Podcast: Giant virus genetics, human high­altitude adaptations, and quantifying the impact of
government­funded science
Podcast: Giant virus genetics, human high­altitude
adaptations, and quantifying the impact of government­
funded science
[email protected]
https://scribie.com/files/8dba890321944fcba6459339672291e7449bf64d
04/24/17 Page 1 of 9
Podcast: Giant virus genetics, human high­altitude adaptations, and quantifying the impact of
government­funded science
[music]
00:06 Sarah Crespi: Welcome to the Science Podcast for April 7, 2017. I'm Sarah Crespi. In this week's show, Danielle Li joins us to talk about the fruits of government funding for science by linking NIH grants to patent approvals. And David Grimm is here to give us the latest tips from our online news. And just a reminder that we are getting free transcripts from scribie.com this week. So be sure to check out the Science site, check out the transcripts, let us know what you think or we will find you through analytics. That's scribie.com audio transcription perfected, 75 cents a minute at 99% accuracy. The best deal on the internet for audio transcription. Visit them at scribie.com/sciencemag and let them know that we sent you.
00:54 SC: Now we have David Grimm, editor for our daily news site. He's here to talk about some recent online stories. First up, we have a story about giant viruses. These guys get a lot of press because their discovery in 2003 upset a lot of apple carts. Viruses are supposed to be tiny and have so few genes that they rely on the cellular machinery of their host to reproduce, but giant viruses are
bigger than some microbes and can have up to 2,500 genes. With so much more complexity than previously seen, some researches said we need a new domain of life. It's just not bacteria, archaea and eukaryotes, now we have those plus viruses, but this isn't settled by a long shot. This latest look
at giant viruses takes place at a sewage plant. Why Dave? 01:43 David Grimm: This is a sewage plant in Eastern Austria. Apparently, this plant that's famous
for having a lot of weird stuff in the water and lo and behold, there is a weird virus or at least by looking at DNA fragments in the water, researchers realize that there were a new family of giant viruses which they call Klosneuviruses. And as you alluded to Sarah, these guys have a lot of genes.
Your typical viruses may only have a small handful of genes. These guys seem to have a lot more than that. And what's really interesting about their genomes is they're a lot more cell like than the genomes of other viruses, which means they have a lot of the machinery that viruses aren't supposed
to have. Viruses because they rely on cells to replicate for them and to replicate them basically, they
only need a small handful of genes. But these viruses seem to have a whole host of genes from eating a whole bunch of proteins.
02:36 SC: Does this add to support for this fourth branch of life cause? 02:40 DG: Well, see, it seems like it would because it's like you got these very complex viruses, they must've evolved over millions, maybe billions of years to get to this point, but that's not what the researchers found. The researchers when they took a closer look at these genes realized that these genes are basically genes that the viruses stole from a bunch of other organisms. And so it's not these viruses evolved this complex machinery, they just grabbed it from a lot of other life forms 04/24/17 Page 2 of 9
Podcast: Giant virus genetics, human high­altitude adaptations, and quantifying the impact of
government­funded science
which really goes against this idea that these viruses represent this fourth domain of life, and in fact really gets back to this idea that viruses or kind of these sort of parasites that don't really even deserve to be called life forms in their own right.
03:21 SC: Poor viruses. This doesn't completely close the door on them as the fourth domain. Are there still holdouts out there in the research community? 03:28 DG: There are experts out there that disagree. For example, even humans, we've even stolen genes from Denisovans and others. And so it's still kind of, some people say it's still open to question about whether we can really shut the door on these guys being or not being a fourth domain of life.
03:44 SC: Now we have a story on high altitude adaptations. We've talked about how our bodies adapt to the high altitudes in short term. We did that recently on the podcast, but what about over the course of say 200 generations? Dave, take us to Tibet.
04:00 DG: We're here. We're on the Tibetan plateau which is the world's highest plateau, about 4,000 meters high. So this is not a friendly place to live. The UV rays can be very dangerous at those altitudes. There are oxygen levels up to 40% less than those at sea level, so the air is a lot harder to breathe. And yet, there's nearly 5 million people who live here. How did they do it? 04:24 SC: This new study takes a really broad look at the genomes of people who live in Tibet and that's what's really unique about the study is that they got so many people. How many people did they get and what kinds of things can you find once you get such a broad range of data? 04:40 DG: Well they looked at more than 3,000 Tibetans and more than 7,000 non Tibetans and they're really trying to make these comparisons; what gene alterations do the Tibetans have that the non Tibetans don't have? And we already knew about a couple and these couple seemed to be involved in boosting the body's ability to use oxygen, which makes a lot of sense if you're in an environment that has low oxygen. But the researchers are trying to see if are there any other adaptations that these Tibetans have made. And lo and behold, they found seven additional genes that seemed to be modified, that seemed to have evolved to allow these people to live in these areas.
And when I say evolved, the researchers where looking for evidence of selection pressure on these genes, something that would show that these genes where sort of changing over time.
05:25 SC: As you said, not all of these genes are just about low oxygen living. What are some of the other adaptations they were able to pull out? 05:31 DG: Well there was one gene called ADH7 and a variant that they found was associated with
higher weight and higher body mass index. And why that's important is because that could allow people in this region to maybe help store energy during the particularly lean times you would find on this very hardscrabble plateau. There's also another gene called MTHFR and a variant of this gene helps with the nutrient deficiency, it sort of boosts the production of the vitamin folate which is important for pregnancy and fertility. And actually really importantly about folate, it actually 04/24/17 Page 3 of 9
Podcast: Giant virus genetics, human high­altitude adaptations, and quantifying the impact of
government­funded science
breaks down when there's high levels of UV radiation. So you actually want a lot of it on this plateau where you have high levels of UV and you wanna be making extra folate. So they found things like this. They even found a gene that seems to boost the immune system. You can imagine if
you're living in a much more hardscrabble environment, you're gonna be susceptible, potentially, to a lot more diseases and you're gonna want a hardier immune system.
06:25 SC: This type of statistical analysis is just one step along the way, what's the next thing on the agenda for this research area? 06:33 DG: Yeah. Well, the next step is actually showing that these genes are actually having these functions. And these people mean it's a nice story to say like, "Well, this genes involved in this and it seems to be selected on." But the researchers actually haven't proven that any of these variants are
actually giving these benefits to people and that would be a nice thing to be able to show.
06:50 SC: Last up, we have a story on a new take on dark energy. We know the universe is expanding at an accelerating rate and the current explanation for this acceleration is called dark energy. But some physicists just want this mysterious stuff out of the equation. What do they propose as an alternative Dave? 07:10 DG: Well, they're actually proposing something a lot simpler. And the basic idea is this, the current way we... The current way cosmologists model the universe, how it evolved and how it continues to expand, is to treat the universe relatively simply. They assume, even though they know
this is not actually the case, that we have a smooth and homogenous universe. Now in actuality, there's a lot of messiness to the universe, there's mass and energy all over the place that can warp space time. And these inhomogeneities in the universe can actually cause a lot of feedback. They're not really factored into the current models. And that's what researchers did in this new study.
07:48 SC: Instead of taking this average density of the universe and saying, "Well, how does this expand?" They broke it into 1 million simulated mini universes. So, what happens with the expansion of the universe as a whole when we just add up all these mini universes that do take local
conditions into account? 08:10 DG: Well, what the researchers found is actually that this modeled universe seems to evolve and expand the same way as our real one does, all without the need for dark energy.
08:22 SC: Okay. Let's get the skeptics in here right now. What do people say about this idea? 08:27 DG: Well, others who have attempted similar modeling say that they found a much smaller effect of these inhomogeneities. And in fact, they think that this current study is really overestimating the effect that they're having. And if that's the case, then we still need something to explain why the universe continues to accelerate in its expansion, and that explanation would still take us back to dark energy.
08:52 SC: Alright Dave, we made it through. What else is on the site this week? 04/24/17 Page 4 of 9
Podcast: Giant virus genetics, human high­altitude adaptations, and quantifying the impact of
government­funded science
08:57 DG: Well Sarah, we've got a story about a new fast moving fish that is purely electronic. Also, a story about counting calories when you're a cannibal. [laughter] For ScienceInsider on our Policy Blog, we've got a story about why Norway is planning on exterminating large numbers of reindeer. And we also continue to follow the implication of US President Trump's proposed budget, the impact on science and how science agencies and scientists are reacting. Be sure to check out all these stories on the site.
09:34 SC: Thanks Dave.
09:34 DG: Thanks Sarah.
09:35 SC: David Grimm is the editor for our Online Daily News Site.
[music]
09:44 SC: Science funding is much on our minds these days. The US budget for studies may get a serious chop under the new administration. Now new research into the results of government funded research, how they affect innovation by linking NIH funding to patents shows they're a much stronger influence on innovation than previously thought. Danielle Li is here to talk about what her and her co­authors found out about this relationship. Hi Danielle.
10:13 Danielle Li: Hi Sarah. Thank you so much for having me on.
10:15 SC: First, let's talk about why this is important to study. Why look at the effects of NIH grants on patents? And next, how did you make these connections? 10:25 DL: So I suspect that many policymakers would say that we invest tax payer dollars into supporting science, not because we care about science per se, but because we think these public investments are going to someday be "useful". So in the life sciences, that means we fund life sciences research because we hope it's gonna lead to improvements in health. And yet, when we think about things that improve health, we typically don't think about scientific papers, we more often think about new medicines and other treatments that are actually often brought to market by private firms. So in order to assess the value of public investments on biomedical research, we really need to understand the linkages between those investments and private sector output, which is
measured not in publications, but in patents typically.
11:06 DL: So what we do is we start with close to the universe of NIH grants that were funded between 1980 and 2007. That's about 365,000 grants and we link them first to their publication output. So we can do this because when you get support from an NIH grant and you publish a paper, you often have a footnote they acknowledges that funding. And so once we have the grants linked up to the publications, we search through the text of all the US PTO, the US Patent Office Patents and look for patents that cite those publications. And that allows us to ask whether the NIH is producing research that serves as a foundation for commercial innovation later on.
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Podcast: Giant virus genetics, human high­altitude adaptations, and quantifying the impact of
government­funded science
11:43 SC: Okay. So why specifically focus on the NIH? 11:46 DL: The NIH is the world's largest funder of biomedical research by far. So you can't really understate how important it is for medical innovation and that's the first place to start.
11:55 SC: And what did you find? What percentage of the grants were linked with patents? 12:00 DL: So about 8% of grants are directly acknowledged by a patent. So basically, that means this is patenting by university researchers. But we also find that 30% of grants produce research, produce publications that are cited by private sector patents. So this is a private sector firm, reading academic research, typically done by different people, and using it to inform their own R&D efforts.
12:23 SC: Well, are the citations that you mention in patents, are they different from say a paper­to­
paper citation that would be published in a journal? 12:31 DL: Yes. So I think there are sort of two things to note. The first is that because papers are the primary output of academic research, paper­to­paper citations could just be scientists kind of talking to each other in an academic echo chamber. In order to see if this research is kind of playing
out in the "real world", you have to be able to link the papers to patents. The second is that oftentimes in papers, there's an incentive to cite everyone. You wanna name check all your referees,
you wanna make sure people like you, you wanna list everything that's kind of relevant.
13:01 DL: With patent­to­paper citations, typically you don't do that. You want to cite what you need to cover yourself, but not really much more than that because you don't wanna eat into the novelty of your ideas. So in that way, there isn't sort of this norm to cite a lot of papers. And typically, the average patent will cite maybe four or six publications rather than something like 40 for a paper. But at the same time, we don't really fully understand exactly what the content of academic citations... Patent citations are. There haven't been that many sort of large­scale studies that go through and look to see which papers are cited and what specific role that they play in that particular innovation. And so, that's something that we need to do more research on, in order to get a better sense of the content.
13:44 SC: And you found there was a lot more indirect connection than direct connection between grants and patents. Did that surprise you? Was there anything else that you weren't expecting to see that you did? 13:55 DL: So it didn't surprise me to find more indirect connections. I think that's because we fund the NIH not because we think that academics are gonna go off and produce patents, we typically fund it because we think they're going to produce scientific knowledge that might be useful to others down the line. So, that's precisely what the indirect measure looks at which is in some sense, the rationale for the funding itself. What I did find surprising was just how many connections there are, even among very basic science grants. So 30% is quite high and I think that does really refute the notion that publicly funded science is interesting, but ivory tower kind of otherwise 04/24/17 Page 6 of 9
Podcast: Giant virus genetics, human high­altitude adaptations, and quantifying the impact of
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commercially useless.
14:28 DL: And I should also note that we take a very simple linkage. So we're only crediting the NIH if it produces research that's cited by a patent, but we wouldn't credit it if it produces research that's cited by another piece of research that's cited by a patent, but it's still necessary and it doesn't count for many of the other important ways that public funding could impact medical innovation. So for instance, by supporting the training of graduate students or post docs who end up going into industry.
14:51 SC: Right. And speaking of basic research, we've been talking about very kind of applied science here, drugs or medical devices that are applying for a patent, but you didn't find this distinction between basic and applied research very useful when looking at this data. Why not? 15:09 DL: I think broadly what happens is that people just aren't very good at predicting what knowledge is gonna be useful, especially when we say useful. We're not talking about useful usually a year from now or like... We're usually talking about long lag times between research and applications into the decades. And so I think that when people fund a grant now and they say, "Oh, this thing looks like it's gonna be useful." What they're trying to do is they're trying to predict how useful it's gonna be down the... Like 30 years down the line and I think that ends up being really difficult to predict. And so things that are immediately applicable might not... That might be sort of like a scientific fad of the moment, whereas something that sounds more basic can end up being relevant in a lot of different dimensions and be more flexible in certain ways. So I think, I mean, sort of speaking of kind of what's useful and not useful, I think it just means we need to be very cautious when we think about how to allocate funding and in particular, how much to cut funding.
16:05 DL: What our research is saying is that it's not really possible, based on the current classifications that we use, to identify the set of grants that are more or less likely to be useful. So one thing you might do is you might wanna say, "Oh, we know that basic research isn't as useful, so
let's cut that and let's have the applied research." But I think our research is saying that you can't make that distinction, grants that don't look like they're likely to help cure cancer, so grants that don't even talk about cancer, they don't talk about humans, are just as often linked to drug candidates and other medical innovations as grants that on their face look more applied. So we can make these cuts, but I don't think it... I think we can't be too cavalier about our ability to sort of discern that.
16:42 SC: What would happen if research spending is seriously curtailed? Can we make a prediction about the impact that would have on patents? 16:51 DL: I think we can almost surely say that we're gonna lose out on some future medical innovations, but lose out on them in ways that we can't predict.
16:58 SC: Where will the money come from if the government cuts way back? Are we talking private sector or other countries? 04/24/17 Page 7 of 9
Podcast: Giant virus genetics, human high­altitude adaptations, and quantifying the impact of
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17:06 DL: So I think for the private sector, certainly not. This paper basically provides evidence that the NIH is funding research that's useful to many private firms and this knowledge that's in the public domain so anyone can use it, and it's what economists would call public good. Public goods are precisely what private sector firms aren't going to invest in. So the value of scientific knowledge, especially basic scientific knowledge to society, to the entire kind of collection of organizations and companies that might use that information is much higher than its value to any given firm. And so when given... When specific firms are sort of making investment decisions, they're trying to think about their own profits and their own private value, which means they're gonna under invest in these kinds of basic science, foundational knowledge.
17:47 DL: And so I think in that sense, cutting science funding and expecting the private sector to step in and fill up the difference is gonna be wishful. It's possible that other countries might step in here and that's I think an area of some amount of political contention. So if China for instance wants
to pay for that research and we benefit from the knowledge that Chinese research produces, in the same way that China has benefited from the fruits of NIH funding, I'm fine with that. But I suspect a lot of policymakers who care about American competitiveness might not be. And that's something
they're gonna to sort of take into account when making these budget allocation decisions.
18:20 SC: Danielle, thanks so much for talking with me.
18:23 DL: Thank you so much.
18:25 SC: Danielle Li and colleagues write about the relationship between patents and government funding in this week's issue of Science.
[music]
18:38 SC: And that concludes this edition of the Science Podcast. If you have any comments or suggestions for the show, write us at [email protected] or tweet to us @sciencemagazine. You can subscribe to the show on iTunes, Stitcher and many other apps, or listen to us on the Science site. The show was a production of Science Magazine. Geoffrey Cook composed the music.
I'm Sarah Crespi. On behalf of Science Magazine and its publisher, AAAS, thanks for joining us.
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Podcast: Giant virus genetics, human high­altitude adaptations, and quantifying the impact of
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