Dana Foundation Blog

I’ll Keep My Skull Intact, Thanks

Lots of brain-related books land on my desk. But A Hole in the Head: More Tales in the History of Neuroscience by Charles G. Gross, recently released in paperback by MIT Press, may be the first one with such an evocative cover:

That’s a hole in the head, alright.

So I had to read the chapter that gives the book its name. A warning to delicate readers: reading about trepanation (also called trephination) is not for the faint of heart. Here’s why:

Top: Trepanation tools used by a 17^th century naval surgeon. Bottom: Marks left from (1) scraping (2) grooving (3) boring and cutting and (4) rectangular cuts.

Be glad I left out a drawing from 1761 of a doctor using one of these tools. Yikes.

When archaelogist Ephraim George Squier received the very skull pictured on the book’s cover as a gift from a Peruvian antiquities dealer in 1865 and brought it to the attention of the medical community, no one could believe it (the skull is now at the American Museum of Natural History). The survival rate of trepanation procedures in the mid-1800s was a mere 10 percent. How could an ancient Incan receive such a procedure and, based on analysis of the skull, live to tell the tale?

Since Squier’s skull discovery, archaelogists have found thousands more skulls with trepanation marks from across time and continent—Neolithic, ancient Chinese, Roman, Kenyan. Researchers estimate that the survival rate of ancient trepanations may have been as high as 90 percent.

Why was trepanation so common? We’ll never know for certain why prehistoric cultures performed the surgery. In the Fifth Century BCE, writes Gross, Hippocrates recommended it for all head wounds except those involving “depressed fractures” to “allow the blood to escape.” In Gross’ words, Galen (129-199) recommended trepanation “for relieving pressure, for gaining access to remove skull fragments that threatened the dura, and...for drainage.” It was also used to treat mental illness and epilepsy.

It wasn’t until trepanation moved to a hospital setting in the mid-1800s that the mortality rate skyrocketed. But now that we know about sanitation and sterilization, neurosurgeons today use trepanation successfully, writes Gross, “for exploratory diagnosis, for relieving intracranial pressure...for debridement of a penetrating wound, and to gain access to the dura and thence the brain itself.”

To this day, some still advocate for the use of trepanation as treatment, thinking that it will increase blood flow to the brain and improve brain function. As Gross says, “Just because a procedure is very old does not mean it is necessarily an effective one, at least for enhanced enlightenment and creativity.”

Those sound like wise words to me.

--Johanna Goldberg

Love and Other (Gateway) Drugs

How do you keep things fresh in a relationship after 55 years of marriage? If you are prolific Columbia University scientists Eric and Denise Kandel, you collaborate on a research project for the first time.

While every neuroscience undergraduate knows Nobel Laureate Eric Kandel, his wife, Denise, has some serious science chops of her own. A professor of sociomedical science at Columbia’s Mailman School of Public Health, Denise’s main research interests center on risk factors and consequences of drug use. Decades of epidemiological research suggested that smoking acted as a gateway to harder drugs. After hearing Eric give a lecture on cocaine, plasticity, and histone acetylation, she wondered if perhaps an epigenetic model might help explain the relationship between nicotine and cocaine addiction.

“That’s how the whole thing started, really. It triggered this idea,” she says. “And it is important to mention because I think that oftentimes a scientific collaboration or scientific success arises out of a chance event and a prepared mind.”

Still, she didn’t ask her husband to collaborate on this particular “chance event” at first. “I didn’t think he was interested,” she says matter-of-factly. So, instead, she asked him to recommend a few other scientists who might want to collaborate. None of them were available.

“I don’t know why but Denise had trouble coming up with another collaborator,” Eric says. “But as we discussed it more, I felt the problem was interesting so, at that point, I stepped in. But it was the failure to come up with another collaborator that really encouraged me to try it.”

The study, heralded as a landmark experiment by both the neurobiological and epidemiological communities, demonstrated for the first time how nicotine can act as a “gateway,” accelerating the cellular and epigenetic processes that facilitate drug addiction (see Dana's story about it).

When I asked the Kandels how well their personal partnership translated to one in the lab, Eric laughed. “It was difficult at the beginning. Denise asked a lot of questions that I felt were interfering with my own line of thought,” he said. “But I soon realized that I needed to hear those questions. That’s the point of collaboration. You pick two very different approaches to address a problem. Once I realized that, we fell into step.”

“Eric was exasperated because I said we needed to do more work on the figures for the paper,” she says. “But he admits now that I was right. The figures look very good.”

“Yes, they do,” he says. “The figures look very good.”

And any advice to other couples on the brink of scientific collaboration?

“It’s been very exciting to work together,” says Denise. “But it’s not easy.”

“I don’t think one can give general advice to the lovelorn here,” Eric adds. “We’re both strong, independent people and I think, in any collaboration with two strong, independent people, there’s going to be some awkwardness initially. But I have a sense of enormous satisfaction that we accomplished this together. And I’m glad that we’re continuing on together.”

The two are currently working on a study to see whether alcohol results in a similar gateway mechanism. And they hope to later examine marijuana, too. And while the two are excited by the scientific possibilities, they admit they are pleased to have the chance to work together, too.

“It’s wonderful to be able to spend this time together,” says Eric. “And it’s wonderful to finally have a way to look at these questions about gateway drugs. I’m hoping that our collaboration will inspire a whole new field of translational epidemiology.”

What better Valentine could a scientific couple ask for?

--Kayt Sukel

Sukel's first book, Dirty Minds: How our brains influence love, sex, and relationships, is available now.

The Power of Data

Once a scientist has finished her research and published a paper, where is that data stored?

Three of the panelists at Science Online New York City (SONYC)’s event last night, “Thinking Digital: Giving your research more reach (and making sure others can find it),” are figuring out answers to this question.

Carol Feltes, Rockefeller University’s head librarian, comes from a business background. In a for-profit setting, there are clear policies and procedures for data management, retention, and removal. But at Rockefeller, each lab head is responsible for his or her data—there is no overarching policy for data management.

The library encourages lab heads to store data on its DSpace, “a managed, digital repository designed to archive, preserve and make accessible the scholarly works authored by The Rockefeller University faculty, staff and students.” So far, only six labs have started using the open-access repository. “Unless they absolutely need it, we can’t sell it,” Feltes said.

There are also data storage solutions outside institutional settings. The new repository Figshare invites researchers to post research data, both publically and privately, under a creative commons license (materials can used with proper attribution). Figshare developer Mark Hahnel finished his Ph.D. in September, and during the process realized that most of his research would never be seen outside of his lab group—much of it was negative, or simply didn’t fit into the larger research picture. He wanted to share and get credit for all his research, and found that existing online places to store and share data were too difficult to use. Thus, Figshare was born. Hahnel hopes that the visible metrics on the site, tracking page views, shares, and citations, will encourage people to post their research.

Efforts are also underway to make published literature available. One such undertaking is the Biodiversity Heritage Library (BHL), a consortium of 12 libraries digitizing all published biodiversity literature. To date, said Cathy Norton, library scholar at BHL and the Woods Hole Oceanographic Institution Library, 32 million pages—or 6.5 percent of the literature—has been scanned. Much of that material predates 1923, and is no longer under copyright. In addition, publishers have given the project materials to scan.

But once these materials are available, how can people find them? Rare and old works do not have DOIs or ISBNs, and digitizers must add metadata and discoverability tools. The next step, said Norton, it to contextualize data, providing a story regarding what the collection is all about.

Clearly, research tools are changing as more information becomes available. And, if used well, this could change the speed of science. As Feltes said, “People begin to realize that with greater access to a greater variety [of data], the pace of knowledge generation increases. Having data available accelerates the pace at which problems are solved and disparate disciplines are stitched together.”

--Johanna Goldberg

Changing the Diagnoses

It's not a surprise that each time researchers and other experts revise the "bible" of psychiatric diagnosis in America, they change categories and definitions of disabilities. But when that change hits close to home—say, narrowing the definition of autism spectrum disorder—it gets a lot more press than usual.

The next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which psychiatrists and other practitioners use as a guide to diagnose psychiatric disorders, is in the late stages of a long revision process; it goes to the printers in December. Many of the suggested changes have been posted for comment for the past year. This past week, The New York Times weighed in on two proposed changes.

In "New Definition of Autism Will Exclude Many, Study Suggests," writer Benedict Carey describes a recent analysis by Dr. Fred Volkmar that estimates how many people now classified as having Asperger's syndrome or "pervasive developmental disorder, not otherwise specified" (PDD-NOS) would not qualify as autistic under the proposed guidelines. Without the "autistic" label, these people might not qualify for extra help at school; insurers might not cover their therapy. Small wonder people started to panic (at least in the comments on the Times story). Still, as Gil Tippy of the Rebecca School in New York advised on the Thinking Person's Guide to Autism site, "If you, or your son or daughter has an appropriate diagnosis on the Autism Spectrum now, responsible clinicians will find that you or your children meet the criteria for Autism Spectrum Disorder under the new guidelines."

Another change highlighted this week would add "grief and grieving" to the list of criteria used to diagnose depression (writer Benedict Carey also mentions other changes, too). A lively discussion follows on the Times's Well blog.

Back in 2009, when discussion about the DSM-5 was starting to roll, we invited the scientists leading the revision process to describe their plan. Their essay, for our Cerebrum periodical, may not have been one of our better-read pieces at the time, but has grown in interest since. We paired it with a call from Johns Hopkins psychiatry professor Paul R. McHugh that the editors focus on disorders’ causes and disease processes, in part to improve upon what the two most recent editions of DSM have produced: “a psychiatry that’s boring.”

Early in 2011, former Harvard provost Steven E. Hyman weighed in for Cerebrum on how the process was going—his title: "Diagnostic Classification Needs Fundamental Reform." (Hyman is a member of the DSM revision task force, but was writing as an individual.) In his argument, he acknowledges that radical reform may need more time (i.e., the 10 years until DSM-6). In terms of individual diagnostic categories, though, "I would recommend that the DSM-5 take a conservative approach, leaving criteria unchanged unless compelling new evidence suggests that a change would be beneficial. Whatever the ultimate approach to the DSM-5, it is critical that the scientific community escape the artificial diagnostic silos that control so much research, ultimately to our detriment."

(Also, Seth Mnookin has posted a great roundtable discussion on the image of autism, including who speaks for autistic people and how the spectrum is covered by the media.)

--Nicky Penttila

Our Two Senses of Smell

It’s lunchtime. You heat up those Chinese takeout leftovers in the microwave and the aroma makes you hungry. Then you take a bite—delicious.

Clearly, you process the smell from the microwave through your nose. But did you know that processing flavor also comes from your sense of smell?

In his new book Neurogastronomy: How the Brain Creates Flavor and Why It Matters, Dana Alliance Member Gordon M. Shepherd explains that we actually have two senses of smell: orthonasal and retronasal.

Orthonasal smell is what happens when we sniff—we breathe in through our noses to sense environmental odors, like the smell from the microwave.

Retronasal smell, on the other hand, is where flavor comes from. Try holding your nose while eating some of those leftovers—you won’t taste much. Breathing out while eating is the doorway to flavor. While we are born recognizing sweet, sour, salty, bitter, and  umami—which are tastes, not flavors, writes Shephard,  “retronasal smells are learned and thus open to individual differences. They account, therefore, for the vast variety of cuisines in the world.”

Bon appetit!

--Johanna Goldberg