The human brain, as Francis Collins recently said, “is the most complicated organ in the universe.” We only have vague ideas today of how it works at the level of genes, and neural circuits. Deeper understanding could help us unravel some of today’s great mysteries, from autism to Alzheimer’s to epilepsy.
The sequencing of the human genome was controversial for a long time, but it’s starting to pay off with a new wave of genomic-based diagnostics and treatments. Venturing next into the unknown frontiers of the brain is an opportunity so big, so important, so darn interesting, it should be something our society eagerly supports and expects to pay dividends far in the future.
Yet the inspired idea known as the “Brain Activity Map” runs the risk of becoming a casualty of small-bore thinking in science, politics, and business. In a world where “sequester” has entered everyday spoken language, many politicians and scientists are tiptoeing around, afraid of vocally supporting something perceived as too risky, too ambitious, too unrealistic. But the truth is we can afford it, we can actually afford to spend a lot more on it, and it would be a wise investment of tax dollars.
Many readers have surely seen the headlines from last Tuesday, but for those who haven’t, here’s a recap. President Obama, after alluding to a brain project in his State of the Union address in February, formally proposed a $100 million first-year budget in 2014 for the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) initiative. The goal of this project isn’t clearly defined yet, but loosely speaking, it’s about inventing new technologies to help scientists explore the complex circuitry of the human brain in action. We’re talking about our first serious glimpse into how those 1,000 trillion connections in the human brain work.
Obama, ever the gifted communicator, saw the poetry in this adventure.
“As humans we can identify galaxies light years away, we can study particles smaller than an atom, but we still haven’t unlocked the mystery of the three pounds of matter sitting between our ears,” Obama said on Tuesday.
Immediately, critics spoke up, mostly from some quite nervous camps within science. The goals weren’t clear from the outset, so it’s not really like the Human Genome Project, they said. The funding is small potatoes, not enough to make an impact. The tools don’t yet exist to gather data we need to even ask some of the important questions. There aren’t enough theoreticians in the NIH working group to crystallize the right questions to ask. There aren’t enough nanotechnologists in the group to invent the tools. Why not leave this kind of work to industry, some rich foundations, and billionaire philanthropist Paul Allen? The NIH budget is getting whacked across the board by sequestration, so why start something new? Aren’t we, as a nation, supposed to be broke?
All of those criticisms had made their way to George Church, the prominent genomics innovator at Harvard Medical School, by the time I stopped by his office in Boston about 48 hours after the White House press conference. Church, a veteran of the original Human Genome Project political debates of 30 years ago, has been part of a small group of scientists pushing this brain initiative for the past year through a series of articles in Science, Neuron, and ACSNano.
Church, no surprise, sounded upbeat about what BRAIN can accomplish, starting with the early meetings that have helped define its objectives. “We called it a ‘Brain Activity Map’ to distinguish it from anatomical maps,” Church says. “The new acronym, which has a capital ‘N’ in it, stands for neurotechnologies, as in plural. I like that because the emphasis is not on a map, which sounds kind of static, even if you put the word ‘activity’ in front of it. It sounds a little monolithic, and we were a little OCD [obsessive compulsive] to get that last synaptic link.”
You can almost hear Church, in comments like this, doing his best to disarm the scientific critics that he remembers from the genome project days. Back then, people worried that a “big science” project would siphon money away from other worthy science projects—namely their own. People wondered what the heck we’d learn anyway, since most of the genome was thought to be meaningless “junk.” At the beginning, the sequencing technologies didn’t really exist to give us a full genome map in a reasonably cost-effective way. Besides, who wanted to work on the mere engineering task of automated sequencing, when graduate students were plentiful and worked on manual sequencing for dirt-cheap wages?
Building on the lessons of the genome project, Church is determined to deliver this time on a project that delivers “bang for the buck,” from the start, as he told John Markoff of The New York Times in February. One of the ways to do that, Church says, is to not get carried away, and start small with a diverse group of funding agencies like the Defense Advanced Research Projects Agency (DARPA), the National Institutes of Health (NIH), and the National Science Foundation (NSF). Since DARPA is putting in $50 million, the NIH is chipping in $40 million, and NSF is joining the group as well, these budgets are small enough that there’s no need to steal money away from any other deserving scientific programs. A group of foundations is said to be chipping in even more.
Where the money comes from is important, but so is how the money is spent. Even though the genome project is going down as a truly historic scientific achievement, the really big “Moore’s Law” style advances in genomics didn’t come until after the government invested in 2004 in new frontiers for the improvement of sequencing instruments, Church says. Until then, many biologists resisted technology improvement because they were uncomfortable with it, he says.
“Only in 2004 did the NIH start its Advanced Sequencing Technology (AST) grant program with $18 million a year (compared to $300M/yr for the Human Genome Project ‘production’ groups),” Church told me by e-mail. “The return on investment of eight years of Advanced Sequencing Technology seems far greater than the 14 years of the Human Genome Project, since the AST played the key role in the million-fold improvement in costs in Next-Gen-Sequencing.” Essentially, the advancements in enabling technologies are bringing us into the age of the $1,000 genome that has gotten scientists and physicians so excited the past couple years.
Given the importance of enabling technologies, and his history in the field, Church says he wants to see the BRAIN project invest in technology from the start, even though it’s likely to make some tradition-minded biologists uncomfortable. Scientists need new optical technologies for monitoring brain circuitry without drilling holes through the skull, as well as calcium imaging systems, and voltage monitors that lean on nanoparticles or ‘nanodiamonds,’ Church and colleagues argued last July in Neuron.
Exactly how these technologies will work is unknown. We don’t know exactly what we’ll learn about the brain by making these investments. But by betting big now, in a field of such untapped potential, we can be sure we’ll learn a lot of things that are relevant for human health. And even though $100 million a year is small change by federal government standards, it is enough to create a small market that gives for-profit companies assurance that if they build such tools, someone will buy them.
This next year will be an important one, as the scientific community will have to articulate the priorities. The group, led by Cori Bargmann of Rockefeller University and William Newsome of Stanford University, will need to provide more direction and clarity. The project will eventually need more money.
We can certainly afford this kind of work as a country. Some people will howl in protest, but we can easily cut wasteful spending on things like proton therapy for cancer, which will cost us billions in Medicare spending over the coming decades while offering no better treatment outcomes than today’s standard radiation. While really big money gets wasted on items like that, it’s a shame that really big ideas for science are forced to beg for federal table scraps. There’s a real risk, Church says, that the project will get reined in and just focus on the genetics of the brain, because it’s cheaper and within the comfort zone of many biologists today.
No question, the U.S. government wastes a lot of money. We definitely can’t afford to keep running up trillion dollar deficits forever. But sometimes the federal government is the only entity on the planet capable of planting the seeds for far-sighted achievements, like putting a man on the moon, protecting national parks, developing the Internet, sequencing the genome, or building a university system that’s the envy of the world. These things pay massive long-term dividends—whether or not you believe the 140-fold return on genomics investment cited by the President this week.
Clearly, the BRAIN project is one of these low-cost, high-impact investments for the future. We ought to be talking about how we can free up more money to achieve our neuroscience goals faster, rather than talking about whether we can afford this puny appropriation at all. Billionaire philanthropist Paul Allen, someone unconstrained by Beltway politics, explained his decision last year to spend $300 million on neuroscience with a sense of wonder you see often in 12-year-old boys.
“I’ve always been fascinated by the workings of the human brain, and awed by its enormous complexity,” Allen said at a press conference in March 2012. “Our brains are many magnitudes more advanced, in the way they work, than any computer software.” He added: “Our dream is to uncover the essence of what makes us human.”
The people of the United States collectively have a lot more money than Paul Allen. Every now and then we can afford to think at least that big. We shouldn’t do it for every far-out idea, but this is the time for brain science.
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