Nature Podcast

This is a transcript of the 25th July 2013 edition of the weekly Nature Podcast. Audio files for the current show and archive episodes can be accessed from the Nature Podcast index page (http://www.nature.com/nature/podcast), which also contains details on how to subscribe to the Nature Podcast for FREE, and has troubleshooting top-tips. Send us your feedback to mailto:podcast@nature.com.

Kerri Smith: Coming up, beware the next hospital superbugs.

Maryn McKenna: Infectious disease has been having this resurgence and sneaking back up on us and we are now really behind the curve.

Thea Cunningham: And the palm oil genome gives up its secrets.

Robert Martienssen: Readers can tell immediately what type of tree will come from each seed that they plant, currently they can't do that.

Kerri Smith: Plus flatworms re-grow their heads even when they're chopped into tiny pieces, but how. This is the Nature Podcast. I'm Kerri Smith.

Thea Cunningham: And I'm Thea Cunningham.

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Thea Cunningham: These days if you get tonsillitis or an infected cut, it's no big deal, just pop down to the doctors and get antibiotics to sort it out right. Sadly it's not that simple, ever since the discovery of penicillin, the first antibiotic, bacteria have been fighting back evolving resistance to the drugs we create to kill them. Most of us have heard of MRSA but there are other much more sinister threats lurking around the corner. These bacteria, called CREs that's C-R-E, are resistant to a category of antibiotics called carbapenems, most powerful antibiotics on the shelf. This week Maryn McKenna has written a feature about the bacterial threat and Noah Baker called her to ask what makes their resistance such a problem. Nature 499, 394–396 (25 July 2013)

Maryn McKenna: Carbapenems are really kind of the last resort drugs for very serious infections. The kind that occur when someone is in intensive care or critical care. It used to be that these kinds of infections which can be bladder infections or lung infections or infections of the blood responded to this last ditch, quite small category of drugs, the carbapenems they were four of them and over the past 10 years, resistance to carbapenems has been emerging. It actually emerged first here in the United States and has been moving across the globe and now is in dozens of countries and it's extremely serious because after the carbapenems, there are almost no drugs left.

Noah Baker: And give us an idea of how serious being infected by these CREs is?

Maryn McKenna: The numbers are really quite striking. In March, Thomas Frieden, who's a Physician and the Director of the US Center for Disease Control and Prevention gave a press conference, releasing a report, in which he said, "we have a very serious problem". He called them nightmare bacteria and Sally Davies who is your Chief Medical Officer in the UK, at the same time called this problem catastrophic and as serious as terrorism. The report that Davies released estimated that for as simple an operation as a hip replacement, one out of every six might die. In the United States, the CDCs reports that up to one half of people who get these CRE infections die as a result of them. Both of those numbers are really extraordinary.

Noah Baker: And you mention that MRSA has become quite famous but these more serious versions of antibiotic resistance were first identified 15 years ago and yet people still don't seem to know about them, why is that?

Maryn McKenna: These bugs were perfectly positioned to evade notice in a number of ways, first because the surveillance systems that were set up to look for them were kind of partial, second because the lab techniques that were used to detect them didn't really anticipate these bugs and third because medicine didn't really do as good a job as it might have of getting the word out about this new form of resistance. So, all of these things combined meant that this problem really burgeoned and literally moved around the world before we quite knew what was going on.

Noah Baker: This sounds like a really serious problem, so one would assume that the scientific community is responding by piling loads of money and loads of funding and loads of research in to trying to fix it, is that the case?

Maryn McKenna: Unfortunately that's not the case, it turns out that in almost all countries, prevention research is really hard to fund. We're much better at doing research on behalf of identifying things and then attempting to treat or cure things. Right now, it's also very hard to stimulate research to treat such things because we tend to rely on pharmaceutical manufacturers to do the research that supports new drugs and a number of years ago, pharmaceutical manufacturers figured out that it's not really in their best bottom-line interest to research new antibiotics because unlike most categories of drugs, antibiotics actually cure the thing that they're aimed at. So you don't need to take antibiotics for very long and as soon as an antibiotic is out on the market, resistance such as the CRE resistance that we're talking about now, arises and makes your drug not useful anymore. So, pharmaceutical companies would rather make something like insulin or statins or viagra, those are reliable earners for their bottom-line, antibiotics are not.

Noah Baker: Have scientists just become a bit lax when it comes to researching infectious disease?

Maryn McKenna: You know it's so interesting, here in the US they argue that our war on cancer came about because we decided that we were sort of done with infectious disease and CREs as our story says only really appeared about 15 years ago. So while we've been watching cancer and attempting to fight cancer in this very elaborate and technological and pretty successful way, infectious disease has been having this resurgence and sneaking back up on us and we're now really behind the curve. Alexander Fleming, the discoverer of penicillin, in his Nobel Prize acceptance speech predicted that antibiotic resistance was going to overtake us and said that we would have to keep an eye out and we just didn't take his word seriously and it's well past time that we did.

Thea Cunningham: Journalist, Maryn McKenna talking to Noah. Coming up in the research highlights, birds that navigate by smell and electronic skin that glows when it's touched and we'll be finding out if having the palm oil genome can make the crop more sustainable.

Kerri Smith: But first, "If you can keep your head when all about you are losing theirs" That line is from Rudyard Kipling's famous poem IF and for all we know, he might have been talking about flatworms. Why? Because many of these little creatures can lose their heads and grow a whole new one back. They're not the only animals that can but they are the case study for three papers published this week to try and find out how they do it. Nature editor Henry Gee joins me in the studio to give us a heads-up on what's new. Henry, first off, introduce us to regeneration in nature. Nature (2013); Nature (2013); Nature (2013); Nature (2013)

Henry Gee: The planarian flatworm is a lovely example. You can find them in any pond, they're cute little animals, they're about half a centimetre long, I've got quite a lot in the bottom of a water barrel at home and the thing about them, many pond flatworms, is you can slice their heads off, you can slice them into bits, and they will completely regenerate any body part that is lost. They're proverbially well known for this. And so people have been looking at these flatworms for a long time to try and work out how they regenerate and even Thomas Hunt Morgan, one of the fathers of genetics, he started work on regeneration of these creatures.

Kerri Smith: Now these three new papers have compared species of planarian, of flatworm, that they can re-grow themselves to varying degrees.

Henry Gee: That's correct. There are lots and lots of different kinds of planarian and the three different papers that we're publishing, each one looks at a different species of planarian that is not quite as good at regenerating as your average pond planarian. In particular they're not so good at regenerating their heads depending on how far back you cut the worm in half. If you cut just the worm's head off, it will regenerate a new head, but if you cut it half way down or towards the back it'll be much less good at that until if you just expect it to grow a head from bit of a tail, it won't do it where your average pond planarian will do so. And what the various researchers have been doing is trying to find the molecular pathways that promotes, or in this case inhibits, head re-growth.

Kerri Smith: We're talking about this like it's, you know, just a matter of course. I suppose planarian it is but this is pretty amazing isn't it to re-grow an entire head made of quite different molecules and cells from a, you know, half a tail?

Henry Gee: Yes, it is, a lots of animals can regenerate. I have an axolotl at home called Squirty Benson Wilberforce III and axolotls are known to regenerate limbs and tails but they don't know to regenerate their heads and other animals, crabs and lobsters and things will regenerate limbs if lost. Human beings, we do regenerate a little bit, we heal wounds, and we grow finger nails and so on but wouldn't it be nice if you were an amputee to be able to re-grow a lost limb and I think that's kind of a Holy Grail. One doesn't promise anything and this is completely science fiction, but the strategy that the various laboratories working on these flatworms provide to start because by comparing flatworms with varying degrees of regenerative capability you can see what it is in flatworms exactly that is responsible and in that they show that there's a particular molecular signalling pathway which inhibits the re-growth of heads and when that is blocked heads will re-grow and this particular signalling pathway common to all life it's known as the Wnt signalling pathway and lots of creatures have it.

Kerri Smith: And indeed in some of these worms that have a limited regenerative capacity, blocking this crucial pathway led to their heads being able to regenerate, where they couldn't before.

Henry Gee: That's correct. This pathway had a control over the degree of regeneration in these worms. I suppose you have to have some control otherwise you might grow sort of extra heads where you don't need them or something.

Kerri Smith: So, what can we learn then about perhaps how mammals might regenerate bits of themselves from these worms?

Henry Gee: What we can learn from these worms, there is a particular molecular pathway, the Wnt signalling pathway that is involved in regeneration, the control of regeneration. So, people looking in humans might try and see how this pathway is involved in wound healing or various kinds of regeneration or in activity of stem cells in a sense, these are related, because when you cut the head of a flatworm the cells go into a kind of new mode of programming, they kind of become stem cells. So, looking at these lowly pond life might give us a clue to some quite important insights into human regenerative medicine eventually.

Kerri Smith: Henry Gee thanks for dropping in. You can read all those papers by Rink et al., Umesono et al., and Newmark and colleagues and their accompanying News and View article at http://www.nature.com/nature.

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Thea Cunningham: Open your kitchen cupboard and chances are it'll contain products made using palm oil. From bread to biscuits, the slimy stuff accounts for nearly 50% of edible oil worldwide. You'll also find it in soaps and shampoos and it's used to make biofuels. So, it's a very important ingredient. Palm oil is produced by the fleshy orange fruits of the oil palm tree. In Indonesia and Malaysia, oil palm plantations produce millions of tons of oil per year. But to make room for all the palms, rainforests have been destroyed, endangering native wildlife. The pressure is on to make palm oil more sustainable. This week a team of researchers have something that might help breeders do just that. They've sequenced the genome of the oil palm Elaeis guineensis, the biggest source of palm oil. I called author Robert Martienssen from Cold Spring Harbor Laboratory in New York to ask what they found. Nature (2013)

Robert Martienssen: We were able to identify essentially all of the genes involved in oil biosynthesis and these of course are very important for the quality of the vegetable oils that are produced by oil palm but in addition we were able to link the sequence to the genetic map and consequently we were able to identify important genes in things like the development of the fruit and the seed from which the oil is produced. These genes are really important in controlling the yield, in other words how much oil you get per fruit or per tree.

Thea Cunningham: And one of the genes you've mention is in a separate paper and it's called the SHELL gene.

Robert Martienssen: That's right. The most high yielding trees were actually heterozygous. That's to say one parent contained one form of the SHELL gene and the other parent contained another form of SHELL gene and only when you combine those two forms did you get something called hybrid vigour, in which the offspring produced more oil per fruit than either parent. So, oil palm breeders rely on the SHELL gene to produce optimal hybrids, so after they finish breeding the parents, they cross them together to produce the hybrid oil palm trees that are homozygous for the SHELL gene, usually don't make any fruit at all. They're sterile.

Thea Cunningham: And these mutations determine what kind of fruits the oil palm produces.

Robert Martienssen: That's exactly right. So, if you have the mutation and you're homozygous, if you produce fruit at all, it does not have a shell and that has all sorts of problems. If you have an oil palm tree, that is homozygous for the wild type or normal form of the gene, then you have lots of fruit, but it has very thick shell within the fruit, and that clearly reduces yield. So, like Goldilocks the perfect combination is a tree that has both forms of the gene and now you have a thin shell which means that you have lots of fruit and that fruit is much high yielding.

Thea Cunningham: How do you think these results will help oil palm breeders?

Robert Martienssen: The most important immediate result will be that breeders can tell immediately what type of tree will come from each seed that they plant. Currently they can't do that, and of course it takes between 6 and 10 years for an oil palm tree to produce fruit after you plant it. That means you have to wait a very long time and occupy an awful lot of space in your plantation before you know what tree actually is. And so we'll be able to immediately provide a genetic test that will tell the breeder what sort of phenotype they can expect. In the long term, it will affect yield of oil plantations throughout Southeast Asia and we're really hoping that that will, you know, increase productivity and potentially reduce land use which is a major goal.

Thea Cunningham: There's a lot of concern over how oil palm plantations are affecting the environment. If these results can tell breeders how they might, you know, access more yield, is that going to increase the amount of plantations there are?

Robert Martienssen: I think that's an excellent question and I think, you know, biology can only do so much. Policy has to be an important component of the equation. What we're hoping is that by increasing productivity, this will make oil palm more sustainable actually not so much for the big companies, but for small holders who actually provide a lot of the oil palm that's produced by Malaysia. Now a big company, you know, will have huge plantations in many different places and so they're much less likely to suffer from disastrous yields one year, but the small holder really can and these small holders, you know, have less reproducible yields and that is one of the driving forces in other places in southeast Asia for exploitation of rain forest and so if we can stabilize yield, I think that's going to help.

Thea Cunningham: Malaysia is the second largest producer of palm oil in the world behind Indonesia. The country needs to make sure its oil is sustainable for its industry and its environment. That's according to fellow author, Ravigadevi Sambanthamurthi, Director of the Biotechnology and Breeding Program at the Malaysian palm oil board.

Ravigadevi Sambanthamurthi: The reason we started this project was so that we can increase the productivity and not open up land. One of the major constraints in Malaysia as far as the oil palm industry goes is that we do not have enough land and labour is another problem. So for these two reasons, we wanted to increase the productivity of the oil palm and this discovery is just a start and it's going to be a catalyst we hope for further discoveries of genes for other traits and we really hope to put the oil palm industry on a really, really sustainable footing and decrease the rain forest footprint of this very, very productive crop.

Thea Cunningham: That was Ravigadevi Sambanthamurthi from the Malaysian Palm Oil Board and before her Robert Martienssen. Find both papers online at http://www.nature.com/nature. The genome paper is free to access.

Kerri Smith: The news chat isn't far off and Editor Eric Hand will be joining us on the online from Washington DC but before that it's time for the research highlights read by Charlotte Stoddart

Charlotte Stoddart: Some seabirds can find their way home by smell. The Cory shearwater nests in the remote rocky islands in the open ocean with very few landmarks. Researchers in Italy captured shearwaters from the Azores Islands in the north Atlantic. They washed the nostrils of eight of them to wipe out their sense of smell and glued magnets to the heads of eight more to disrupt any magnetic sense. They left eight shearwaters alone as controls. The birds were then released hundreds of kilometres away from their island home. Within a few days, the control birds and nearly all of the magnet-headed birds had reached home, but the birds with no sense of smell got lost. Only two of them returned home before the breeding season was over. Read more about that in the Journal of Experimental Biology. Nature 499, 382 (25 July 2013)Pregnant ladies have it, people who've been out in the sun have it. They glow and now a team at the University of California have made a flexible electronic skin patch that glows when touched. The researchers made the small patch of e-skin by layering transistors, pressure sensors and light-emitting diodes on top of a thin piece of plastic. The diodes are switched on locally where the surface is touched. The harder someone presses on the skin, the brighter it lights up. The team says the technology could be used to give robots a better sense of touch and maybe make interactive wallpaper that doubles as a touch screen. Find that paper in Nature Materials. Nature 499, 382 (25 July 2013)

Thea Cunningham: Finally this week, it's time for the news chat and on the line from Washington D.C. is US news editor Eric Hand and the first story you've got for us today is about a meeting at the end of this month in Minneapolis.

Eric Hand: That's right; it's a meeting of high energy physicists. These are all the people that dream up the world's big physics machines, things like Large Hadrons Collider at CERN things like the Tevatron at Fermiab and now it's time for them to get together again and think about what's next.

Thea Cunningham: And I'm guessing it's a chance for America to think about its aspirations for that field.

Eric Hand: That's right. The center of gravity for this world has shifted to CERN with the Large Hadron Collider and in fact, Fermilab which is the center of US high energy physics had to shut down its big machine, the Tevatron, a couple of years ago. So this meeting is all about looking ahead to what's next for US high energy physics.

Thea Cunningham: What kind of cases are delegates going to be putting forward?

Eric Hand: Well, one interesting idea that appears to be getting a lot of enthusiasm is to bring back the cyclotron. Cyclotrons are 80-year-old accelerators but they can be built really cheaply and in a small space and a few physicists have an idea to use these to generate a really powerful neutrino beam.

Thea Cunningham: So, you mentioned these cyclotrons are around 80 years old. Are you surprised that this technology is, you know, returning?

Eric Hand: Yeah and I think other physicists are as well. Cyclotrons have long since ceded ground to a different type of machine called the synchrotron which is more of an accelerator ring. Cyclotrons accelerate particles that spiral out from the center of the device out to a ring. The key here though is for the particular type of neutrino research that they're pursuing, they need not so much high energy particles but a very intense or powerful beam of neutrinos and cyclotrons still are very good at doing that.

Thea Cunningham: And what about cost, is this likely to be an expensive project for the US.

Eric Hand: Well, there is an existing proposal for Fermilab that is quite expensive. It's on the order of 800 million dollars. This upstart proposal to use cyclotrons would be significantly cheaper, may be on the order of 400 million dollars.

Thea Cunningham: And who else apart reside from those in the states is likely to be watching the outcome?

Eric Hand: Well, everyone really, I mean, this is a grassroots exercise that takes place every so often and the results from this meeting will filter up into various advisory panels both within the US Department of Energy and then elsewhere in the world, Japan and Europe, you know, two other big players in high-energy physics were sure to be, they will be watching as well.

Thea Cunningham: Okay, and the next story we have is about stem cells.

Eric Hand: A very particular type of stem cell that may not in fact even exist.

Thea Cunningham: That sounds very intriguing, can you tell us more.

Eric Hand: Well, for the past few years, some researchers have been pushing very hard to make claims about a certain class of stem cell like cells called VSEL or VSELs, Very Small Embryonic-like Cells and they've been claiming all sorts of therapeutic value for these cells which are less than six micrometers or so and they've even started companies, and have started human trials, but some new evidence in new papers this week showed that these cells may not even exist.

Thea Cunningham: What reason did scientists have to doubt their existence?

Eric Hand: Well, the evidence has been coming from a few different directions. This week a researcher at Stanford University found that they aren't exhibiting any of the molecular signatures of pluripotency which is what would constitute stem cell like behaviour and in another set of experiments they found that the cells, these things, whatever they are did not grow into spheres invitro in order that they differentiate into blood cells, you know, which kind of begs the question, what are these things at all and not only are they being used in research, they're being used in human trials. One of the big proponents for these class of cells has started a trial and is injecting 60 patients who have angina with a particular VSEL preparation.

Thea Cunningham: And is their use dangerous?

Eric Hand: I think it's too early to say that but I mean there's a lot of enthusiasm across the world for many different types of embryonic-like adult cells. You may have heard of another class of cells called Mesenchymal stem cells and there are similar doubts about these. The doubts aren't so much about their safety as they are whether claims have been exaggerated as to their efficacy or their benefits.

Thea Cunningham: And they understand there's a political angle to this too.

Eric Hand: That's right, the polish researcher, who patented his discovery of these VSELs have partnered and licensed the rights to these cells to companies that have the support of the Vatican. In fact they've donated a million dollars to a foundation that is pushing therapies based on these cells and that's at least in part because the Vatican lobbies for adult stem cell treatments as an ethical alternative to embryonic stem cell therapies

Thea Cunningham: And presumably if their existence is disproved, that will remove them from research?

Eric Hand: Not necessarily, I mean you could still go down a round of doing the basic research and figuring out what these things are but certainly it would be a blow to the companies that have been set up around this type of cell and those that are trying to push them very quickly into the clinic.

Thea Cunningham: Thanks Eric. All those stories and more are available at http://www.nature.com/news. Most popular on the website right now a giant virus with very few known genes and one of the world's slowest experiment, the pitch-drop experiment in Dublin yields a result.

Kerri Smith: That's it for this week. Join us again next time when we'll be having a latte and talking about milk tolerance. I'm Kerri Smith.

Thea Cunningham: And I'm Thea Cunningham.