Saturday, November 16, 2013

#SfN13 Follow-Up: My Interview of Allan Jones, CEO of the AllenInstitute for Brain Science

During the annual Society for Neuroscience meeting this year, I had the privilege to be one of the official meeting bloggers. Aside from covering some more of the traditional aspects to the meeting like posters, nano-, micro-, and full symposiums, I thought it might be interesting to some of my readers if I interviewed some of the people that are in attendance. 

Announced this summer were the new building plans for the Allen Institute for Brain Science coming to the South Lake Union neighborhood of Seattle, Washington. In what is becoming the biggest basic neuroscience research powerhouse of the world, the institute is finally growing out of its first building and is expanding into a new one. This impressive structure appears to be best suited to help the institute on its mission to understand the human brain. So, I thought a key interview to conduct would be with Allan Jones, Ph.D., Chief Executive Officer of the Allen Institute for Brain Science. Dr. Jones graciously gave me over 30 minutes of his time at their wildly popular exhibit booth during the Society for Neuroscience meeting for this exciting interview on their work.

Steven Miller:   What makes the Allen institute different than academia, pharma, or biotech?
It's tough explaining in it to people sometimes, like my fellow graduate students.

Allan Jones:      Well I'll give you a little bit of my speech when I talk to potential employees when we're recruiting. I do think we're kind of this unique blend of what I always say is the best of all worlds, which is that we get to approach science with the discipline of industry. And so the organization as we built it was modeled around a biotech company. That was my environment. I worked for a biotech company, Merck a big pharma company. I like the discipline and approach that you can take in this team-based science approach where truly you've got products that you're trying to create and everybody is jointly working on them together. We always talk about being multi-disciplinary but we truly are and this atlas product is the collective work of PhDs in math, physics, IT, and all of that. And it's been like a relay race where until the final product is done, we all succeed or fail. I think that's the thing that differentiates us most from a traditional academic environment. The other thing that makes us unique is that what we pick to work on is done through advisory councils and that's where a lot of collective decisions are made to say, 'What are the next interesting things to work on as an establishment? What is the next direction for the institute?' That's done in convention with a lot of external advice and input. We have science advisory boards that are the premier scientists in their field that come in. It's not a rubber stamp. We actually really want them to guide and shape us. Another aspect that's different about us is that I'm the head of the organization; I'm the CEO but it isn't about running my agenda. I think my goal really is about building great teams, making sure we're aligned and obtaining the resources we need and putting them in place to be able to execute.

SM:            Unlike in the pharmaceutical industry where the product is going to be directly obtaining revenue for you, how do you see your products obtaining revenue for the institute? Do you see them as a means to obtain public or private funding to continue work in the future?

AJ:             This is the beautiful part of what we get to do, because we're non-profit; Paul Allen funds us for impact. Paul's return on investment is whether or not we have impact on to field moving forward. We always have the metric of saying, 'How can we best impact the field?' It allows you to sort of bulldoze and steamroll a lot of the traditional way of doing things. We share anything. One of the things I don't think people realize is that they use our atlases and all but, three of the top ten all-time selling mice by Jax were produced at the Allen institute. I think we have an openness of sharing of our tools, as well as the data. Again, that return is all about having impact.

SM:            I think that's great because there are a lot of smaller groups and organizations trying to push for open access, but not with the kind of financial backing of the institute.

AJ:             Right. And, there are times at which, and something we trying to be very careful of is that being the 800 pound gorilla, if you are an 800 pound gorilla you can...

SM:            Stomp out those little guys.

AJ:             You just have to be careful about how you want to use that. We've always said that that is what enables us to do things like helping the field move forward, help establish standards and put this data out there. Sometimes the atlases and other things act as frameworks around which people do the work. You can get caught up in small decision making as opposed to saying, we're just going to do it. We're not trying to take over the world, but it just needs to get done. We need to move forward and get on with it.

SM:            As someone with a background in genetics, how do you think that's helped you at the Allen institute?

AJ:              I always say it's a great devilish sword. Because the way the institute runs, I don't have a dog in the fight. I don't have a neuroscience background. My background included work on everything from C. elegans to plants. I think biology is just cool. There are so many interesting problems in biology and neuroscience is one of those areas. I just want to have maximum impact. I don't have a pedigree. I'm not there to prove any one theory or one way of doing things. Rather, what do we think–based on what our scientists are saying, what our advisors saying–are the best directions are to move forward.

SM:            In terms of advice for the habits of scientists and regarding your position as Chief Executive Officer or Christof Koch's position as Chief Scientific Officer, what would you tell people who are just starting out in their science training?

AJ:             That's an interesting question...

SM:            Some people say you should spend an hour on PubMed everyday to make sure you are current on the literature. What are your habits?

AJ:              My habits were to be an omnivore.

SM:            Ha ha. Good answer.

AJ:              I always tried to cross-cut my ideas with others. I had a really good friend of mine in grad school that was in a post-doc position that said, "The mark of a great scientist is to believe in something passionately and have data change your mind." I always liked that because it is really easy as scientists to sort've get into your own dogma. Personally, for me, it is just more interesting to try and keep an open mind.

SM:            I completely agree. People in science should be able to accept evidence in disagreement of their dogma and that's often not the case.

AJ:             Right. One of the things I always enjoyed doing in undergrad was opening up my textbooks and asking myself, "What is actually real?" When you look at all these pictures in undergrad it feels like all you're learning are facts. When you get to that higher level you start digging in and ask yourself, "What is the actual evidence of the facts that I'm learning?" You should always be questioning these things. The other thing I often tell people for data sharing and openness is, if you only have one good idea in your career you are in the wrong field. The people that I see in the field who hang onto things and their piece, I don't see them really enjoying their work or ultimately having as much impact. People who are more open and are involved in sharing their ideas enjoy their work much more.

SM:            On the topic of sharing, what do you think of groups like Faculty of 1000 and how they allow you to publish your research posters?

AJ:             You know, I'm a huge fan of overhaul in the publishing industry in one way, shape or form. I think we need to take a look at how every other field has been disrupted by technology. Ours is sort of ripe for the picking for being disrupted in ways that can only help us do better science. I look at those kinds of things and think about the coding community and all of their open source-type work. They've developed mechanisms for that kind of sharing. There are mechanisms for us to do it. The funding agencies could really get behind this movement and say, we need to live this. One of my challenges is that a lot of organizations now are just giving lip service to sharing. They don't necessarily live it. It's a hard thing to live. Sharing your reagents or sharing you data goes a bit against human nature. But, you just got to do it.

SM:            Especially now since some journals will say, hey we'll publish your article open access but you have to pay more and that can be cost prohibitive for some labs to do that.

AJ:             The challenge is that I understand from a business perspective that money has to come from somewhere. One of the challenges is our field is always eager for the things that are free or do not cost money but the reality is you have to spend money. If you want to have great editors you have to pay them great salaries, if you want to have great information dissemination somebody is going to have to pay. But, whether or not there are ways that this can be done differently, I'm sure there are more people who think about that more than I do.

SM:            Moving on to talking about the ten year project of mapping and understanding the visual system, would you say this project is exclusively part of the BRAIN initiative? Or, was this something the Allen Institute was planning on doing on its own?

AJ:             We were doing it on our own. We started planning our ten year plan in 2010. Christof Koch came on board, we did another year with the planning and we launched our initiative in March of 2012. A full year before the EU launched their project or before the BRAIN initiative was talked about. As I like to say, what's significant about the number 225? That's the number of panel discussions on the BRAIN initiative that occurred in the last 6 months and the number of full-time employees at the Allen Institute that are full steam ahead on our initiative. I should clarify, because it's hard in short soundbytes to layout what our broader plan is but there are elements to it that are continuous from our atlas work. This initiative is all focused on cell types. Also, it's not just mouse, it's mouse and human. We thought it was very important that ultimately we want understand the human brain. In parallel to working on the mouse and describing cell types in detail, we're working on human cell types as well. We have an active program with a lot of resources going towards that program. A lot of those studies are the ex vivo studies we can do. For in vivo studies, obviously in human they are very limited but we have active program, which we intend to build around using human stem cells to make neurons in a dish. This with the idea of being able to test some of the fundamental properties of human circuits in a dish. That is a very long-term goal but I think that the likelihood that you are ever going to be able to do an kind of invasive study on a human to get down to that level is highly unlikely. We are going to need some kind of in vitro system to do that. Then, of course the big thing is the MindScope part which is looking at the awake behaving mouse and all of the activity that is going on in the visual system and kind of systemically chipping away at understanding every transformation that's going on.

SM:            When the article came out in Neuron last year on how to map the brain and the technologies we could use to do this, one piece of technology discussed were the small synthetic cells that might attach and record activity from human cells. What do you think of in terms of how feasible it might be for getting these technologies approved? These technologies sound great but getting them approved by an IRB, that's challenging.

AJ:             Are you going to be the one to sign up?

SM:            No, I don't think I will.

AJ:             The reality is I think it is going to be somewhere in the middle. The thing that I always marvel at is the statistic now that there are over 100,000 people on this planet that have implanted devices in their brains and that number is only going up. The analogy I like to make is to a pacemaker in your heart. So if you told people 40 years ago that we are going to put an electronic device on your heart and it is going to control its beating, I'm sure the reaction then was, 'no way', 'that's crazy', 'I'm not going anywhere near that.' Now, it's an outpatient procedure, it's easily done, and the battery lasts a very long time. Whether or not people are going to accept an injection with little nanobots that crawl your brain, I'm not sure but I see it moving in that direction.

SM:            I think it was two years ago when Ed Boyden gave his TED talk on optogenetics discussing how that technology could be used as a pacemaker for the brain in the case of epilepsy. It could detect seizures, turn on and stop the seizure activity dead in its tracks. If I had epilepsy, I would be very interested in this and I think it is the kind of use case where I think people would want to sign up.

AJ:             Right and I think that's exactly the case with people that have severe Parkinson's disease. These are the kinds of things where I think about how people can have depression so debilitating that they would get a pacemaker implanted in their brain but so many people are. And, it has actually been shown to be quite effective. That said, maybe some of the non-invasive methods are going to get so good that there will be improvements there.

SM:            So let's say you accomplish your ten year mission, what do you see as what's next?

AJ:             There we would be on the cusp of saying–broadly speaking–what the principles are for the language of the brain. 100 years ago the language of chemistry was unfolded. 50 years ago was DNA and information coding. Now, you're 50 years later and I think all of the technologies are here. I mean, look there are 30,000 of us here working on the brain. We ought to be able to do this. There are going to be general principles learned. Then the challenge will be now that we understand that toolkit, we understand that basic language, how does the human brain work? I think that is sort of our ten years and beyond. I think what we're going to get over the next ten years is an of understanding of that language...

SM:            And applying it to other systems?

AJ:             Applying it to understand the basics of human computation and go from there. I think a lot would have to be done in vitro, which is why we are trying to prepare ourselves to do that so you can test a hypothesis.

SM:            Vision is the most heavily researched of the special senses. What is the Allen institute going to provide to that field that is not already known? People have studied retina, studied visual cortex, etc...

AJ:             Sure but if that's the case, explain to me how vision works. It's not a knock on all great work that's been done but one of the things we can do as the 800 pound gorilla is to approach this systemically. One of the challenges, as you said, great vision work has been done but one group will find one thing and one group find a different thing and this is probably due to non-standard conditions or something like that. We have the ability to do it all in one place, all in one shot and systemically march through all of the information transformations. Paul Allen and the institute is making the bet that that is going to be the path forward. You’re going to need to put all of that knowledge together so you can iterate on it and be able to test your hypotheses. Then, you can go back and gather data in iterative ways that will require big data sets. Not just recording from a handful of cells but all cells. Then, mapping them functionally, seeing who they're connected to and putting all of that data together and doing it over and over and over again. I think those are the kinds of things that we are pretty uniquely set up to do.

SM:            Especially since it would be very challenging for an academic lab to do this kind of work.

AJ:             It’s the kind of work where the scientific challenges are matched equally by the operational challenges. It may sound easy for people to scale but it’s not. It is exceptionally difficult.

SM:            I talked to Jim Berg last night who is running the slice electrophysiology core and I was very excited because this is the kind of work I do. So, hearing some details about how this is going to be set up at the institute was fascinating.

AJ:             Jim cracks me up because he’s one of those people where we are getting him to be a believer. He had that same sort of notion that electrophysiology is like an art. Everybody said that about in situ hybridization, ‘You can’t have a technician doing in situ, you need your best post-doc with tender, love and care to be able to do this.’ I would say that if that is the case, you are doing something wrong. You’re just not systematic enough about it. Any process can be automated and systematized.

SM:            I think that it is very important that the field does standardize conditions, especially for electrophysiology. In the literature, as you said with vision research, one lab finds one thing, one finds another and no one is publishing enough methods details so it can be easily replicated.

AJ:             Right. That’s why our thing is, we will put it all out there. You will see exactly what our protocols are, exactly what we did. You can have at the data, you can see what models we’ve run. The idea would be ultimately to have an online community that is there going back and forth saying, ‘What if we tried this parameter?’ Then we could run it and comment what our result was and it didn’t work so well, or it added to the improvements. Now, let’s add that and keep it.

SM:           That is why I think the white papers available on your website are great. It is the level of detail for methods that needs to be published but that publishers do not give you the room for. The work the institute is doing is excellent. Thank you for your time today.

If Paul Allen's bet is right, this is the place where the brain is going to be unlocked. I hope you all found my interview of Allan Jones to be as interesting as I did. For anyone interested in neuroscience and the brain, this organization is who you should be watching over the next decade and beyond.