Showing posts with label Science policy. Show all posts
Showing posts with label Science policy. Show all posts

Friday, June 1, 2012

Publicly available or not?


I have always had the naive understanding that databases such as GenBank were public, and that one was free to do research on data accessed from there, and eventually publish the results. However nothing seems to be as simple as that, since many of the genomes deposited in there have not been published yet. I have experienced myself and heard from many colleagues problematic situations regarding the use of genome data taken from public databases but yet to be published. Current guidelines are open to different interpretations, and different stakeholders (editors, reviewers, users, data producers) may have entirely different and conflicting views. With the current trend we will soon have more unpublished than published genomes in public databases, so I think it is worth re-assessing the policies. Here I share some views.

Policy guidelines regarding the use of genomic sequences prior to publication are available (see NHGRI rapid data release policy http://www.genome.gov/10506376), and set reasonable rules. For instance that data producers should deposit the data publicly and should produce a paper citable for the source of the data within a short period of time. This could precede a full genome paper in which a more througough analysis is produced. Users should not take the public data to publish an analysis focused on that genome. But this situation should not be prolonged too much. The underlying idea is to reserve the opportunity to describe the main characteristics and findings to the researchers that do the effort of sequencing, assembling, and annotating a genome, while ensuring that the data serves the advancement of science by allowing other groups to perform research on the genome data as soon as it is produced. However, there are many interpretations on what possible uses of the data should be allowed. Moreover, although indicative time-frames for the preferential exploitation of the data are given (e.g. 6 months), these are only indications. In the absence of clear-cut rules, the situation is calling for conflict. With the current flow of sequencing data, we will increasingly face the situation that data produced for public use and accessible through public databases is not associated to a paper and thus unclear whether its use should require permission. In such situations one may have different interpretations on existing rules, that of the leader of the sequencing project, that of the researcher that is accessing the data, that of the agency that financed the sequencing, and even that of the editors and reviewers of papers using available but unpublished data. Below I list some undesirable situations that highlights the contradictions of the current system. These situations are not hypothetical but rather correspond to real cases that I experienced or heard from colleagues

  • Users of public databases may unadvertedly download unpublished data, specially when they use they do this at large scales. After all they are using a public repository, and it is contradictory that public databases provide data that are not usable.
  • Most genome sequencing projects are financed using public money or from agencies that require that the data is made publicly available as soon as it is produced, but this leads to the situation above, making it difficult to sequencing project leaders to know what use is being made of their data.
  • Referees may specifically ask authors to use genomes that are in databases, or simply reject a paper because it does not use this or that “publicly available” genome in the comparative analyses. In addition referees or editors may ask for evidence of a specific permission to use unpublished data.
  • Authors willing to ask for the use of an unpublished genomes may be required to explain the exact use of the data, which expose their ideas to possible direct competitors.
  • Leaders of genome projects may feel in the right to ask for authorship in exchange of data that is available on public databases.
  • Leaders of genome projects may intentionally delay the publication of the genome paper to extend the period of preferential use. They may even decide to publish partial analysis before the genome paper.
  • Some unpublished genomes are in public databases for several years, and still different interpretations are possible of whether these data could be freely used.
  • Some genomes may never be published in the form of a genome paper, because they were sequenced with a very particular purpose.
In my opinion the current situation is too ambiguous, generates conflicts and ultimately jeopardizes the advance of science. We need clear rules, rather than guidelines, and I below propose four simple rules that would simplify the process.

  • Granting agencies and sequencing centers should specify a reasonable time-frame for preferential use (6-12 months) before the data is released. This should suffice for giving the upper hand to the research team that is doing the sequencing effort, but will also force them to focus on publish inga genome paper as soon as possible.
  • During this period, sequencing projects may announce the availability of the data for restricted use, through a specific repository that can be accessed only after a specific permission is granted. This will enable use of the data from time 0.
  • Data is released to the public repositories (at least in the form of bulk download) only after that period.
  • All data in public repositories should thus be free to be used for any purpose, regardless whether a genome paper is published.

Personally, for what the activity in my lab concerns I have taken the decision that we will use any data publicly deposited in GenBank for more than a year, for any purpose other than doing a “genome paper” (of course!). I think this is in perfect agreement with the NHGRI recommendations and will definitely save us time, and worries.

Saturday, March 10, 2012

Open Letter for Research in Spain

As you surely have heard, Spain is facing a serious crisis in the context of a globalized market-economy (yes, it used to be a time when economical crisis related to something more tangible, such as a serious drought or a plague, but now one can only blame abstract fluxes of financial speculations). The new government is preparing a new budget which is predicted to include the most dramatic cuts in our history. Researchers here, who have already been hit by previous cuts (see this letter), are now embracing for the worst. 


 In this context, an open letter has been put together by the Confederation of Spanish Scientific Societies, the Federation of Young Researchers and others. I recommend you to read it (some cited figures and data are very revealing), and if yo agree with it sign it, as I just did.

 Open letter for research in Spain.

Sunday, January 29, 2012

Interview with Nick Lane

As I reported in an earlier post, I had the opportunity to meet Nick Lane during the Spanish Evolutionary Society meeting. We had a very interesting discussion over a couple of beers around mitochondrial endosymbiosis and the origin of eukaryotes. Some days after the meeiing, Andrés Moya, the President of the society, suggested to me to interview him for the Society's  Bulletin eVolución.  You can find this interview translated to Spanish in the current issue of eVolution 7(1), however I think the interview might be of interest for a broader audience and thus I paste here the original, English version. 


TG- After your recent visit to Spain as an invited speaker to the III SESBE congress (Madrid, November 2011), what is your opinion about the field of Evolutionary Biology in Spain?
 
NL- Well, I thoroughly enjoyed the few talks I attended, but my Spanish is poor and I could hardly judge many of them; and unfortunately I missed much of the conference. But I liked the great range of themes that were being discussed. And in general I am impressed with a lot of evolutionary research going on in Spain. There is a tendency to consider comparative physiology in evolution more than there is in England, for example, and I find that a very insightful approach. One thing that has struck me over the years is that Spanish researchers are not cited as frequently as they ought to be. This does not reflect the quality of the research, but rather the US-dominated English-language citation bias.

TG- Your career has been quite unconventional. Can you summarize for our readers which have been the major steps in your career path?
 
NL- It sure has! I had a medical research background, and my PhD was on mitochondrial function and oxygen free radicals in transplanted organs. But I was getting nowhere with that, and couldn’t see a way of getting from there into what was really an interest for me: evolutionary biology. So I took to writing instead, for several independent agencies doing medical education for pharmaceutical companies. That was an eye opener, and I learnt to write clearly and quickly, but it was also a frustration. After quite a lot of hard work I finally got a contract to write Oxygen, which was initially conceived as a book about free radicals, mitochondria and medicine, but ended up reflecting my interests in evolutionary biology to a much greater extent. That was the beginning of a decade spent writing books on evolutionary biochemistry, drawing heavily on my background in bioenergetics but ranging widely over any material that interested me. It was fantastic fun but no way to make a living. And ultimately frustrating too, in that in writing on that scope, you can’t help but come up with new ideas, essentially a broad synthesis with gaps, that you sketch in with speculations, which can be reframed as testable hypotheses. That’s what drew me back into research – the frustrated desire to test some of these hypotheses.

3) Thus, you have been active as a science writer, a researcher, and now you seem to combine both aspects. Do these two tasks reinforce or rather interfere with each other?
 
Both. I think I’ve benefited tremendously as a researcher from the decade I spent thinking and writing. I now have a coherent set of hypotheses that are testable in one way or another – experimentally or by some kind of mathematical modeling, or just by empirical analysis of existing data. So I’m drawing heavily on this ‘credit’ now. At the same time it is hard to think synthetically or to write books while in research, there are so many demands on time. So on a daily basis, writing and research interfere with each other, but I think if you are able to focus on one or the other for periods then they can, and should, reinforce each other. The trick is to balance each so that they reinforce each other over time. I’m not sure I’ve mastered that trick yet, but it is my long term goal: for me, it is the best way to understand the most interesting evolutionary questions, and that is what I want to do.

4) In your view, where lies the main responsibility of communicating science to the general society (e.g scientists, funding agencies, scientific societies etc, science journalists)?
 
Good question. There is certainly a responsibility, but being responsible counts for nothing if nobody listens to what you have to say: as a writer, you must be interesting to be noticed at all. And society is rarely interested in responsible but boring views. So there is a balance that you have to wrestle with every sentence, between interest and accuracy. That’s another reason I’m happy to be back in research: to write accurately (in precise scientific language) is at least as much pleasure for me as to write interestingly. Frankly it is the questions themselves that interest me. I think that the real challenge in writing for the public is to find ways of phrasing questions in an interesting way, which draws attention to the problem, without sacrificing the accuracy. That is the ideal: responsible (boring) and interesting at the same time.

With respect to which group has the responsability, I don't think that one group alone can be considered responsible communicating science to general society. Each group can address different needs, and each has its own responsibility. Scientists are responsible for sculpting new ideas, for conveying the excitement and intellectual thrust of science. The best ideas in science are still driven by individuals with passion, insight and ingenuity, and there is nobody better to convey this intensity to the general reader, although it is rare. Journalists are responsible for balanced reporting, explaining ideas clearly and intelligibly, providing context for the reader, ideally some commentary from other scientists. It is unusual for journalists to drive the scientific agenda, but serious journalists have a broader perspective and can sometimes see things that scientists can't.

Scientific societies can provide very helpful consensus statements on difficult issues, from global warming to the effectiveness of chemotherapy. It's not really for them to give a sense of the cut and thrust of science, more the strength of the conclusions that emerge from the uncertainty.

Finally, funding agencies. In my view, funding agencies have a duty to explain to the public and to politicians that research is open-ended and unpredictable. Research that appears to have little immediate societal impact can have immense and unimagined benefits in the future. Most major scientific breakthroughs, with the greatest economic benefits, came from unexpected quarters, and could not have been anticipated by either the scientists themselves or the funders. This perspective is being lost in a political drive to justify spending by societal impact. As with so much, short-term political cycles are trumping long term good sense. It is up to funding agencies to explain why research should be funded on its own merits, without constant recourse to some hoped-for and probably illusory impact.      

 TG- In one of you articles, to commemorate the 150 anniversary of “The Origin of species”, you discuss about what Darwin would love to know about the origin of the eye if he were still alive. Darwin is granted for being the first who used a “tree of life” to describe the evolutionary relationships of species and their shared ancestry. What do you think he would love to now in this respect if he were still alive?
 
NL- Well I think he’d love what’s going on in microbial genomics. The picture that has emerged over the last couple of decades of lateral gene transfer and endosymbiosis in microbes is radically different to the idea of gene sequence divergence between populations. Having said that, I see all this as a juxtaposition to standard Neodarwinian population genetics. He would have loved that too, although it is old hat to us now; but given that Darwin knew nothing about genes, he would have been thrilled by the Neodarwinian synthesis, and what amounted to a genetic basis for a tree of life. All of this means that variation is more complex than any of us imagined; and in this sense, Darwin’s coyness on the mechanisms of variation was well placed: it really is wild and fascinating.

  TG- In one of your last books, you mention 10 major transitions in the evolution of life on earth. Which one of them is, according to you, the most enigmatic or difficult to explain?
 
NL- Consciousness, without a doubt. Frequently the origin of life and consciousness are put forward as the twin pinnacles, the two big unanswered questions in biology. I think we’re actually quite close to understanding the origin of life in conceptual terms, but I personally can’t understand consciousness well at all. I read a lot on the subject and came to the conclusion that nobody really does. We still can’t answer the simple question: how does the depolarization of a neuron give rise to a feeling or sensation of anything at all? They are two different languages, and we don’t seem to have any kind of Rosetta stone at the moment.

  TG- Some of these transitions seem to have happened only once in the history of life. If they were so advantageous why they have been restricted to a single lineage?
 
NL- I think each transition has to be taken on its own terms. These are tremendously difficult questions and you will find diametrically opposed answers to each question from very insightful researchers. The answers reflect temperament more than anything else. Christian de Duve actually wrote a book called ‘Singularities’, and my reading of that is that there isn’t a single answer that would apply to the origin of life, the origin of photosynthesis, the origin of the eukaryotic cell, the origin of animals, and the origin of consciousness. Obviously for some reason, each was improbable or it would have happened more than once (like eyes), but the reasons for improbability differ and are very dependent on context. In the case of eukaryotes, I would say their unique origin was based on an improbable endosymbiosis between prokaryotes, followed by a problematic reconciliation of selfish interests between two entities that had to live in intimate union. There were no advantages at all until they had come out of that tight bottleneck; on the contrary, all the advantages were with the bacteria that just kept on doing their bacterial thing. From that point of view, the difficult question is why did it happen at all?

  TG- Some of your research interests concern very ancient events (e.g. the origin of eukaryotes, of life itself). This is a field in which different hypotheses are difficult to prove right or wrong given the difficulty of direct experimentation. What are the criteria used by scientists in your area to reach a consensus over which is the support for the different  scenarios?
 
NL- There is a consensus on quite a lot: cell structure, behavior (phagocytosis or sex) genome sequences (albeit with disputes over methodology), the existence of introns in certain positions and so on. Where consensus breaks down is when different methods give different answers. That happens all the time. I’m actually focusing a lot of my attention now on the origin of life itself, because this seems to me to be more experimentally tractable: we can ask specific experimental questions that involve chemistry and thermodynamics, which are much more reliable than biology and genes, so although the event was the most ancient of all, it is not necessarily the most inaccessible. I think we’re making progress on many questions, but in the case of the origin of eukaryotes a lot of the evidence is oblique and disputable. The reasoning is often equivalent to historical reconstruction in that you need to weigh the evidence: there’s no doubt that it happened, and there’s plenty of evidence, it’s just that some of it is unreliable and some is irrelevant, so there’s plenty of scope for argument still.

  TG- In this respect. What is the impact on your field of the ever-growing number of genome sequencing projects?. What are the species or environments you would like to be sampled in order to help answering important questions in the origin and evolution of complex life.
 
NL- Genome sequences have made a tremendous difference, the only trouble being that they tend to reflect pathogens or industrially interesting bugs, rather than those most relevant to, say, the origin of eukaryotes. I would love to see more genomes from anoxic or anaerobic deep ocean environments, or the deep hot biosphere. I’m especially interested in two questions: the variation in eukaryotic genomes, and the variation in mitochondrial genomes. There is a brilliant and bold hypothesis that the origin of the eukaryotic cell was an endosymbiosis between two prokaryotes, an archaeon host cell and an alpha-proteobacterium (or somesuch). The prediction is that all eukaryotes should have mitochondria or organelles derived from them like hydrogenosomes or mitosomes; and that in terms of mitochondrial genomes we should find more overlap between bacterial metabolic capacity and metabolically versatile mitochondria. This is a wonderful prediction because it is so easy to falsify, and yet all the genome sequencing so far has failed to disprove it. The places most likely to disprove – or prove – it are precisely those anaerobic environments that have been undersampled so far.

TG- Carbon has always been considered a hallmark of life on earth, but life (elsewhere) based on other molecules (e.g Silicium) has been speculated. You seem to favor the idea that oxygen was the molecule that enabled the appearance of complex life on earth, could you speculate on the theoretical possibility of other molecules playing a similar role in other forms of life.
 
NL- I think it is most likely that life elsewhere would be constrained by much the same issues that constrain life here. I doubt very much that there will be silicon based life forms. There are two important properties of carbon: it is much better than silicon at organic chemistry; but equally important, it is available in the form of a gaseous oxide, a Lego brick if you will. There are no gaseous silicon oxides, only sand, which is vast and unwieldy in comparison. You can’t build a house on sand and you can’t build an organism from sand. My feeling is that not only is carbon especially useful, it is also more abundant than silicon. Likewise, water is more abundant than methane and a much better solvent (you can’t dissolve carbon chains of more than about 5 carbon atoms in methane). And so on. On the basis of usefulness and abundance, I would argue that life would mostly be carbon based. I would go further to argue that it is likely to require proton gradients over membranes for thermodynamic reasons. When I say that oxygen is necessary for complex life, I mean large active animals. I doubt that anything else could do the job: nothing else could accumulate to the appropriate level in an atmosphere and at the same time be sufficiently reactive to provide the power needed. So I’d say that in terms of their broad biochemistry, alien life won’t be all that different. In terms of morphology or the specifics of their biochemistry, they could be very different, of course.

  TG- Are you already working on your next book?, can you advance something on what is it about?
 
NL- I’m not writing yet, but I do have a contract… and it will be about everything I have talked about here. The origin of complex life, and why it was a unique event here on Earth.

Thursday, November 3, 2011

Sad news from CIPF: the rise and fall of the "flagship" of valencian research

For those who don't know. I am originally from Valencia. There, one of the deepest traditions and the main festivity are the so-called "Falles", which in part consist of building huge temporary cardboard sculptures which are exposed for little more than a week and then burned in a big fire. For some people is hard to understand how so much time and money is invested in something that is then left to the flames.

Apparently, something similar is happening with a research centre!!!

 The "Centro de Investigación Príncipe Felipe" was created in 2005 by the local Valencian government with the idea of making it the "flagship" of research in the region. It came with a strong investment from the regional and central governments and soon attracted many scientists. I was one of the seduced scientists, who originally from Valencia, and at that time in the Netherlands was enthusiastic about a move aiming to put biomedical research in Valencia at the forefront.



 Five years after its creation, the cuts started. Crisis had hit Spanish economy and many local governments had big debts, particularly that of Valencia who has been famous for investing in huge events such as the America's cup or the formula 1 competition. When things went complicated, research was seen as one of the most superfluous thing in which a government could invest, and thus cuts were announced. This year the centre is firing 40% of the personnel, including PhD candidates at the middle of their PhD. I guess many of the remaining researchers will leave this downsized center for a better live elsewhere. The flagship is now sinking, "burned" after so much investment and efforts, the comparison to our "Falles" is unavoidable.



The whole story is reported by Nature and by many articles in the Spanish press. As Juli Peretó reports, the local government is letting CIPF fall, while keeping investing on other type of events, such as an international Golf tournament in Castelló, or increasing the funds for a motorbike circuit. This is most ironic, and deeply sad.

 I just wish the best for my many ex-colleagues that are still at CIPF and hope this is not the kind of science policy that the future government of Spain (according to polls is likely to be the same conservative party that is now governing in Valencia) is planning.