The Tell-Tale Brain: A Neuroscientist's Quest for What Makes Us Human

“You know my methods, Watson,” says Sherlock Holmes before explaining how he has found the vital clue. And so before we journey any further into the mysteries of the human brain, I feel that I should outline the methods behind my approach. It is above all a wide-ranging, multidisciplinary approach, driven by curiosity and a relentless question: What if? Although my current interest is neurology, my love affair with science dates back to my boyhood in Chennai, India. I was perpetually fascinated by natural phenomena, and my first passion was chemistry. I was enchanted by the idea that the whole universe is based on simple interactions between elements in a finite list. Later I found myself drawn to biology, with all its frustrating yet fascinating complexities. When I was twelve, I remember reading about axolotls, which are basically a species of salamander that has evolved to remain permanently in the aquatic larval stage. They manage to keep their gills (rather than trading them in for lungs, like salamanders or frogs) by shutting down metamorphosis and becoming sexually mature in the water. I was completely flabbergasted when I read that by simply giving these creatures the “metamorphosis hormone” (thyroid extract) you could make the axolotl revert back into the extinct, land-dwelling, gill-less adult ancestor that it had evolved from. You could go back in time, resurrecting a prehistoric animal that no longer exists anywhere on Earth. I also knew that for some mysterious reason adult salamanders don’t regenerate amputated legs but the tadpoles do. My curiosity took me one step further, to the question of whether an axolotl—which is, after all, an “adult tadpole”—would retain its ability to regenerate a lost leg just as a modern frog tadpole does. And how many other axolotl-like beings exist on Earth, I wondered, that could be restored to their ancestral forms by simply giving them hormones? Could humans—who are after all apes that have evolved to retain many juvenile qualities—be made to revert to an ancestral form, perhaps something resembling Homo erectus, using the appropriate cocktail of hormones? My mind reeled out a stream of questions and speculations, and I was hooked on biology forever.

I found mysteries and possibilities everywhere. When I was eighteen, I read a footnote in some obscure medical tome that when a person with a sarcoma, a malignant cancer that affects soft tissues, develops high fever from an infection, the cancer sometimes goes into complete remission. Cancer shrinking as a result of fever? Why? What could explain it, and might it just possibly lead to a practical cancer therapy?¹ I was enthralled by the possibility of such odd, unexpected connections, and I learned an important lesson: Never take the obvious for granted. Once upon a time, it was so obvious that a four-pound rock would plummet earthward twice as fast as a two-pound rock that no one ever bothered to test it. That is, until Galileo Galilei came along and took ten minutes to perform an elegantly simple experiment that yielded a counterintuitive result and changed the course of history.

I had a boyhood infatuation with botany too. I remember wondering how I might get ahold of my own Venus flytrap, which Darwin had called “the most wonderful plant in the world.” He had shown that it closes shut when you touch two hairs inside its trap in rapid succession. The double trigger makes it much more likely that it will be responding to the motions of insects as opposed to inanimate detritus falling or drifting in at random. Once it has clamped down on its prey, the plant stays shut and secretes digestive enzymes, but only if it has caught actual food. I was curious. What defines food? Will it stay shut for amino acids? Fatty acid? Which acids? Starch? Pure sugar? Saccharin? How sophisticated are the food detectors in its digestive system? Too bad, I never did manage to acquire one as a pet at that time.

My mother actively encouraged my early interest in science, bringing me zoological specimens from all over the world. I remember particularly well the time she gave me a tiny dried seahorse. My father also approved of my obsessions. He bought me a Carl Zeiss research microscope when I was still in my early teens. Few things could match the joy of looking at paramecia and volvox through a high-power objective lens. (Volvox, I learned, is the only biological creature on the planet that actually has a wheel.) Later, when I headed off to university, I told my father my heart was set on basic science. Nothing else stimulated my mind half as much. Wise man that he was, he persuaded me to study medicine. “You can become a second-rate doctor and still make a decent living,” he said, “but you can’t be second-rate scientist; it’s an oxymoron.” He pointed out that if I studied medicine I could play it safe, keeping both doors open and decide after graduation whether I was cut out for research or not.