6:30 PM – Taking Drugs Like Driving Without Brakes
The day ended with another emissary from the NIH, as Nora Volkow, director of the National Institute on Drug Abuse, gave the week’s third Presidential Lecture. I’ve heard Volkow speak a couple times now – I was actually at NIDA when she was named director in 2002 – and I’ve always found her work to be some of the most convincing data available about addictive drugs change the way the human brain works. The operative word there is human, since most studies of drug addiction (including my own work) has been performed in animals, and there are several nagging questions about the human relevance of research in animals on complex behaviors like addiction.
The directorship appears to be keeping Volkow busy with administrative duties rather than scientific work, as much of the talk was unchanged from when I saw it seven years ago. But the story is still a good one, using imaging of a particular neurotransmitter system in the brain, dopamine, to search for differences in the brains of people who habitually use drugs and people who don’t. Dopamine is increased in response to drugs of abuse, and without getting too technical, Volkow found that one type of dopamine receptor, called D2, is severely reduced in people who repeatedly use drugs such as cocaine, heroin and alcohol. Simultaneously, another region called the prefrontal cortex (PFC) shows reduced activity in drug addicts. The role of the PFC is to control people’s impulsivity – Volkow described it as the part of the brain that told her not to have a glass of wine before her talk. So repeated exposure to a drug such as cocaine can actually remove a person’s natural control of impulses, leading to more drug use and binge drug-taking behavior.
“You basically disrupt any ability to control that drive,” Volkow said, “So the person is really without brakes, and is unable to stop taking the drug.”
but the more recent data indicated an interesting flip as relatives of alcoholics, who don’t drink themselves, also show lower D2 receptors and PFC activity. So it creates a chicken and egg situation – do addicts lower their D2 receptors, or do lower D2 receptors predispose a person to become addicted to drugs. Regardless, coming closer to understanding this relationship means that improved therapies for addiction may not be far off.
And with that, I’m off to the dopamine party, made up of dopamine researchers raising their own dopamine via drinking, listening to music and social interaction. See you tomorrow.
The big talks get all the attention, but lectures are just the very tip of the iceberg at a Neuroscience meeting. The bulk of the scientific exchange happens in aisle after aisle of posters, roughly 3,000 of which are set up every morning and afternoon for the conference’s five days like the world’s biggest science fair (minus the baking soda volcanos). That’s not the same 5,000 posters either – we’re talking a whole new round of posters every four-hour session, adding up to a total somewhere around 30,000. No wonder the program for each day of the meeting is phonebook-sized.
I took a whirl through the Monday afternoon batch, happy that I wasn’t among their number this year. It’s not that presenting a poster is a negative experience – it’s actually pretty motivating to share your research, kept inside the lab the other 364 days of the year, with dozens of people in your field. But it’s an exhausting process, four hours of non-stop talking and critical thinking.
So, cruel as I am, I visited with a handful of University of Chicago researchers at the tail end of their session, when fatigue was beginning to set in. But they were all somehow still able to walk me through their projects, which ranged from animal behavior models of psychiatric disease to studies drawing a functional map of the brain’s intricate architecture.
Margaret Distler and Stacey Kirkpatrick, from the genetics laboratory of Abraham Palmer, told me about their research into the genetic origins of anxiety disorder. Both use mice, who vary in terms of their anxiety not unlike humans – except it’s measured by the willingness of the mouse to run around the center of an open cage, not in ulcers and chewed fingernails. Distler studies a gene called Glo1 which has been associated with mice that show high anxiety; her research indicates that having multiple copies of the Glo1 gene leads to increased anxiety. Kirkpatrick is working the other direction, selectively breeding mice that show high anxiety to narrow down, step by step, the area of their DNA that holds genes responsible for the behavior.
In a bank of three posters from the laboratory of Murray Sherman, chairman of the Department of Neurobiology at the University, researchers were applying the latest in cell-recording technology to re-draw decades-old maps of how neurons in the brain connect. Previous maps were based upon anatomy, with researchers making their conclusions from looking at microscopic slides of brain tissue. But Brian Theyel and Elise Kovic from Sherman’s lab were replacing those maps by activating regions of the brain and recording the results elsewhere, finding previously undetected connections or reversing dogma about how well-known connections operate. Kovic said her day had been debate-filled, as scientists resisted new information about how the brain’s cortex operates…but she also mentioned that some were impressed enough to offer jobs. Theyel made his case with some multimedia in his poster: a laptop, connected to a cell phone, taped to the poster and displaying colorful clouds of cellular activity rippling across the brain. Even better than an erupting volcano!
The Neuroscience meeting is about more than just presenting research and networking (and parties), it’s also about arming neuroscientists with new tools and ideas. Most of these workshops are irrelevant to me now that I’m no longer a scientist, but I sat in for an hour of one that hits closer to home with my new career as a science writer and communicator: Wikipedia and Neuroscience. Moderated by three scientists who are heavily involved in the writing and editing of scientific articles on Wikipedia, the workshop was half convincing scientists that they should use Wikipedia as a resource and half convincing scientists that they should get involved, adding their expertise to improve the accuracy of articles.
The first argument was made convincingly by Tim Vickers, a Scottish biochemist who helps edit topics of molecular and cellular biology. Vickers pointed out that the page for the H1N1 “swine” flu was read by more than a million people a day when the disease first started to attract attention in the spring, and still is visited by over 100,000 readers daily. Surely, Vickers said, there is no faster or efficient way to get one’s scientific research out into the general public. And with mass media devoting less space and time to scientific topics, readers left with scientific questions from the news can answer those questions easily on Wikipedia, following countless “webs of information” and finding articles that meet the level of detail they require.
But the question with Wikipedia, as always, is the accuracy of the articles and whether they can be trusted. Personally, I often use Wikipedia as a scientific resource, but always try to back up any fact I learn there with another source. Vickers argued that the majority of scientific topics on Wikipedia are, in fact, accurate, and said that the biggest problem is not accuracy but “stubs,” articles left in shortened and incomplete form. But as William Skaggs, one of two caretakers of Wikiproject: Neuroscience, appealed to the crowd for help in editing articles and providing scientific images, one audience member brought up a good point. If articles rely on scientists to upload their own images (say of an MRI taken while music is played), how does someone else verify that the image shows what it claims to show? Skaggs answered that “a certain amount of faith” is required, highlighting a flaw that may keep Wikipedia from ever attaining primary source status.
2:00 PM – Francis Collins Gets a (Skeptical) Hero’s Welcome
It’s a good time for the director of the National Institutes of Health to make his first visit to the “largest of all medical research gatherings,” as Francis Collins called it in his remarks. Less than a month ago, the announcement of $5 billion in grant funding as part of the American Recovery and Reinvestment Act gave U.S. scientists a much-needed infusion of cash for their research, and with more than 12,000 projects funded, a good proportion of the people in the room for Collins’ talk probably got at least a piece of that jackpot. So Collins was greeted with warm applause from the largest audience I’ve seen yet at the meeting, and was introduced by Society for Neuroscience president Tom Carew as “one of us.”
Collins, once director of the Human Genome Project, has only been NIH Director for 2 months, and he likened his experience thus far to a child taking a drink from a fire hose. So as you might expect, Collins mostly stuck to broad strokes in his talk, identifying five particular opportunities that he feels the world’s largest research institution – and by extension, the scientists it funds – should be focused on. Much of these goals were rooted in genetics and translational medicine, the process of bringing discoveries from the laboratory bench to the medical clinic. Some scientists are troubled by this, feeling that they are being forced into emphasizing the direct human impact of research rather than receiving grants to build the essential foundation of basic science that eventually (but maybe not soon) will pay off in human benefits. So part of Collins’ mission appeared to be reassurance that other types of research will be funded, and that young investigators and people outside the realm of genetics (which has dominated the conversation at Neuroscience) would share in those spoils.
But what will those spoils be after the stimulus money is gone? Collins was here, in part, for political reasons, emphasizing the commitment of the Obama administration to science. But he was also here as a cheerleader for science, reminding the room that NIH grant success rates (the percentage of grant proposals that are funded) have been on a downward slope for the past 30 years, and that a record low in 2011 is “entirely possible.” So, like an NPR anchor asking for pledge money, Collins begged the audience to contact their government representatives and make a case for science, not just in terms of the medical advances that could be made, but in terms of the jobs that a thriving scientific environment can create – that ARRA cash is estimated to create 50,000 scientific jobs in the next 2 years.
So a bit of worry, but not a lot of controversy. Collins quickly defused the hubbub over his religious beliefs at the start of his lecture by quipping, “Some of you who may not know me except from what you’ve been reading in the op-ed section of the New York Times or on some of the blogs may have been worried that I’d start with a benediction. I want to assure you that’s not part of the plan. I won’t ask you to pray for anything except maybe the FY11 budget.”
But if there was a subtle religious message to his talk, it was one of a new science-friendly administration leading biomedical research out of the wilderness. Talking about the grants the NIH was able to hand out to young investigators with risky ideas thanks to the ARRA money, Collins spoke as if the new administration were a Prince Charming come to awake science’s Sleeping Beauty:
“Clearly, our community, after five years of flat budgets, came back to life with this opportunity provided by the recovery act and put forward some bold and brilliant new concepts,” Collins said.
I raced at unsafe driving speeds up to McCormick Place in time to catch a press conference about the hot prospect of the meeting so far: optogenetics. Tomorrow morning, the inventor of the method Karl Deisseroth will present the topic to the entire neuroscientific community, but us lucky people with green “press” ribbons on our conference badge got a sneak preview over the lunch hour.
Essentially, optogenetics is a method of controlling very specific neuronal populations with light, and it answers an age-old question of neuroscience – how do you control the neurons you want to study without affecting their neighbors? Deisseroth solved this problem by transplanting an unusual kind of molecule, called rhodopsin, from certain algae and bacterial species into neurons. Rhodopsins have the unusual characteristic of being sensitive to light – for one rhodopsin, flashing blue light will cause the protein to turn on, while for another, flashing yellow light causes it to turn off.
Deisseroth, and subsequently several other labs, have capitalized on this light sensitivity to create experiments that activate particular neurons or synapses with more selectivity than ever before possible. Only four years old, the method has already been applied to studies of depression, drug abuse, Parkinson’s disease and memory. In one incredible video, Garret Stuber from the University of California at San Francisco showed how a mouse with rhodopsin placed in a particular connection of the brain associated with reward (the synapse between amygdala and nucleus accumbens neurons) finds the mere application of blue light pleasurable. On the video, the mouse could be seen poking its nose repeatedly into a button that flashes neon blue light through a fiberoptic into his head – the same behavior typically seen from mice asking for cocaine in lab studies.
Another video, from Deisseroth’s laboratory, showed a mouse with rhodopsin in it’s motor pathway, and turning on the blue light caused it to walk briskly in a counter-clockwise circle until the light was shut off. Could this remote control by light be used in humans, say as a more selective substitute for a therapy like deep brain stimulation in Parkinson’s? Maybe, said the researchers on the press conference panel. But in the meantime, optogenetics is only beginning to show its promise in helping neuroscientists unravel the tangled connections of the brain and their relationship to behavior.
8:30 AM – Neuroscience Envy
Judging by my drive into work this morning, everyone is getting an early start for Neuroscience today – almost every corner in downtown Chicago was packed with badge-wearing conventioneers waiting for their shuttle bus. Unfortunately, I won’t be joining them until this afternoon due to some obligations in the office, but as soon as those are done I’ll be racing up to McCormick Place to get a seat for Francis Collins’ talk at 1:00. Also this afternoon: neuroscientists and Wikipedia, drug addiction in the brain, optogenetics (seemingly the buzzword of the conference), and a nightcap with the dopamine researchers.
To tide you over this morning, here are a few attempts to capture the awesome size of this meeting, with my camera phone, none of which really succeed.