Isegoria

Mangan has gone down another rabbit hole in his health research, prompted by a reader’s unusual experience:

This started when a reader told me that he had started donating blood after reading this site and my book on iron.

He said that he had had seborrheic dermatitis of many years standing. (Click here if you want to see what that looks like.) It’s basically something like really terrible dandruff, but can be on any part of the body. He had tried both anti-fungal medication and topical steroids, and nothing worked. Since it didn’t bother him much, he quit worrying about it.

After his first blood donation, it started clearing up, and after his third donation, it completely disappeared.

What in the world? It turns out that both dandruff and seborrheic dermatitis are linked to a fungal infection by the fungus Malassezia. So is tinea versicolor, a skin infection; when I lived in Sierra Leone, virtually everyone had it to some degree.

Dandruff is caused by a fungal infection.

All microorganisms that invade man and cause disease require iron. (Every living thing requires iron.) Withholding iron from microbes is at the center of an evolutionary arms race. It stands to reason that donating blood can treat fungal infections of the skin by lowering skin iron levels. (Donating blood will also make you look younger.)

Shampoo that contains salicylate and ciclopirox effectively treats dandruff. Ciclopirox is an iron chelator (attaches and removes iron). So is salicylate. By attaching and removing iron, they deprive fungus of required growth material, it dies, and dandruff is treated.

Ketoconazole, an anti-fungal chemical that works by inhibiting fungal steroid synthesis, also treats dandruff.

Male pattern baldness has been linked to fungal infection as well, and the antifungal drug ketoconazole treats male pattern baldness just as well as minoxidil (Rogaine).

If this holds true for many or all cases of male pattern baldness (androgenic alopecia), then our notions of why some men go bald (that it’s due to testosterone metabolites) may be all wrong. Curiously, folklore has it that hats cause baldness — perhaps by giving fungus a warm, moist environment in which to grow?

Male pattern baldness is also associated with heart disease. Severe baldness was associated with a 2.5 fold greater risk of death from heart disease. Huge increase.

If fungal infection in the skin causes both male pattern baldness and dandruff, then iron is implicated, because all invasive microorganisms must take iron from their hosts.

High iron (ferritin) is also associated with heart disease. The mechanism usually postulated is increased oxidative stress of the walls of arteries; iron is a very reactive metal capable of damaging biological structures.

But another mechanism might be the stimulation of fungal growth. “Occult fungal infection is the underlying pathogenic cause of atherogenesis” (from the journal Medical Hypotheses).

Researchers at the Salk Institute are resetting the clock of the aging process — in genetically engineered mice:

Ten years ago, the Japanese biologist Shinya Yamanaka amazed researchers by identifying four critical genes that reset the clock of the fertilized egg. The four genes are so powerful that they will reprogram even the genome of skin or intestinal cells back to the embryonic state. Dr. Yamanaka’s method is now routinely used to change adult tissue cells into cells very similar to the embryonic stem cells produced in the first few divisions of a fertilized egg.

Scientists next began to wonder if the four Yamanaka genes could be applied not just to cells in glassware but to a whole animal. The results were disastrous. As two groups of researchers reported in 2013 and 2014, the animals all died, some because their adult tissue cells had lost their identity and others from cancer. Embryonic cells are primed for rapid growth, which easily becomes uncontrolled.

But at the Salk Institute, Juan Carlos Izpisua Belmonte had been contemplating a different approach. He has long been interested in regeneration, the phenomenon in which certain animals, like lizards and fish, can regenerate lost tails or limbs. The cells near the lost appendage revert to a stage midway between an embryonic cell, which is open to all fates, and an adult cell, which is committed to being a particular type of cell, before rebuilding the missing limb.

This partial reprogramming suggested to him that reprogramming is a stepwise process, and that a small dose of the Yamanaka factors might rejuvenate cells without the total reprogramming that converts cells to the embryonic state.

With Alejandro Ocampo and other Salk researchers, Dr. Izpisua Belmonte has spent five years devising ways to deliver a nonlethal dose of Yamanaka factors to mice. The solution his team developed was to genetically engineer mice with extra copies of the four Yamanaka genes, and to have the genes activated only when the mice received a certain drug in their drinking water, applied just two days a week.

The Salk team worked first with mice that age prematurely, so as to get quick results. “What we saw is that the animal has fewer signs of aging, healthier organs, and at the end of the experiment we could see they had lived 30 percent longer than control mice,” Dr. Izpisua Belmonte said.

Paul Graham knows a thing or two about risk and discovery:

Because biographies of famous scientists tend to edit out their mistakes, we underestimate the degree of risk they were willing to take. And because anything a famous scientist did that wasn’t a mistake has probably now become the conventional wisdom, those choices don’t seem risky either.

Biographies of Newton, for example, understandably focus more on physics than alchemy or theology. The impression we get is that his unerring judgment led him straight to truths no one else had noticed. How to explain all the time he spent on alchemy and theology? Well, smart people are often kind of crazy.

But maybe there is a simpler explanation. Maybe the smartness and the craziness were not as separate as we think. Physics seems to us a promising thing to work on, and alchemy and theology obvious wastes of time. But that’s because we know how things turned out. In Newton’s day the three problems seemed roughly equally promising. No one knew yet what the payoff would be for inventing what we now call physics; if they had, more people would have been working on it. And alchemy and theology were still then in the category Marc Andreessen would describe as “huge, if true.”