March 22, 2007
You don't have to be brainy to chat with about his world of negative feedback loops, glucocorticoids and neurosecretory cells, but it really, really helps.
Jeffrey Tasker sits behind his desk pointing to his head, throat and mid-section as he patiently explains a complex series of chemical interactions that can occur in what he calls the "hypothalamic-pituitary-adrenal axis," and all I can think about is the kid's song "Heads, Shoulders, Knees and Toes," in which parents demonstrate basic anatomy through a series of similar gestures. Focus, focus, I tell myself. This is important stuff.
But I find that I'm not really following the trail of glucocorticoids and endocannabinoids that Tasker is carefully laying down. Rather, I'm wondering if Tasker has any idea of how really out there he is when he talks about this stuff and does he have any friends who are not scientists and how small are these "hypothalamic neurosecretory cells" anyway?
I pose this last question, to which Tasker responds: "These cells are maybe 10 microns in diameter. And a micron is, what, one one-millionth of a meter?"
I was hoping he would say something like, well, "the head of a pin," or "the size of a period." I mean, how many angels can dance on a millionth of a meter? I'm in way over my head here, and it's my brain's fault, not Tasker's.
Up to this point he has been pretty good at explaining how the very primitive part of the brain called the hypothalamus maintains an ongoing relationship with the rest of the body and in doing so keeps any number of vital processes on an even keel.
This almond-sized collection of nerve fibers and synaptic connections, he explains, not only regulates heartbeat, body temperature, blood sugar levels, blood pressure, body weight and other routine bodily functions, but it is also thought to play a role in emotional and sexual behavior. Nodding, I write down "almonds" and "sex" and hope that the cheap, creaking tape recorder I've placed on his desk is getting the rest of this. Lucky you, dear reader.
Thanks to your hypothalamus, your heart is thumping away, keeping time to the universe while you sit there, comfortably perusing a magazine. Your body temp hovers at a deliciously tropical 98 degrees as it metabolizes lunch and sends out a series of messages between your brain, an internal pharmacy called the endocrine system and various organs. You breathe and don't even know it.
As for me, the same things are going on inside as I sit here in Tasker's office located in the basement of Percival Stern Hall, though my vital signs are getting a little wobbly. My heartbeat quickens as I fret over the tape recorder and the propensity of its batteries to run out at inopportune times. My breathing is getting shorter and shallower as I recall every science course that I now regret not taking. I again command my mind to focus but ultimately wind up thinking about dinner. And somewhere, barely audible beneath Tasker's words, the insistent hum of the building's cooling system drones in mindless harmony to my own growing angst.
Either the AC is beginning to fail or something else is going on, because I'm beginning to sweat. Sweating it out--I contemplate that expression as Tasker explains that while the cerebral cortex, the outer area of the brain in which higher thought is generated, is vastly more developed in humans than in other species, the function and role of the hypothalamus is not unlike that of most mammals. I wipe my forehead with a sleeve.
"Because our body is being accosted by the environment all the time and is being thrown off balance in different ways, it is the job of the hypothalamus to serve as a kind of thermostat to sense deviations and correct them. When you have chronic stress, for instance, it can throw your system out of whack," says Tasker, as if he is reading my mind, or at least my hypothalamus.
How surreal for my own system to be going out of whack on cue, I think, as Tasker tells me that the thrust of the research going on in his lab focuses on why and how the hypothalamus reacts to various stresses that disrupt the body's status quo.
Surreal--or is it ironic? Or maybe correlated--that sounds kind of scientific... I surface from the reverie to hear: "So the hypothalamus releases a factor called a corticotropin-releasing hormone that acts on the anterior lobe of the pituitary, causing it to release another hormone called the adrenocorticotropic hormone--" Jeff Tasker, professor of cell and molecular biology, this nice guy with a boyish face who holds the Catherine and Hunter Pierson Chair in Neuroscience, this rising star in the university's academic firmament, is stressing me out.
If Tasker could take a sliver of my brain and slap it under a microscope, I'd bet he'd find an interesting array of stress-induced chemical activity going on. Fortunately, Tasker needs to go no higher up the evolutionary order than rats, as he and his group of lab assistants pit their brains against what, for me at least, is an unimaginable set of complexities in order to untangle the secrets of the human experience, one neuron at a time.
It feels like science fiction, but it isn't. I'm now standing in front of a large piece of equipment that dominates the corner of a small research cubicle. Part Jules Verne, part Bill Gates, it turns out to be a monster microscope. The lab folks refer to as a "rig," which has a fetching and unexpectedly rugged ring to it. Tasker is explaining how they use the rig to view the cells represented in the tissue-thin slices of rat hypothalamus. The cells receive certain kinds of stimulation--stress--and then the chemical activity between these cells is recorded onto a computer for further study.
"The cells we are studying are living cells embedded into little microcircuits in a slice of the hypothalamus, kind of like little nodes in the circuit of the computer chip in your PalmPilot," says Tasker, and then, pausing for effect adds, "I like to think of it as a little slice of heaven."
I write down "circuit nodes " and "heaven," and check that the cassette's spokes are still turning. The conversation progresses to obesity and how it may be related to the interplay of the hormones that help regulate our feeding habits with those hormones that effect how we deal with stress. If you've ever felt the desire to down a pint of Haagen Daz after a bad day at the office or a fight with your significant other, you may have experienced the effects of this interplay.
Blame it on endogenous cannabinoids, a substance produced by the hypothalamus that is similar to the active ingredients in marijuana. Shi Di, a research assistant professor working in the Tasker lab, has led research indicating that during moments of stress, the body's stress hormones not only put us into an excited "fight or flight" state, but also tell the hypothalamus to release endocannabinoids, which in turn begin to suppress that excited state. The brain may initiate this kind of feedback regulation so the body doesn't deplete its stock of stress hormones, in case we need them for another crisis.
Renato Malcher-Lopes, a PhD graduate student in the Tasker Lab, has found that these endocannabinoids are controlled by other hormones, particularly glucocorticoids, which also happen to regulate how the body gains and uses energy resources, including our desire for food. And so an indirect result of stress is hunger, which goes a long way to explain why I'm wondering if there is a candy machine somewhere in Stern Hall. More importantly, perhaps, for the first time, science is beginning to develop a possible neurological blueprint to describe why we soothe our blues with food.
Because the response to stress is connected to the system that controls how we acquire and use energy, this chain reaction of chemicals may explain why people who are depressed are often prone to become obese. "I'm not saying all obesity can be explained like this," says Tasker, "but we think the imbalance between stress hormones and nutritional hormones can affect weight and obesity."
While Malcher-Lopes says he is less concerned with cashing in on his research than with simply understanding "how these things work," he is aware of the potential of commercial application. "I think the research I've done will provide a map for people to design drugs and therapeutic approaches to deal with important and relevant pathologies in our society."
None of this has yet been proven on the behavioral level, though Tasker says his lab is currently collaborating with researchers in Cincinnati to look at feeding behavior and interactions between glucocorticoids and other hormones that control feeding in rats and mice.
Trust me, all the above science has been adapted to fit your TV screen. Even without the pages of chemical formulas, however, you get the idea. What's interesting to me is that despite the awesome precision of thought and painstaking attention to detail that goes on inside the Tasker Lab, its denizens exhibit a surprising amount of right-brain activity. In fact, they can be downright poetic.
"It sometimes sounds rather cold to say we think about ourselves as a biological machine," muses Malcher-Lopes. "That there are mechanics that underlie the way we think and feel. But that is why it is so beautiful. You have such wonderful machinery in your brain."
Tasker, too, is aware of the Big Picture--of the complexity and splendor into which he and his lab mates peer. How is it that a set of chemical reactions can make us who we are? Just take the idea of homeostasis--the body's steady state so routinely perpetuated by the hypothalamus. "It is frustratingly complex," says Tasker, who is in his 15th year at Tulane.
"I have this love-hate relationship with it because on one hand I feel like there is this immense bank of information and we are only scratching its surface and sometimes I feel we will never understand it completely. Yet, there is this wealth of information...."
Back in his office, Tasker recalls when he first started in research, as a volunteer lab assistant in a French lab studying the role of the hormone oxytocin in rats. "We were working with whole rats at the time and doing recordings in vivo. Working with a living thing was just fascinating and awe inspiring and intimidating at the same time. To be able to probe a living thing by asking a question and answering the question by understanding this living thing was very impressive."
My endocannibinoids must be kicking in because I'm feeling a tad less stressed. Tasker also is talking my kind of language now, and I can't help but doing a little probing myself. Earlier, Tasker mentioned that he has the scientific view that everything is explainable in terms of the brain. Everything? He must be generalizing. What about love?
"Even love and happiness and these sorts of things that we think of as abstract feelings and concepts," says Tasker. "It can all be explained by this intricate interplay of chemicals and electrical activity of the brain. Ultimately, it all comes down to brain chemistry." How unromantic. "That's what my wife says," admits Tasker, smiling. "It is sort of inherently unromantic. But it doesn't have to be that way. It's not because we can't explain love that makes it romantic."
And God? Is He explainable? Tasker pauses. "I think ultimately it is all going to be explainable," he demurs. "I believe there is a lot we don't understand, be it our physical selves, our emotional and spiritual selves, or the world around us. It's a miracle in its complexity and wonder, and we face it with awe. But it is all ultimately explainable, it's just that we can't explain it right now."
Maybe he's right. Throughout time, people like Tasker and his colleagues have asked a lot of questions and have come up with a lot of answers. As for me, I came into the interview with a lot of questions and leave with a lot of questions. We started out talking about neurons and wound up talking about God, and it's my own fault, not Tasker's.
Yet, no doubt I know more now then I did a couple of hours ago. I know I'm going back to the office, rewind the tape and begin to sort through all of this. But first, if I'm not mistaken, I know where I can find a Snickers bar and a quiet bench on campus where I can have a good, long think.
Nick Marinello is a senior writer in the Office of Publications and Tulanian features editor.
Tulane University, New Orleans, LA 70118 504-865-5000 firstname.lastname@example.org