From Our Neurons to Yours

The BRAIN Initiative: the national vision for the future of neuroscience is now in doubt | Bill Newsome

• Wu Tsai Neurosciences Institute at Stanford University, Nicholas Weiler, Bill Newsome • Season 6 • Episode 4

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Earlier this year, President Obama's signature BRAIN Initiative, which has powered advances in neuroscience for the past 10 years, had its budget slashed by 40%. 

Over the past decade, the BRAIN Initiative made roughly $4 billion in targeted investments in more than 1500 research projects across the country and has dramatically accelerated progress tackling fundamental challenges in neuroscience. As we head into the next federal budget cycle, the future of the initiative remains uncertain. 

Today we take stock of how the BRAIN Initiative transformed neuroscience over the past 10 years, and what the outlook is for the future of the field.

To give us an unparalleled behind the scenes view, we are fortunate to have Bill Newsome with us on the show. A world renowned expert in the brain mechanisms of visual perception and decision-making, Bill co-chaired the original BRAIN Initiative planning committee in 2013 (the same year he became the founding director of the Wu Tsai Neurosciences Institute here at Stanford). Don't miss this conversation!

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Episode Credits

This episode was produced by Michael Osborne at 14th Street Studios, with production assistance by Morgan Honaker. Our logo is by Aimee Garza. The show is hosted by Nicholas Weiler at Stanford's Wu Tsai Neurosciences Institute. 

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Nicholas Weiler:

Hey, everyone. Nicholas Weiler here. Before we get into this week's episode, we have a favor to ask. We are working to make this show even better and we want to hear from you. We're in the process of gathering listener input and feedback. If you'd be willing to help out, send us a short note and we'll be in touch. We are at neuronspodcast@stanford.edu, and you can find that address in the show notes. Thanks so much. Now, let's get to today's episode.

Welcome to From Our Neurons to Yours. This is Nicholas Weiler. 

In 2013, President Obama during his State of the Union Address slipped in a reference to a major investment in brain science. This effort came to be known as the BRAIN Initiative. And over the past decade, the initiative has made roughly $4 billion in targeted investments in more than 1,500 research projects across the country and has dramatically accelerated progress tackling fundamental challenges in neuroscience.

Unfortunately, in last year's budget battle in Congress, the BRAIN Initiative budget got cut by 40%. As we head into the next federal budget cycle, the future of the initiative remains uncertain, and we'll get into that in today's episode. But mostly today, we wanted to take stock of how the BRAIN Initiative transformed neuroscience over the past 10 years. 

To give us an unparalleled behind-the-scenes view, we are fortunate to have Bill Newsome with us on the show. Bill is the founding director of the Wu Tsai Neurosciences Institute here at Stanford. And in 2013, he was invited by President Obama to co-chair the original BRAIN Initiative Planning Committee. 

One quick note before we get to our conversation. We had some technical issues during the recording and there's some background noise. We've done our best to improve the quality. Hopefully it's not too distracting. 

Bill Newsome, thank you so much for joining us on From Our Neurons to Yours. Welcome to the show.

Bill Newsome:

Thank you very much for having me, Nick.

Nicholas Weiler:

So back in 2013, you were the co-chair of the BRAIN 2025 working group that was making a plan for how the BRAIN Initiative could have the biggest impact on neuroscience over 10 years. Now it's 10 years later. I'd like us to imagine we're going back in a time machine and we're telling 2013 Bill Newsome about what BRAIN has accomplished for the field by 2024. Could you give us some examples of some of the major breakthroughs or advancements in neuroscience in the past 10 years that would most surprise or gratify 2013 Bill Newsome?

Bill Newsome:

Yeah, Nick, that's a great and important question, and I can set up my description of these surprising breakthroughs best by telling you what the problems were in 2013 when we started this thing. So our job as neuroscientists is to do something called reverse engineering the brain. And you have to put yourself in the shoes of an electrical engineer who's given a piece of instrumentation and said, "We don't know anything about this instrument. It's up to you to take this thing apart and figure out how it works and tell us what it does."

And we had five major roadblocks. One is that any engineer would want to know the parts list, what kinds of cells are actually in the brain. Second, any engineer would want to know a circuit diagram, how different pieces of the brain connected to each other and different neurons connected to each other, was woefully incomplete. Three, you want to be able to measure the activity or the signals, the flow through of that circuit.

And in the brain, that's action potentials and synaptic potentials and neuromodulation inside the brain tissue, and techniques for doing that were very limited usually to just one cell at a time. And then fourth, you want to be able to intervene on those signals. You want to be able to go in and change the signals in the instrument and see if you get the predicted output from the instrument. Finally, you want a theory about how this thing works.

Nicholas Weiler:

Okay, so you said define the cellular building blocks, what is this thing actually made of? Map out the circuits, how do they connect to each other? Track their activity. This is an electrical device, so how are they communicating with each other? Test and modify their function. If I tweak it one way or another, how's that going to change the output? Develop a theoretical model. Okay, how do I think this thing is working?

And then actually probably applying that to the human brain is a whole other level that makes this hard because a lot of those experiments were going to be done in mice, rodents, flies, and other organisms. So taking this back to 2013 Bill Newsome, you were thinking about all of these problems, what are some of the places where we've really made progress on actually making some of those things easier?

Bill Newsome:

One of the first things right off the bat is on the parts list. In 2013, we knew some things. We knew about excitatory cells and inhibitory cells and pyramidal cells and stellate cells. We thought the parts list has just exploded over the 10 years of the BRAIN Initiative, and that is largely due to these new techniques that we have for doing single cell analysis of what we call transcriptomics.

So every cell in the body has the same genome, but liver cells are different from kidney cells, from brain cells. And what makes them different, it's how and when those genes get transcribed or translated into proteins that actually do the work of cells. For the first time in the last 10 years, we've been able to actually look at the transcriptome and that has enabled us to identify the real cell types at their natural level in ways that were just undreamt of before.

And the BRAIN Initiative has sponsored a major cell type cooperative enterprise and we now know every cell type in the mouse brain, which is our best mammalian animal model for studying the brain, and we're set up and started on doing primate brains, including humans.

So the parts list has just been a phenomenal discovery that we could barely have dreamed of even in 2013. In brain connectivity, we've had the Human Connectome Project and we've had detailed synaptic level connection and circuit diagrams worked out for animals like Drosophila and the mouse retina and other different brain structures.

Nicholas Weiler:

Drosophila is the fruit fly.

Bill Newsome:

The fruit fly, exactly, which is a very convenient animal to work with for looking at genetic effects on nervous system and behavioral function. So the connectome technology has been painstakingly developed. We now know these connectomes at levels that we could only really have dreamed of in 2013.

Nicholas Weiler:

I remember back at that time there were still pretty vigorous debates about whether the connectome was even a meaningful enterprise. Does it really matter to know all of the connections? What's the retrospective pitch on that?

Bill Newsome:

Well, the retrospective pitch, Nick, is that there are still debates about what level. Everyone agrees that we need to know the connectional anatomy. But the question and where the debate still exists, is it necessary to get the connectome at a synapse by synapse level account for every synapse on every cell, or are what we're looking for is more coarse scale anatomical motifs?

Nicholas Weiler:

More of a statistical approach.

Bill Newsome:

Yeah, and that is a big debate, whether looking at every single synapse, which requires a lot of microscopes and a lot of people, and what level the signal really lies. But no one questions that we need better connectional data than we had in 2010, 2013.

Nicholas Weiler:

Okay, so we've made a lot of progress on identifying cell types. We've got these massive enterprises to understand the connections between the cell types. How's our progress looking on seeing how those circuits are working in real time?

Bill Newsome:

Yeah, amazing actually, and the glimmers of this were here before 2013. So we knew before 2013 that we had to scale up our ability to record the signals from single cells in the nervous system. Those signals typically before were using microelectrodes to record the signals one cell at a time. And then at the end of a year, you'd clutch your two or 300 cells closely to your chest and try to figure out how they all work together to accomplish some intelligent or adaptive behavior.

But now with the new technologies, it's easy to record from hundreds or thousands even of single neurons in one experiment. And the first paper has just been published within the last year claiming, and we'll see whether it's verified or not, to have recorded a million neurons. It's single cell resolution from a million neurons at one time. That is just astounding.

I can't tell you, from the point of view of someone who spent his career studying one cell at a time, it's made many of us just stop and say, "We've got to rethink what it means to be a neuroscientist now in the coming decades." Because even while we were recording one cell at a time, we knew that the secrets to brain function and brain information processing had to lie at the population level.

But now we can really record from these populations either through electrode arrays or through optical means actually, which we can talk about. And that has been a real game changer. And the other game changer that you mentioned, Nick, has just been our power to intervene. And not just listen to the signals and read them out, but actually to put new signals in.

We knew we had to take these tools and make them better, adapt them hopefully to be non-invasive so that we could actually doing it without cutting a hole in the skull so we could actually use these kinds of things to treat patients. These kinds of technologies have also come up to scale, and we've been able to verify that you can insert memories into a mouse, for example, about how to run a maze by artificially intervening on a set of cells.

And we can foresee that kind of thing maybe being a treatment for human diseases like PTSD, erasing certain memories and replacing them with healthy memories. So in the reporting and the interventions, we're coming along very well as well.

Nicholas Weiler:

I found that study in particular. I remember when that came out, the idea that you could identify particular circuit, particular set of cells involved in making a memory and go in and tweak that, as you said, potential applications in future to say, well, you had this terrible experience and that's giving you a lot of trouble getting through your day-to-day life. What if we just soften some of those connections?

We can see where they are. And as you said, that means we need to know what the cells are, how they're connected to each other, how the activity is passing through the circuits to have tools to do something about it. So that's a really helpful overview of what the roadblocks were back in 2013 and what some of the directions that the BRAIN Initiative took to accelerate that.

I mean, are there other examples that you can think of where, again, thinking about our time machine, we're chatting with 2013 Bill Newsome, are there things that we have accomplished in the past 10 years that you might not even have thought possible back in 2013?

Bill Newsome:

Yes. One of the things that the BRAIN Initiative identified as a high priority was an emphasis on human neuroscience, taking some of the rich things that we're learning in animal models and translating them into the actual study of the human brain, because animal models are just models. What we really want to know about is the human brain.

And there have been some remarkable advances in human neuroscience where these new electrophysiology probes that can actually record from hundreds or thousands of neurons at a time can be used in neurosurgery to record signals from the human brain while the human being is talking, which is a natural part of some neurosurgeries where the human patient is conscious and alert during the surgery.

Nicholas Weiler:

Mostly so that the surgeon knows what areas to avoid and what areas are okay. They want to make sure they're not damaging the speech areas if they can avoid it.

Bill Newsome:

Exactly. Eddie Chang up at UCSF has actually been studying the speech areas of the human brain, and he's revealed coding strategies for human speech, both listening to the sounds and understanding them and producing phonemes in speech. And we're actually able to study uniquely human capacities like speech and understanding speech. That is a startling development.

Now, this has to be done, Nick, and this was another distinguishing feature of the BRAIN Initiative, this has to be done with a fine sense of ethics. These interventions in the human brain are always done in the context of surgery that has a very therapeutic goal for the human subject. And the human's volunteer.

While they're in surgical treatment, they volunteer actually to have some of these studies carried out, which don't take much time, but give a gold mine worth of data. The BRAIN Initiative has really been trying to encourage that, though we had no idea how successful it would be, but I think it's been great. Now, another example that I would give you that I could never have dreamed of back in 2013, we treat psychiatric and neurological diseases all the time by giving drugs.

The problem with drugs is they are delivered by the bloodstream, the vasculature, and they go to all parts of the brain. And they may go to targets where they're really having useful effects, and then they may have off-target effects, which we call side effects that are frequently detrimental.

And the question has always been, can we deliver drugs to some precise location in the human brain and do it non-invasively so that we don't have to cut holes in the skull and things like that? A lab here at Stanford, Rog Ahrens, a young associate professor in radiology, we had this marvelous idea of packaging drugs into little tiny lipid bound nanospheres, injecting them into arteries. And these nanospheres get transported all through the brain.

But as long as those drugs are bound in the nanospheres, they're not having any effects. But then he does focused ultrasound where he beams ultrasound into the brain through the skull and actually releases the drugs from the nanosphere. So it lysis the nanospheres. It breaks them apart and releases the drug in a small area that he can focus down to a millimeter or two millimeters, something like that, so that those drugs when they're released act locally on the brain.

Now, that's amazing, and he's shown this now in mice to begin with, in rodents. I think they've done some work in monkeys at this point, but Rog is a clinician. He's an MD PhD, and he sees a way to getting this stuff into clinical trials within the next two to three years. I think that's an amazing technological accomplishment with amazing clinical applications in the future.

Nicholas Weiler:

Yeah, no, that work is really amazing. We should definitely have Rog on the show.

Bill Newsome:

Do a podcast with him, absolutely, if you haven't already.

Nicholas Weiler:

He's definitely on the short list. Yeah, those technologies are amazing, and I think it goes to show just how much knowledge we need to have in the bank to be able to translate it to benefit for people. If we don't know the specific cells we're targeting to help a disorder, we can't do one of these targeted approaches to therapy.

So you said something very interesting that I want to come back to about what you can get done in a year or in five years, and you said it makes us realize we need to rethink what it means to be a neuroscientist. And I want to come back to that idea. But first, actually, we've been talking a lot about the early ambitions of the BRAIN Initiative and what it's accomplished, but maybe before we move on, could you tell us a little bit about how you got involved in the first place?

Because 2013 was a very big year for you. You were also just launching the Wu Tsai Neurosciences Institute as our founding director. So that must've been an interesting experience to do both of those things at the same time.

Bill Newsome:

Yeah, at times it had my cerebral hemispheres drifting apart.

Nicholas Weiler:

Right. Left brain for Stanford, right brain for NIH.

Bill Newsome:

Yes, exactly. In 2013, President Obama gave his State of the Union Address, and there was just this snowflake dropped into the State of the Union Address about some new big BRAIN Initiative Project that was going to unlock our neuroscientists to really understand how the human brain works in natural thought, at the speed of thought, and how it goes wrong in disease. And neuroscientists all over the country are like, "What? What?"

Nicholas Weiler:

I haven't heard about that. Are you working on that? I'm not working on that.

Bill Newsome:

You can just see hair standing on end from neuroscientists around the country. Everyone was in a tizzy trying to figure out what in the world was going on. It turns out this had been generated through a series of meetings sponsored by the Kavli Foundation, and some of the Kavli people had connections inside the Office of Science and Technology Policy at the White House. President Obama likes to have these things come up to him, these technological things that he was really interested in.

And he selected this BRAIN project to something that he really thought was important and really wanted to do. And then he just announced this with no neuroscientists going on, and neuroscientists were really worried that this was a harebrained idea and has it been properly vetted? Francis Collins, the director of the NIH at the time, to his great credit said, "NIH needs to take the lead in this thing."

But one thing that Francis knew was that for this to be done right, is that there needed to be a serious planning committee to really map out what we knew, what we don't know, what technologies do we have, what technologies do we need, and how do we actually go about doing this and spending tax money wisely in order to make a real major push on understanding the brain and addressing it in health, as well as in disease.

So I got this phone call in April of 2013 from Francis outlining his plan for this committee, and I was asked to serve on it and worked with Cory Bartman, my highly esteemed colleague at Rockefeller University, to co-chair the Planning Committee. At the beginning, I thought this might just be a fool's errand, honestly. I told Francis, I said, "Francis, let me call Cory and talk with her, and I'll have an answer to you in 24 hours."

I talked to Cory and I said, "Cory, we're going to spend hundreds or thousands of hours on this thing. There's no assurance that this report will have any impact at all on how Washington really works and what really happens." And Cory, there was this 10 seconds or so of silence, and she said, "Bill, if the brain is important enough to take up President Obama's time, then it's important enough for us to write the best report for him that we can write."

She took the high road on me. And at that point, what can I say? I said, "All right, let's go for it." And so I called Francis and said, "We'll do it." We had a great committee of about 18 people. We didn't know what we were doing at the beginning. We had to invent what we were doing just procedurally. How do you go about this? And we knew that we had to consult the stakeholders out there.

So over that summer of 2013, we had a series of meetings, one in molecular neuroscience, one in systems neuroscience, one in human neuroscience, one in theory and computation and data sciences. We invited leading scientists to come and meet with us, and we listened, and then we debated among ourselves. And our first report was due to President Obama in September of 2013, and then we had our final report a year later. But it was quite a challenge to get into that stage one report.

Nicholas Weiler:

So you had six months to come up with how do we plan the next 10 years of neuroscience in a sense?

Bill Newsome:

Exactly. And that was from scratch, from the first phone calls from Francis to the time the first report was due was six months.

Nicholas Weiler:

One thing I love about what you came up with, it needs to start by being about technology. And I get the sense that that was strategic to say, look, we don't know what questions people are going to be asking in five years, much less 10 years. But if we can invest in the technologies that will let them ask the questions that they're interested in, then we're going to advance the field.

Bill Newsome:

Yeah. Another thing that we realized early on, Nick, that a lot of people had realized, but maybe it had not been formulated at the level of policy at NIH funding, was that neuroscience is inherently probably the most interdisciplinary of scientific subjects. Maybe climate change rivals it. But right up there with climate change and sustainability, neuroscience is there.

And we had to break out of the mold of thinking that the brain is something you study in medical schools only, alongside the kidneys and the lungs and the skeletal system, musculoskeletal system. Understanding the brain is an all hands on board effort. We have got to get critical contributions from molecular biologists to geneticists who make many of the probes that we use.

We have to get critical contributions from engineers, CS people who know about computational architecture and about algorithms and about how to deal with complex data sets, and the modern era of data science and neuroscience is right in there in that. And we have to get contributions from physicists making new instruments, as well as clinical neuroscientists and the standard basic neuroscientists.

So we cannot afford to be parochial, and this sort of all hands on deck mentality is critical to the effort. We will not understand the brain, we will not invent the right technologies, we will not get the right experiments done if we don't have that team science mentality. And I think that's something we really emphasize from the get-go that the BRAIN Initiative has really delivered on.

Nicholas Weiler:

Well, we've talked a lot about some of the amazing advances that the BRAIN Initiative has delivered on. What are some of the things that we thought were going to be slam dunk, so we were really hopeful we were going to make progress on that we haven't seen as much progress as maybe we hoped or maybe we're just on the verge of some progress, but we haven't seen it yet?

Bill Newsome:

Yeah, great question, Nick. And I would say that the BRAIN Initiative has set the stage for a golden age of neuroscience, but it has only set the stage. We have developed amazing technologies, some of which were at least on the horizon in 2013, some of which like this whole cell transcriptomics and cell type Atlas. I mean, I went back at one point and looked through our report, when I semi-panicked about three or four years under the BRAIN Initiative whether we even mentioned the word transcriptomics in our report.

Nicholas Weiler:

Did we forget this?

Bill Newsome:

It was there once. It was there once. Well, it was just being invented at the time. But this shows that these developments can come about that you just have no idea. I mean, that's a technology that unleashed tons of progress in terms of parts list, which in turn gives us avenues to be able to manipulate and know the circuits meaningfully and intervene on them meaningfully when we really know the parts.

But I would say the places where that has been the toughest is one that's dear to my heart is neural coding. We know that circuits talk to other circuits and they interact at the population level. And we talked a while ago about being able to duplicate simple memories or erase them or maybe create them at least in mice, and that means we're learning something about how the brain codes its messages.

But really our human brains are 100 billion neurons sitting there twinkling on and off with action potentials and messages going from cell to cell. And we're sitting there listening to this activity and saying, "What does this mean? What's the code here?" And there may be no single code. There may be different codes for different brain regions, and I think in some ways that's the toughest nut to crack.

It's much tougher than cell types. It's much tougher than connectomes. It's tougher than just listening to the signals. It's understanding the signals and having a theoretical appreciation for what they mean. This is something where we've been a little slow, but there are rather dramatic developments just in recent years about understanding what we call high-dimensional spaces and coding and high dimensional spaces, which we could unpack a bit if you want me to.

Nicholas Weiler:

That is something I want to talk more about. Actually, I had a thought that might help listeners understand this idea of high-dimensional, which is we talked to Lisa Giocomo recently about place cells, and I think that we've talked about the idea of the grandmother cell on the show before.

And these are ideas where with technology where you can record from a single cell, you can see that when an animal is in a particular place, that place cell fires, or there was some evidence that there are certain cells that fire when you see the face of a particular familiar person. And that you can think of as one-dimensional, the firing of that cell goes up representing a particular thing.

But what it sounds like is that over the course of the last 10 years, and probably before that, we've realized that most things in the brain, thoughts, memories, experiences, dreams and so on, are represented by the activity not of one neuron, but of thousands of neurons or hundreds of thousands of neurons.

The question of how do you even represent that, it's not one neuron going up and down, but it's this complex pattern, and then that's where you say it's high-dimensional. It's thousands of dimensions of activity that all mean something into our experience.

Bill Newsome:

That's right. The coding is not at the single cell level or single cell type level, but it's a pattern of activity among a large populations of cells.

Nicholas Weiler:

And that's something where we still have a lot of work to do to figure out how do we decode those patterns.

Bill Newsome:

A ton of work to do. We're making progress. I mean, I think the most exciting work to come out of my lab over the last decade is exactly in this space, but it's a tough problem to solve. A way in to start understanding what I mean by high-dimensional is to think about the coding of color in the retina.

So in the retina, we have three types of cones, three types of cells that absorb light, some that absorb in long wavelengths, that would be reddish colors, one that absorbs in the mid-wavelength, that would be greenish colors, and one that absorbs in the short wavelengths, that would be bluish or purplish colors. The color that you actually see, you cannot know just by recording from one cone type alone. The color you see is not dependent on any one cone. It's dependent on the ratio, the pattern across those three cones.

And those three cone types define a three-dimensional space, and all the colors you see are somewhere in that three-dimensional space. Now, take those three cone types and multiply them by 100,000 and think of all the dimensions of the space when you've got say 100,000 neurons rather than just three cone types, and you start to perceive the complexity of the problem, the complexity of the mathematics that's going to be necessary to solve that problem, the statistics, the data once they start coming out.

It is a formidable problem, but really essential to understanding ultimately how humans perceive, how we remember, how we learn, how we attend, how we plan, how we think.

Nicholas Weiler:

All of which are high-dimensional experiences.

Bill Newsome:

High-dimensional experiences. That's right.

Nicholas Weiler:

I would love to transition to talking about the BRAIN Initiative cuts. There was another example that you were about to give before we got into this interesting conversation about high-dimensionality.

Bill Newsome:

The other thing is the time I became involved in the BRAIN Initiative, one of my goals, ultimately what we want to do is understand how the human brain works and be able to treat brain diseases that are so devastating on so much of our society, especially as people like me age and look at the various neurological diseases of old age. This is personal for me. This is not abstract.

My fondest hope would be that at the end of 10 years, we'd be able to pick one of these diseases that we've made real progress on, and we can say, we can at least stop the progression of this disease, if not reverse it and hold out hopes for reversing in future decades. And I would say that these diseases, the more we've learned about the human brain and the diseases, they just turn out to be a whole lot tougher than we realize. And we have made progress.

My father died of Alzheimer's disease. I know that I have a genetic mutation that makes it more likely that I'm going to get Alzheimer's disease. We have solved Alzheimer's disease 30 times in mice. We've tried to translate them at billions of dollars of expense into humans. And truth is we've made very little progress. That fact sends you back to the basic science and says, what are we missing?

And I think the BRAIN Initiative tools and discoveries that we've made so far are going to help us look at these diseases differently. But it's been slow, quite honestly, and that's something that I had hoped we'd be able to show more return on after 10 years. But it's reminiscent of the War on Cancer. President Nixon declared War on Cancer in 1970s, and it wasn't until the last 10 years that 30 years of intervening research has yielded dramatic results in improvement of our treatment of cancer.

That kind of sustained effort is going to be necessary, I think, to yield dramatic results in our treatment of neurologic and psychiatric disease. So that's something that I'm still looking forward to in the future.

Nicholas Weiler:

Well, speaking of the future, let's come to the hard pill here, which is that the NIH budget did cut the funding for the BRAIN Initiative by 40%, which is pretty drastic because the BRAIN Initiative is funding a pretty significant amount of the neuroscience that's being done in this country right now. Can you explain to us briefly how these 40% cuts came about and what the effects are looking like being on the field?

Bill Newsome:

I can tell you my understanding, Nick, which I think is accurate at a high level, although I don't know all the ins and outs of it. But the BRAIN Initiative funding, some of it was dedicated funding by Congress. And by the way, the BRAIN Initiative, it's one of the few things in modern political life that's enjoyed bilateral support in Congress from both sides of the aisle. Turns out both Republicans and Democrats get Alzheimer's disease. So everyone has a stake in seeing these things solved.

The BRAIN Initiative, part of the funding came from dedicated funding voted by Congress for the BRAIN Initiative. Another piece of it came through the 21st Century Cures Act that Congress passed about a decade ago. The Cures Act funding was scheduled to sunset sometime right around 2024. And then the budget negotiations for fiscal years 2024, all the listeners may remember that Congress had a very tough time agreeing on a budget. And the situation was actually rather desperate because of politics in Washington.

As a result, a big broad solution was found, which basically involved cutting lots of things rather indiscriminately. So I don't think anyone voted to reduce funding to the BRAIN Initiative specifically. But as part of the whole compromise just to get a budget passed and Washington, certain things got reduced with a shotgun rather than with a rifle, and the BRAIN Initiative was a victim of that. I can't tell you how devastating this is. I mean, we can survive this for a year.

John Ngai, the director of the BRAIN Initiative, and his working council that steers NIH research have made all kinds of compensating moves and cut some grant budgets here and there, put off some new initiatives, trying to preserve the best of what's going on. You can get through a year like that, but that is not a program for the future. I mean, that's going to really start hurting if we don't get this stuff restored in the next fiscal year.

So the impact of this on neuroscience and on health of our citizenry is going to be huge if those budgets aren't restored for the BRAIN Initiative and for the Cures Act. What we've accomplished in the BRAIN Initiative now is really impressive, but it's very small compared to what can be accomplished in the coming 10, coming 20 years. Basically, we have turned out a lot of technologies that are now just primed and ready to be used.

But the main thing we need to do now is to switch our focus from technology and from basic science into really exploiting these discoveries and these technologies for human neuroscience and understanding the brain's coding properties and intervening and disease. We've set the table. This 10 years has been an amazing 10 years, but it's only preparatory. And we are right now poised to reap the benefits of all of the seeds that have been sown over the last 10 years.

And if we just stop it now or if we cripple it now, it just makes no sense. It's just not a smart thing for the United States to do. There's a lot at stake here and a lot worth fighting for to reverse those budget cuts because they will be devastating if they're maintained.

Nicholas Weiler:

Well, this is obviously a very tough time for many researchers. Hopefully there will be a restoration of funding in the next budget, but I wonder if there are also other places that might pick up the slack from this cut funding, if there are areas of research that might be ready to move from NIH funding out into the marketplace, or if you think this is just a wake-up call for the research community to get involved and make the case for a next generation of neuroscience research investment.

Bill Newsome:

I certainly think that it's a wake-up call to all of us to make our cases to the decision-makers in Congress. And honestly, the stakeholders for psychiatric and neurological disease are every person in this country. I don't think there's a replacement for NIH funding. As you alluded to early, Nick, I spent nine years, 10 years really involved in leadership at this Neurosciences Institute at Stanford, and part of my leadership responsibilities was fundraising.

And over the period of a decade, I was involved in raising maybe two or $300 million, something on that order, from donors and philanthropists and Stanford community. But the NIH budget is $40 billion. Let's make no mistake about it. NIH is the engine that runs American Biomedical Science. Now, a lot of that $40 billion is spent on clinical trials. Clinical trials are extremely expensive, so attempting new treatments for disease is a high priority for NIH.

And that $40 billion gets spread over all the fields, everything from cancer to cardiovascular to allergies. So maybe four or $5 billion of it might come to Neuroscience in one way or the other. That's still a lot of money. And the private fundraising that we can do at universities is, honestly, it's a very, very minor role compared to NIH. So the health of NIH and the support of NIH by our federal funding agencies and the decision-makers in Congress is extremely important.

In terms of getting industry to do it, I don't know if there's a good model there. There is this much discussed gap between discoveries in the lab versus demonstrated therapeutic potential that's enough for a private company to take up that and then get it into an actual commercial product. And that gap between discovery and being compelling enough to get into commercialization is frequently referred to as the valley of death.

We've got to put mechanisms in place on the university side that take the discoveries and get them farther along that valley of death, that bridge to commercialization, where we have to create possibilities for the commercial entities to take greater risks. And the only way to really cross that thing compellingly is for funding. It's all expensive. It all costs money.

So I think building bridges from both sides, both from the industry side, if we could have some government-industry partnerships that maybe buffered some of the risk for industries to take these new discoveries and to turn them into commercial devices or drugs, that would be helpful. If we could build bridges from the university side to teach faculty how to take our discoveries and move them more toward a case that would be compelling for industry, that would be useful.

So those are problems that have to be solved. But if those problems can be solved, then I think there's just so much reason to be hopeful. I mean, if we just look at what's been accomplished in the last 10 years that we did not necessarily have on our radar screen 10 years ago, it has been so impressive. We've succeeded in bringing so many new people into neuroscience, physicists, statisticians, computer scientists, electrical engineers, materials engineers, applied physicists, psychologists, for crying out loud.

I mean, we've created excitement. We've created buy-in in young people. I mean, in the theoretical neuroscience, which I told you is one of the toughest nuts to crack, we can't keep enough theoretical neuroscientists here at Stanford to accommodate all of the graduate students and undergraduates even who want to work in this field because people accurately see the brain as one of the most interesting and formidable and challenging problems to be solved in this century.

So the BRAIN Initiative has created the excitement, has created the buy-in, has created the communities, has integrated the ethics into the effort, that gives so much reason to be optimistic about what we can accomplish in the coming decades. So despite the bumps in funding, if we can just keep this thing on a reasonably even keel, there's so much hope for the future, and I'm quite optimistic about it. I tell young students all the time, this is the best time in history to be a neuroscientist is right now. Right now.

Nicholas Weiler:

Fantastic. That's I think a great note to end on. This has been a really fascinating conversation. Thank you so much, Bill, for coming on the show, telling us about what's been going on in neuroscience for the past 10 years and what the future is going to look like.

Bill Newsome:

Well, you're very welcome, Nick. It's been my privilege. And you guys, I listen to your show all the time and keep up the good work.

Nicholas Weiler:

Thanks, Bill. 

Thanks again so much to our guest, Bill Newsome. 

We heard from Bill after the recording, and he asked us if we'd be willing to share one additional reflection, just to clarify his position on how neuroscience gets funded.

He said that while NIH is a crucial source of funding, private philanthropy does have an important role to play – particularly for projects that are early stage research and that may be too new and untested for NIH to take a risk on. 

If NIH is the blue chip heavyweight of biomedical funding in the US, he said, private philanthropy funds can be like VC investors looking to make a big bet on disruptive new ideas that can move a field forward with lightning speed.  Bill told us: we need both.

Newsome is the Harman Family Provostial Professor of Neurobiology and Founding Director of the Wu Tsai Neurosciences Institute at Stanford University. To learn more about his work and the BRAIN Initiative, check out the links in the show notes. If you're enjoying the show, please subscribe and share with your friends.

It helps us grow as a show and bring more listeners to the frontiers of neuroscience. We'd also love to hear from you. Tell us what you love or what you hate in a comment on your favorite podcast platform, or send us an email at neuronspodcast@stanford.edu. From Our Neurons to Yours is produced by Michael Osborne at 14th Street Studios, with production assistance from Morgan Honaker. I'm Nicholas Weiler. Until next time.