In 2017, the National Institute of Allergy and Infectious Diseases declared that the best way to avoid or minimize peanut allergies was not to withhold peanuts from very young children, as had been believed for decades, but rather to give them small exposures as a way of hardening them to peanuts. Other authorities have suggested that leaving parents to, in effect, experiment on their own children is not a good idea and that any program of habituation should only be done under close, qualified supervision.
The most common explanation for soaring rates of allergies is the well-known hygiene hypothesis, which was first put forward in 1989 in a brief article in the British Medical Journal by an epidemiologist from the London School of Hygiene and Tropical Medicine named David Strachan, though he didn’t use the term “hygiene hypothesis.” That came later. The idea, very loosely, is that children in the developed world grow up in much cleaner environments than children of earlier ages did, and so don’t develop resistance to infection as well as those who have a more intimate contact with dirt and parasites.
The hygiene hypothesis has some problems, however. One is that the big rise in allergies mostly dates from the 1980s, long after we began to get clean, so hygiene alone can’t account for rising rates. A broader version of the hygiene hypothesis, known as the old friends hypothesis, has now largely supplanted the original theory. It postulates that our susceptibilities aren’t based just on childhood exposures, but are a result of accumulated lifestyle changes dating back to the Neolithic period.
The bottom line in either case is that we don’t know why allergies exist at all. Dying from ingesting a peanut is not something that confers any obvious evolutionary benefits, after all, so why this extreme sensitivity has been retained in some humans is, like so much else, a puzzle.
Disentangling the intricacies of the immune system is much more than just an intellectual exercise. Finding ways of using the body’s own immune defenses to fight diseases—what is known as immunotherapy—has the promise of transforming whole areas of medicine. Two approaches in particular have attracted a good deal of attention in recent times. One is immune checkpoint therapy. Essentially, it is based on the idea that the immune system is programmed to fix a problem—kill an infection, say—and then withdraw. The immune system is a bit like a fire brigade in this respect. Once it has put out a fire, there’s no point in it continuing to play water over the ashes, so it has built-in signals that tell it to pack up and go back to the firehouse to await the next crisis. Cancers have learned to exploit this by sending out stop signals of their own, fooling the immune system into retiring prematurely. Checkpoint therapy simply overrides the stop signals. The therapy works miraculously well with some cancers—some people with advanced melanomas who were near death have staged complete recoveries—but for reasons still not well understood, it only works sometimes. It also can have serious side effects.
The second type of therapy is called CAR T-cell therapy. CAR stands for “chimeric antigen receptor,” and it is about as complicated and technical as it sounds, but essentially it involves genetically altering a cancer sufferer’s T cells, then returning them to the body in a form that allows them to attack and kill cancer cells. The process works really well against some leukemias, but it kills healthy white blood cells as well as cancerous ones and therefore leaves the patient vulnerable to infections.
But the real problem with such therapies may be cost. CAR T-cell therapy, for instance, can cost the better part of $500,000 per patient. “What are we going to do,” asks Daniel Davis, “cure a few rich people and tell everyone else that it is not available?” But that is, of course, another issue altogether.
*1 The bursa of Fabricius is named for Hieronymus Fabricius (1537–1619), an Italian anatomist who thought it was connected to the production of eggs. Fabricius was wrong, but its actual purpose remained a mystery until 1955, when it was solved by a happy accident. Bruce Glick, then a graduate student at Ohio State University, removed bursas from chickens to see what effect it had on them in the hope of solving the mystery. But the removals had no discernible effect, so he gave up on the problem. The chickens were then passed on to another student, Tony Chang, who was studying antibodies. Chang discovered that the birds without bursas produced no antibodies. The two young researchers realized that the bursa of Fabricius was responsible for antibody production—a really big discovery in immunology. They submitted a paper to the journal Science, but it was returned as “uninteresting.” Eventually, they got it published in Poultry Science. It has since become “one of the most cited papers in immunology,” according to the British Society for Immunology. “Bursa,” incidentally, comes from a Latin term for “bag” or “purse” and can describe various structures. Bursas in humans (which are responsible for bursitis) are little sacs that help to cushion joints.
*2 Crohn didn’t use the term himself, preferring instead to call it regional ileitis, regional enteritis, or cicatrizing enterocolitis. It was later discovered that Thomas Kennedy Dalziel, a Glasgow surgeon, had described the same disease almost twenty years earlier. He called it chronic interstitial enteritis. Crohn obituary, New York Times, July 30, 1983; “Crohn of Crohn’s Disease,” Gastroenterology, May 1999.
13 DEEP BREATH: THE LUNGS AND BREATHING
I am in the habit of going to sea whenever I begin to grow hazy about the eyes, and begin to be over conscious of my lungs.
—HERMAN MELVILLE, MOBY-DICK
I
QUIETLY AND RHYTHMICALLY, awake or asleep, generally without thought, every day you breathe in and out about 20,000 times, diligently processing some 4,000 gallons (or 440 cubic feet) of air, depending on how big you are and how active. That’s about 7.3 million breaths between birthdays, 550 million or so over the course of a lifetime.
In breathing, as in everything in life, the numbers are staggering—indeed fantastical. Every time you breathe, you exhale some 25 sextillion (that’s 2.5 x 1022) molecules of oxygen—so many that with a day’s breathing you will in all likelihood inhale at least one molecule from the breaths of every person who has ever lived. And every person who lives from now until the sun burns out will from time to time breathe in a bit of you. At the atomic level, we are in a sense eternal.
For most of us, those molecules come pouring in through the nares, which is what anatomists call the nostrils (for no very compelling reason, it must be said). From there the air passes through the most mysterious space in your head, the sinus cavity. Proportionate to the rest of the head, the sinuses take up an enormous amount of space, and no one is at all sure why.
“Sinuses are strange,” Ben Ollivere of the University of Nottingham and Queen’s Medical Centre told me one day. “They are just cavernous spaces in your head. You would have room for a good deal more gray matter if you didn’t have to devote so much of your head to the sinuses.” The space isn’t a complete void, but rather is riddled with a complex network of bones, which are thought to help with breathing efficiency, though no one can say quite how. Whether or not they have a function, the sinuses cause a lot of unhappiness. Thirty-five million Americans suffer sinusitis every year, and about 20 percent of all antibiotic prescriptions are for people with sinus conditions (even though sinus conditions are overwhelmingly viral and thus immune to antibiotics).