News Article | February 15, 2017
Excerpted from The Perpetual Now: A Story of Amnesia, Memory and Love, by Michael D. Lemonick. Published by arrangement with Doubleday, an imprint of The Knopf Doubleday Publishing Group, a division of Penguin Random House, LLC. Copyright © 2017 by Michael D. Lemonick. Reprinted with permission. I pulled the New York Times out of its plastic delivery bag on the morning of December 5, 2008, unfolded the paper, and read this headline on the front page: “H.M., an Unforgettable Amnesiac, Dies at 82.” He was certainly unforgettable to me. I’d first read about H.M. in my freshman psychology textbook at college, in the fall of 1971, less than twenty years after the experimental surgery that robbed him of most of his existing memories and also of ability to form new ones. The idea of living in a perpetual “now” seemed appalling, and, along with the two hundred or so other students in the class, I tried to imagine what such an existence might be like. Naturally, I failed. I would come back to H.M.’s case several times as a science journalist, whenever I wrote a story that touched on the science of memory. I never knew his name, though, thanks to the absolute insistence of Brenda Milner and Suzanne Corkin, the scientists who studied him for five decades, that he remain anonymous while he lived. But there it was at last, in paragraph seven: “On Tuesday evening at 5:05,” the story read, “Henry Gustav Molaison—known worldwide only as H.M., to protect his privacy—died of respiratory failure at a nursing home in Windsor Locks, Conn.” In the summer of 2015, I sat in Suzanne Corkin’s office at MIT, talking with her about her long relationship with Henry, both as a scientist and as the closest thing he had to a relative after his mother died. I was now writing about Lonni Sue Johnson, another amnesia victim with a condition very similar to Molaison’s. (Johnson’s mother and sister, her prime caretakers, had decided to make her full name public, in order to help publicize the need for research into the brain). I was asking about Molaison’s death, and the postmortem research that she’d been planning for decades in anticipation of his passing. “We’ve barely begun that research,” she said, and then looked at me expectantly. I looked back, blankly. “Your next question,” she prompted me, “should be ‘Why?’” I still didn’t get it. “Why … what?” I asked, baffled. “Why,” she continued, “seven years later, we do not know anything about the details of his brain?” Seven years did seem like a long time, now that she mentioned it. I assumed that this simply represented the slow and careful process of science. Immediately after Molaison died, his body was rushed to Massachusetts General Hospital, where his brain was carefully removed and preserved. Thanks to surgical notes, X-rays, CAT scans, and MRIs, neuroscientists and neuroanatomists had a good idea of which parts of his brain had been destroyed in the surgery meant to cure his intractable epilepsy. The surgeon, William Scoville, had removed the front sections of both of Henry’s hippocampi, along with much of his entorhinal, perirhinal, and hippocampal cortices, now understood to be crucial to memory. Scoville had also taken out the amygdalae, which process the experience of emotion. Extensive memory tests, meanwhile, had probed the extent of his memory loss (which was enormous). But without knowing precisely how much of which organs had been taken out—and, crucially, what the untouched parts of his brain looked like in fine detail—Corkin and other scientists couldn’t know whether his brain was abnormal to begin with. Perhaps his severe epilepsy had caused some damage that might have contributed to his memory problems. So Molaison’s brain was gently separated from his body and given into the care of Jacopo Annese, a neuroscientist at the University of California, San Diego, who had created an entire lab devoted to preparing it for future study. Annese understood how important it was to preserve Henry’s brain in as pristine a state as possible. “I remember the unfortunate fate of other illustrious brains,” he told me in an interview. “You know what happened with Einstein’s, right?” I did know that bizarre story. When Albert Einstein died in 1955, the hospital pathologist, William Harvey, removed the brain and cut it up into more than two hundred small chunks. Harvey doled out a few chunks to researchers, but kept most of them in a couple of Mason jars, swimming in alcohol. He ended up in Wichita, Kansas, where journalist Steven Levy tracked him down in 1978. Einstein’s pickled brain was still in the jars, under a pile of boxes in Harvey’s basement. Eventually, some pieces were acquired by the Mütter Museum of medical oddities, in Philadelphia. You can visit them there, where you can also see a tumor removed from Grover Cleveland’s mouth; a slice of tissue from the chest of John Wilkes Booth; the shared liver of the famous conjoined (“Siamese”) twins Chang and Eng Bunker; and a collection of cysts, tumors, and deformities of all sorts. The research that came out of the few specimens of Einstein’s brain that Harvey gave to actual scientists was sparse, and some of it turned out to be questionable. In contrast, Annese would freeze Molaison’s brain, then slice it into more than two thousand thin sheets, each just seventy microns thick. (A micron is equal to .000039 inches; a human hair is about one hundred microns thick.) Scientists would then be able to look at the slices with microscopy and other techniques to learn precisely what the brain looked like, right down to the cellular level. The painstakingly careful slicing, which lasted fifty-three hours (and which was both filmed and webcast), happened almost precisely a year after Molaison died. “The brain was cut very well,” David Amaral, a neuroscientist at the University of California, Davis, told me. “There was no problem with that. But ….” He hesitated, then continued: “From my scientific perspective, there was a lot of unnecessary showmanship.” Amaral felt that Annese was using the event as a way to attract donations for what he was calling the Brain Observatory. On the organization’s Web site it says: “The Brain Observatory is committed to maintaining the highest standards in open science, sharing all the images and data that are created in our laboratories with other researchers and the public.” It didn’t quite turn out that way, however, at least according to Amaral and also to Corkin, who died last year. A number of the slices were mounted on slides, just as Annese had promised, with the rest preserved for future mounting. But that was evidently pretty much it. Normally, Amaral said, a scientist in Annese’s position would go on to develop collaborations with other neuroscientists to study such a valuable specimen. “For example,” he said, “my expertise is on the hippocampus, so either I or people like me should have been approached to carry out those studies.” Other parts of the brain should have been examined by other experts. But in fact, Amaral said, “nothing happened, nothing happened, nothing happened.” Corkin spoke with Amaral and others in an effort to see what might be done. “We tried to intercede,” Amaral said, “and still nothing happened.” Annese, Corkin said, “turned out to be a bad collaborator. He basically brought the science to a screeching halt by not living up to his agreements.” Annese did publish a paper in Nature Communicationsin 2013 that described the structural damage to Henry’s brain, along with “diffuse pathology in the deep white matter and a small, circumscribed lesion in the left orbitofrontal cortex.” According to Corkin, however, who was listed as a coauthor on the paper, this did not amount to a full pathology report. Annese rejects these accusations. “It is regrettable,” he said by email, “that some colleagues have been led to have this impression about my work with H.M. The question of the neuropath examination, which was only a portion of the overall planned work, has been brought up several times over the years and there’s ample evidence of my good will and concrete actions to facilitate the process.” At the institutional level, he wrote, “there have been many delays that were beyond my control. In my opinion, difficulties were spurred by a failure to communicate expectations and intents directly, effectively and in a transparent way. This was very frustrating at times, but I did my very best in being very open about my prerogatives throughout.” All of the money for cutting and preserving Henry’s brain, he said, came from his own grants, without any contribution from MIT or Mass General. He asked for assurances that the Brain Observatory would receive proper credit in any scientific publications, and that it would have a long-term role in the science. “Oddly,” he wrote, “I wasn’t able to obtain a suitable response. In fact, I personally had very minimal if any response at all after a certain point.” That’s not how Corkin saw it. Finally, she said, she simply got fed up with trying to pry information out of Annese. She enlisted administrators at MIT, Mass General, and the University of California, San Diego, to help force the issue. In the end, the higher-ups agreed that Henry’s brain should be transferred to another institution—specifically, to Amaral’s lab at the University of California, Davis. “It took a very long time to negotiate that,” Amaral said, “and the whole process was not facilitated by Dr. Annese.” Annese’s lab at UCSD was shut down, and when he and I spoke by phone, before I learned any of this backstory, he told me he was looking for funding to secure a new home for the Brain Observatory. After I’d heard Corkin’s and Amaral’s accusations, I asked Annese by e-mail why his university agreed to give custody of Henry’s brain and other materials over to another lab. He didn’t really answer. “The transfer of the collection,” he wrote, “without concrete scientific or logistic reasons followed negotiations at the institutional level, well above my jurisdiction. I resigned from UCSD in February of this year  because while I respected the fact that UCSD’s delegated leadership felt that this solution was in the University’s best interest, their decisions were ultimately not aligned with the long-term success of my lab and projects, which are now governed by an independent non-profit organization.” Now that the brain has been relocated, the research is finally getting under way in earnest. Amaral and his colleagues have begun digitizing the slides Annese prepared, creating high-resolution images that will go up on the Web. They’ve concluded an agreement with someone Amaral calls “a very well respected neuropathologist” to scrutinize the tissue for diseases that might have caused Henry’s cognitive decline. And they’ve begun putting together several consortia of experts who will look at specific parts of the brain to try to understand precisely what happened when Molaison’s memory-making apparatus was destroyed more than sixty years ago. “We will be able to provide a very definitive description,” Amaral said, “of what has been removed, what’s intact.” And with that, the brain that launched the modern study of memory in the 1950’s will make its final, crucial contribution to science.
News Article | September 28, 2016
In recent years, brain-mapping initiatives have been popping up around the world. They have different goals and areas of expertise, but now researchers will attempt to apply their collective knowledge in a global push to more fully understand the brain. Thomas Shannon, US Under Secretary of State, announced the launch of the International Brain Initiative on 19 September at a meeting that accompanied the United Nations’ General Assembly in New York City. Details — including which US agency will spearhead the programme and who will pay for it — are still up in the air. However, researchers held a separate, but concurrent, meeting hosted by the US National Science Foundation at Rockefeller University to discuss which aspects of the programmes already in existence could be aligned under the global initiative. The reaction was a mixture of concerns over the fact that attempting to align projects could siphon money and attention from existing initiatives in other countries, and anticipation over the possibilities for advancing our knowledge about the brain. “I thought the most exciting moment in my scientific career was when the president announced the BRAIN Initiative in 2013,” says Cori Bargmann, a neuroscientist at the Rockefeller University in New York City and one of the main architects of the US Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. “But this was better.” One of several goals for the initiative is the creation of universal brain-mapping tools. Promising experimental tools exist, but labs make their own variations in-house and also tend to run experiments in their own ways. This makes it harder for different teams to collaborate or exchange information. At the Rockefeller meeting, physicist Michael Roukes at the California Institute of Technology in Pasadena noted that the industrial revolution only took off once factories with interchangeable components began replacing companies that had one-off machines. “We’re still in the neuroscience craft era,” he says. “Everyone has their secret sauce.” Another idea proposed at the meeting is the creation of an International Brain Observatory, with tools such as powerful microscopes and supercomputing resources that scientists from around the world could access — similar to the way that astronomers share telescope time. “If you just give people the basic tools, they’ll do better science,” says Alan Evans, a neurologist at McGill University in Montreal, Canada. Scientists cheered the idea of a virtual, cloud-based data-sharing resource, analogous to the GenBank genomics resource. It can be difficult to align data as each neurology lab has a preferred method of collecting, formatting and analysing their data sets. But Joshua Vogelstein, a neuroscientist at Johns Hopkins University in Baltimore, proposes a virtual International Brain Station that could automatically convert data from human brain scans or animal gene expression into standardized formats that would allow more people to analyse them. But many attendees worried that marshalling the numerous proposals under one umbrella could backfire. Existing brain-research programmes have different priorities: Japan and China, for instance, are investing heavily in primate research, whereas the United States tends to avoid it for ethical reasons. The European Union’s flagship Human Brain Project (HBP) is focused on understanding the basic science of how the brain works, whereas Canada is mainly interested in creating technologies that can be applied to medicine. Other concerns expressed at the US-led Rockefeller meeting, intended to marshal support and ideas for the new International Brain Initiative, felt that some attendees were ignoring existing resources. Canada’s nine-year-old CBRAIN programme serves as a clearinghouse for data and methods, and is already used by neuroscientists in 22 countries and the HBP. But Evans says that it is similar to the International Brain Station proposed at the Rockefeller meeting. “It’s like, let’s reinvent the wheel,” he says. Others worry that the supposedly global initiative would exclude developing countries. “If the only way to do international is for each country to put in $300 million, that will not be international,” says Sandhya Koushika of the Tata Institute of Fundamental Research in Mumbai, India. Although smaller countries cannot afford to map a marmoset brain, as Japan is doing, Koushika says that they could contribute to resources with patients, model organisms and efforts to design more affordable technologies. Bargmann says that the point of the Rockefeller meeting was to get a sense of the kinds of programmes already out there, and notes that future meetings will be more focused once they know who will participate. Overall, scientists are hopeful that this new global initiative will enable them to take brain mapping to the next level. Because several brain research projects have been around for a while, it's easier to compare their strengths and weaknesses and begin to talk pragmatically about what we need to align them, says Christoph Ebell, executive director of the HBP. “I think it is the right moment.”
News Article | October 27, 2016
The Allen Institute for Brain Science has completed the three-dimensional mapping of the mouse cortex as part of the Allen Mouse Common Coordinate Framework (CCF): a standardized spatial coordinate system for comparing many types of data on the brain from the suite of Allen Brain Atlas resources. "Maps of the brain have always been created in two dimensions, but even a stack of flat maps sitting on top of each other does not necessarily align with the complex three-dimensional nature of the brain," says Christof Koch, Ph.D., President and Chief Scientific Officer of the Allen Institute for Brain Science. "The Common Coordinate Framework is a remarkable effort to capture a typical mouse brain in its true three dimensions, and serves as a valuable platform on which to present many of our other data resources." "Annotating the cortex in three dimensions was no small task," says Lydia Ng, Ph.D., Senior Director of Technology at the Allen Institute for Brain Science. "It required the expertise of both technologists and anatomists working closely and for many long hours to generate the data. The CCF enables quantification and comparison of many types of data, including gene expression, connectivity, single cell characterization and functional imaging. This is a truly unique resource for the neuroscience community to understand the structure and function of the mouse brain." The Common Coordinate Framework was built by carefully averaging the anatomy of 1,675 specimens from the Allen Mouse Brain Connectivity Atlas. Researchers used transgenic mouse lines and data from viral tracers to draw boundaries between 43 regions of the cortex. The end result is a template brain rendered faithfully in three dimensions, which serves as a useful guide to mouse brain anatomy as well as a platform for comparing data across many Allen Brain Atlas resources. The October data release also includes updates to several other resources. The Allen Brain Observatory, launched in May, received a back-end overhaul that enables robust search and the addition of more than 30 new datasets and additional engineered mouse lines. The Allen Cell Types Database and the Allen Mouse Brain Connectivity Atlas are also updated with new data. The Allen Institute for Brain Science is a division of the Allen Institute (alleninstitute.org), an independent, 501(c)(3) nonprofit medical research organization, and is dedicated to accelerating the understanding of how the human brain works in health and disease. Using a big science approach, the Allen Institute generates useful public resources used by researchers and organizations around the globe, drives technological and analytical advances, and discovers fundamental brain properties through integration of experiments, modeling and theory. Launched in 2003 with a seed contribution from founder and philanthropist Paul G. Allen, the Allen Institute is supported by a diversity of government, foundation and private funds to enable its projects. Given the Institute's achievements, Mr. Allen committed an additional $300 million in 2012 for the first four years of a ten-year plan to further propel and expand the Institute's scientific programs, bringing his total commitment to date to $500 million. The Allen Institute for Brain Science's data and tools are publicly available online at brain-map.org.
News Article | August 10, 2016
Why did it take a private foundation to do public science right? Microsoft co-founder Paul Allen funded the Allen Brain Observatory, a detailed, rich data-set derived from parts of a mouse-brain: what's striking is that the Allen Institute released all the data into the public domain, at once, as soon as it was available, which is exactly what you'd want the publicly funded alternatives to do, and what they almost never do. Mark Humphries discusses how the incentives for public science -- the need to publish a lot of papers, quickly and early, in order to secure grants -- means that publicly funded scientists end up hoarding their data, lest they inadvertently give someone else the material that they need to work on their next paper. By contrast, the Allen Institute's targets are "tight deadlines for reaching project milestones, rigour of the methods, and quality of the resulting science." Humphries argues that universities can get off the publish-early/often treadmill and its data-hoarding demands by reapportioning their own budgets: less on new buildings and administrators, more on long-term investments in high quality science and development of scientific tools like high performance computing software and analysis frameworks. What all these have in common is their origin in dedicated, privately funded research institutes. These researchers are somewhat immune to the science incentive problem that pervades universities. This is because universities drive the quest for money. Research grants pay a lot towards universities’ infrastructure, services, and administrative people. So universities want grants. And papers, as noted above, play a key role in getting grants: so they want papers too. (In the UK we also have the direct equation that papers = money, thanks to the REF). A solution is thus that universities should adopt the private institute model: stop pressurising researchers to obtain grants and papers. Instead they could spend their own money sustaining the research programmes of their own researchers (rather than on, say, yet more bloody buildings , or administrators). This would remove the pressure to get short term grants, but leave open the need for high value grants for major programmes of work. Reward quality and rigour, not output. Reward the work effort, not the luck of the draw in where the paper finally came out. How a happy moment for neuroscience is a sad moment for science [Mark Humphries/Medium]
Annese J.,Brain Observatory |
Annese J.,University of California at San Diego |
Schenker-Ahmed N.M.,Brain Observatory |
Schenker-Ahmed N.M.,University of California at San Diego |
And 14 more authors.
Nature Communications | Year: 2014
Modern scientific knowledge of how memory functions are organized in the human brain originated from the case of Henry G. Molaison (H.M.), an epileptic patient whose amnesia ensued unexpectedly following a bilateral surgical ablation of medial temporal lobe structures, including the hippocampus. The neuroanatomical extent of the 1953 operation could not be assessed definitively during H.M.'s life. Here we describe the results of a procedure designed to reconstruct a microscopic anatomical model of the whole brain and conduct detailed 3D measurements in the medial temporal lobe region. This approach, combined with cellular-level imaging of stained histological slices, demonstrates a significant amount of residual hippocampal tissue with distinctive cytoarchitecture. Our study also reveals diffuse pathology in the deep white matter and a small, circumscribed lesion in the left orbitofrontal cortex. The findings constitute new evidence that may help elucidate the consequences of H.M.'s operation in the context of the brain's overall pathology. © 2014 Macmillan Publishers Limited. All rights reserved.
News Article | July 14, 2016
Zika Virus - What You Should Know Ticked Off! Here's What You Need To Know About Lyme Disease The brain is a complex "biological machine" made up of neural networks with different regions that each perform a certain function. Just like tinkering with the underpinnings of a computer, scientists at the Seattle-based Allen Institute for Brain Science are working to understand how exactly the brain works and what makes it tick. On Wednesday, July 13, the institute launched a new observatory known as the Allen Brain Observatory, designed specifically for the study of the brain. "The Allen Brain Observatory is to biology what an astronomical observatory is to astronomy," says neuroscientist Christof Koch, the institute's president and chief scientific officer. "Think of it as a telescope, but a telescope that is looking at the brain," adds Koch, who is also the creator of the observatory. Koch says the goal is that thousands of scientists from anywhere in the world will look through this "telescope" and help unravel mysteries of the human consciousness. For instance, we can see our family's faces and we can see what's being shown on the TV screen. But how exactly does our brain create images from the muddled stream of visual information coming from the external world? That is what researchers wanted to find out. There is no easy way to study the human brain while it processes visual information. This is why the observatory has been collecting extensive amounts of data on mice. Fortunately, mice possess a visual system that is very similar to that of humans. The mice in the study were allowed to watch a classic film noir by the prominent director Orson Welles. These mice were initially genetically altered so that a computer could monitor the activity of about 180,000 neurons in their brain. The lab animals ran on a wheel while watching the film, similar to how one runs on a treadmill at the gym while watching TV. The animals also ran on the wheel as still images were presented for their viewing. Koch says scientists can look at the neurons and decode what goes through the mind of the mice. The neurons were active when the animals watched first few minutes of the film "Touch Of Evil." Researchers chose this film because it is black and white, has nice contrasts, and contains a long, uninterrupted shot. At one point in the film, the camera follows two people through the streets of a border town in Mexico. As the mouse looks at the action on screen, its brain activity changes in response to the images. For instance, brain cells that usually respond to vertical lines began firing as the couple goes past a building with vertical columns, scientists said. But this response is only a small part of the entire brain system that allows mice to create a mental map of its world. Additionally, when scientists flashed 120 still, natural images to the mouse, its brain cells lit up upon seeing the black and white photo of a butterfly. The results of this first research are published in the observatory's website. Anyone with an internet connection can access and see the findings. Researchers say by making the data available publicly, scientists can test their own ideas about the mechanism behind perception, experience and consciousness. Koch says they expect that other scientists will uncover things they themselves never suspected. Watch the video below to know more about the research. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.