A Nobel for GFP

Congrats to Roger Tsien for winning a share of this year’s Nobel Prize in chemistry. Tsien was honored for unraveling the mechanisms of green fluorescent protein (GFP), and more importantly for developing a dizzying array of GFP variants that work more efficiently and emit different colors of light.

Fluorescent Proteins from the Tsien Lab

Fluorescent Proteins from the Tsien Lab

It’s particularly exciting to see scientists rewarded for developing tools that transform the way we do our work. It’s hard to overstate the importance of GFP and its cousins for modern biology. They have revolutionized methods for the imaging of living materials – allowing us to follow the dynamics of individual cells and even molecules, and leading to countless new discoveries.

But all that aside – fluorescent proteins are just f***ing cool. They were originally isolated from jellyfish by Osamu Shimomura (one of the other two scientists who won the prize with Tsien) – part of the mechanism that gives jellyfish their etherial glow. When Roger Chalfie (who was the 3rd prize recipient) and Doug Prasher (who unfortunately was not one of the chosen 3) first heard about GFP they didn’t just marvel at the mysteries of nature, they immediately thought of ways they could use it in the lab. It’s an inherrently wonderful – and I think not generally appreciated by the public – aspect of biological research that so much of what we do in the lab on a day by day basis epxloits the cool molecules and processes that evolution has invented.

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Commercial Ascendance of Open Access – Springer buys BioMed Central

The long-rumored sale of BioMed Central – the first true open access publisher – has finally been consumated.

I am sure some will lament the sale of the innovative BMC to a publishing behemoth, but this is an unambiguously good thing for open access. This proves what we at PLoS have been saying since we launched – that open access is not just a crusade to do what’s right and best for science – it’s also good business.

Springer’s CEO Derk Haank sums it up:

This acquisition reinforces the fact that we see open access publishing as a sustainable part of STM publishing, and not an ideological crusade.

Back when the open access movement started, a lot of people in the academic publishing world were hostile to PLoS, BMC and open access in general. Most of their objections fell flat – but the one that stuck in the minds of most scientists was the idea that open access might be a nice idea, but it was not a sustainable business model. But Haank – who was then the head of Elsevier – adopted a more practical attitude. He said to me at a meeting once (and I paraphrase):

We make a lot of money selling subscriptions to our journals. We’re not just going to stop. But if the scientific community wants open access and can prove it is good business, we will gears and embrace open access publishing. And we’ll make a lot of money publishing open access journals.

Well, with this transaction it’s clear that we’ve succeeded. Springer sees open access as the future of scientific publishing. While PLoS now has a bigger and richer open access competitor than we had before, a major psychological obstacle for authors has been overcome, and I expect we’ll see more and more commercial and non-profit publishers move towards open access in the near future.

(see also Peter Subers comments on the deal).

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Tij to head HHMI

HHMI just announced that my Berkeley colleague Robert Tjian (Tij to everyone) is going to be the new president of HHMI.

As I am now an employee of HHMI, I was quite interested in the search to replace Tom Cech – and I couldn’t be more thrilled with the result. Tij is a fantastic scientist at the height of his powers and has myriad attributes that will make him a great leader: He has an eye for quality research; he does not suffer fools; he is creative scientifically and organizationally; and above all else he is wise.

I’m glad to see he’ll be keeping his lab at Berkeley. As someone who works in a field (metazoan trancription regulation) he played a leading role in creating (something for which he and Bob Roeder deserve a Nobel Prize), my lab benefits directly from his lab’s presence.

It will be interesting to see how Tij will deal with open access publishing. HHMI has taken several important steps in promoting open access to the work its investigators produce. And while Tij’s lab favors Nature and Cell rather than PLoS Biology, he’s been supportive of my efforts with PLoS.  I don’t expect open access to be a major issue for him (though I will try :-)), I am sure he’ll appreciate the importance of open access in furthering HHMI’s scientific and educational mission.

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Crayons on a Kindle?

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Well, at least someone asked about evolution

Barack Obama’s answers to 18 science questions posed by Nature were just published (John McCain declined to answer, although Nature answered many of these questions from his public statements).

These questions were much more pointed and science-related than the ones posed by Science Debate 2008. For example, they asked:

Many scientists are bitter about what they see as years of political interference in scientific decisions at federal agencies. What would you do to help restore impartial scientific advice in government?

to which Obama gave a very strong answer. And Nature corrected the obvious omission from Science Debate by asking about evolution:

Do you believe that evolution by means of natural selection is a sufficient explanation for the variety and complexity of life on Earth? Should intelligent design, or some derivative thereof, be taught in science class in public schools?

Obama: I believe in evolution, and I support the strong consensus of the scientific community that evolution is scientifically validated. I do not believe it is helpful to our students to cloud discussions of science with non-scientific theories like intelligent design that are not subject to experimental scrutiny.

McCain said last year, in a Republican primary debate: “I believe in evolution. But I also believe, when I hike the Grand Canyon and see it at sunset, that the hand of God is there also.” In 2005, he told the Arizona Daily Star that he thought “all points of view” should be available to students studying the origins of humanity. But the next year a Colorado paper reported him saying that such viewpoints should not be taught in science class.

All pretty predictable, but I think Obama gets to the heart of the matter by saying that teaching ID clouds students’ minds. In the debate about evolution and ID that much of the focus is placed on which of these theories is right (which is of course an essential part of the debate). But I’ve always been surprised at how little attention is paid to the effects that teaching made-up crap in science class, and the accompanying implication that science is  – at least on this issue – a fraud, has on the way students think about science in general.

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Contest: If you could ask a single science question at the real presidential debate

What would it be?

I am so disappointed in the much hyped Science Debate 2008. As I said before, I read the questions before the answers and found them to be really lame. And the answers to these overly general and often unsciency questions were predictably uninteresting. The candidates support science! Yay! But did anyone really learn anything about their policies we didn’t already know?

The real problem is that these questions were clearly not answered by the candidates – but rather by some scientifically literate advisor. And so we don’t get to answer what to me is really are the most important questions:

1) Do they understand science? Not in the textbook sense, but rather in the sense that they understand how it works and the ways that their policies actually can encourage/discourage science and scientists.

2) Do they believe in science and will they believe the things that scientists tell them?

I don’t think there’s any way to answer these questions by reading their science advisors’ online answers. The only way to do it is to ask a pointed question about science to the candidates at one of their debates.

So, with a bit over a week to go – if you could pose ONE science question to Obama and McCain at a debate, what would it be? Send me your suggestions.

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Science Debate 2008 questions are really lame

Most of you have probably heard about Science Debate 2008, an effort “to restore science and innovation to America’s political dialogue” by having the candidates discuss pressing issues in science. Since Obama and McCain won’t have an actual debate, the organizers of this effort have posed 14 questions (culled from 3,400 submissions from the community).

Obviously this is a well intentioned effort. And I’ll have more to say about Obama’s and McCain’s answers once I read them. But I wanted to look at the questions before I looked at the answers. And my first impression is, “Man, these are lame questions.” I have several problems:

1. The questions are all obvious and overly general. They basically call on the candidates to say “Rah Rah Science!” And yes, I understand that, sadly, in this climate it’s important for presidential candidates to actually stand up and say “I support Science.” But still, I wish they’d asked them more difficult and more specific questions.

2. Many of the questions aren’t really about science. For example:

Climate Change.  The Earth’s climate is changing and there is concern about the potentially adverse effects of these changes on life on the planet. What is your position on the following measures that have been proposed to address global climate change—a cap-and-trade system, a carbon tax, increased fuel-economy standards, or research?  Are there other policies you would support?

Whether the president supports a carbon tax, cap-and-trade or increase fuel-economy is a political question about which science is neutral. Now scientists may have an opinion on this. But Science only tells us that the planet is warming and that we need to do something to reduce carbon emissions now. It says nothing about how we should do that. To conflate these two issues is a huge mistake that only serves to foster the idea that science somehow favors different political solutions to our problems, which in turn undermines politician’s and the public’s sense that science is neutral.

3. They avoid controversy and controversial questions.

Why pussyfoot around the important question of the day? Where’s “Do you believe that the release of CO2 from human activity is dangerously warming the planet?”

And hello, evolution anyone? Can there be a more important topic to ask about? Not because evolution is so important relative to other aspects of science. But rather because the assault on evolution is a direct assault on science. And our failure to defend evolution is one of the major reasons Americans do not believe in science.

Here are some questions I would have asked just off the top of my head:

1. Much has been written about declining public understanding of and belief in science. Why do you think this has happened, and what would you do about it?

2. Do you believe in evolution, and what are you going to do as president to make sure that it is taught in schools. For example, would you support legislation requiring that schools receiving federal funding teach evolution, including human evolution, in their high school biology classes?

3. What do you think is the appropriate balance between basic and applied research, and how would this be reflected in your budgets and agency appointments?

4. Fewer and fewer of our brightest young students are going in to careers in science. Why do you think this is and what will you do about it?

5. Many of the important questions you will face as president will involve or be potentially informed by science. What will you do to insure that you receive unbiased and unvarnished advice from scientists studying the issues of the day?

6. The reception of many important scientific issues – from evolution to stem cells to global warming to human genetics – has become highly partisan. What will you do as president to have policy decisions made on the basis of a commonly agreed-upon set of scientific facts?

7. Human genetic research is advancing at breakneck speeds and having an increasingly important impact on the diagnosis, treatment and prevention of disease. As genetics increasingly enters daily life, there have been calls to place limits on research and on the kinds of genetic knowledge that are available to the public. What would you do as president to make sure that we effectively confront the ethical issues raised by human genetics without slowing down its progress.

8. To promote public faith in genetic testing, would you agree to have your genome sequenced and made freely available online?

(These last two are issues that are perhaps of more interest to me than the general scientific community – but if I’m getting a chance to grill the next president…):

9. The Bayh-Dole act is very popular in Washington, but many scientists (ok, at least me) are concerned that it has overly blurred the line between academic and commercial research, that it has created needless obstacles to the exchange of research material amongst scientists and that it inhibits rather than promotes the commercialization of government-sponsored research.

10. Along the same line, what steps would you take to ensure that the public has access to and benefits from the results of Federally funded research?

UPDATE: Dr. Free-Ride felt the same way. She has her own list of great questions for the candidates.

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Congressional testimony on NIH Public Access repeal effort

The House Judiciary Committee held hearings today on the newly introduced “Fair Copyright and Research Works Act (H.R. 6845),” which is a publisher-promoted effort to repeal the NIH Public Access Policy.

Peter Suber’s Open Access News discusses the hearings here and here. Karen Rustad at Little Green River has a great post about the hearing.

I’m still reading and watching the testimony from the good guys: NIH Director Elias Zerhouni and SPARC’s Heather Joseph, and the bad guys: GWU Law Professor Ralph Oman and the APS’s Marty Frank. I’ll have more to say (and if the video is good, maybe some attack ads) later.

Now I disagree with Marty Frank on almost everything: he’s short-sighted, often misleading and places the interests of his journal over the broader scientific good. However, I understand why he was invited to testify – he has become the chief spokesman (some would say apologist) for the anti-open access publishers.

But I have to say when I saw the list of witnesses, my first reaction was “Who the hell is Ralph Oman?” OK, I’m not a copyright lawyer, and maybe he’s well-known in those circles. But as far as I can tell he’s never been interested in science publishing.

So, of course, I googled him. And here’s the top hit. A list of campaign contributions he’s made. These lists are fascinating. Oman is clearly no Democrat. He gave money to Bill Frist, Henry Hyde and even Katherine Harris when she ran for Congress!! So it’s curious that he also gave $500 to John Conyers, head of the House Judiciary Committee who is holding this hearing. Hmm. I wonder why he was invited…. Are our representatives really this cheap?

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Identifying individuals in "anonymous" genetic studies

Most people who participate in genetic studies do so with the expectation that their participation – and more importantly their phenotype – will be anonymous. To preserve this anonymity, raw data (individual’s genotypes and phenotypes) are not made publicly available. However, to enable validation and further research, pooled data – the average allele frequencies in cases and controls – have been made available through public databases like dbGaP.

But a really cool new paper in PLoS Genetics demonstrates that if you know an individual’s genotype you can actually figure out whether they participated in a particular study. This may seem counterintuitive, but if you think about it for a sec it makes sense. An individual’s inclusion in a dataset leaves a fingerprint – in terms of shifting the allele frequencies in the direction of their particular genotype. Obviously, if you only have a small number of genotypes this is meaningless. But if you have 500,000+, as most modern genotyping platforms do, the authors show that you can essentially just count up the number of times the pool’s allele frequencies diverge from the expected allele frequencies in the direction of an individual’s genotype. If this number is significantly higher than expected by chance, it is very likely that the individual was part of the pool.

A cute trick, no? But are there any practical implication? Clearly yes. As more and more people get whole genome genotyping from companies like 23andMe, Navigenics or DecodeMe (full disclosure – I am an advisor to 23andMe), and as many people start to share their genotypes – either intentionally or unintentionally – it would be theoretically possible for someone to take that person’s genotype and scan all existing genome-wide association studies to see if they participated. And if they haven’t had their genotype done, and someone else REALLY wanted to know if they participated in a study, that someone could steal a piece of hair and pay to have it genotyped. (It’s not discussed in the paper, but I bet you could use a sibling, parent or even perhaps a more distant relative and get a similar answer – although presumably with less certainty).

Surprisingly, the paper has received little notice in the popular press. Bit it’s created quite a stir in the human genetics community. The National Institutes of Health immediately shut off public access to its genome-wide association data, and urged others with similar data to follow suit. This is a rather shocking reversal for a community that had been pushing the open availability of these data.

It’s really rather amazing that no one thought about this before. There are a lot of very bright people involved in human genetic mapping, yet none of them realized that individuals could be relatively easily “unpooled”. I bet there are a lot of quantitative geneticists kicking themselves. And I hope some of them are working on a way around this.

Interestingly, the authors seem more interested in the forensics angle here. They offer up their method as a way to tell if a particular individual was in a room, handled a weapon, or anything else where a lot of different people might have left their DNA in the same place. You can see where this is going – get an individual’s genotype and you can trace them all over the world.

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Legislative threat to NIH public access policy

Two Democratic congressmen (Howard Berman or CA-28 and John Conyers, Jr. of MI-14) are planning to introduce a bill into the US House of Representatives that would effectively kill the NIH Public Access Policy. They are responding to complaints (and donations) from the American Association of Publishers (the lobbying wing of the journal publishers).

The bill – Owellianly titled “Fair Copyright in Research Works Act” – would make it illegal for any federal agency to require grantees to transfer to the federal government any aspect of the rights given to authors under copyright. Oddly, this legislation follows on the highly dubious assertion by the AAP that the current NIH policy violates copyright law. But by attempting to modify copyright law to make this transfer illegal, the AAP is saying that it currently is legal.

My sources tell me that this bill is unlikely to pass, but supporters of open access and the NIH public access policy should write the their representatives, especially is they are on the House Judiciary Committee. Hearings are apparently scheduled for September 11th.

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