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.

Tuesday, January 24, 2012

RECOMB 2012 (Barcelona): one week left for early registration

 As I reported in an earlier post, RECOMB 2012 will be held in Barcelona and CRG's Bioinformatics and Genomics program is part of the local organizing committee.
 This post is a reminder that the deadline for early registration with a reduced rate is approaching and will expire 31st of January. More information here.

 See you there!

Friday, January 13, 2012

SMBE 2012 early registration deadline and symposium on orthology

 For those who don't know, the deadline for abstract to the next Society for Molecular Biology and Evolution meeting (Dublin 23-26 June) is approaching. I am co-organizing a workshop on orthology/paralogy and function in collaboration with Marc Robinson-Rechavi, Matthew Hahn, and Iddo Friedberg. Find below an invitation to submit to SMBE2012 and more info on this workshop.

 Hope we can meet in Dublin. 

Dear colleague,

We invite you to submit an abstract to the symposium "The complex relationship between orthology, paralogy, and function" to take place at the meeting of the Society for Molecular Biology and Evolution in Dublin (23rd-26th June, 2012).

The deadline to submit an abstract is the 27th of January 2012, for more details please visit:

Symposium "The complex relationship between orthology, paralogy, and function"

Orthology and paralogy have been central concepts in molecular evolution since the distinction was first proposed by Fitch in 1970. A long standing interpretation of this distinction has been that orthologs would be more similar in function than paralogs. Until recently, this interpretation was rarely tested, and in fact rarely explicitly articulated in a testable manner. Yet it has been widely used, from undergraduate teaching, to the practical application of orthology searches for genome annotation. There has been a recent increase of research, seeking to define and test this "ortholog conjecture". Notably, a recent paper (Nehrt et al. 2011, PloS Comput. Biol.) has reported a higher functional similarity of paralogs than of orthologs. This paper has generated much attention and debate, while at the same time recent work on orthologs has shown the vitality and importance of this field to a broad range of applications and questions. Our symposium will feature speakers addressing the fundamental relationships between molecular evolution and biological function, focusing especially on the role of orthology and paralogy in modulating such relationships.

Confirmed speakers: Eugene V. Koonin, Jianzhi Zhang

If you have any question regarding this symposium please do not hesitate to contact us:

Toni Gabaldon , Matthew Hahn , Iddo Friedberg, Marc Robinson-Rechavi

Tuesday, January 10, 2012

Diversity arises whenever, wherever, and at whatever rate is advantageous

 This is the conclusion from a recent paper from the group of Mark Pagel, in which they analyzed a dataset of body sizes of 3,185 extant mammals in a phylogenetic context.

  They modeled the evolution of body sizes across the  phylogeny using a Bayesian approach that allows evolutionary rates to vary at every branch. 

This provided them with an idea of where burst of evolution (big shifts in sizes) had occurred. The main idea was to contrast a long-held hypothesis that the early radiation of mammals was accompanied by increased rates of body-size variation (i.e burst in species diversity coincided with burst in body-size). This was explained by the idea that mammals expanded into a largely-unoccupied niche which provided opportunities for diversification. When the niche was filled up, diversification and evolutionary rates decreased. 

  Results from this team are in stark contrast with such view, since they see bursts at many different places of the phylogeny, which are uncoupled with the early radiation of mammals. 

 Reading this paper was very useful to me since, I was by then preparing the evaluation of a PhD thesis by Victor soria-Carrasco (see some related paper here) on, precisely mammalian, diversification. In the thesis they found that most mammalian orders showed a decline in the rate of diversification (in terms of forming of new species), which may seem compatible with the idea of a niche being filled-up. This highlights the importance of properly delimiting what evolutionary rates we refer to (sequence variation, variation in some morphological character, speciation rate...), since we may reach apparently different conclusions. Complicating the issue further, one does not know whether niche limitation may select for or against diversification. 
 In any case it is comforting to see that the increasing amount of genetic, phylogenetic, and other type of data, as well as sophisticated models, enable us to explore such interesting issues at the edge between evolution, phylogenetics and ecology. I was really impressed by the works mentioned.