The New Science of Hair Growth
Robot folliculr surgeons, invisible micrografts, in vitro hair cloning . . . scientists have a wider array of weapons than ever before in the war on baldness. Many believe we're finally on the verge of banishing it forever
By: Michael Behar
Source: menshealth.com
Training Hair Cells to Grow
Nude mice are the foot soldiers for the war on balding. These dainty pink-hued rodents have been bred or genetically altered to remain hairless throughout their lives. They can be ordered by the mischief-load from medical suppliers and endure poking and prodding and other unspeakable horrors for the sake of balding men everywhere. In Philadelphia, Ken Washenik, M.D., Ph.D., executive vice president of scientific and medical development for Aderans Research Institute and a clinical assistant professor of dermatology at New York University's Langone Medical Center, shows me slides of nude mice on his laptop. They have undergone a new type of hair-cloning procedure that Dr. Washenik has been developing for Aderans. The company, which has its headquarters in Tokyo, is the world's largest manufacturer of wigs. It also owns Bosley, which operates 88 hair-transplant clinics in North America.
When I arrive at Aderans, Dr. Washenik hastily ushers me past several labs, perhaps wary I might glimpse some sort of trade secret, and into an empty conference room. What he does reveal is that his approach to hair cloning (he calls it follicular neogenesis) doesn't rely solely on dermal papillae. "We are using a two-cell construct, growing not just dermal papillae, but also another type of cell from the follicle," he explains.
As the thinking goes, disparate cell types already communicate with one another in the follicle to regenerate hair. Dr. Washenik believes that if he can re-create that environment in the lab, cultured cells won't get dementia and forget how to make hair. "The different cells in the follicle are smarter than we are," Dr. Washenik says. "They already know they are supposed to be hairy. In 8 days, we grew a ball of hair that never existed before on the back of a mouse."
Dr. Washenik clicks an image file on his computer: The photo shows what looks like Piglet with a sable Mohawk. But there is a caveat: "These were hair cells from a mouse that were injected into a mouse. When researchers injected human cells into a mouse, they didn't get the same results."
This disappointed Dr. Washenik and other researchers, because unlike other organs, follicles are supposed to be immune privileged: When transplanted across or between species, they're expected to grow normally, without being rejected or provoking infection. He hopes to have better luck in clinical trials, when he will transplant human cells into humans. Aderans is in the second phase of a human trial, which is expected to be completed by the end of the year.
The company is pouring serious cash (Dr. Washenik won't say how much) into its hair-cloning effort. Dr. Washenik is also intrigued by other researchers who are pursuing another pathway. They're cultivating in vitro microscopic hairs, or "proto-hairs," as Dr. Washenik dubs them. "These are early follicular structures that you can place in the scalp with the same technology that's used for a hair transplant," he says. "The big hurdle so far is getting the cells to multiply to make enough hair. Once we culture them, they sometimes die or de-differentiate."
But Dr. Washenik remains confident. "The sooner we figure this out, the better," he says. "So many people are waiting for this technology. I know that with every medical advance, the first one to market becomes the leader, and everyone else plays catch-up." Like many of the scientists I meet, his passion for a cure is personal. "I started going bald at 25," he says, tussling his hair to flaunt his 2,200-graft transplant. "While I was working on my Ph.D., I was mixing up homemade minoxidil [the active ingredient in Rogaine] in my lab."
A few blocks away is a start-up called Follica. One of its cofounders, George Cotsarelis, M.D., is a cutaneous biologist and associate professor of dermatology at the University of Pennsylvania. In 1990, Dr. Cotsarelis was investigating the biological mechanisms of skin regeneration. "I was studying stem cells and found a population of them in the hair follicle, in a strange area called 'the bulge,'" he tells me when I stop by his office at U. Penn's School of Medicine. "We didn't know the function of the area, and we almost blew it off."
From then on, Dr. Cotsarelis started paying more attention to hair follicles. After a series of more recent experiments on mice, he made two important discoveries. First, he found that bulge cells aid in the formation of new hair follicles, suggesting that these cells influence hair growth during embryonic development, when we were bobbing around in the womb. He also learned that, throughout our lives, these same stem cells awaken to mend minor cuts and burns, as well as deeper wounds in the skin. What baffled Dr. Cotsarelis is why, if a healing wound is populated with bulge stem cells, new follicles don't form. The answer would at least explain why hair doesn't grow from scars.
Dr. Cotsarelis conducted further studies designed to reveal what kinds of molecular compounds (e.g., hormones and proteins) are present during hair-follicle development in mice embryos and are also present in adult mice. A major one, which he wrote about in a 2007 Nature article, was something called Wnt (pronounced wint), a network of proteins first identified in fruit flies.
Curious, Dr. Cotsarelis applied Wnt to small lesions purposely cut into nude mice (such gracious, noble critters). To his shock, follicles formed and sprouted hair. So if a person is bald, the obvious strategy would seem to be to douse his scalp with Wnt and wait for hair to grow. "The problem is that Wnt is involved in a lot of other things, one of which is skin cancer," Dr. Cotsarelis says. "It's very tricky business."
The idea behind Follica is to develop a procedure in which a surgeon would lightly wound the scalp—something akin to microdermabrasion, an antiaging treatment—to disrupt the skin and then apply a compound that would influence hair development in the area. This would trick the cells into reverting to an embryonic state, one in which they are genetically pre-programmed to make hair rather than simply repair skin, as they're predisposed to do after we're born. "Just when cells are deciding, 'Do I make a hair follicle? Or do I make an epidermis?' we can influence them with a protein to go down a hair-follicle pathway."
Testing the Science on Humans
My hair started thinning when I was 32. I'm now 40, and my shedding has eased up. Dr. Harris informs me I have plenty left for a follicular unit transplant. But after watching Scott's procedure, I'm a little freaked out. Yet, all the specialists I speak with urge anyone dealing with hair loss to act fast, because once the hairs are gone, they're gone for good.
"Absolutely no one concerned about hair loss should wait," Dr. Washenik says. He started taking Propecia when he was in his thirties (he's now 50), and he uses Rogaine religiously. He is a big advocate of drug therapies, and readily champions surgical options such as follicular unit grafting.
Dr. Washenik examines my scalp and announces, "Rogaine is made for you. You're not bald; your hairs are just miniaturized." I'm a chemical-phobe, so I'd rather save my dough and wait for a viable hair-cloning procedure, which many of the experts I talked to claim is less than 5 years away.
Intercytex, a public company based in London, may be closest to a marketable product, says Jerry Cooley, M.D., a transplant surgeon who has been consulting for the firm since 2001. Nobody directly employed by Intercytex would speak to me for this story. "We do not feel that exposure of our research is helpful," wrote Jeff Teumer, Intercytex's director of research, in a curt e-mail. But Dr. Cooley, who works closely with Teumer, tells me that Intercytex scientists have successfully grown large batches of cloned proto-hairs similar to those that other researchers have been struggling to keep alive.
What's more, in animal experiments, the Intercytex team has observed cloned hair follicles growing hair again after the original hairs were plucked. This suggests that their cloned follicles cycle through the entire life span of hair—three phases known as anagen (growth), catagen (transitional), and telogen (resting)—something no other researchers have been able to do.
A key to the team's success has been growing proto-hairs in a special medium, licensed from a Japanese inventor, which contains cultured skin cells known as keratinocytes. "I'm very excited about this technology," Dr. Cooley says. "It's not a matter of if, it's a matter of when."
Bessam Farjo, M.D., a hair-restoration surgeon contracted by Intercytex to run its ongoing clinical trials, says, "All I can tell you is that we've grown a significant number of hairs on animals through this technique." It sounds encouraging, and Dr. Farjo expects to complete clinical trials this year.
Hair cloning will be pricey initially, so early adopters may be men who are not only wealthy, but also desperate because they don't have enough hair left to do a follicular unit transplant. Cloning could also be ideal for younger men who aren't good candidates for follicular grafting. "Younger guys aren't suitable for current surgical techniques because we don't know how much hair they are going to lose," Dr. Farjo says.
Imagine if the receded hairline of a 25-year-old male were replaced with a follicular unit transplant. If the rest of his hair were to fall out—and going bald at an early age generally means it will—he wouldn't have enough hair to complete a second or third follicular unit transplant, so he'd end up with a solitary plume sprouting from his forehead. "It would look like unfinished business, which is why we typically avoid working on young guys," Dr. Farjo says. "But if I know I'll never run out of hair, thanks to the new cell therapy, I can treat anyone."
Nobody is sure how the actual cloning process will be implemented. Most surgeons speculate that they'll use boring tools similar to the existing ones used for harvesting follicular units. The follicular units will be sent to centralized labs, where industrial incubators will mass-produce millions of follicle cells for a relatively low cost.
Another question is how will the cloned cells be transplanted? Instead of transplanting follicular units, your surgeon may inject cloned cells into micro-incisions, or he may implant lab-grown hair follicles. It could be fast, clean, and painless. Or it might entail something closer to Dr. Cotsarelis's method at Follica. At Intercytex, technicians are tinkering with sundry techniques. "We're experimenting with varying the number of cells in each injection, and whether we have to inject the cells into the skin as it is, or if we have to pre-stimulate the skin," Dr. Farjo says.
Whatever the outcome, choices will abound. In the future, hair cloning will coexist alongside follicular unit transplants, drug therapies, and emerging technologies still incubating in the labs. For his part, Dr. Harris is also part of a team designing the world's first follicular extraction robot: It will fully automate the procedure, making it magnitudes faster and less expensive.
While Scott was being prepped for surgery, Dr. Harris took me into his office to show me a photo of the $25 million speed surgeon (the actual machine was locked in a storage closet a few floors above us). At about 6 feet tall with a fixed base and a mechanical arm with multiple joints, it resembles one of those space-age automatons you might see on a vehicle assembly line at a Toyota plant. Dr. Harris has already tested it on a couple of willing volunteers (with no alarming mishaps) and is preparing to apply for FDA approval under the name Restoration Robotics.
"We think the robot might be able to extract a thousand grafts an hour," Dr. Harris says. "That's more than triple what can be done by hand. This will broaden the market so that more people can afford the procedure. There may be a time soon when hair-transplant surgery will be available to everyone."
