Nature Podcast

This is a transcript of the 10th September edition of the weekly Nature Podcast. Audio files for the current show and archive episodes can be accessed from the Nature Podcast index page (, which also contains details on how to subscribe to the Nature Podcast for FREE, and has troubleshooting top-tips. Send us your feedback to


The Nature Podcast is sponsored by GE Healthcare, taking the industrial standard to the next level with AKTA avant.

End Advertisement

Geoff Brumfiel: This week, the genes behind the Irish potato famine.

Sophien Kamoun: It is certainly important to know your enemy and in this case understand how the genes of the blight are organized in the genome.

Kerri Smith: And was the great oxidation event actually more of a gradual increase, we re-think the history of oxygen in our atmosphere.

Robert Frei: The question is now how far back do we see this pulses of oxygen and that has vast implication for explaining the evolution of life forms at that time and also climatic implications.

Kerri Smith: This is the Nature Podcast. I'm Kerri Smith.

Geoff Brumfiel: And I'm Geoff Brumfiel. If it were up to me which genomes to sequence, I think a potato disease would go pretty low on the list, behind rhubarb may be, but Phytophthora infestans or blight as it's more commonly called is one of the most important crop diseases in human history. The blight was directly responsible for the Irish famine of 1800s which killed up to a million people and led millions more to flee to America. In this week's Nature researchers revealed the genetic sequence of the blight and I called up Sophien Kamoun at the Sainsbury Laboratory at Norwich to learn more. Nature advance online publication 9 September 2009

Sophien Kamoun: The organism that causes the blight is not a fungus, many people call it a fungus, but it's actually water mold, we call it an oomycete and it's related to diatoms, brown algae, it's even related to the malaria pathogen.

Geoff Brumfiel: I mean, where did the blight come from?

Sophien Kamoun: Well, the blight naturally occurs in Mexico on wild potatoes and the idea that the pathogen has somehow gotten out of Mexico and invaded agricultural fields of potato and then spread throughout the world and this is what happened in the 1840s, this is how the pathogen made it out of Mexico into North America and then to Europe and that's how it reached the Island of the Diamond. And these days it is all over the world, wherever potato is grown basically have they blight. The new strains of the blight that are emerging, it's actually all over the news these days, it's raging right now in the US on tomatoes and there's also new strain in the UK now, in Britain, that's called Blue 13 and it's actually very nasty and very destructive. It took off in 2007 and it's all over the place these days.

Geoff Brumfiel: And this is still causing a lot of problems for farmers?

Sophien Kamoun: Oh! Yes, yes, it is still very important. It's essentially a world wide problem wherever we have the right conditions, right weather conditions, which is usually cool and humid, you tend to have blight, so it's a problem in the western world and commercial and organic potato farming, but is also a problem in developing countries, for example, China, India which are the major producers of potato too have the blight.

Geoff Brumfiel: So you've gone and sequenced the genome of the blight, is that right?

Sophien Kamoun: Yeah, that's correct, yeah.

Geoff Brumfiel: What did you find in the sequence that was interesting to you?

Sophien Kamoun: Well, the genome is very unusual. It's very large, it's several folds larger than relatives of the potato blight and what was really interesting about the genome is this very unusual organisation it's over three-quarters of the genome is essentially non-coding sequences, so it doesn't contain coding genes and it's containing repetitive DNA and this repetitive DNA is not randomly distributed across the genome, we have two different regions, so that's why we think that the genomes suggest that we have a two-speed genome.

Geoff Brumfiel: So what do you mean by a two-speed genome?

Sophien Kamoun: Well, what I mean by that is that we have two different organizations in the genome, we have a region of the genome, regions of the genome that have very densely packed genes and other regions where the genes are very sparsely distributed that are full of these repeats.

Geoff Brumfiel: And I mean would that serve any function for the potato blight or I mean, is there any reason for it to be that way or?

Sophien Kamoun: Yes, what's interesting, what we found in those regions, the genes that are important for the blight to cause disease, they carry these genes, we call effector genes which are genes that perturb plants essentially and help the pathogen cause disease. And so we think that these genes are located there because the blight then can generate more viability in these genes and it's better able to adapt to resistant potatoes.

Geoff Brumfiel: That's interesting. So, I mean do you think ultimately though that despite this sort of tool for adapting to overcome resistance, you might be able to beat the blight, now that you have this genome.

Sophien Kamoun: Well, I wouldn't go as far as saying the genome will help us immediately defeat the blight, but it's certainly important to know your enemy and in this case, understand how the genes of the blight are organized in the genome and the genes that we want to target are these effector genes, we want to target disease resistance against those genes and know how they're organized and how they're distributed would help us be more effective at picking the right targets that we can breed potatoes again.

Geoff Brumfiel: You mentioned earlier that the blight is related to things like malaria, I mean, is there any chance that some of your research here could be applied to the malaria genome.

Sophien Kamoun: I mean, not directly, but years ago, actually couple of years ago, we and collaborators at Northwestern University in Chicago, we discovered that some of these effector proteins of the blight that are delivered inside plant cells use a very similar mechanisms for delivery inside these host cells as the malaria parasite. So there are actually some similarities in the way different parasites can infect and can colonize and establish themselves on their host. Whether that will lead to a common target that's too speculative at the moment, but there are some similarities in the way these pathogen infect the host.

Geoff Brumfiel: That was Sophien Kamoun

Kerri Smith: Coming up shortly, we learn more about a process that happens in your body one million times a second, but before that it seems that oxygen may have appeared in our atmosphere, not with a bang, but in a series of whimpers. Here's Charlotte Stoddart.

Charlotte Stoddart: Two and a half billion years ago, the Earth was a very different place, life consisted of simple single celled organisms and the atmosphere contained almost no oxygen at all. Then in two major leaps, oxygen levels increased, kick starting the emergence of multicellular life. Until now, evidence for the rise of oxygen has mostly come from sulphur isotopes found in sediments. But Robert Frei from the University of Copenhagen and colleagues have found a new trace of atmospheric oxygen, the heavy metal chromium and it tells a rather more complex story. The team identified pulses of oxygenation suggesting a much more gradual rise in O2 than previously thought. Nature 461, 250–253 (10 September 2009)

Robert Frei: Everybody is interested to understand how the connection is between life, climate and the rock records that we have, so it's very important for us to know how the Earth's atmosphere actually developed and the reasons for oxygenation events.

Charlotte Stoddart: We've known for a quite a long time now that there were two major oxidation events, tell us about those.

Robert Frei: The first one of these happened around 2.5 billion years ago and it's generally referred to as the Great Oxidation Event and that's the first time where we see from other situations that has been studied that there must have been an increase of oxygen compared to the entire history before. And then there was the second rise of oxygen around 700 to 500 million years ago and this is an even more dramatic event and some research even go on and say that the evolution of soft bodied multicellular life formed as actually been triggered by this massive event around that time.

Charlotte Stoddart: So this is a very important story for the history of our planet and of life on Earth, do your new findings change the picture at all.

Robert Frei: Our new studies they actually don't change the basic picture, what our results show is that the story is not as simplistic because our results actually show in both events that there are pulses of oxygenation and again pulses where the oxygen levels in the atmosphere fall again. So we have actually fluctuations in these oxygen levels, so it is not a monotonous increase of oxygen throughout the Earth's history. Our major finding is also that we see such pulses of oxygen before the Great Oxygenation event around 2.5 billion years ago.

Charlotte Stoddart: Where does your evidence come from, what kind of fieldwork did you do.

Robert Frei: Our evidence comes from the study of iron-rich rocks that are precipitating from the seawater and we have done is basically collecting a multitude of such rocks that records the entire Earth history as best as we can. We have also gone ourselves into the field for example in Uruguay where there's such a profile where you can sample banded iron formations that are directly datable. We know how old they are and this is of course an important issue that we know how old these sediments are when we do our study.

Charlotte Stoddart: And it's the chromium inside these iron formation that you are interested in, isn't it?

Robert Frei: Yes, that's correct, it's the chromium which we think essentially comes from the weathering of the continents, a lot of oxygen will enhance the weathering on the continent and this chromium is basically flushed via rivers into the seawater where it's then caught into this rocks that formed within the seawater.

Charlotte Stoddart: So you are using the chromium as a measure of how much oxygen there is in the atmosphere.

Robert Frei: Yes exactly.

Charlotte Stoddart: Going back to your findings then, you talk about these pulses in atmospheric oxygen that you have identified and in particular you've found that there was a dip in oxygen just after the Great Oxidation Event. Was that surprising?

Robert Frei: Yes, this is one of the findings that again shows the importance of, in detail looking at the evolution of oxygen because in one of the profiles that we have studied in detail which is in Canada we have actually seen that the first part of these profiles are not showing any signs of an oxygenated atmosphere and that means that we went back to a state in the oxygen levels that look similar to the state it was before the Great Oxygenation Event. And only in the progression of these deposition of these rocks there we can see that oxygen in the atmosphere becomes again enriched which we see in our chromium isotopes in this profile. So this is one example where we actually can unravel the system in detail the story of oxygen over a short period of time.

Charlotte Stoddart: So this changes the way we think about the increase in oxygen in our atmosphere. What kind of reaction are you expecting to four findings?

Robert Frei: I am very sure that there will be some debate particularly about the findings that before the actual Great Oxidation Event that there were pulses of oxygenation available. The question is now how far back do we see these pulses of oxygen and that has vast implications for explaining the evolution of life forms at that time and also climatic implications in terms of whether we can correlate such pulses, for example, with glacier deposits in the past and so on, so I am pretty sure that these findings they will create a lot of discussion about that issue.

Kerri Smith: Robert Frei talking to Charlotte.


Geoff Brumfiel: In just a minute, Mark Peplow will be rushing in from the newsroom to talk about what's hot off the presses this week.

Kerri Smith: But first every minute in your body a million cells quietly kill themselves but don't be alarmed this is supposed to happen. This cell suicide helps bodies get rid of cells that are old, misbehaving or have become infected. Biologists call it apoptosis and they know that during this process, dying cells are sought out and ingested by garbage-eating cells called phagocytes, but one of our standing puzzle is how the phagocytes know where these ailing cells are. Now Kodi Ravichandran at the University of Virginia and his team revealed a nature of this come get me signal. Here's Kodi. Nature 461, 282–286 (10 September 2009)

Kodi S. Ravichandran: We clear roughly about 200 billion cells everyday, every minute we have this conversation we would have turned over roughly about one million cells. The cells commit suicide in the interest of the whole organism that there are many processes that lead to such suicide such as we make a lot more excess cells in the body than we need, that are cells that are older which you want to replace, that is another possibility, the beauty of that process is that the cells, during the process of death also alert the neighboring cells such that the dying cells are quietly and without any damage to the neighboring cells remove quickly.

Kerri Smith: Now obviously because this is such an important process and because so much of it goes on, there's been quite a lot of research on apoptosis, hasn't there? But what question did you want to address in this new paper?

Kodi S. Ravichandran: The system is so well designed that the dying cells are recognized as being in the process of death very quickly but professional phagocytes, these are cells that can eat other cells basically, but what has been unclear is how do the dying cells sort of advertise their ongoing death to the professional phagocytes, how they then be recruited to come in and clear these cells that are in the process of death.

Kerri Smith: So in other words you know how do they signal please come and kill me to these phagocytes.

Kodi S. Ravichandran: In fact we call these as find me signal, or come get me signal.

Kerri Smith: What were your hints as to what these signals might be, before doing your experiments in this paper?

Kodi S. Ravichandran: The first signal we knew was the fact that even in tissues where we had deliberately induced death, the dying cells, even though we lost many of the cells they were extremely quickly cleared and second was that we could take the supernatants or like kind of what the dying cells release and add them in certain tissue culture tubes, they would attract the professional phagocytes, that was the first clue that there must be an attraction signal that must be released by the dying cells.

Kerri Smith: And so you did a couple of different experiments one in cells and one in mice, in live animals, to try and find out a little bit more about what these signalling molecules consisted of didn't you and what did you find?

Kodi S. Ravichandran: So what we have found is that a nucleotides which are small molecules that are released by the dying cells called ATP and UTP, these are the nucleotides. When these dying cells release them, they are attractive to the monocytes both in vitro and then we inject the supernatants in a model in vivo within a day you actually attract a number of about three to five folds more monocytes that are specifically recruited to those sites.

Kerri Smith: So it's nucleotides then, I mean, my sort of previous experience of nucleotides is as the building blocks of DNA but are these different signals to that.

Kodi S. Ravichandran: That's an excellent question, so the nucleotides are used in many many different processes, for energy we constantly use ATP for every movement or every cells energy metabolism is using an ATP as a source of energy but the sites in energy processes, the ATP and UTP are used for many enzymatic reactions in the cell but it is normally stored within the cell and it is only released in a very regulated way. Plus we also have mechanisms, there are a few nucleotides that may be released are quickly sopped up but the apoptotic cells seem to release them in sufficient quantities that in turn set up a gradient to attract these professional phagocytes.

Kerri Smith: I suppose there might be circumstances in which we might want to kill cells when they themselves don't want to be killed, for example in the case of cancer cells that just keep growing. Do you think this result feeds into perhaps treatments for cancer down the line. Does that make it easier or harder or possible to use this information to kill cells?

Kodi S. Ravichandran: So there are a number of steps that are relevant here, so you could kill a cell by another process called necrosis which releases a lot of nucleotides or this process of apoptosis which is a very regulated process that releases much smaller amounts of nucleotides. The difference between them is that at a very high level of release you actually induce what's known as inflammation. The advantage of releasing a very small amount is actually that it's sort of immunologically quiet in the sense the macrophages sort of eat their meal but they don't talk about it. In the context of tumour cells what we could envision is that inducing a regulated release of nucleotides as process of apoptosis would actually be beneficial to remove them, but immunologically quietly.

Kerri Smith: Kodi Ravichandran of the University of Virginia. And now the news, news editor Mark Peplow has joined us in the studio. Hi Mark.

Mark Peplow: Hello.

Kerri Smith: Now, first the future of space flight funded by NASA.

Mark Peplow: Yeah, that's right and as we speak a panel of experts is pleased to deliver quite a grim assessment of NASA's human space-flight programme to Barack Obama.

Kerri Smith: Now the current goals were set by Bush who was quite famously pro-space, I suppose and pro-NASA, what did he set out for NASA to achieve.

Mark Peplow: Well, he set out a grand vision for space exploration which included building a moon base as a prelude used to sending people on to Mars.

Kerri Smith: So a service station basically on the way.

Mark Peplow: That' right. So this was a really big vision idea and NASA was charged with developing what it needed to do there and this all fitted in with the fact that it needed a replacement to the space shuttle. The international space station was due to be de-orbited, burned up in the atmosphere by 2016 so that project was coming to an end. So it was really looking beyond the shuttle in the ISS to go back out beyond low Earth orbit and start getting out into outer space again.

Kerri Smith: Now big ambitions, pricey ambitions though as well. How does Obama's view of space differ from Bush's?

Mark Peplow: Well, from what we are seeing so far it looks like he is not keen to punch up the cash or at least not quite as much as will be required to do this. So for example NASA's exploration programme known as constellation under Obama's 2010 budget request, it would receive about 6 billion US dollars a year which is a billion less than Bush had asked for in the preceding budget and is actually several billion less than what it had been slated in previous budgets. We talked to a guy called Scott Pace who is the Director of the Space Policy Institute in Washington and he points out, you know, the Bush budget stressed the system because it costs, but the Obama budget if it is left as is, it just breaks it, you simply can't achieve this Bush vision for space under Obama's budget.

Kerri Smith: So what can we do with this money that Obama is funnelling into space research then, what does the new report say?

Mark Peplow: Well, you can do lots of things but what they have done is funnelled down about 3000 different permutations and just a handful for Obama to actually have a look at and he gets to pick one of this essentially. Basically under a lot of the scenarios it looks like Ares 1 which was the rocket that was specifically been developed to carry crew astronauts over to the moon and I would say it's already at 6 billion dollars invested in it, that would just be scrapped they just wouldn't do that at all. Another option is to say ISS, international space station we are going to keep you going for a bit longer, keep you going till 2010 and try and do more stuff in space that way. One of the other options is that there might in a longer term be possibility to go to sort of some deep space flight options not necessarily making a moon base but may be being able to send astronauts out to asteroids, other flybys of the moon, maybe flybys of Mars, things like that but those are the longer term options. In the shorter term it looks like keep the ISS going might be something that happens and the Ares programme might well be for the chop.

Kerri Smith: I mean there are going to be a lot of rather disappointed unhappy scientists as a result of these cut backs, but do you got a sense of which of these options is the scientific community's favourite?

Mark Peplow: Well, it's difficult to say, I think broadly the message that seems to come over from the scientific community time and time again is that they do believe in human space exploration and that is something worth investing in and Steve Squires has been very clear on this point, Steve Squires is in charge of the two Mars Rovers that are still trundling around after years on Mars doing science up there and you know, you would expect him to be a big fan of robotic exploration and he is, but he points out that you know what takes Rovers weeks and weeks and weeks you can do in just a few hours if you actually had a real-life geologist up there. So I think broadly the community's message is if you can do it, if you can find a way to do it, just push human exploration.

Kerri Smith: Right, well moving on I think to our second story and this is a follow-up to a report that we had two weeks ago on toxicity testing.

Mark Peplow: Yeah that's right, basically as of a conference in Rome last week, the World Congress on Alternatives and Animal Use in the Life Sciences, Europe has unveiled the largest ever injection of money into developing alternatives to animals for toxicity testing. Now this follows upon the report that you mentioned from a couple of weeks ago which we have in Nature, which was reassessing just how many animals and how much it would cost to do this sort of toxicity testing that has been mandated under relatively recent European legislation.

Kerri Smith: So what's behind this new research programme then, this is a big chunk of funding for a new research programme into animal alternatives?

Mark Peplow: Yeah, it's 50 million Euros. It's split two ways, the European Commission has provided half and the other half has come from the cosmetics industry and it's really driven by two things and one is the REACH legislation, I won't spell out the acronym but basically it says that all the chemicals that are on the European market have to be much better tested than they have been up until now. Now one of the consequences of that is that largely it is going to require you to use quite a lot of animals and actually testing the safety of these chemicals. But there is a parallel piece of legislation as well a 2003 amendment to European cosmetics Directive that says you must phase out testing of all cosmetic ingredients on animals by 2013. So you've got these two sort of slightly competing bits of legislation, you need to be safer but you can't test them on animals after 2013 and in fact the phase out has already begun because it's kind of graduated. So the solution to this supposedly is this European project to try and come up with non-animal ways of testing toxicity and that's not just the topical toxicity, you know, you drop stuff on skin or whatever, but systemic toxicity where you are going to be using things like human stem cells, cells scaffolds to stimulate human organs at much better computer models for toxicology things like that.

Kerri Smith: Finally then, previous weeks on the news chat we have been keeping you up-to-date with the latest on swine flu and there is a further piece of news on that this week, Mark what is in there?

Mark Peplow: Yeah that's just in actually, the first conformed case of a death ultimately caused by the H1N1 virus has been in the Galapagos Island.

Kerri Smith: Tell us a bit more about this case, who was this?

Mark Peplow: So this is a 29-year-old man who died of a heart attack last Friday and that resulted from complications caused by the viral infection of the swine flu. Now since the middle of August when the first confirmed case of swine flu came up in the Galapagos, the island has been really on sort of high alerts, lots of bars and shops shut down, schools everything like that and it's actually been having a major impact on the number of people going to the island as tourists have been put off travelling there.

Kerri Smith: Now that doesn't necessarily sound like a bad thing, there does seem to be this decline in the tourist industry, could that not have an upside for the wildlife on the island?

Mark Peplow: Well yeah, it's certainly a possibility, there has been really a massive increase over the last decade about 15 years in the number of tourists visiting the Galapagos and it is kind of WHO they do contribute some money which ultimately goes into constellation projects but also it does increase the human foot print on the islands effectively and one of the interesting things is that there has been recent research showing that malaria carrying mosquitoes are interested into the Archipelago on both the twice daily flights to the islands. We spoke to one of the researchers behind that bit of science Simon Goodman at the University of Leeds and he says that, you know, now very starkly seeing the outbreak of swine flu on the island, just proves that what was previously thought was this as a beautiful, pristine geographically isolated Galapagos that isolation is completely eroded now.

Kerri Smith: And presumably it was the tourists that brought swine flu to the island in the first place.

Mark Peplow: Don't know for sure, it seems by for the most likely explanation but at the moment authorities are still looking into exactly how swine flu arrived there and what the sources are and obviously keeping tabs of people moving in and out the island as well.

Kerri Smith: Now people is now thing, but could this virus spread to other species?

Mark Peplow: Well, so far the infectivity is only been confirmed for pigs, humans, ferrets, and macaques, all mammals. It is possible that it could spread to another mammal but certainly if you look at the species that dominate the Galapagos wildlife it tends to be reptiles and birds and as Kristien Van Reeth an animal virologist that I spoke to at Ghent University he told this to me, I have never heard of reptiles with influenza, so it's likely that most of this, most iconic wildlife on the Galapagos shouldn't be troubled by swine flu.

Kerri Smith: So ferret flu yes, frog flu not really, good stuff, thanks Mark. More to be found at

Geoff Brumfiel: And you might also want to check out the opinion section of Nature this week which has two specials on data sharing and science, who should own the data you produce, how can we encourage the culture of sharing find out more at

Kerri Smith: That's all from us, hope you enjoyed the show and you come back next week, when we will have ice sheets, sex chromosomes and droplets in electric fields, I am Kerri Smith.

Geoff Brumfiel: And I am Geoff Brumfiel, the Rhubarb genome, ring it on...


The Nature podcast is produced by Nature publishing group and sponsored by GE Healthcare, inspired to accelerate your process development with AKTATM avant.

End Advertisement