6:45 PM - The Opposite of a History Lesson

Eric Kandel is 80 years old, was present at the first Society for Neuroscience meeting in 1969, is 9 years removed from winning the Nobel Prize for physiology and medicine. He’s also so well known at the Neuroscience meeting, he can go by one name, “like Bono,” said SfN president Tom Carew in his introduction to tonight’s Presidental Lecture. So you might have expected Kandel’s talk to be a history lesson, a retelling of how he uncovered the cellular chain of events that underlie learning and memory in sea slugs, fruit flies, mice and, by extension, you and me.

But Kandel, looking like The Sopranos’ Uncle Junior and speaking with Woody Allen’s Brooklyn accent, had very little interest in looking back. After 75 minutes of him excitedly flashing through graphs and figures explaining recent findings in his laboratory at Columbia University, he could only narrow his talk down to four conclusions. My thesis adviser, who was sitting next to me, leaning over and whispered in amazement, “these aren’t conclusions at all, he’s still forging ahead.”

That relentless drive in someone so late in his career was infectious. Kandel said the goal of his talk was to explain how a person remembers his first love for the rest of his life, as if that was a simple quest, but his lecture portrayed science as it should be: a never-ending story, with each answer giving birth to several more questions. While some researchers settle on a single technique and pass the torch to younger researchers when the limits of that technique are reached, Kandel proved that he has stayed on the cutting edge of science, bringing fresh talent into his lab to apply new tools to his endless questions about how neurons encode memory.

As a result, almost a decade after his Nobel victory, Kandel was excitedly telling 10,000 of his colleagues about a new cellular signal, called CRB-3 in mice, which he humbly described as “a new class of functional proteins” and “an entirely new model of synaptic plasticity.” The work was backed up with the latest in genetic, cellular biology and imaging evidence, testimony to both Kandel’s ability to keep up with the fast-moving world of science as well as the sprawling world of neuroscience itself.

“One of the wonderful things that has happened in my forty years in the society, is that neuroscience, which really was quite fragmented when I entered the field…has become a unified organism,” Kandel said.

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Sam Volchenboum has his head shaved by Joshua Crosby, Sept. 24, 2009 (photos by David Christopher)

A researcher will do a lot for grant money, the fuel necessary to power a laboratory’s work. Sam Volchenboum, a pediatric oncologist at the University of Chicago Medical Center, took that adage to its follicular extreme last week, volunteering to go bald for funds from the St. Baldrick’s Foundation.

St. Baldrick’s, a California-based organization which raises funds for pediatric cancer research, asks their volunteers and award recipients to shave their heads in solidarity with cancer-stricken children who have lost their hair to chemotherapy. Thursday evening, Volchenboum went under the razor himself, shedding his dark brown hair with the help of Joshua Crosby, a 13-year-old cancer survivor. A small price to pay, Volchenboum said, for a $330,000 award that will help him design faster and more specific diagnostic tools for neuroblastoma.

“It can often take a while and be a little frustrating to get to the diagnosis,” Volchenboum said. “Despite all we know about this disease, even with aggressive treatment - chemo and radiation and surgery - over half of the kids will still die from their disease.”

Despite what its name implies, neuroblastoma is not brain cancer, but rather a cancer of the sympathetic nervous system that connects the spinal cord to organs of the body. Though it’s rare as far as diseases go - with only about 800 new cases a year in the US - it’s nevertheless the most common solid-tumor cancer seen in children and is responsible for about 15% of childhood cancer deaths. But not all neuroblastomas are fatal; in fact, some tumors in infants even regress spontaneously without treatment. That wide variation in prognosis presents a challenge to oncologists, Volchenboum said, who must decide the best course of treatment for a child with neuroblastoma, doing as much as possible to attack the tumor without over-treating with therapies that can be toxic and harmful in an adult, never mind a growing kid.

“We need to be able to sub-stratify the patients to predict outcome better,” Volchenboum said about the goals of his project. “There are probably some patients that will do poorly despite any conventional treatments, so let’s give this patient emerging therapy, let’s try something new. Likewise, there are some patients with apparent high-risk disease who get lots of therapy and are ultimately cured but may not have needed all that therapy.”

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Decades of research advances have made depression less mysterious and less stigmatized in most circles, accepted as a neurobiological disorder rather than a more abstract (and untreatable) entity. But some news about depression remains surprising, at least to people outside the realm of psychiatry. Tuesday’s newspaper had one such example: a new study out of Washington University in St. Louis following a group of clinically depressed and young – very young – children, between the ages of 3 and 6.

Diagnosing a preschool child with major depressive disorder was a new concept to me. But it turns out that it’s relatively old news to psychiatrists, who have been studying the diagnosis and treatment of early childhood depression cases since at least the mid-1980’s. Prior to that, even practitioners  had trouble grappling with the idea of toddlers and kindergartners suffering from a traditionally “adult” disorder like depression, said Sharon Hirsch, section chief for child and adolescent psychiatry in the Department of Psychiatry and Behavioral Neuroscience at the University of Chicago Medical Center.

“People used to have a different concept about kids,” Hirsch said. “They figured, from a developmental point of view, that if you didn’t understand abstract concepts – if you only knew right and wrong, black and white – you didn’t have to worry about the larger concepts in life. Therefore, you weren’t really capable of becoming depressed, because you were only focused on food and basic necessities, which are all provided for you, so what is there to get depressed about?”

But as theories of depression focused less on psychoanalysis and more on neurochemical causes, researchers began asking whether the brains of very young children might be vulnerable to mood disorders such as depression. They found that depression does strike kids, but it takes distinct physical and emotional forms.

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Gina Kolata has an interesting story in the New York Times today about the lack of volunteers for cancer research trials, but she left out a facet that has puzzled me: Even though few adults enter cancer studies, the vast majority of kids with cancer do get enrolled in trials. Why?

Kolata offers many possible reasons for the shortage of adult volunteers, including anxiety and a reluctance to make the extra office visits that a trial often requires. But those are factors in pediatric cancer too. And yet at least 75 percent of kids with cancer get enrolled in trials, compared with just 3 percent for adult patients. We did a piece recently for the University of Chicago Medical Center magazine describing how clinical trials have transformed pediatric cancer care for the better. Among other things, the studies probably raise adherence to treatment regimens because each center must document that participants follow the required course of therapy.

One likely reason for the adult-pediatric gap, as Kolata mentions, is that many adult patients are satisfied with existing treatments, especially for types of cancer with a good prognosis. If a regimen of surgery plus chemotherapy is likely to work, and patients can get the chemo at a local cancer treatment center, they’re less motivated to make the trip to a major research center conducting a trial.

But once again, the same factors could affect pediatric trials. Many pediatric treatments are highly successful, and parents would seem to have less incentive to enter their children in trials. Yet they do enter those trials, time after time.

Could one answer be that we adults are sometimes more hyper-vigilant about our children’s health than our own? Are we just more willing to suffer inconveniences for the sake of our kids? Perhaps entering a study that could result in extending the lives of other adult patients by a few months or years seems like insufficient payoff. But give those same months or years to a pediatric patient, and the calculus starts to look better, the time gained somehow more precious.

Maybe recruiters for cancer trials should try an experiment with prospective patients: Imagine you were making this decision not for yourself, but for your child. Would you be satisfied with the standard of care, or would you want to try something that might improve your child’s outcome, if only by a little? And if you would do it for your child (and most people do), why not do it for yourself?