1. Sledge, George W. Jr. MD

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Here's an old question: what makes us human? By old, I mean Greek philosopher-old. Aristotle pondered this and came up with a pretty good answer: humans are rational animals, beings capable of carrying out rationally formulated projects. He added that "man is by nature a social animal."

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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

The biologist in me has a quite simple-sounding answer to the question. Homo sapiens, like any species, is defined as (per the great evolutionary scientist Ernst Mayr) "groups of interbreeding natural populations that are reproductively isolated from other such groups." Currently, there are no "other such groups," given our ability to eliminate close relatives, but once there were. Neanderthals and Denisovans were natural populations that interbred with our ancestors.


We, their descendants, have lost most Neanderthal and Denisovan genes, and lost them in a selective fashion. Still, evolutionary biologists now think about questions such as "were the Neanderthals really a separate species?" The consensus seems to be yes, they were separate, though separate along the lines of horses and zebras. Horses mares and zebra stallions, when bred together, make zorses, or zebra mules. They are infertile. Homo sapiens and Neanderthals were right on the edge of infertility. Perhaps as few as 80 parings were responsible for all the Neanderthal contribution to the modern human genome. By and large, the answer to "What is a human?" is "Humans are that species that breeds with other humans."


But that biological answer is both true and remarkably unsatisfying.


Just having the ability to ask the question may be part of an answer. "Humans are the species that ponders what it is to be human" may be a pretty good partial definition. I suspect, though I do not know this for a fact, that cows do not ponder their cowness, nor ants their antness. There has never been a Cowistotle. Cowness and antness, to the extent they exist, are genetically hardwired mindsets. We are hardwired as well, but we seem to be hardwired for software as much as hardware. We call the software "culture," but what stands out is out essential malleability, our stubborn refusal to be defined by our past.


I often wish that I was an archeologist. Archeology, it seems to me, asks the big question of "how did we get here from there?" In the great sweep of history, the human experiment seems to be defined by that question of malleability, that transition from hardwired behavior in a constrained physical form to an existence defined by our software. Our software is now in the process of altering our hardware, but that is a relatively late development in the human story.


Archeology always gives tentative answers. The average modern is associated with so much sheer stuff that it is hard to imagine a time when material possessions were defined by what one could carry on one's back, or in one's arms, or draped over one's body. The average modern home, I have read, contains around 300,000 "things." How many "things" can you carry with you if you are walking across the Bering Strait? Fifty? A hundred? And how many of those make it to your grave, and how many graves are ultimately discovered by an archeologist? The ancient human thingome (an "omics" word I just now invented) barely existed. We are now buried in our thingome.


But there are some answers, and I find them intriguing.


First, we seem to have been defined, for much of modern existence, by our pets. "Pets" isn't the right word for those animals that shared our space, any more than calling them "domesticated animals" quite fits the bill. If cats could speak, they might well claim to have domesticated us. And dogs are so finely attuned to human behavior that they might be considered relatives rather than pets.


How long have humans and dogs hung out together? Dogs are the oldest domesticated species, so the "man's best friend" trope is probably right. The archeologic record is somewhat confusing on this issue. A human grave site dating from ~14,700 years ago contains a dog mandible whose genomic DNA sorts with modern dogs, the first unequivocal evidence we have of the relationship. Other genomic data suggests that dog and wolf lineages separated somewhere around 36,000 years ago, so "a long time ago" is the current answer. And some quasi-wolves must have worked out with our ancestors even before that genetic divergence.


Where that domestication occurred is also something of a mystery: somewhere on the Eurasian land mass seems to be about as precise as is safe to commit to at this point. Regardless, dogs were snapping at our heels before we started farming. Penn State archaeologist Pat Shipman has theorized that the demise of the Neanderthals might be linked to the partnership of dogs (or wolf/dogs) and modern humans, with the latter two combining to out-compete the former for scarce food resources. Maybe, maybe not, but Neanderthals never seem to have had friends named Fido or Rover.


By the way, why did wolf/dogs decide to hang out with our ancestors? It is an interesting question. Wolves are loners, and wolves in the wild usually avoid humans right up until they decide to eat us. A recent paper comparing dog and wolf genomes suggests that the reason is that most dogs have Williams syndrome. You may never have heard of this syndrome, since only one in 10,000 people suffer from it (if "suffer" can be said to be the right word). Williams syndrome patients are routinely bubbly and extroverted, quite literally the friendliest people on Earth. They have other health and developmental issues, but the extreme sociability stands out.


The genetic event underlying Williams syndrome has been identified (the loss of a 27-gene stretch of DNA), and its canine homolog turns out to be common in dogs and rare in wolves. The friendliest of wolves also have the Williams syndrome genetic kit, and more stand-offish dog breeds are less likely to have the Williams genetic defect. So maybe dogs were "socialized" as much by a mutational event as by our tossing chunks of meat to them on the edge of some ancient fire pit.


Cats represent a later stage in human history, and are intimately associated with the advent of agriculture. A just-out paper in Nature Ecology and Evolution dates their association with humans to around 10,000 years ago in the Near East. The story goes something like this: humans raise wheat, store it, and attract mice. The mice, in turn, attract the African wildcat, Felis silvestris lybica, whose virtues as vermin exterminators are appreciated by our ancestors. As farmers fan out from the Near East, the now-domesticated cats travel with them. They eventually travel to the ends of the earth, brought along on ships where they guard the stores against rats.


Whether cats are actually domesticated is an interesting philosophical question, but they tolerate us for the moment because we continue to supply them treats and don't bother them too much. I find it interesting that while we can easily tell wolf and dog skeletons apart, cat skeletons are indistinguishable from those of African wildcats. But the passion felines generate in some humans is undeniable. I had a patient delay potentially life-saving surgery until her cat underwent surgery. My patient could not face the prospect of living without that cat.


So, add "humans are the species that lives with cats and dogs" to Aristotle's "Man is by nature a social animal." They may even be the same answer to the "what makes us human" question. We don't just socialize with each other, we socialize with dogs and cats. Dogs and cats hung around for purely Darwinian reasons: today there are lots more dogs than wolves, and far more cats than African wildcats. But there probably were, as well, more humans because of dogs and cats: hunt wooly mammoths more efficiently, save more wheat, and you will prosper.


But the archeologic record has another interesting answer to the "what makes us human" question: humans are the species that creates art. We've been drawing pictures on cave walls for 35,000 years or more, beautiful work like that found at Lascaux in France. The first cave art we have involves hand stencils on the wall of the cave of Pettakere in Indonesia. The first figurative paintings date to 32,000 years ago, in the Chauvet cave in France and the Coliboaia cave in Romania. These paintings are filled with large mammals: bisons, aurochs, horses. So perhaps another answer to the "what makes us human" question is "Humans are the species that creates symbolic art."


And, at roughly the same time, musical instruments. The first musical instruments we have are flutes, made from mammoth and bird bones, found in the Gei[latin sharp s]enklosterle Cave in Southern Germany, and dating to about 42,000 years ago. Humans are the species that uses tools to make music.


Again, the comparison with our Neanderthal cousins is telling. We lack convincing evidence for Neanderthal cave art or musical instruments. This may only represent a flawed archeologic record, or it may suggest that art and music represent something crucial about the development of the modern human brain, and quite specific to Homo sapiens.


I will often see patients who are artists, or patients who are musicians (and with a fairly wide range of instruments, my favorite being the accordion). I have patients who have dogs and cats, indeed are passionate about them. These things are so common, so normal for us that we fail to recognize how absolutely extraordinary they make us as a species. Medical oncology is the new kid on the block, while art, music, and our pets tap into something deeper, something more ancient in the human psyche. Something we are designed for, if it truly separates us from our closest ancestral cousins.


I once had a patient with small cell lung cancer who presented with brain metastases. The metastases were accompanied by seizures, and the presenting aura for the seizures was Elvis Presley's "Blue Suede Shoes." Every time he would hear the song, he would wake up a few minutes later on the floor. We radiated his brain and Elvis Presley went into hiding. We treated his cancer with systemic chemotherapy, and the small cell responded, brilliantly but briefly, as is its wont. When the cancer recurred, so did "Blue Suede Shoes." I find it amazing that there is, somewhere in the human brain, a clutch of neurons devoted to "Blue Suede Shoes," but that is apparently a design function for modern humans. At least it wasn't "You Ain't Nothing but a Hound Dog."


Sometimes outlandish claims are made for the dogs and cats. Remember the news reports a few years ago suggesting that dogs could sniff out cancers in their owners? Or Oscar the cat, a Rhode Island nursing home denizen who appears to predict impending death, napping next to those next to pass? In both cases hand-waving explanations ("maybe Oscar is good at smelling apoptosing cells" or "maybe that melanoma is releasing aromatic chemicals the dog recognizes as malignant") have been made. All I know for sure is that if Oscar ever shows up at my door it will be the last prediction he ever makes. Maybe cats and dogs are part of what makes us human, but I am thoroughly unsentimental about feline diviners of death.