Showing posts with label Arvid Carlsson. Show all posts
Showing posts with label Arvid Carlsson. Show all posts

Wednesday, August 26, 2009

Cool Stuff I Love Talking (and Writing) About


If you're a serious researcher wanting to know more about your field, you don't waste your time attending the Annual Meeting of the American Psychiatric Association. The week-long meeting is largely regarded as a junket where clinicians can pick up the CME credits they need to remain in good professional standing.

But if you know what you're looking for, you can learn a hell of a lot. In eight years of APAs, I've had the honor of listening to three Nobel Laureates, plus numerous others who deserve a free trip to Stockholm. I particularly enjoy hearing the brain scientists, who are kind enough to dumb down their presentations for the psychiatrists, which means people like me can kind of follow along.

Here's how it works: When Daniel Weinberger of the NIMH is at the APA and happens to mention the COMT Val 108/158 Met variation, he pauses to explain what that means. Not only that, he has cool PowerPoint slides that even psychiatrists and Geico cavemen can follow. When the same Dr Weinberger is at, say a schizophrenia research conference, addressing an audience that includes 2000 Nobel Laureate Arvid Carlsson (pictured here), he doesn't even bother to let on what the COMT Val-Met variation is all about. He just assumes everyone knows. And forget about a cool PowerPoint.

Research conferences don't intimidate me. Remember, raccoons respect my piss. In San Diego in 2009, at the International Conference on Schizophrenia Research, I approached a table where very smart people were drinking their morning coffee, and introduced myself as the only C student at the table. The line worked so well I used it the rest of the day. It didn't take me long to get into the spirit of this particular conference, and soon I was referring to my coffee as my "neuro-cognitive starter."

Naturally, I knew exactly what to say to the likes of Dr Carlsson. Being a journalist, I assumed a totally professional demeanor and introduced myself as someone about to become a grandfather who would like to thank his son-in-law for his participation in the effort - who happens to be a neurosurgeon in training - if he (Dr Carlsson, that is) would be so kind as to provide an autograph.

Dr Carlsson, to his credit, smiled indulgently, and graciously signed the back of my program. His co-Laureate, Eric Kandel, did the same for me a few years earlier at the APA in Atlanta when I told him about my nephew who is as smart as Einstein. "I really admire your work," I burbled to Dr Carlsson, as my parting remark. I'm sure that was the high point of his life, coming from a C student.

A little background: Dr Carlsson literally discovered that dopamine is a neurotransmitter. Finding a new neurotransmitter was to brain science what the discovery of Uranus was to astronomy, only far more significant. At least, back in William Herschel's day, we knew what a planet was and what it did. By contrast, as late as the early 1960s, we had only the vaguest idea how brain cells - neurons - communicated.

Back in those days, scientists were divided into two hostile camps that literally didn't talk to each other - those who believed cells instant-messaged each other electrically and those who thought that chemicals were the prime agents. So for Dr Carlsson to even arrive at the concept of neurotransmitter and dopamine, first he and his contemporaries had to figure out the Newtonian physics of that mysterious inner universe we call the brain.

We now take it for granted that a neurotransmitter is a packet of chemicals that is delivered from one nerve cell across a gap (or synapse) to another nerve cell. The neurotransmitter glutamate, for instance, literally instructs neurons to get excited. It's all about chemicals outside the brain cell setting off chemical reactions inside the brain cell (after first being assembled inside a different brain cell). Technically electricity is also involved, but we don't need to go there.

Had Dr Carlsson stopped right there, he certainly would have earned his plane ticket to Stockholm. (Wait, Dr Carlsson is Swedish - he probably only had to drive across town to collect his prize, assuming he could find a place to park.) But no, Dr Carlsson connected dopamine deficiency in the brain to Parkinson's, which led to L-dopa and other agents for its treatment, thereby significantly improving the lives of countless millions.

That isn't the end of the story. Dr Carlsson's discovery literally opened up the field of biological psychiatry, which posits that - hello! - the brain is not undifferentiated tofu. You can argue till the cows come about whether the mind and brain are the same or two entirely different entities, but when all is said and done, how we react to the environment around us and how we anticipate our future is mediated through the elegantly intricate processes of the meat housed inside our skulls.

We think with our meat. Newtonian meat, quantum meat, highly specialized units of meat, 100 billion cells - as many as the stars in the Milky Way - arranged in infinite connections switched on by some 16,500 genes out of a total of about 25,000 in the human genome.

So when I told Dr Carlsson I admired his work, I really meant it. Not only that, I was in awe of it. I would have felt the same way had I a chance to shake Einstein's hand. So - seriously - I didn't mind at all that I looked like a fool. Every day, when my very smart son-in-law is conferring with neurologists and prepping for surgery with a precious life hanging in the balance, he is literally performing his work in the very considerable shadow of Dr Carlsson. And now he has Dr Carlsson's autograph hanging from his wall.

To be continued ...

Monday, March 30, 2009

Figuring Out Schizophrenia


I'm back home after an exhilarating and exhausting day at the International Congress on Schizophrenia Research in San Diego, 40 miles "down the hill" from where I live. To briefly recap:

Early morning: I'm up at 5 AM and out the door an hour later. Shortly after seven, I announce myself to a small breakfast gathering of brain researchers as, "The only C student at this table."

The line works so well I use it the rest of the day. It doesn't take me long to get into the spirit of the conference. I start referring to my coffee as my "neuro-cognitive starter." I find myself talking to a woman who is not a brain scientist. Her doctorate is in education, and she is involved in changing behavior in patients that just about everyone else has given up on.

"You can change the brain by changing behavior," she lets me know. Little steps at a time. You will probably hearing a lot more about her, if for no other reason than I plan to be writing more about her.

Late morning: I arrive at my appointed symposium for two hours of dopamine. These are brain scientists talking to brain scientists. To give you some perspective: When brain scientists talk to psychiatrists, they dumb down their talks. That way, I can almost understand their presentations.

Not the case here. Daniel Weinberger of the NIMH is one of the presenters. A couple of years ago, at the American Psychiatric Association annual meeting, I heard him explain to his audience the val-met COMT variation. Today, he just assumes that the people in the audience understood. Then he gets really technical.

Just over the aisle, in the same row where I am sitting is Arvid Carlsson, recipient of the 2000 Nobel Prize in Medicine (with Paul Greengard and Eric Kandel). Dr Carlsson received his Nobel for his work into dopamine. Let's put it this way: BC (Before Carlsson), dopamine had minor chemical status. Then Dr Carlsson started investigating and suddenly dopamine was a major neurotransmitter. (That's Dr Carlsson's photo to this blog post.)

In order to appreciate the environment Dr Carlsson was working in at the time, science only had theories about how brain cells communicated. Chemical? Electrical? Dr Carlsson and his contemporaries resolved that debate, but not without bucking a lot of the conventional wisdom of the day. In addition, Dr Carlsson connected dopamine deficiency to Parkinson's, which in turn led to L-DOPA for treating the illness, thus benefiting untold millions.

So here's Dr Carlsson listening to a younger generation of scientists carry on his work. Immediately after the session, I walk over and ask for his autograph. (I was a C student, remember? I can get away with this behavior.) He graciously signs the inside back cover of my conference booklet. My son-in-law is a neurosurgeon in New Zealand and a great guy. He's gonna be thrilled when this autograph arrives in the mail.

Don't tell - it's a surprise.

Early afternoon: Over lunch and at the poster session, I get to talk to the researchers one on one. First, let me make a confession - the technical stuff is way over my head. I'm here to simply get a feel for things, develop an appreciation. One of the things I notice is that the posters on the cognitive aspects of schizophrenia outnumber the psychosis side of the illness by a ratio of at least three to one.

Was it this way ten years ago? I wonder. I'll have to ask. Antipsychotics work very well against psychosis, but when your basic thinking is messed up - never mind the psychosis - your life is going to involve smoking cigarettes in front of TV in some dreary day room someplace.

No wonder the people I'm talking to are telling me that doctors and patients and family members got oversold on the new generation of antipsychotics. From what I can gather, certain systems in the brain go down. Systems we are only just finding out about. Systems we haven't even discovered yet. Systems all over the brain, interdependent, so when one system goes down, different parts of the brain all over fail to talk to one another.

Some of it is genetic. Some of the genetic mischief occurs during fetal development, other mischief further on in the life span. There may be direct genetic impact, or it may be like billiard balls caroming off one another. Or it may have something to do with a new area of gene research called epigenetics (which has something to do with why identical twins aren't really identical).

And forget about finding schizophrenia genes. These guys seem to be concentrating on "endophenotypes," symptoms common to the general population, as well, say, delayed reaction time to an event. If, say, we find a delayed reaction time gene and connect it to neurons and connect the neurons to brain systems and connect the brain systems to behavior, and connect the behavior to schizophrenia, maybe then we can really start connecting some dots.

Then there's environmental factors. The brain is shaped by literally everything, such as the way a mother holds her baby. African-Caribbean immigrants in the UK, for instance, have a nine-fold higher schizophrenia risk than the rest of the population there. What is going on?

Later afternoon: My brain is on overload. I leave the conference at four and am home at five. Twenty minutes later, I'm crashing in my own bed.

Evening: Dinner, chill time, and this blog post. Time to kick the cat off the prime spot on my bed. Up at five again tomorrow. I love my job ...