Shawn Douglas: Bio-origami: Building at the Nanoscale

March 30, 2015

Douglas: I want to start by channeling my former advisor, George Church, who always starts every talk with a conflict of interest slide and actually I don’t have, George has been doing this for 30 something years with his lab. I just started two years ago and I can only kind of put up an interest slide with only a few conflicts. So I’m going to just start with, you know, I have funding from these groups, I’ve worked on CAD software for DNA nanotechnology, so self assembling nanostructures built from DNA. I used, with collaboration with George Church, my other advisor, William Shih, and Ido Bachelet, we built these DNA nanobots that we see as a prototype for a targeted delivery of drugs to cancer cells or maybe any type of cell that you want to target.

I also think a lot about communication and how do we take these complex and potentially scary ideas and transmit them to people in a very clear and simple way. And so I like to employ diverse forms of media to do that. And actually growing up in this kind of syn-bio area, I was really inspired by people like Drew Endy and the whole syn-bio community, which also includes George and I was actually a mentor to the Harvard team for the iGEM Competition in 2006 and so a few years later, I realized I actually want to start my own iGEM, which I called BioMod and I think this year, we’re going to have our 1,000th student come through. And so it’s kind of like iGEM but rather than reprogramming nanomachines by rewriting their DNA or their genetic material, this is kind of like taking those building blocks and self-assembling nanostructures at the nanoscale. And now I started my lab in the CMT department at UCSF.

And so what I want to tell you about today is actually I want to start with this CLL, or this chronic lymphocytic leukemia that’s been in the news recently. Just to refresh your memory, this is a form of leukemia that is going to cause close to 5,000 deaths in the US this year and the interesting thing is actually this company, Pharmacyclics, has developed a drug that seems to work kind of less badly against CLL than other things that are available and AbbVie actually just purchased this molecule for $21 billion dollars but that’s actually not the price of the molecule; that $21 billion dollars is for half the molecule. J&J owns the other half of it. And so the true price is actually $42 billion dollars. So this is how much it costs I guess now to buy a drug that works for some small fraction of leukemia patients and this is of course FDA approved and it’s really been de-risked but it’s a bit crazy that this number is larger than the entire NIH budget by like $10 billion dollars. So that’s kind of all the basic research that’s going on, well not all of it, but like in the biomedical area in the country so everybody that’s doing all sorts of things and yet we’re investing this amount of money in these drugs.

And then another interesting trend which maybe fewer of you have heard about, well I think we realized that cancer immunotherapy is the future; it’s on the horizon. And in particular, these enzymes like IDO and TDO, which seem to suppress T-cells in the tumor micro-environment, so kind of shut off your immune system when you have cancer. This company, Flexus, has been developing a compound, it doesn’t have a generic name yet, but it has potential to inhibit these enzymes and basically allow your immune system to do its job around your tumor or around your cancer cells. And this company was just bought by BMS for $800 million dollars and this is actually I think much more interesting, right? This is pre-approval. These are like pre-clinical trials, right, and that’s just one molecule. So this is really high risk and we get even kind of, big numbers are going in this direction as well.

And so the connection that I want to make for you today is that all this work has really been done without the aid of real bio-CAD software and by real, I know that everybody here used computers to do this and they software and actually some quite impressive software but it’s not really real software in the way that the taxi companies that use software to route the taxi drivers five or ten years ago, they were not using kind of real software that we, like real transportation software that we have now, which requires GPS, satellites in space, and everybody to have a smartphone. But then you get to kind of make the real software that you want to write, in that case when those tools become available. And so what we can do with both biology and computer aided design is basically now 3D print anything that we want and actually, so there’s a nucleosome and there’s a 3D printout of this and it was actually easy for me to make the slide because I had exactly this slide on the first talk that I gave as a grad student ten years ago. And so I’ve been thinking about this for a while and what I want to suggest to you is that maybe CAD-nano could be the Zip2 or the Viaweb of this space, right? And it’s actually really hard to write this software. It’s really complicated. It’s not obvious how to do it. But I’m happy to say that actually I’ve just moved into an office in Genentech Hall, so I’m located right here and I’m actually surrounded by many dozens of dedicated, hardworking scientists who are all doing amazing basic research, and they also don’t yet have access to real CAD software and so what I’m planning to do is actually collaborate with them and help them write that software that I think is going to be transformative for science. And so if any of you in this audience, if this resonates, I would love to hear from you, I would love partners, collaborators, investors, whatever you think you might want to bring to the table, I would love to talk to you.

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