When I was in medical school I loved disease eponyms. Duchenne muscular dystrophy, Kaposi's sarcoma, Christmas disease, and hundreds of others were redolent of medical history, exotic passports to the world of medicine.
That the eponyms taught you nothing about the disease attached to them -- a frequent objection to medical eponyms -- did not bother me even one little bit. After all, Marrakesh has a much more romantic sound than "dusty North African city inhabited by Arabs," and in its own way is more descriptive, more emotively potent.
So I loved eponyms, but it was a love tinged with envy. The envy came from the sense that the good ones were already taken: Paget's disease of the nipple, Virchow's node, and (a personal favorite) Sister Mary Joseph's nodes. All were apportioned in the land-grabs of the late 19th or early 20th century. Graduating from medical school in the late 20th century doomed one to eponymic obscurity. Once you name the Straits of Magellan, it’s named for good, unless you pull a Ho Chi Min City for Saigon switch, and I lack an invading army to make good my claims.
Well, if not a disease, then one could always hope to have a classification system named after oneself: a Child-Pugh classification of liver failure, or a Clark's level 3 melanoma. But with all due regard for Drs. Child and Clark, who I am sure were wonderful fellows, it just isn't the same thing as having a disease named after you. Classifications come and go, but diseases, like diamonds, are forever, and attaching one’s name to a disease confers medical immortality, or something approaching it.
Lakes & Craters
There is something powerful, even primal, about the naming of things, but also something difficult and problematic. It's not an issue limited to medicine, of course. Let me give two examples among many: lakes in Minnesota and craters on the moon.
Minnesota, the Land of Lakes, has some 10,000 of them, almost all named. Minnesota takes the naming of lakes seriously, as befits a state defined by its waters, the process being guided by state law (Minnesota Statute 83A.04-83A.07, in case you were curious). Trust me, it’s complicated.
So far, so good. But what is a lake? There is no standard, agreed-upon definition. When does one transition from a lake to a pond? The dividing line is important, a weighty matter for Minnesotans: change the definition and you greatly increase or meanly shrink the quantity of lakes, hence the number of names you can apportion. You have to draw the line somewhere, of course. Otherwise you would end up naming puddles in your back yard after your Aunt Sally, and Aunt Sally probably wouldn't appreciate that diminutive honor.
Minnesotans don’t, interestingly enough, define lakes by size. Instead, according to the Minnesota Department of Natural Resources, a lake is “an area of open, relatively deep water that is large enough to produce a wave-swept shore.” A functional, not an anatomic, definition, and suitably vague: how open? How deep? What is “large enough”? And “wave-swept shore?” That’s a poem, not a definition.
Or take craters on the moon. The moon is pockmarked with impact craters, the residua of eons of meteoric bombardment. There is little water on the moon, or they would be called lakes and covered by Minnesota state law. Instead the honor belongs to the International Astronomical Union, which vets the naming process. But the issue is the same: how big a pockmark before you name a crater? Who decides, and what are the rules?
The large craters, the ones easily visible to the naked eye or primitive telescopes, tended to be named after great astronomers (Tycho, Copernicus, Kepler), but the number of craters exploded as the resolving capacity of telescopes improved, and as satellites opened up the real estate on the far side of the moon. There are estimated to be roughly 300,000 craters a kilometer or larger in diameter on the near side of the moon alone.
Obviously many craters remain unnamed. Most of the larger ones are named after scientists, artists, or explorers. Some 45 craters have been named after Nobel laureates alone: we probably have some of the smartest craters in the universe.
I'd like to propose that we name a few of them after prominent (one hesitates to use the word “famous”) oncologists: Farber, Zubrod, DeVita, Einhorn, or... well, no, that would be immodest. Maybe a little crater? OK, I accept. But only if you get one too.
Back to the naming of human diseases. We used to think of diseases as discrete entities, as opposed to more loosely defined collections of signs and symptoms, which we denoted as syndromes. But it’s increasingly obvious how fragmented a "disease" may be. To quote Jonathan Swift:
Great fleas have little fleas upon their backs to bite 'em,
And little fleas have lesser fleas, and so ad infinitum.
Take, if you will, the delightfully named Charcot-Marie-Tooth disease. Leaving aside the fact that it took three names to eponynymize the disease, and the obvious questions (was Marie Charcot's main squeeze, and did he have cavities that needed fixing?), this neurological disease is a namer's nightmare. CMT is divided into several major types (with boring names such as CMT 1, 2, 3, 4, 5, 6, and X), and each type has subtypes, defined by distinctive molecular lesions.
All told, CMT has some 46 different genetic subtypes, which is not bad for a disease that affects only 1 in every 2500 people. Should each subtype have a name? I vote yes, but the neurologists apparently don't care for my opinion, though CMT3 has the rather cool-sounding eponym of Dejerine-Sottas disease.
The same is certainly true in cancer. In my own field of breast cancer, we have "intrinsic subtypes": luminal A and B, HER2-like, basal. And then the subtypes had subtypes. So-called triple negative breast cancer (ER and PR and HER2-negative, a definition by exclusion) has recently been reported to have six subtypes. Triple-negative breast cancer is characterized by genomic chaos, and if you are a splitter rather than a lumper, you might even conclude that each patient has a distinct disease, or something close: Barbara Ann Smolenski disease type I, perhaps.
So there are still "diseases" out there to be named, diseases to which I could attach my own name were I of a mind to attach my moniker to a puddle rather than a pond or a lake. I might, of course, still envy Paget or Kaposi, because they got to name decent-sized lakes, but in the genomic era we will all have a disease named after us, our own personal 15 minutes of fame. Andy Warhol would be proud.
I recently asked Chuck Perou, who first defined (named) breast cancer's intrinsic subtypes, about the ever-expanding subtyping. "What is a subtype?" he told me. "It's almost a philosophical question. In the end what matters is whether the subtyping is useful in the clinic." Indeed.
Rare diseases, like puddles, are surprisingly common. Eric Lander, reviewing the impact of the sequencing of the human genome in Nature last year, noted that prior to the Human Genome Project, fewer than 100 disease genes had been identified. Just one decade after the first human genome, more than 2,850 Mendelian disease genes have been identified. Lots of unnamed craters out there in the universe of disease: It’s raining new diseases.
And that’s only the beginning, we can be sure. Matthew Nelson recently published a fascinating paper in Science focusing on the sequencing of 202 drug target genes in 14,002 patients. Rare variants are astonishingly common: one every 17 bases.
And it is common, the paper predicts, for the variants to have deleterious effects. To remind you of what Chuck Perou told me, “In the end what matters is whether the subtyping is useful in the clinic.” Probably so, for many of these variants, though given the rarity of most we may have trouble teasing out all of the implications of this genomic cornucopia.
When I was in medical school I was taught (along with the eponyms) that "when you hear hoof beats, you should think of horses, not zebras." That was reasonable for an era when a physician depended, for better or worse, on his or her memory. The differential diagnosis was typically small, and even when it was large one could readily access it by opening up the internist’s scriptural text, Harrison's Principles of Internal Medicine.
In the genomic era, those hoof beats you hear are large herds of zebras, and they all have different numbers of colored stripes, arranged in almost infinite and contrasting patterns. And, like curious children seeing zebras for the first time, we’ll stare in fascination and say, “look at all the funny horses!”