1. Sledge, George W. Jr. MD

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We do not really see ourselves when we look in the mirror, and that is just as well. I only peer into the mirror during that brief period when I shave in the early morning, and then I just focus on not cutting myself. I'm barely awake, and shaving is a rote process devoid of even minimal thought. But a few days ago, I looked at myself, really looked at myself, looked more or less objectively at what I have become: the aging sun-damaged skin, the somewhat jowly cheeks, the sleepy-looking eyes. And I saw my hair.

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George W. Sledge, Jr... - Click to enlarge in new windowGeorge W. Sledge, Jr., MD. GEORGE W. SLEDGE, JR., MD, is Professor of Medicine and Chief of the Division of Oncology at Stanford University. He also is

Of course, I look at it when I comb: a center part, an attempt to provide some minimal order to what otherwise resembles a particularly untidy bird's nest. My hair used to be brown, then transitioned to salt and pepper, and now is mostly salt. Every time I go to the barber I see less black in the cuttings. And the hair itself seems coarser, more fragile, than I remember it. Someday soon I won't even be able to pretend: I'm just getting old.


Hair was the original biomarker of aging. Why does hair turn from a vibrant dark brown (well, that's my claim, any old photos notwithstanding) to a pale, pitiful shadow of its youth? Why did my hair follicles stop producing melanin? And why are my eyebrows still so discordantly dark? What's with that?


The shortening of hair follicle telomeres, those caps on the tips of our chromosomes, have been implicated in hair aging. A decade ago it was shown that if you re-introduced telomerase into epidermal stem cells you could reverse the effects of aging on hair follicles. In mice, anyways: it doesn't seem to have caught on in humans. Though I note, for the record, that one can buy Delfogo Rx Telomere DNA Cell Cream with Telomerase (Medical Grade) Anti-Aging SkinPro Repetitive Nucleotide Sequences from a company called SkinPro for just $45.59. And that's just one of many telomere-related products available on the Internet. Whether they are any better than hair dye is a question for others to answer.


My patients, of course, have a different take on the hair question. Hair matrix keratinocytes in hair follicles divide continuously, rendering them sensitive to many anticancer therapies, particularly chemotherapy. Every chemotherapy conversation eventually involves a discussion on the loss of hair, its timing, the relative merits of cold caps as prevention, the velocity of return, and the temporary waviness ("chemo curls") of the returning hair. Prescriptions for a "scalp prosthesis" are common; insurers, for some reason, won't pay for a wig. A colleague once wrote a scrip for a "total head prosthesis," which didn't fly either. Go figure.


Hair stories, for some reason, stick with me. I remember patients-usually those with metastatic breast cancer-who have chosen one chemotherapy over another based on relative amounts of hair loss. The conversation frequently starts with, "I know it sounds vain, but...," followed by my reassurance that there is nothing the least bit vain about a cancer patient wishing to look normal. For better or worse, hair is one of those things others judge us by and is the first thing one notices in meeting someone. None of us wants to be an object of undue interest, even pity, because we fail to wield a shock of embalmed scalp keratin.


I remember the patient who told me of her trip to the Department of Motor Vehicles when chemotherapy overlapped with driver's license renewal. A wig covered her scalp. As she sat there, the thought crossed her mind that the only people ever to check her driver's license were untrusting merchants cashing her checks and cops ticketing her for speeding. At the last second, she snatched the wig off, and the license showed her with a triumphant grin.


Then there was the woman who, on her last day of adjuvant chemotherapy, came to clinic wearing a fluorescent green clown's wig. Everyone she met that day heard the same thing: "Dr. Sledge did this to me."


And there was the young woman with long, beautiful blond hair who asked, "Dr. Sledge, when my hair grows back, will it be the same color?" Like an idiot I assured her that it would, which allowed her to say "Good. I won't need to use the Clairol anymore."


These are funny stories, but funny with a tinge of sadness, courage, even anger.


One last story, and this one haunts: the patient who, heading for hospice, said "I hope I live long enough to die with a full head of hair." In the grand scheme of things, hair may not have the same importance as hemoglobin, but it matters. We care. Ever since the Biblical story of Samson and Delilah, the loss of hair has been associated with infirmity, and re-growth with the return of strength.


And that's just chemotherapy. What intrigues me about hair biology is the extent to which it overlaps with cancer biology. The body loves to re-use biologic motifs, which is why the old idea that "targeted therapy" would be less toxic than chemotherapy turned out to be so wrong. If I administer an agent with EGFR-inhibiting qualities, my patients will develop a rash. Indeed, the rash was considered a crude biomarker for EGFR inhibitory activity. The rash is at least in part a function of the drug's effects on hair follicles, which are loaded with, and depend on, EGFR.


Or consider the JAK-STAT pathway. Oncologists care about JAK-STAT because pharmacologic inhibition of the pathway is a useful treatment for myelofibrosis. But inhibit the JAK-STAT pathway and patients with alopecia areata (which we now know to be an autoimmune disorder) rapidly regrow their lost hair. In contrast to EGFR inhibition, this is a positive side effect and has been embraced by the dermatologists. Topical JAK inhibitors are on their way to the clinic.


As a society we care a great deal about hair. I measure how much Americans care about something in terms of NCI multiples. The 2018 NCI budget is around $5.5 billion, whereas the amount spent on hair products is estimated at around $75 billion, or 13.6 NCI multiples. Think about 75 billion dollars-worth of gels, waxes, mousse, pomade, hair sprays, and volumizers. Add in hair coloring products. Also add to the pile all the hairstyling equipment: rollers, straightening irons, hairbrushes, blow dryers, and combs. Much of this equipment, Wikipedia informs me, already existed in ancient Egypt, though someone living on the edge of the Sahara probably didn't need a blow dryer.


Hairdressing is a rapidly growing occupation, with a current estimate of around 757,000 hairstylists in the U.S., not too far below physicians in total number. Hair stylists have been around a long time, as have doctors, and parallels abound between the two professions. Like physicians, they receive specialized training in special schools, and like them they are licensed by the state. And, like doctors, they can commit malpractice and can get liability insurance. There are lawyers who specialize in salon injuries. Reading one law firm's website, the injuries include cuts and abrasions, chemical burns, hair loss, allergic reactions, and slip and fall injuries (all that hair on the floor, I guess). It's like visiting an unexpected parallel universe.


Hair has its own history. Two Napoleon stories bear this out. A couple of decades ago, the case was made that the Emperor, having lost the battle of Waterloo and been exiled to St. Helena, had been poisoned with arsenic by his perfidious British captors. His end-of-life symptoms, the claim was made, were due to the poison, not the stomach cancer many had thought.


The claim seemed to have been backed up by forensic analysis of his hair, a lock of which had been kept by an admirer after his death. Screamingly high levels of arsenic were detected. When I started this blog, that was my memory of things. But it turned out to not be the whole story. Other investigators, skeptical of the claim, looked at locks of his hair collected at multiple timepoints (what is with early 19th century Frenchmen and their keepsakes?). It turns out that just about every hair sample was full of arsenic. What now seems likely was that the hair products of the time were loaded with arsenic.


So if arsenic did not kill the emperor, what about common, everyday ordinary hair products? There is an impressive literature on this subject. Hairdressers, who apply the stuff daily to women's scalps, suffer from slightly increased rates of multiple cancers. The data on the women receiving the hair dyes have disagreed. One recent article, for instance, said that hair dyes have no effect on overall cancer rates, but that African-American women using black hair dyes suffer higher rates. As with much of the epidemiologic literature, the hair dye literature is a morass, a deep bog of conflicting stories. Or so it appears to a non-epidemiologist.


Back to Napoleon. In 1812, the emperor invaded Russia with a huge army, which then suffered catastrophic reverses in a miserably cold winter retreat. Observers on the march home noted that bald men were the first to fall. While I don't know that it is a general law of thermoregulation, "don't invade Russia in the winter if you are bald" seems a useful dictum to live by.


So, my hair is gray. At least I have some. For now. Though I have no plans to invade Russia.


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