I found this article to be extremely informative and comforting -- no gimicks or sales pitches, just good, sound info. So if you've got the time, enjoy!
New Scientist, Oct 13, 2001 v172 i2312 p28(8)
Keep your hair on: bald men are used to having their hopes dashed, but researchers say they're finally getting to the roots of hair loss. Douglas Fox combs through the evidence. Douglas Fox.
Full Text: COPYRIGHT 2001 For more Science news and comments see http://www.newscientist.com.
DAVE'S reasons for seeking his first hair transplant were typical. The 26-year-old Internet consultant in Los Angeles wanted to feet confident dating, wanted to feel at the top of his game in a competitive workplace. Unfortunately his receding hairline had gotten worse lately--so bad he'd taken to wearing a baseball cap much of the time, and when he did take it off, people were surprised that he suddenly looked 10 years older.
Nine years later, Dave has had eight hair transplants at a total cost of $11,000. But instead of rejuvenating his pate, the trauma of repeated surgery killed many of the hair follicles. Now Dave just wishes he could hide the evidence that he ever had those operations.
"I don't even have the option of shaving my head because of the scars," he says. "I look like I was in a bad car accident."
Dave's experience is far from unique (see "Transplants unplugged," p 32). In the quest for a full head of hair, each year hundreds of thousands of otherwise level-headed men subject themselves to costly procedures that at best can offer a little extra coverage, and at worst end in disappointment and disfigurement.
So what's the answer? Hiding under a baseball cap forever? To date, Science hasn't exactly distinguished itself in the search for anything better. Neither of the two anti-baldness drugs currently approved by the US Food and Drug Administration will transform a comb-over into a mop. The best, finasteride, offers 50 per cent chance of a few extra hairs after one year of use, while it's a mystery why minoxidil, originally sold as a treatment for blood pressure, works at all. So when scientists researching hair loss start talking optimistically about a new assault on baldness, about high-tech treatments ranging from gene creams to "cloned" hair follicles, about making bald pates as outmoded as toothless gums and hearing trumpets, it's hard not to be just a teeny bit sceptical. Nevertheless, this is what the experts are now saying. And this time there might even be something in it.
What's changed is the unprecedented level of understanding that scientists are now acquiring about the causes of baldness. The new assault will be waged not with dubious tonics or hit-and-miss surgery but with drugs and therapies that target the actual genes, proteins and hormones that conspire to turn some men into slapheads.
"Over the next 10 years, we're going to see a different approach to therapy," predicts Rodney Sinclair, a University of Melbourne dermatologist who is gearing up to run one of the largest ever efforts to track down genes that predispose men to baldness. "We're going to start seeing more gene-based treatments that will last longer and be more specific."
Multimillion-dollar research programmes committed to unraveling the mysteries of hair loss? The might of gene technology unleashed on a superficial problem like balding? Hair loss research, it seems, has transmogrified into a deadly serious business up there with curing cancer. Is it worth all the effort? The would-be patients certainly think it is.
"It's amazing how important this is to many people," says Ron Crystal, director of the Institute of Genetic Medicine at Weill Cornell Medical College in New York City. "I get two or three e-mails a week from men around the world, people who are really devastated by baldness, pleading for us to do something about it. People send me scanned pictures of their heads." Crystal is best known for his efforts to develop gene therapies for cancer and heart disease, but as a sideline he has also discovered a gene that makes hair grow--at least in mice.
About 15 per cent of men, like Dave, have lost an obvious amount of hair by 30, and 50 per cent have by 45. Usually it's the classic male pattern baldness, which begins at the temples or crown and advances until all but the back of the head is bare. But what's classic for human males is decidedly rare in the rest of the animal kingdom, with stump-tailed macaques being the only other primates to routinely suffer receding hairlines. Women also suffer age-related hair loss, but it is usually diffuse and far less dramatic than the male version.
As for the rest of the human body, it might look bare compared with most other mammals bar the naked mole rat, but in fact its whole surface is remarkably hirsute: five million hairs in total coat everything except the palms of our hands and feet. Like the peach fuzz on the tip of your nose, it's mostly fine and very short hair, whereas the 100,000 hairs on your scalp are thicker, longer and darker--at least for the first few decades of life.
In an effort to solve the mystery of where it goes, hair loss researchers track individual follicles on the heads of balding men with all the single-mindedness of field biologists tracking endangered gorillas. Once a month, they photograph the same square centimetre of scalp and its hundred or so hair follicles, shave it, and then re-photograph it two days later.
Their research makes it quite clear that, contrary to expectations, baldness is not about having no hair--it is about having the wrong sort of hair. Each hair grows independently of the others. What's more, its growth is far from constant. On average, a hair follicle on a non-balding head spends about 18 months growing, with the hair lengthening by about 0.4 millimetres per day. The hair-producing cells then die off and the follicle goes dormant for around six months, before eventually shedding its hair, sprouting a fresh one and entering a whole new growth phase. When a man goes bald, the fresh hairs become progressively finer and less coloured until they're practically invisible, at which point the scalp looks bare.
But the man still has as many follicles as a hairy man, it's just that the hairs have been miniaturised. There's clearly something about certain follicles that make this happen. And now, with the help of some detailed computer modelling, Bruno Bernard, a biochemist at the L'Oreal Hair Biology Research Group in Clichy, France, thinks he knows what it is.
In his view, each follicle is "programmed" to go through a finite number of normal cycles, after which they run low on hair-producing cells and are able to produce only miniature hairs. But this alone doesn't explain why some men go bald and others don't. So what does? The follicles of bald men go through just as many cycles as those of their richly maned counterparts, says Bernard. The problem, he suspects, is that they go through them much faster.
Sure enough, when Bernard looked at men's scalps he found follicles in balding areas chewing rapidly through cycles, spending only six months actually growing. And the computer modelling cemented things. Teaming up with Albert Goldbeter, a mathematician at the Free University of Brussels, Bernard developed a set of equations that describe individual hairs going through a limited number of growth cycles at speeds typical of different parts of the head. The two researchers then applied their mathematical model to a theoretical head of 10,000 hairs and aged it by 25 years.
The model head lost hair on the crown, just as in a real man. The results, published last year, suggest Bernard's hunch was correct: a variation in cycle speed can easily account for the classic pattern of male balding. But what shortens the hair cycle in the first place?
Hippocrates was probably on the right track 2400 years ago when he noted that eunuchs didn't go bald. It turns out that hair loss usually only occurs if the scalp has a steady supply of the male hormone dihydrotestosterone or DHT. Castration removes a man's main supply of this hormone. What's more, although levels of DHT in the blood of balding men are the same as in hairy men, DHT levels in the follicles tend to be much higher in parts of the scalp that are going bald. This is because follicles in these areas have higher levels of the enzymes that manufacture DHT from testosterone.
It was against this backdrop that geneticists Stephen Harrap and Justine Ellis of the University of Melbourne went trawling for genes that cause baldness, hoping to find an entree into the multibillion-dollar hair loss market. At first their nets came up empty--the genes for the enzymes that make DHT turned out to be innocent, as did several other long-suspected culprits.
Then, earlier this year, the two researchers discovered that baldies--almost to a man--have a particular version of a protein that carries DHT's signal into the nucleus, compared with about three-quarters of the non-balding men. This suggests that you can't go bald without this version of the carrier protein, but it clearly isn't the sole cause, because so many hairy men have it too.
In the quest for a blockbuster anti-balding pill that wouldn't have mattered if only the protein's vital functions had been limited to the hair follicle. In fact the carrier protein is vital in many other parts of the body, ranging from muscles to vocal cords. "If you interfere with it," says Sinclair, "there's a risk that you'll interfere with all male hormone functions in the body. It would be like creating a eunuch."
Still, Harrap and Ellis's find looks set to put the search for baldness genes on track after years of floundering. Their gene resides on the X chromosome. That corroborates the old wives' tale that men inherit their baldness from their mothers, but can't explain the clinical studies that clearly show that in some families it's bald fathers who sire bald sons. In other words, the new gene clearly shows that baldness can be inherited from your mother or your father--a revelation that gives researchers like Sinclair new leverage. Past efforts to find the genes may have got hopelessly muddled because the researchers unwittingly included men who inherited the two different types of baldness in the same study.
"We're going back and looking for men who inherited it from their mother's side, to give ourselves a better chance of finding the [other genes]," says Sinclair. He is preparing to search for baldness genes among no fewer than 40,000 Australian men and women. And besides tracking down other DHT-related genes, he's also going to look at a dozen or so "patterning" genes.
As their name suggests, these give us our basic anatomy, ensuring for instance that an embryonic mouse or human grows the correct number of limbs in the correct places. They do this by ensuring that cells go down particular developmental pathways according to their position in the embryo. Genes that are associated with embryonic development may seem like strange candidates for underpinning a condition that usually hits in middle age, until you take into account a string of curious observations.
Firstly, infants (both girls and boys) born with a full head of hair often temporarily lose it in the classic male pattern soon after birth. Secondly, follicles on the back of an adult man's head don't miniaturise when they are moved to balding areas--the rationale behind hair transplants. In other words, there's something about the original position of a follicle on the scalp that determines its growth pattern, and that's determined by patterning genes very early in life.
But perhaps the best evidence for the role of patterning genes in baldness comes from studies of a gene called sonic hedgehog. It ensures that your developing brain divides into two hemispheres, and that you get two eyes and two front teeth rather than one, but it is also vital for the development of normal follicles. Mice that are genetically engineered to lack the gene die at birth, and they have follicles that are strangely distorted and lack some of the key cells needed to make a hair.
What's more, sonic hedgehog also continues to play its "embryonic" role throughout adult life. That's probably because hair follicles are one of the few tissues--the lining of the uterus being another--that constantly die off, only to regenerate again and again. And as Crystal discovered in 1999, sonic hedgehog can kick-start hair growth even in adult mice. When he injected the gene into the skin of mice, the mice sprouted new hairs.
While sonic hedgehog seems like an obvious choice for gene therapy for baldness, you've got to be careful, warns Crystal: too much of it causes tumours. Crystal knows how to attach the gene to a virus that could be used to deliver meagre doses every few months, thereby reducing that risk, but since he has bigger fish to fry--such as developing gene therapy against killer cancers--for now he's leaving that for others to try.
And there are plenty of others positively salivating at how accessible hair follicles--unlike most organs--are to gene creams that could be slapped on like sunscreen. One researcher who's keen to show that such an approach might work is Christopher Wraight, a biochemist at the Royal Children's Hospital in Melbourne. He's developing a gene cream for another skin disorder, psoriasis, in which cells proliferate madly. For now he's shown that injecting the skin of mice with "antisense" molecules--pieces of DNA that block gene signals--stops the out-of-control cell division, and he's about to test an antisense cream. Wraight envisions the same approach being used for hair loss: an antisense cream that's rubbed on daily could, for example, be used to block a gene that transmits DHT's harmful signals to the cell nucleus without turning anyone into a eunuch.
But there's a catch. Using a gene cream every single day would break the bank of all but the wealthiest bald men. One solution would be to synchronise all your hair follicles so that they enter their growth cycles en masse, which is the only time the progenitor cells can take in new genes. Then you'd simply apply your gene cream once and enjoy the rush that goes with having a full head of hair for the 18-month duration of the cycle.
And a drug capable of synchronising hair cycles is already available, points out George Cotsarelis, director of the University of Pennsylvania Hair and Scalp Clinic in Philadelphia: retinoic acid, which regulates cell division and is prescribed for acne. Using that pharmaceutical ploy, Cotsarelis has taken a giant step towards making gene therapy for baldness a reality. He has used a lotion to introduce "marker" genes into progenitor cells of synchronised hair follicles taken from a man's head and implanted on the back of a mouse. Targeting genes specifically into the progenitor cells of a follicle is a tricky task--but if you can do it with a marker gene, you should be able to do it with any gene. "It's very important. It shows you can put [genes] where you want to, and not all over the skin," says Angela Christiano, a geneticist at Columbia University in New York, who works on hair loss.
But solve one problem and another rears its ugly head. At the beginning of those synchronised cycles you'd lose every hair on your scalp--a big downside for a man so devastated by hair loss that he feels compelled to use a treatment as radical as gene therapy. What's more, Cotsarelis still has to test different genes to find out which ones will do the job best, and satisfy rigorous safety requirements. So it will be some time before such a therapy becomes available.
Still, if Cotsarelis succeeds, he could end up the Rupert Murdoch of hair restoration. "There are drugs that haven't been enormously successful, and they are still doing $400 million a year," points out Sinclair, referring to the hair-growth drugs minoxidil and finasteride.
For now, hair transplants remain the most effective treatment going, despite the fact that they suffer from one major limitation: the procedure doesn't add new follicles, it just rearranges them. Christiano and Colin Jahoda of Durham University think they can get round this. They've found that certain cells harvested from human follicles grow into entire new follicles if they're implanted on a bare patch of skin, in a process dubbed "follicle cloning" by an enthusiastic lay public. Unfortunately, getting enough cells to grow one new follicle means destroying 20 donor follicles. But if the researchers can multiply the cells they harvest by growing them in a test tube, which they're now trying to do, they could create many new follicles from a single donor follicle.
"Cellular therapies like this will be the next wave," predicts Christiano. "It will take a lot longer to figure out rational drug targets that really work. These cellular techniques shouldn't take as long."
And Christiano has a very personal stake in getting such techniques to work. She used to study genetic skin blistering diseases, but six years ago she abruptly switched her research interest when her waist-length brown locks began falling out for no apparent reason, and she was diagnosed with alopecia areata (see "Bald for a day", above).
"It was one of the first times I'd really been a patient with anything," she says, "and not only do they not know what causes it, but they can't tell you if it's going to get worse, better or stay the same. It was frustrating."
Clearly Christiano is not alone in her frustration. The voicemail greeting at her lab informs callers that she's not a physician and isn't conducting clinical trials, but she still gets up to 10 e-mails, calls and letters a week, including clinical histories and photos of scalps. "I get whole bags of hair," she says. "They collect the hair in their brush, and in their drain, and send it every month with a note that says, 'I hope this can help.'"
And perhaps it will, by acting as one more spur to the research efforts that are beginning to hold promise that in the future men will have the option of keeping hold of their hair even as they struggle to keep hold of their Zimmer frames.
Hair to stay
Hair leaves no fossil record, so no one knows exactly when animals started to sprout it, but the best guess is that it was probably some 225 million years ago, when the first mammals merged. While their reptile-like forebears were much larger and were active during daytime, the mouse-sized morganucodon and other early mammals gained their evolutionary foothold by hunting insects at night.
Cold night-time temperatures and small body size made heat loss a real problem--even for warm-blooded mammals. "The only way to survive was to have insulation," says Judd Case, a palaeomammalogist at Saint Mary's College in Moraga, California.
"Hair was necessary for mammals to originate and make that jump into being these little nocturnal insectivores."
The days when a middle-aged man's concern about balding was seen as comical are ending, as study after study shows that hair loss may be a warning of serious medical problems to come.
One huge study found that men who by 45 had hair loss comparable to Captain Jean-Luc Picard (that is, they'd lost most of the hair off the top and front of their heads) are 36 per cent more likely to suffer a non-fatal heart attack than men with a thick thatch. Numerous other studies point in the same direction, with some finding a whopping threefold increase in death from heart disease among baldies.
No one's quite sure what the connection is between baldness and cardiovascular disease, but the prime suspects are male sex hormones. These contribute to heart disease, and are also involved in hair loss--that's why castrated men don't go bald. It's possible that men who lose their hair and get cardiovascular disease have higher levels of sex hormones, or are simply more sensitive to them.
What is certain is that excessively high testosterone levels are not a good idea. When monkeys are fed high-cholesterol diets, and given extra testosterone, their blood vessels become far more clogged than when they are given high-cholesterol food alone. Rabbits that were forced to inhale cigarette smoke for 10 weeks had constricted blood vessels, with testosterone injections making the problem far worse.
Sex hormones are also likely to be the hidden link between prostate cancer and baldness. One of the most comprehensive attempts ever to identify risk factors for cancers, the US-based National Health and Nutrition Examination Survey, found that men aged 25 to 75 who had lost a noticeable amount of hair were 50 per cent more likely to develop the disease. Prostate cancers depend on male sex hormones to grow, and the disease is often treated either by blocking the production of the hormones with drugs or castration, which doctors euphemistically call "orchiectomy".
But it's not all doom and gloom for men with reflective domes. The National Cancer Institute is testing the ability of the anti-balding drug finasteride to prevent prostate cancer. That makes sense--the drug was first developed to treat prostate enlargement--and it means that a thicker head of hair and a cancer-free prostate may one day go hand in hand.
A hair on your head grows 0.3 to 0.5 millimetres per day, with its final length determined by the duration of its growth cycle--generally about 2 years.
Rare people with growth cycles of 10 years can grow hairs up to 1.8 metres long. But even that pales in comparison with the world record: Hoo Sateow, a Thai medicine man who died a few weeks ago, had tresses 5.15 metres long. Sateow's secret was to wind his hair into one serpent-like plait, so that individual hairs weren't lost as they were shad from the follicle.
Hair transplants have come a long way since the early 1980s, when surgeons used hair plugs of up to 20 hairs. The hair grew, but in clumps like on a cheap plastic doll.
Modern transplants frame the face by creating a new hairline. Under a local anaesthetic, surgeons cut a 2-centimetre wide, 8-millimetre deep, ear-to-ear strip of donor scalp from the back of the head. They then cut it into grafts of one to four hairs each, and insert each graft into a hole created with a special blade. The hole is angled forward at 45[degrees], which creates an illusion of fullness, because the hair has to be brushed back to stop it falling over the face.
Transplanting 1200 grafts takes five hours, and most patients require up to four procedures (with at least six months between). If all goes well, the transplanted hairs should continue to grow well into the patient's dotage.
Despite the advances in the technology, not everyone is happy with the results, and websites bristle with stories by angry patients who feel the procedure fell far short of its promises. It's impossible to know how many of the quarter-million hair transplant procedures carried out in the US each year aren't up to scratch. But at least some of the disappointment is due to patients having a distorted body image that can't be treated by physical means alone. "There are some people who see the hair between the spaces; there are others who see the spaces between the hairs," says Thomas Cash, a psychologist at Old Dominion University in Norfolk, Virginia, who studies the emotional impact of hair loss.
Yet hair transplants carry some real risks. If too many procedures are performed, scar tissue may kill the transplanted follicles by choking off their blood supply, while placing the grafts too deeply causes bumpy, "cobblestone" scarring. The potential for problems increases in some of the cheaper, "assembly-line" clinics, which may keep prices down by hiring physicians with little surgical experience, warns Richard Martin, a cosmetic surgeon at Connecticut Surgical Arts in Norwich.
No shortage of bright ideas: hair regrowth through the ages
Hippocrates's anti-baldness formula
Rubbing a mixture of opium, horseradish, pigeon droppings, beetroot and spices into the scalp supposedly encouraged hair growth, suggesting that this Ancient Greek was in danger of violating his own oath to "first, do no harm"
Ebers papyrus anti-baldness formula.
This formula-contained in the world's first medical text, an ancient scroll from Egypt-recommended a mixture of iron, lead, onions, alabaster and honey, which was to be swallowed after a religious ritual
A secret remedy causing "a splendid crop of hair to spring up and flourish where before all was barren". This was used worldwide for a century or more
Dr Scott's Electric Hair Brushes
Magnetic hairbrushes that treated not only hair loss, but also malaria, rheumatism, paralysis and constipation
Bowen's Genuine Crude Oil Hair Grower
"A secret formula Mending crude oil with other rare material of wonderful value for the hair and scalp." Strong words but don't be taken in. According to Rodney Sinclair, a University of Melbourne dermatologist, "[Bowen's] may cause cancer, is likely to be irritating, and there's no rational basis to presume that it would work"
Dr Okuda's hair transplants
The first known reports of hair transplantation were published by this Japanese dermatologist. Though legitimate, the work was ignored in the West until after the Second World War
A helmet sealed onto the head with a rubber gasket and attached to what was effectively a vacuum cleaner stimulated the scalp with alternating vacuum and pressure. Similar devices were sold by several companies. Some claimed that they sucked impurities out of hair follicles, some that they sucked the hair out from where it was trapped inside the scalp. Not recommended
Boots with hooks on for hanging upside down from a purpose built rail. Hanging like a bat for 30 minutes a day supposedly promotes follicle survival by increasing blood flow to the head. Our experts say there is no evidence that this would help
The first baldness treatment to gain approval by the US Food and Drug Administration
A peer-reviewed article in the International Journal of Dermatology claims that painless, 12-minute treatments with this hood-like device triggers hair growth by "caus[ing] the scalp to be passively 'bathed' with the emitted electrical field energy".
It's true that electrical stimulation can boost bone and wound healing, but hair growth is a different biological process, points out George Cotsarelis, director of the University of Pennsylvania Hair and Scalp Clinic in Philadelphia. He scored this technology low on plausibility
Patients pay up to $7000 per year for weekly sessions sitting under a gadget that showers their head with low-power laser beams, supposed to promote hair growth by heating the scalp and improving circulation. The researchers we spoke to say there's no evidence that increasing circulation is important for hair regrowth
The first FDA-approved baldness treatment that can be taken as a pill
Freud meets follicle
Flipping through the hair loss section of the Yellow Pages is a bit like strolling down the sleazier streets of Las Vegas. Flashy come-hither ads, picturing Leonardo DiCaprio lookalikes, offer Virtual Reality Hairlines, Hair Support[TM] and Cyberhair[R]. Follicularly Precise[TM] technology is only a phone cell away. Thicker hair can be had in one hour.
The follicularly challenged are big business, which raises the question: why are some men so desperate to hide their hair loss in the first place?
Numerous studies show that both sexes perceive bald men as older than their woolly-headed counterparts of the same age, as well as less physically attractive, less likable and less confident Of course if you've got the personality of Patrick Stewart, other people's first impressions won't hold you back. But for a man already beset by insecurities who's invested heavily in his looks, hair loss can make him feel he's lost control over his life. Attempts to reassert control can take the form of seeking treatment or trying to conceal the hair loss, says Thomas Cash, a psychologist at Old Dominion University in Norfolk, Virginia. But What begins innocently enough as a comb-over, he warns, "can go to an extreme, where somebody's got three hairs that are 14 feet long wrapped around their head like a turban."
Even when it works, disguising hair loss is not always a good idea, says Cash. "The more you avoid what you're afraid of, the stronger the phobia gets." Some men go to inordinate lengths to prevent even their families from seeing their balding pates, by having baseball caps glued to their heads, for instance, and never allowing their partners to touch their hair or see them with wet hair.
But baldness isn't all bad. It may even have served an important evolutionary function, signaling that the individual is mature and wise, and should be accorded status. "Reaching maturity is an indication that you've got a lot of survival skills, and that others should learn from you," says Michael Cunningham, a psychologist at the University of Louisville in Kentucky.
Bald for a day
No one's surprised when a middle-aged man loses the flop in his mop, but when a 10-year-old girl suddenly goes as bald as the day she was born, people notice.
The cause is alopecia areata, a condition in which immune cells attack the follicles. The result is anything from bald spots the size of five-pence pieces, which gradually regrow, to hair loss over the entire body, including eyebrows and eyelashes. One in fifty people is struck by alopecia areata at some time during their lives, and while it affects both sexes and all ages, it has a particular predilection for children.
The good news is that alopecia areata causes no damage to health; the bad is that it can emotionally devastate patients, and the treatments are limited. Alopecia areata is usually treated with painful injections of immunosuppressant steroids into the scalp. Minoxidil is also used. In addition, a few clinics are trying a newer treatment in which chemicals that cause allergic skin reactions are rubbed on repeatedly. No one knows why this may work. One idea is that the immune system becomes overwhelmed, causing it to simultaneously pull the plug on both the allergic reaction and the autoimmune reaction.
Further reading: "Modeling the dynamics of human hair cycles by a follicular automaton" by Albert Goldbeter and others, Proceedings of the National Academy of Sciences, vol 97, p 8328 (2000)
"Polymorphism of the androgen receptor gene is associated with male pattern baldness" by Justine Ellis, Martin Stebbing and Stephen Harrap, Journal of Investigative Dermatology, vol 116, p 452 (2001)
"Efficient delivery of transgenes to human hair follicle progenitor cells using topical lipoplex" by Alevtina Domashenko, Sonya Gupta and George Cotsarelis, Nature Biotechnology, vol 18, p 420 (2000)
Douglas Fox is a Science writer in California. His friends reckon he's a Norwood-Hamilton III