDA’s recent persecution of pharmacies offering bioidenticals for antiaging purposes. The agency had gone after the pharmacies because, in its somewhat tortured logic, the use of the term “bioidentical” somehow implied that something was natural and better, an assertion for which there were no FDA-vetted clinical trials, and therefore one couldn’t say it in an advertisement. “We need someone to sponsor a medical free speech bill,” Wright told me, arching a silver-white eyebrow. “Pharma has their DTC ads. We need to be able to communicate fair science freely.”
The Marcus Welby part of Wright grew from a predictable past: Raised in a small, confining Ohio town, he was a precocious student who graduated from high school two years early and was then recruited by Harvard. He leaped at the chance and majored in cultural anthropology. (“Um, small town? I wanted to learn about the world out there.”) He went on to the University of Michigan Medical School, where he studied family medicine—not exactly a hot area in 1969, when specialization dominated. It was then, there, that the ironic side of Wright’s medical personality emerged; things were not all that they seemed in big medicine, and there might not be much one could do about it. He wondered why the university kept its huge collection of works on homeopathy and natural medicine under lock and key. “They didn’t want us to even see it. What, were they afraid of the competition?” Later, as an intern at Washington University Medical Center, he began treating a number of women who experienced complications from birth control pills, many of which he found could be alleviated with nutritional supplements—B6, C, and E. “It gradually occurred to me that what I’d been trained to use did not come from molecules in nature.” That sparked an interest in hormonal deficiencies, and, because of his success with vitamins and minerals, the possibility of making a product that would more naturally resemble the human hormone molecule.
Today, flooded with natural products advertising, it is easy to downplay Wright’s innovation, and, because oversell inevitably produces skepticism and cynicism, to dismiss it entirely, as have many in the leadership of traditional medicine, especially geriatrics. One might quarrel with many of Wright’s other issues, his borderline conspiracy chatter about the FDA and drug companies, but what Wright did with hormones is clearly worth a second look. Thousands of elderly Americans continue to benefit from them today, and if insurance companies could get better data on them, they might find them useful in developing a lower-priced geriatric armamentarium.
Wright commenced work on bioidentical estrogen in the early 1980s. At the time, hormone replacement therapy for women was undergoing one of its perennial reformulations. The principal change grew out of estrogen’s implication in endometrial cancer, which had been ferreted out by researchers in the 1970s. The findings were clear: Estrogen is a growth factor, and, not properly balanced with progesterone, another human hormone, it can lead to excess and malignant growth. The pharmaceutical industry responded by repackaging its estrogen, Premarin made from the urine of pregnant horses, with progestin, a progesterone-like molecule also made from mare’s urine and branded Provera. Provera—the “pro” in Prempro—was made to play the role of progesterone, the ovary’s natural estrogen controller, or “opposer.” At all of this Wright scratched his head. Something didn’t feel right. He looked closely at the composition of Premarin: Of the three main estrogens, it was composed of 75-80 percent human estrone, 6-15 percent equilin, or horse estrogen, and 5-19 percent human estradiol and other horse estrogens. He then asked: what are the average estrogen proportions in humans? He talked a local blood lab into some records research and found that the average human had three major estrogen molecules in play, in the following percentages: estriol, 60-80 percent; estrone, 10-20 percent; estradiol, 10-20 percent. The natural question: why had the drug companies abandoned estriol? The answer: estriol had always been characterized as a relatively minor, weak estrogen, at best a by-product of estrone and estradiol.
“But that was a wrong assumption,” Wright says. “If you look at the best reviews—of six decades of estriol research—what you find is that scholars are constantly concluding that that makes no sense. One of them said it perfectly: ‘It would be unusual if nature produced three estrogens of which only one is utilized.’” More, the natural estrogen supplements, first derived in the 1930s and dismissed by many as too weak to be useful, had undergone a revolution as well, and, through transdermal cream and patch technology, were absorbed just as well as Prempro pills. (Wright makes much the same case for testosterone supplementation for men: Use frequent, low-dose transdermal applications rather than infrequent high-dose injections to get the benefits without the side effects.)
Wright’s innovation, along with those of the progesterone pioneer William Lee, was to seek out natural but pharmaceutical-grade sources of the three estrogens, and then compound them in human physiologic proportions. These he dubbed bi-est and tri-est. He then used lab tests to determine the rate at which patients were absorbing them, making dose and composition adjustments in response to individual variations. The results, he has demonstrated in hundreds of case reports, are remarkable and consistent. Used with compounded natural progesterone, natural hormone replacement—NHR as he has named it—seems to confer most of the benefits of pharmaceutical HRT, with fewer of its side effects. Because his various compounds have not undergone gold standard clinical trials (“We just can’t afford them,” he says), he is forever hounded by the FDA for making unproven statements. The FDA, in turn, is frustrated by something else: Wright may be right. In the agency’s own pending review docket are expensive new drug applications from large pharmaceutical companies looking to brand estriol, the once-discarded, “weak” estrogen. Another frustration for Wright’s foes: some research on hormone replacement seems to suggest what Wright has been saying about dosage and manner of application. Low-dose estrogen therapy commenced before or upon menopause may confer the benefits—from better blood fats to better bone and brain health—without the increased risk of cancer and heart attack. A parallel effort reassessing long-term, low-dose testosterone replacement in men is also under way, with a number of studies suggesting that some form of testosterone replacement may delay onset of age-related dementia.
In struggling through all of this, Wright has discovered much, he says, “that has been lost.” He has the propensity to extol the “ignored” past, perhaps without fully acknowledging the solid medical science that was responsible for burying that past. Like Hertoghe, his reference points gravitate toward the early twentieth century, the so-called golden age of hormonal medicine. His favorite “lost treasure,” and one he cites frequently in speeches and writing, is a man named Henry Harrower. Harrower was the founder of pluriglandular therapy—the notion that human hormonal deficits can be treated with extracts of animal glands—and the president of Harrower Laboratory, which sold said extracts. If nothing else, his story shows just how permeated was Jazz Age America with hormones, even at the small-town level.
Harrower, a big, handsome man with a well-trimmed barbershop mustache and flair for nice clothes, originally hailed from England; after earning a degree in massage therapy in Sweden, he landed at Battle Creek, Michigan, where he earned a medical degree and fell under the spell of John Harvey Kellogg, the Andrew Weil of fin de siècle America. He later traveled back to Europe, where he became friends with Eugene Hertoghe and learned the fundamentals of thyroid therapy. Swimming in semidiscoveries and half-surmise, he confected his own unified theory of hormonal action. Reasoning outward from thyroid’s success as an oral supplement, Harrower said that all hormonal deficiencies could be righted by a process he called homostimulation—ingesting the extract, often desiccated, of corresponding animal glands. Desiccated sheep’s adrenals could be used for human adrenal failure, extracted cow pituitary for human growth failure, tonics of bovine ovaries for human estrogen deficits, and so forth. He concocted a universal dosing theory, which he dubbed Harrower’s theory of hormonal hunger. The essence: one could not give too much glandular extract, because the body knew how to pick out just the right amount and discard the rest. He was a vigorous synthesizer of medical science, and, even after being thrown out of the Endocrine Society, which he cofounded in 1919, for his obvious conflict of interest, his ideas loomed large. (Harrower Laboratory became the largest employer in the Southern California city of Glendale—known in that time as “Gland-dale,” and Harrower himself may have been Aldous Huxley’s model for one of the protagonists in his anti-aging novel, After Many a Summer Dies the Swan.) Through journal articles and his laboratory’s monthly brochures and newsletters, Harrower prefigured much of modern-day doctor detailing. As Harvey Cushing observed of it: “Surely nothing will discredit the subject in which we have a common interest so effectively as pseudo-scientific reports which find their way from the medical press into advertising leaflets, where, cleverly interwoven with abstracts from researchers of actual value, the administration of pluriglandular compounds is promiscuously advocated for a multitude of symptoms, real and fictitious.”
It was Cushing, perhaps the greatest of early modern endocrinologists, who destroyed much of Harrower’s credibility. This he did in a famous presidential address to the young Endocrine Society in 1921. Aside from thyroid, Cushing said, endocrinology was in a primitive state, “so what is there to say on pluriglandular complex except to acknowledge an abysmal ignorance?” Hormonal hunger was “buncombe.” Homo-stimulation too: “The Lewis Carroll of today would have Alice nibble from a pituitary mushroom in her left hand and a lutein one in her right and presto! she is any height desired.” As the medical historian Theodore B. Schwartz acutely notes of Cushing’s address, “This presidential diatribe was published not in Endocrinology, but in the Journal of the American Medical Association, where it would receive the widest attention.”
I asked Wright about that. Given Harrower’s faulty science of dosage and reliance on oral administration, did he really think that returning to his ways was wise? Wright acknowledged only one problem—that Harrower relied too much on oral dosing, which was ineffective. Whole gland extracts, administered intramuscularly, were “absolutely the way to go in the future.” I rubbed my liver nervously as he described to me his latest putterings—an experiment with his mother-in-law and injections of the adrenal cells of a fetal pig. “We did this for three to four rounds, and all of her friends wanted to know, you know, ‘what spa have you been to?’” He had a study from Europe—from which century he did not specify; it showed that nearly 75 percent of tissue cell injections reach their target organs. To his mind, that suggested that all kinds of cell and gland therapy will soon become huge in the antiaging field. “Not just stem cells, but all kinds of cells.” Glaucoma can be alleviated with shots of lamb’s cortin, an adrenal extract; the same for hearing loss. Both were heavily promoted for such in the 1930s, before the hormone receptor theory came to dominate.
For $75,000, in fact, one can go to the offices of David Steenblock, an Orange County osteopath, and get “autologous bone marrow stem cell therapy” for just about any medical problem. I first met Steenblock at a conference on aging in England, where he was to give his presentation to a crowded Cambridge University conference room filled with antiaging activists, mainstream scientists, medical entrepreneurs, and assorted wingnuts. He is a convivial man, balding and routinely dressed in Tommy Bahamas Hawaiian shirts and tan slacks and loafers. Despite that, I did not hate Steenblock. Over breakfast, I caught him casually bad-mouthing the previous night’s presentation. “Oh my God, could you be more complicated?” he said. His own slide show, a few hours later, was not. Pointing to slides on a jumbo screen, Steenblock walked the audience though his typical procedure, one laced with references to science. As he explains it, he first places the patient in a hyperbaric chamber, the better to increase stem cell production in their bones. (There is some evidence that this works.) “Then we, kind of, er, hurt them a little,” he said, apparently to stimulate more cell proliferation. He did not clarify what he meant by “hurt a little,” but I assumed he likely bruises the patients in the shins rather than, say, kicking them in the testicles. Steenblock then uses a needle to withdraw marrow from one of the patient’s larger bones, puts the fluid through a kind of purifying process, and then reinjects the fluid back into the part of the body that needs repair. “And, let me add, this is entirely legal, and doesn’t need FDA approval, because you are just using the patient’s own cells—you haven’t added anything.” Steenblock claims a wide range of improvements from the procedure. Nevertheless, he has been investigated regularly by the State of California and has been disciplined by the state osteopathic board for a number of infractions.
Once the door of his hyperbaric chamber (which had been custom designed and installed for Steenblock) blew out while a patient was in the chamber, causing injuries to people outside the chamber.
He would not consent to an interview, but he did sell me a copy of his latest book, Umbilical Cord Stem Cell Therapy.
The longer I mingled with antiaging types, both those with traditional degrees and those without, the more I came to appreciate the reason that Big G hates them. It is this: They are surfing on—and making money from—the establishment’s science, long before scientists—and most of the time, even ordinary folk—would deem the science sufficient. And unlike Harvey Cushing, Big G has little faith that such pseudo-science will debunk itself. They may be right. If anything, the marketing is slicker and ever more soaked in science. A whole new category of public relations, in fact, specializes in antiaging science.
The latest trend in antiaging marketing is to hook your product to an established “big” theory of aging, just as pharmaceutical companies hook the selling of Lipitor to a theory of cholesterol and heart disease. At A4M, Noel Patton, a tall and serious-minded former farm implement salesman, and his wife, a former beauty queen and TV weather anchor, were selling something called TA-65. It was a natural product, synthesized from the Chinese milkvetch plant, or astralagus. Cost: $25,000. Patton’s claim was that TA-65 would slow down the age-associated shortening of telomeres—the chromosome endpieces that Leonard Hayflick insists are a kind of internal cellular clock. TA-65 works by stimulating production of telomerase, a telomere-lengthening enzyme. Patton had obtained the “nutriceutical,” or nondrug license to TA-65, from Geron Corp., a late 1990s start-up that received a huge amount of press for its telomerase efforts until it was shown that telomerase might cause cancer; after all, telomere shortening might be the body’s way to check uncontrolled cell division. I asked Patton if that bothered him. No, he said. “We are constantly checking the blood work on our fifteen clients and haven’t seen that at all. If anything, we’ve seen a slowing of telomere length loss.” That telomere length and aging are, at best, an association, and not a causal relationship, did not seem to bother him either. I asked Professor Rita Effros, an esteemed UCLA pathologist whose work on telomeres and the immune system was used by Geron, if she knew Patton; after all, he was featuring her and her work on his website, and in various lectures he’d chatted about her as if they’d just gone dancing together. She had never heard of him. “Who is he?”
Another way to sell a product based on a theory of aging is simply to take the tools that bench scientists use to measure aging in mice and sell it to people. As Vincent Giampapa, a plastic surgeon and cofounder of A4M tells it, he was “looking for a way to affect human aging on a deeper level” when he began reading about the free radical theory of aging, and the ways in which mammalian scientists, like Masoro and Walford, measured oxidative stress. He then began using it on people, determining first their baseline level of DNA oxidation, then taking blood tests after his patient/subjects had been on an extract of the herb known as cat’s claw, or Uncaria tomentosa. He saw that certain markers in a group of fifteen patients declined after administration of cat’s claw for four months, and then began selling the tests ($285.00 apiece) and the herb ($69.95), along with a book, The Gene Makeover. Although a trial of fifteen people for four months would never pass muster at the FDA, there remain even deeper problems with Giampapa’s approach. “These tests are, at best, preliminary and tentative, even in the world of rodent science,” says Arlan Richardson of the Barshop Institute at the University of Texas Health Science Center in San Antonio. Richardson has been studying oxidative stress, aging, and mice for thirty years, and one emerging aspect of that work is deeply troubling, not only for people like Giampapa, but anyone who claims to base an antiaging cure on the free radical theory of aging. “Recent findings do not bode well for the free radical theory,” says Richardson. “We are seeing mammals that live very long lives, but with lots of free radical damage. We are seeing that oxidative stress may be important to specific disease, but not so important to the underlying aging process. Oxidative stress may simply be a gray hair.”
But gray hairs matter, and, in the world of commercial antiaging medicine, so does one other thing: skin. Treatments to ameliorate its deterioration, from wrinkle cream to Botox, make for a $50-billion-a-year industry alone—and that’s just for the stuff that doesn’t work, stuff that does not affect the basic aging processes. In fact, the basic aging process of skin seems so intractable as to preclude any serious discussion of altering it. Consider the basics, as laid out by none other than Edward Masoro, the rodent aging scientist who came to know so much about fundamental human aging at the cell and molecular levels. In his classic work, Problems of Biological Aging, Masoro covered the basics of skin aging. As humans age, a number of changes begin to occur at all three levels of the skin. In the upper, most visible level, is the epidermis. In it, three things go wrong: It stops shedding old cells, it slows down the process of replacing them, and it stops making new cells that fight infection and disease. At the middle layer, the dermis, the process gets even weaker. The two things that make skin youthful—the proteins known as collagen and elastin—begin to shrink and dry up; the surrounding area, the so-called matrix, gets stiff, while blood vessels grow fragile, encrust, and break. The third, or subcutaneous fat layer, grows thinner. All of this causes, as Masoro might put it, very unsuccessful aging. You can play around with hormones, and you may well see some skin improvements in that process, but what, outside of hormones, can slow down that internal process, or even, as the A4M crowd might have it, “reverse age” it?
I first noticed the work of John Shieh, MD, on a website called “aging backwards.” It was the typical bonkers net magazine, but it led me to Shieh’s own site, and eventually to his practice, in South Pasadena. There, he has opened a clinic called RejuvaYou, where he specializes in using a combination of low-level laser, radio waves, and heating elements to, as he puts it, “trick your skin into making more collagen.” A congenial forty-year-old graduate of a major U.S. medical school, Shieh had come to antiaging medicine via an increasingly familiar path. He’d got sick of the way contemporary medicine was being practiced. “I was seeing twenty-five patients a day in a family practice, which is what I had always wanted to practice, but I started seeing too many unanswered issues in patient care, like, what happened when you put people on statins and they have muscle weakness, what else did modern medicine have to offer those people? Nothing. I had gone to a few A4M conferences, and I saw that had something to offer. Of course, my partners were a little put off—’Why is John ordering testosterone tests for a thirty-five-year-old?’ And I’d have to explain to them something that seemed self-evident to me. That, here you have some guy who’s doing all the right things, eating well and exercising, and here his buddies are all getting muscular and he’s not. Why not treat somebody on the so-called low-normal end if it is affecting his quality of life?”
He began using some of the A4M arsenal on himself. He tried a growth hormone stimulator. “It was amazing—not fast—but remarkable. I remember sitting up one evening and feeling, gosh, I have all of these ideas for how I can make my practice better. It was like being twenty-five years old again! I can conquer the world. Or I would look in the mirror and I could see, hmm, I’m a little tighter here, I can see my abs here …”
Then he got the chance to try out a new skin rejuvenation system, one known as ELOS. The system was created by an Israeli company called Syneron and was an attempt to deal with a basic problem in all “wrinkle reduction” systems: They often use such a high level of laser and heat energy that they end up damaging the skin more than helping it. The idea behind ELOS was that, instead of using high levels of one kind of energy, what if you combined traditional heating and cooling methods with radio frequencies and low-level light energy? A number of studies—almost all carried out with Syneron money—showed that you would reduce wrinkles and make skin look younger without the traditional laser resurfacing problems. The theory trades on an older idea of inducing repair by making cells “think” they are injured; an entire body of theoretical molecular biology, in fact, has sprung up around the arena of “heat shock proteins” that do just that, but it is a nascent field. ELOS simply made a machine to induce them, at least theoretically. Shieh tried it out on himself. “There was no doubt, I looked younger. Ask my brother, who’s younger than I am! I look younger than he does!” He tried it out on his father, who’d survived years of cancer treatments, with results so striking that he posted the photos on his website.
But where was the science? None of the studies really proved that ELOS worked by “tricking” the body into making new collagen—the essence of any real antiaging claim. And even if it does, it is a temporary fix; relying on ELOS would mean a lifetime of $500-a-pop treatments, maybe three times a year. What about that? How far, really, do any of these treatments take us with regard to reversing the aging process? Shieh and I both went over Ed Masoro’s brilliantly simple exposition of skin aging. “You know, he’s right, in that a lot of research still needs to be done on this,” Shieh said. “But what you’ve got to keep in mind is that this is safe, and that people get visible results, and that, in itself, can be transforming.” I asked Shieh if he simply meant that if you feel good about how you look, then you are likely to take better care of yourself—the classic mantra of the modern plastic surgeon. And, by the way, wouldn’t society be better off if guys like him remained as family practitioners?
He didn’t have an answer for that, but he did have a number of case studies of his own patients. As we reviewed them, one by one, he grew visibly more animated. I had seen this happen with other medical people who, after years of doling out statins and telling sour-pussed sick people to eat right and exercise more, started seeing patients who were … happier. He began to tell me a story of one patient, a middle-aged Cambodian woman who’d come to him for skin treatment after traditional laser resurfacing had made her skin look even worse.
“She was a very shy woman who’d hide in the back of a local beauty salon, washing hair, because of some damage done to her skin during years of working in the field in Cambodia during the war. She’d had some inappropriate laser resurfacing and my mother-in-law brought her in and said, you’ve got to help her!” Shieh put her through a series of complimentary RejuvaYou treatments. “And, as I did, something happened. I realized even I had not noticed that this was a beautiful woman. Her eyes. Her cheekbones. Gosh. Wow!” He didn’t see the woman for a while and went to visit her at her old beauty parlor job. “‘Oh, she doesn’t work here anymore,’ they told me. I said, ‘Where is she?’ And they said, ‘Oh, she got a boyfriend, a very rich surgeon. She doesn’t have to work anymore.’”
Am I growing tits? I ask this because, for all the high-flown discussions about DNA damage, glycation rates, GHRKO mice, and caloric restriction, tits, male tits, are the real issue with aging men in America. And I don’t want them. Yet I read in the scientific literature that while too little testosterone causes hypogonadism and, thus, gynecomastia, so does too much testosterone. I ask Rothenberg about it. He replies, “It could be that the testosterone/estrogen ratio is low and E dominant with hypogonadism. High T can cause it if there is a lot of aromatization [a type of conversion to E] and even though the ratio is OK the absolute amount of E is over a threshold.” Upon examination, it is clear that I have what most aging American men have—chubby pecs, not actual glandular growth, or true gynecomastia.
But Rothenberg’s message reminds me how much I have come to think of my body as a test tube. It seems to me that antiaging medicine—just like CR—requires an enormous amount of self-absorption to work, a constant monitoring of enzymes and vitamins and hormones and proteins. I wonder whether, in an age of such tremendous self-absorption, including my own, it’s the best way to go. Perhaps I am simply being lazy, but part of me asks: Can’t I just chuck all this and go in for a tune-up once in a while? Instead of trying to make a perfectly running car (as in CR), or giving the car all kinds of expensive new fuels (as in hormonal, or cash, therapy), can’t we reengineer it occasionally to just keep running?
As I was soon to find out, a whole new field of antiaging science and medicine is trying to do just that.
Saints Cosmos and Damian Attaching a New Leg to a Wounded Soldier (ca. 1495).
