Brain initiatives galore, smiles aplenty

Vivien Marx reports on the Society for Neuroscience meeting in San Diego and the big brain projects in the EU and US.

SfN attendance sign

The Society for Neuroscience annual meeting in San Diego clocked record attendance.{credit}Vivien Marx{/credit}

The brain is hot.

Despite dismay about the recent 16-day US government shutdown, the impact of automatic budget cuts–the sequester–taking effect in light of federal budget disagreements in Washington, and the general economic malaise, there is palpable excitement. New large-scale initiatives are getting underway around the world to develop technologies to empower neuroscientists.

This year’s Society for Neuroscience (SfN) meeting in San Diego that has just ended, clocked a record attendance of over 30,000 attendees, noted society president Larry Swanson to attendees with a broad smile in one of his conference announcements. “It is an inspirational time to be a neuroscientist,” he said, with the field drawing attention, for example, across the European Union and in the White House. In a town hall meeting for the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, there was no lack of critical comments and suggestions of aspects to include in BRAIN. But smiles stayed plentiful as funders explained their plans.

The fact that the US president chose neuroscience as his multi-year, signature project is something “we should all be pretty excited about,” says Tom Insel, director of the National Institutes of Mental Health. In addition to projects in the US, such as  (BRAIN) Initiative and the EU’s Human Brain Project, large neuroscience projects are just emerging in Australia, China, Japan and Israel. “This is beginning to feel like a global movement,” he says. And projects are unfurling in the private sector, too.

The new tools, says Story Landis, director of the National Institute of Neurological Disorders and Stroke, will help neuroscientists do their work “bigger, better, faster” and expand the research strides made in recent years.

Much remains to be done. Compared to what is known about the kidney or heart, very little is known about the brain, says Insel. Adding to the neurological diseases, he noted, are the “invisible wounds of war” such as traumatic brain injury and post-traumatic stress disorder. Tools to help diagnose these illnesses are urgently needed.

Nora Volkow, director of the National Institute of Drug Abuse says that the BRAIN initiative stands to “act like a catalyst” in ways not unlike the decoding of the human genome and its successive “avalanche of discovery.”

Besides attending SfN’s hundreds of sessions and 17,000 posters, scientists had the chance to get up close and personal with representatives from the funding agencies and to hear about and discuss the new opportunities. Here is a snapshot of some of the announcements.

European Union
As Daniel Pasini from the European Commission’s programme on future and emerging technologies explained, the 10-year European Human Brain Project has invited the scientific community to present “grand ideas” for a massive effort to computationally reconstruct the human brain using supercomputers.

The model will help to study brain-related diseases, which are a major health challenge, an economic and social burden, and to pool data and expertise more effectively and translate results for treatments.

The project, which took three years of planning, involves over 250 scientists across Europe in 135 research groups in 22 countries, including groups in the US and Asia. The program began officially in October and has a budget of $1.6 billion. Half of the money will come from the EU the other will come from national funding sources, Pasini says. The first phase is slated to last 30 months and is funded with $100 million.

Six platforms are to be developed including, for example, the neuroinformatic platform as a single point of access to all neuroscience and clinical data along with software tools. The other platforms involve brain simulation, high performance computing, medical informatics, neuromorphic projects and neurorobotics. The idea is to keep improving the model as new data become available. All tools and data are set to be made available to the global scientific community. The plan is to create the ‘CERN for brain research.’ Not unlike a telescope facility or a super-collider, scientists will be able to perform experiments and use this platform to help continue to expand the model.

Deconstructing Henry

The Brain Observatory at UC San Diego is running ‘Deconstructing Henry’ an examination of the Brain of patient H.M.{credit}Vivien Marx{/credit}

US Defense Advanced Research Projects Agency (DARPA)
“Yes, we build guns and bombs, that is true,” says Colonel Geoffrey Ling of DARPA more generally. He is a neurologist who also served in Afghanistan and Iraq and currently deputy director of DARPA’s division responsible for defense sciences, which does not build bombs and guns. He and many other neuroscientists want to cure diseases ranging from Alzheimer’s to schizophrenia to post traumatic stress disorder to traumatic brain injury. DARPA is indeed “zeroed in” on the problems facing soldiers returning from the battlefield.

Speaking directly to fellow panelists from NIH, he says: “I wish they would double the budget yet again for you guys,” which was greeted by SfN attendees with vigorous applause.

Two DARPA solicitations for proposals are now open, offering “real money,” as Ling says, collecting projects that relate to memory dysfunction and psychiatric disorders. More solicitations are “in the works,” he says. “It’s not for us to decide what you’re going to build,” he says, highlighting the importance of imagination and taking a diversity of approaches.

The funding model at DARPA is shaped by use cases to assure that what is developed serves his constituency, the servicemen and women.

Multidisciplinary research, for example, is not achieved with the collaboration of a cellular neuroscientist, a neurophysiologist, and a neurologist. Rather, for DARPA interdisciplinary efforts can be a team comprised of a mathematician, a physicist and “a crazy guy in his backyard putting together some Rube Goldberg thing,” says Ling.

Unlike NIH, DARPA issues no grants but rather contracts, which are “deliverables-driven,” and may seem more rigid that NIH. But he sees strength in the synergy of the different funding approaches by NSF, NIH and DARPA. DARPA is committed to this project over the next decade, says Ling.

Data-sharing provisions are built into each contract, which DARPA takes “extremely seriously,” and breach of contracts are pursued. The DARPA solicitations issued are just the beginning, he says.

Systems based Neurotechnology for Emerging Therapies (SUBNETS)
Deadline: Dec. 17, 2013
This project seeks proposals to develop devices, perform model organism based research, or enable modeling of human neural systems, which are geared to help treat patients with neuropsychiatric and neurologic disease.

Restoring Active Memory (RAM)
Deadline: Jan. 6, 2014
This project seeks proposals in the area of analyzing and decoding neuronal signals which can be used to help patients recover memory function after injury.

SfN attendee bag

Companies in the neuroscience field may benefit from funding in the emerging large-scale projects. Here a scientst at SfN wears one company’s advertisement.{credit}Vivien Marx{/credit}

National Institutes of Health (NIH)
No grants have yet been awarded through the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. But grants are in the pipeline. True, says Insel, some see the project as a perhaps $40 billion dollar challenge, but he views the funding in 2014 as an “initial investment.”

The first report of the BRAIN initiative’s working group, says Landis, offers a guide for how the project could begin to move forward in its first year. The working group, is the advisory committee to the NIH director is chaired by Rockefeller University’s Cornelia Bargmann and Stanford University’s Bill Newsome. Landis says excitement is high in the Obama administration and across NIH. The hope is that this enthusiasm would be reflected in the budget allocations.

The NIH first year funding is “a down payment,” she says.

Insel says that the NIH’s $40 million to be allocated in 2014 is drawn from the following sources:

  • $10 million are coming from the NIH Director’s discretionary fund
  • $10 million are from the NIH Blueprint Neuroscience a program to enhance collaboration across NIH institutes
  • $20 million are split among four NIH agencies: National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Mental Health (NIMH), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institute of Drug Abuse (NIDA)

These monies were previously slated for initiatives of the individual institutes’ choice. As Landis explains, these four agencies agreed that the BRAIN Initiative was the one they selected for fund allocation. She says she and her colleagues are “optimistic” that the excitement, opportunities and promise of the BRAIN initiative will power the budgets of the future. Throughout sessions at SfN, she, Insel and others were quick to squelch fears that BRAIN would draw funding away from investigator-driven grants.

The first NIH Requests for Applications (RFAs) are currently begin hashed out with cross-communication happening across NIH, NSF and DARPA, says Insel.

All BRAIN Initiative projects will be peer-reviewed and perhaps unlike the more classic grants, they will have milestones and there will be expectations of data-sharing. “That’s going to be baked into everything we do in this project,” says Insel. Evaluations will accompany the projects after they are funded.

A number of awards are likely to be cooperative agreements, which are part way between a contract with deliverables and R01s, says Landis. These agreements are accompanied by milestones. If researchers do not share data and that provision is in their notice of grant award “there can be consequences,” she says.

Update: In mid-December NIH announced six funding opportunities. Approximately $44 million will finance six new funding opportunities.

Sunset at SfN

Two of the 30,000 attending scientists take a break outside the SfN conference halls.{credit}Vivien Marx{/credit}

National Science Foundation (NSF)
Cora Marrett, the acting director of the NSF says her agency will “very energetically” support the BRAIN Initiative. She says that funders need to take “the long view” to let the forces of scientific discovery play out with a long-term commitment. “I’m feeling very optimistic, too, about what the long-run prospects for additional resources will look like.”

Evidence of NSF’s engagement with neuroscience in general can be seen in the recent $25 million grant to fund the Center for Brains, Mind and Machines at the Massachusetts Institute of Technology. The intent is to blend computer science, math, robotics, neuroscience and cognitive science.

The BRAIN Initiative will require intense collaboration across disciplines and scales, she says. Neuroscience has been more devoted to small science, she says, the work of individual principal investigators and small lab groups. Marrett agrees with Alan Leshner, the executive publisher of Science, that neuroscience’s strides will benefit from a change in the culture toward larger-scale, interdisciplinary efforts.

At the same time, this shift will occur without prescriptions that all work needs to be on “the huge scale” of a particle accelerator, for example. Indeed neuroscientists will need to integrate findings across the scales of their research and link physiology, biophysical and genetic data with cognitive and behavioral findings (see Leshner Editorial in Science).

The projects will require data management plans of the grantees, she says, to explain how they will handle data-sharing, which is to the benefit of the entire enterprise.

Scientists rally as sequester-based budget cuts loom

Vivien Marx reports from the AACR meeting and Rally for Medical Research in Washington, with details of the AACR plenary address by Harold Varmus.

Leaving the talks and conference halls behind, around 8,000 researchers and clinicians attending the American Association of Cancer Research (AACR) in Washington, DC joined patients and patient advocates on the Carnegie Library grounds to rally against cuts to research budgets. Members of Congress, patient advocates and celebrities involved in the organization Stand Up to Cancer, which also funds research, made their loud and forceful case against sequestration, the impending across-the-board forced 5% budget cuts facing government agencies, including the US National Institutes of Health.

Rally participant, University of Wisconsin scientist Nihal Ahmad, says that the sequester is already hitting his research, cutting into his ability to buy tools and reagents, which is work on signal transduction in tumors.

Overcoming cancer is a “very significant outcome for this country,” says Daniel Pollay of Weill Cornell Medical Center, explaining why he attended the rally. Andrea Russello, a product scientist at Cell Signaling Technology took part in the rally because her customers include academic scientists whose work is being affected by the sequester. She also knows many young scientists who cannot find jobs after their post-doctoral fellowships. The risk now is not just a budget plateau. “I think we’ll really regress if we can’t keep pushing forward,” she says.

Columbia University Medical Center researcher Jeanine D’Armiento looks at matrix metalloproteinases in tumors, in lung diseases in particular. Her latest grant scored in the 9th percentile. “Last year funding was at 10% and now it’s at 6%, if it were last year I would have received that grant. But right now, I don’t have it.” Staff cuts have been inevitable and she feels that her dream to move from mouse models into humans has to be put indefinitely on hold. According to NIH rules, the grant can only be resubmitted after 36 months.

Prior to the rally, National Cancer Institute Director Harold Varmus in his AACR plenary address encouraged delegates to attend it in order to highlight the importance of doing science to counter illness. The new BRAIN Initiative proposed by President Obama, may bode well for the future of science, he says, but it is an initiative that will “come too late” to address the problems cancer researchers face this fiscal year and the near future, he says.

Instead of just a fall over a fiscal cliff, research funding has actually been declining since 2003, he says. Inflation has eroded the agency’s spending ability to 2001 levels.

At the same time, he feels optimism about the new inroads against cancer that researchers are making and the possibilities the current $4.8 billion dollar budget provides. To manage the sequestration, his agency will keep the number of funding grants constant this year with a grant-funding success rate around 13%-14%.

He also took the opportunity to talk about initiatives the NCI is rolling out, also as a way to manage sequestration. The NCI is rolling out new initiatives geared toward ‘precision medicine’, including:

  • A Cancer Knowledge Commons, which is an informatics-based approach to aggregating data from many sources, will help to promote the use genomic analysis to improve research, treatment and outcomes.
  • A new Center for Cancer Genomics to continue the work of such projects as the The Cancer Genome Atlas
  • Clinical trials that find drugs that match the genomic profile of patients to drugs that stand to help them.
  • Continuation of the Provocative Questions Initiative, which is geared toward unanswered questions related to the biology of cancer and which are high risk but are also high reward opportunities.
  • A focus on RAS mutations, which are found in around one quarter of all tumors, leveraging proteomics and immunotherapies.
  • Looking at new ways to perform pre-clinical testing of drugs.
  • Global health initiatives.
  • Programs that take on the cultural change across the research community necessary to allow better sharing of results, reagents and reporting of outcomes from clinical trials.

Pittcon: Mixing the old and the new

After attending the Biophysical Society Meeting in Boston last week, I am now in Chicago at the annual Pittcon meeting. For those of you do not know about Pittcon, the focus of the conference is on technology development for the fields of biology, analytical chemistry, and nanotechnology. Being so broad it should come as no surprise to learn attendance is usually quite large – around 17,000 attendees are here now. This year sessions have included advances in mass spectrometry, in vivo imaging, nanotechnology sensors and surfaces, vibrational spectroscopy, biofuels, nanomedicine, magnetic resonance and biomarker discovery/analysis along with an exhibit hall requiring a tram to move people between sections (more below).

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Biophysical Society Meeting: A patch of déjà vu

Sunday afternoon at the 2009 Biophysical Society meeting in Boston, Massachusetts, I found myself wandering the aisles of the exhibit hall with an odd sense of “high-throughput patch clamping” déjà vu. Every row I walked down had at least one company demonstrating the latest in automated patch clamping instrumentation. Apparently, these automated approaches for patch clamping cells are becoming more and more common since their initial introduction in 2001 and here in Boston six different companies are showcasing their approaches. The systems range from being “adaptable” – capable of patching a range of cell types — to “high-throughput”— capable of patching up to 48 individual cells in 48 wells in a single run in their current versions but with a 96-patch system in the works.

For me this information was simply amazing. You see I have always thought there is a limit to what can be automated in the lab. Oh sure, liquid handling applications and reaction set up have benefited incredibly from robotic automation and many parts of microscopy are now automated as well. But patch-clamping – where a very narrow tube must be carefully placed on a single cell to measure the conductance of ions through a channel in response to a stimulus — is different. I can still recall one of my earlier research endeavors where our group was thinking about trying a single patch-clamp experiment only to find the technique required a tremendous amount of skill, experience and patience (Lacking all this, I was extremely thankful for the expert help of a patch-clamp specialist in the department). So you can understand my amazement at seeing these robotic systems capable of doing it all now. And by all, I mean the whole process in a single box. These platforms obtain cells from either a culture flask or a holding tray (cells can be cultured for hours in the instruments prior to the experiment starting), centrifuge the cells to remove culture media prior to patching, place individual cells into wells for testing, form a seal to the cell surface (in most cases this is accomplished using a specific amount of suction which differs from cell to cell and has to be calculated for each patching experiment), add any compounds to be tested to the wells and finally record the conductance across the membrane in each well. All this in a basically unattended format.

Although these systems are expensive, it turns out that they are not much more than two or three complete traditional patch-clamping apparatuses without the cost of a couple electrophysiologists. All this got me to wondering as I rode the escalator out of the hall at the end of the day — is there a limit to what can be automated?