Nature Podcast 10 August 2006
Introduction
This is a transcript of the 10 August 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
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Chris Smith: This week a gene has surfaced which could help rice to survive a spell under water.
Dave Mackill: I think it's conservatively estimated to cause about a billion dollars of rice crop loss per year.
Chris Smith: Also, it seems plants have long memories for what's happened to their ancestors.
Barbara Hohn: The offspring of those plants are still somehow memorising this effect.
Chris Smith: And a question as old as the Universe.
Andreas Korn: From lots of lithium in the big bang, too little lithium in stars, where has all the lithium gone?
Chris Smith: And the answer's lying in a nearby cluster of stars, as we'll be hearing later. Hello, I'm Chris Smith, welcome to this week's show. Around the world an estimated 3 billion people rely on rice as their dietary staple, and with 20 years that number looks set to rise by about 50%. Increasingly, both livelihoods and lives are being lost because the most popular strains of rice are susceptible to drowning if they're submerged under water for any length of time. But that's not true of all rice strains. And now Dave Mackill, from the International Rice Research Institute in the Philippines, has isolated a gene known as Sub1A which might hold the key to solving the problem. Nature 442, 635–636 (10 August 2006) ; Nature 442, 705–708 (10 August 2006)
Dave Mackill: This paper reports the discovery of a gene in rice that confers tolerance to submergence. Most rice varieties are susceptible to submergence and the plants would die within a week of complete submergence, but there are a few varieties that can tolerate two to three weeks of submergence, and we've found a gene which is involved in conferring this tolerance in rice.
Chris Smith: Economically speaking, how much of a problem is it, this submergence issue?
Dave Mackill: Well, it's a big problem in many rice areas. The exact estimates are difficult to obtain but it seems that there's probably about 10-20 million hectares of rice lands that are affected regularly by submergence stress, and I think it's conservatively estimated to cause about $1 billion of rice crop loss per year.
Chris Smith: So how did you home in on this particular genetic region which is important for making plants resilient to the problem?
Dave Mackill: It turns out that there's only a handful of varieties that really have a very high level of tolerance to submergence, and so we picked one of these varieties and we did a genetic analysis of this variety and we found that about 70% of the tolerance level is conferred by this single genetic region, and we were able to map that on the rice chromosomes, on rice chromosome 9.
Chris Smith: So genetically speaking, what's actually going on to make the crop resistant?
Dave Mackill: Well, what we've found in our studies is that there is a gene, a particular transcription factor. It's a type of gene known as ERF or ethylene response factor that is present in these submergence tolerant varieties and this gene is strongly induced during submergence.
Chris Smith: Now given that you've been able to move the traits into a plant that was previously not tolerant of being submerged and it became so, this must have huge economic implications.
Dave Mackill: That's a good question. We have been trying to breed submergence tolerant varieties for quite some time and we've been able to develop varieties that have tolerance, but unfortunately they don't have all the other requirements that farmers want. The benefit of being able to transfer this single gene into any variety is that we can now put it into varieties that are highly productive and that have very desirable features, varieties that have high yields and good grain quality. And, by transferring only the region of this Sub1 gene into that variety, we then ensure that none of the other desirable features of the variety are changed.
Chris Smith: So there's no risk that you could compromise the productivity by moving this gene in?
Dave Mackill: That's right. In fact, we've found, in our studies here, that a variety with the Sub1 gene introduced into it, has the same yield as varieties without the gene under the normal growing conditions. With this new discovery we will be able to accelerate the development of varieties with the characteristics that the farmers would like and, in addition, with the tolerance to submergence.
Chris Smith: That's Dave Mackill talking to me this week from the Philippines. Now sticking with plants, a lesson in why it's not just animals that have memories, stressing a plant with pathogens or exposure to ultraviolet radiation triggers it to increase its defence mechanisms, including DNA repair. That much was known, but no one expected the plant's offspring to behave in exactly the same way. Barbara Hohn.Nature advance online publication 6 August 2006
Barbara Hohn: What we found is that plants that are exposed to stress, and stress in this respect means UV and bacterial pathogens, we actually used a chemical which emanates from this bacterial pathogen, that such plants exhibit an increased frequency of homologous recombination. But the new part of that is, the offspring of those plants are still somehow memorising this effect and still exhibit this increased frequency of recombination.
Chris Smith: Even though you've now removed the thing that was toxic to them before?
Barbara Hohn: No, they have not been influenced by themselves.
Chris Smith: Is that a protective measure, then, if you increase the amount of recombination you can help to weed out some of the damage that may have been accrued in the DNA?
Barbara Hohn: This is probably DNA repair, but then we thought, and this was completely out of the blue sky, what do pathogens do to plants? We wanted to know whether pathogens have an affect on the genome, whether the effect is stability of the genome. Now, with our recombination assay, we found that, indeed, pathogens did have an effect, increasing the frequency of homologous recombination. But then the question was, what happens in the next generation? And this was pure serendipity. One of my former students, Gerhard Ries, found that in plants which are originating from exposed plants, plants exposed to the UVC, still had increased level of recombination. We could confirm this by analysing six different, completely independent lines of transformed Arabidopsis.
Chris Smith: So what do you think is going on?
Barbara Hohn: I have the feeling that something is going on on the chromosome level. Somehow, the chromosome remembers, and chromosome means DNA, DNA methylation, histones, histone decorations, methylation, acetylations, whatever, somehow remembers what the exposure to these threatening agents meant to it, and then transferred this, in a manner unknown to us, to the next generation. The details we have to work out which probably takes years and years and years.
Chris Smith: How are you going to try and get to the bottom of that, though?
Barbara Hohn: The idea is to analyse mutants. There are many mutants known for Arabidopsis. It's a fantastic model organism as you may read in, maybe, two-week old Nature summary article by Joe Ecker (Nature Reviews Genetics 7, 524–536 (July 2006) ). We can use many mutants to see whether this affect would still persist in the mutant background.
Chris Smith: And the hope being that then you can identify a mutant in which the affect is abolished and if you can then identify the mutation you know what's causing it?
Barbara Hohn: Right. The other possibility, which probably is too difficult in this case, is to make a random mutagenesis approach and to look for mutants in which this transgeneration process, as we call it, no longer persists.
Chris Smith: Barbara Hohn from the Friedrich Miesher Institute in Switzerland. Nature's podcast bringing the world of Nature to life.Coming up, how researchers have given the Solar System an x-ray and spotted billions of tiny objects out beyond Neptune. But what are they? And also, where's all the lithium gone? We've got the answer to conundrum that's been bothering space scientists for some time. First, though, to discuss two issues of increasing significance here on Earth, Anna Lacey is talking with Erika Check. Anna.
Anna Lacey: Today we're going to be looking at the ethics of egg donation, but first we're going to look at AIDS treatment in Africa.
Erika Check: Yes, the reason that we wanted to look at this question is because the biannual AIDS conference is opening in Toronto on August 13th, and the theme for the conference is time to deliver on promises that were made about treatment access in the developing world. And one of the really controversial arguments raised about rolling out treatment to poor countries about five or six years ago was the people in these countries would not be able to stay on complex treatment regimens and that would be a problem because they might develop resistance to drugs. Nature 442, 610–611 (10 August 2006)
Anna Lacey: Why would people think that people in Africa would be any worse than people in a Western country anyway?
Erika Check: Well, part of the problem is that the poor state of the healthcare system in Africa led people to fear that it would be difficult for patients to get continuing access to the drugs, and these are drugs that need to be taken every day for the rest of a patient's life, in many cases, and there was a fear that, due to the inadequate state of healthcare generally, this wouldn't be possible.
Anna Lacey: But has this actually happened?
Erika Check: So far in studies where people have looked at adherence of patients to antiretroviral medication, they've found that anywhere between 60 to 70, to even higher percentages, of patients are adherent, that is, they stay on their regimens. These numbers are better and sometimes comparable to adherence in the rest of the world. The researchers have found that in cases where they don't adhere to their treatments, it's largely due to forces beyond their control. In other words, interruptions in drug supply from donors or Governments, and so they suggest that that is where a lot of effort needs to go now.
Anna Lacey: But what will happen if there aren't enough resources to carry on supplying drugs to Africa?
Erika Check: Well, that indeed would be a problem. Right now researchers are reporting pretty low levels of drug resistance in African patients, but if the drug supplies are interrupted that's when you start to see problems. And there's an additional problem which is that many patients in Africa have started treatment on what are called first line regimens, in other words, the first generation drugs that are being used to treat HIV, when they develop resistance, they're going to need to switch to second and third line regimens, which are not nearly as widely available. So, there's a big push to make these drugs more available in addition to just the first line medications. What they're also arguing is that a lot of the early roll out programmes happened in very highly structured, say, clinical trial settings that now, as the treatment programmes, they're becoming part of the wider healthcare system generally. It's going to be very challenging to maintain the good results that have been gotten in the early days.
Anna Lacey: Well, now to egg donation and some of the ethical considerations surrounding that.
Erika Check: Yes, and this is something that it's important to look at now because for the first time in history healthy women are being asked to donate eggs specifically for research, and what my colleague, Helen Pearson, found is that there's a huge unknown question about what affect these fertility treatments could have on healthy women in the long term. Nature 442, 607–608 (10 August 2006) , Nature 442, 606–607 (10 August 2006)
Anna Lacey: Stepping back a second for a moment, what happens if somebody wants to donate an egg?
Erika Check: Well, what you'll typically do is first take a drug that stops your eggs from maturing. Then you take a drug that will stimulate your ovaries to produce a lot of eggs, a lot more than they normally would in a month. And then you will undergo surgery to collect the eggs.
Anna Lacey: But there are quite a number of problems with this such as ovarian hyper-stimulation syndrome, aren't there?
Erika Check: That's right. That is the potentially fatal complication that can arise when, for some reason that researchers aren't quite sure about, you stimulate many more eggs than you're supposed to at a given time. So, that's one of them, but there are many risks related to this. For instance, the surgery itself can cause problems. And, one study of 12,000 women found that the women who received fertility drugs were almost two times more likely to develop uterine cancer, but they weren't more likely to develop breast and ovarian cancer, and there have been other studies that find exactly the opposite.
Anna Lacey: So are people with this in mind going to want to be carrying on donating eggs, especially if it's not for the benefit of, say, giving an infertile woman a baby?
Erika Check: Well, that's a very good question, something people aren't quite sure about yet, but I think ethicists who look at this think there could be potentially other reasons why women might want to donate eggs that are very strong motivations. Researchers suspect that potentially people who have relatives who are sick or ill with diseases that could be carried by stem cell research might have a very strong motivation to participate in it. And that's one thing that they're actually a little worried about, will these patients be doing this purely altruistically, or do they have another motivation in mind that could be exposing them to some kind of a risk?
Chris Smith: Nature's Erika Check talking with Anna Lacey about HIV, and the sensitive issue of egg donation. And to continue with that theme here's Case Western Reserve University Bioethicist, Insoo Hyun, who Chairs the subcommittee on Human Materials Procurement, to explain why he feels that women who provide eggs for research deserve better.
Insoo Hyun: According to ethical guidelines that have been issued in the United States by the National Academy of Sciences and the California Institute for Regenerative Medicine, and also states like Massachusetts, women who undergo hormonal induction to provide their eggs for embryonic stem cell research may receive financial remuneration just for their direct expenses. Now, this rather narrow payment restriction has been emerging as a conventional position amongst stem cell policy-makers.
Chris Smith: Do you not think that that should be the case?
Insoo Hyun: Actually, no. I think that the opposite should be the case. Women who provide their oocytes for stem cell research, who must undergo quite burdensome procedures for that, ought to be compensated for their time, their effort and inconvenience in addition to their direct expenses.
Chris Smith: So, what's the argument for saying that they shouldn't?
Insoo Hyun: There are many people who worry that by introducing compensation beyond direct expenses we might produce one of two effects. One might be to undermine the voluntary nature of the informed consent process and/or that we would produce very unwelcome ethically bad consequences of doing so. Now, what I find fascinating is that it's not enough simply to say that there are worrisome possibilities with this practice because both sides of the debate will agree on that point. Those who argue that women in this case ought to be treated in a very different manner from all other healthy volunteers must do more than simply say, there are worrisome implications. In fact, they have to argue that there is no reasonable practical way to avoid these sorts of consequences, and I think therefore the burden of justification is actually extremely high.
Chris Smith: I have to say, as someone who's come through medical school, the lure of £100 was still sufficient to convince me and many of my colleagues to try as yet untested live, flu intranasal challenge in order to try to develop new ranges of vaccines. So, in my case, I was one who was lured by the offer of money.
Insoo Hyun: That's an excellent point. Some may argue that the offer of compensation for time, effort and inconvenience, could provide a financial incentive. Now, compensation and incentive are different concepts in research. Compensation is to provide money in recognition of somebody's effort and time. An incentive is actually a recruitment tool. Now, the key issue is whether or not compensation for time, effort and inconvenience produces an undue influence. Now the definition of an undue influence is that it is so attractive and they are unable to adequately weigh the risks of their involvement. Now that should be properly handled and monitored by the local review bodies.
Chris Smith: So what would be the long term view that you would take? Where do you think this is going to end up ultimately?
Insoo Hyun: Well, it would be my hope that we don't have to use direct donations for stem cell research, that we develop alternative means. My position is this, however, if a team is going to go ahead and be approved by their local review body for direct, human oocyte donation for their research, one ought to pay for time, effort and inconvenience. This is not to say that this is optimal, that women donating oocytes for stem cell research is really the preferred way for this field to advance. I'm uncertain on that point, but my point is simply that if you're going to do this, you ought to treat them like all other healthy research volunteers, because there's not sufficient justification to make an exception in this case.
Chris Smith: Insoo Hyun. And perhaps you'd like to comment on this issue via the Nature news blog. You can find it at http://www.nature.com/blogs. Just look for this podcast's entry which is listed there. And now from embryonic stem cells to the embryonic universe and a question which has worried scientists for some time which is, where has all the lithium gone? Andreas Korn. Nature 442, 636–637 (10 August 2006) , Nature 442, 657–659 (10 August 2006)
Andreas Korn: We have resolved the so-called cosmological lithium discrepancy, which is the discrepancy of the amount of lithium known to be produced shortly after the big bang and the amount of lithium we measure in old stars of the galaxy. There was a discrepancy which was discovered in recent years by detailed measurements of the cosmic microwave background and isotropies, and the discrepancy is quite large and significant, and now we know who the culprit is.
Chris Smith: So where do you reckon it's all gone, and how have you gone about showing where it's all gone?
Andreas Korn: We have investigated whether the physics of stars can be responsible for this discrepancy. Diffusion theory predicts chemical imbalances in stars to vary with time and heavy elements will tend to sink out of the atmospheres into the stars where we cannot observe them. Now, the main observational obstacle here is that there is a lack of a reference point. For a single star you cannot really tell whether its chemical composition has changed over the course of its billion-year long lifetime. But the situation is different when looking at a bunch of stars, at a star cluster. So, using one of the four 8.2m mirrors of the very large telescope in Chile we took spectra of dwarf and giant stars in a nearby ancient star cluster and compared the abundances of elements in the atmospheres of stars in different evolutionary phases.
Chris Smith: So what's the significance of the fact they're in a cluster, though, Andreas? Why does that help you?
Andreas Korn: The cluster, the fact that they're in one cluster means that these stars were all born at the same time with the same initial composition.
Chris Smith: And so by comparing one against the other it's a much more sensitive measure of, actually, the real abundance in that context?
Andreas Korn: Exactly. Diffusion theory predicts that the effects of abundance variations are a function of the evolutionary stage of the stars, and in one certain stage, in the giant phase, the effects are expected to be minimal, while in another phase, in the dwarf phase, they are expected to be very large. And comparing these two groups of stars we can actually learn something about the effects of diffusion.
Chris Smith: And what did you find when you did this?
Andreas Korn: For a variety of elements we find trends of chemical abundance with evolutionary stage. They are specific for the element and they are actually in good agreement with the theoretical predictions. So, this means that, probably, diffusion is responsible for the low apparent stellar lithium abundance.
Chris Smith: But why was it just lithium that had a discrepancy? Is that because it was just one of the few things that was produced in the big bang, along with hydrogen and helium, or was there other reasons for it?
Andreas Korn: Yes, the effect is general so all elements are affected, but they are affected by different amounts. As a matter of fact we determined the effect mainly on heavier elements like iron and calcium, and then make an inference towards lithium. But, yes, you're right, lithium is one of the few elements we can observe in these cool stars that is also produced in the big bang.
Chris Smith: Andreas Korn, from Uppsala University in Sweden. Now, finally this week, what's out beyond the orbit of Neptune? The answer is, a lot of small so-called trans-Neptunian objects, but most of them are too small to be able to see. To solve the problem Taiwan's Hsiang-Kuang Chang has used the brightest x-ray source in the sky, a neutron star called Scorpius X-1 and watched for occultations, in other words, momentary dips in the x-ray intensity when an object passes in front of the star. The technique has spotted literally billions of objects, many as small as 100m across. Nature 442, 640–641 (10 August 2006) ; Nature 442, 660–663 (10 August 2006)
Hsiang-Kuang Chang: The trans-Neptunian objects are objects in the outskirts of our Solar System. In the early history of our Solar System planets formed and also small bodies formed at that time and people believe those bodies are the debris or relic of our ancient Solar System. So, if we can know the total number of those objects and also the size distribution then we can know better the history, the process of how the early Solar System formed.
Chris Smith: And what do you do to do that?
Hsiang-Kuang Chang: We use the method of occultation to detect smaller bodies. Scorpius X-1 is a binary system containing a neutron star which emits strong x-rays. We analyse long term data of Scorpius X-1 and we check to see whether there is a sudden drop in the photon counts or not. So, based on this we can estimate the total number of trans-Neptunian objects of this phase.
Chris Smith: And how many are there?
Hsiang-Kuang Chang: 10 to the 15th power.
Chris Smith: That's a huge number. So, what are the implications for having found that?
Hsiang-Kuang Chang: First of all I think it's a huge number so we know there are a lot of things out there. Isn't it fantastic, right? And, the implication, basically, is related to our understanding of the early history of our Solar System. So, many models, theoretical work, indicated that that size distribution of those small bodies should follow a power law and that power law should also get flatter below a critical size and that critical size is usually estimated to be around a few kilometres, and this time our discovery indicated that the power law actually extends down to 100m. So that means in earlier theoretical models one has to think again carefully which co-parameter should be modified.
Chris Smith: Hsiang-Kuang Chang from Taiwan's National Tsing Hua University, explaining how he has used the stream of x-rays from the neutron star Scorpius X-1 to discover at least a million billion previously invisible trans-Neptunian objects some of them just a hundred metres across. Well on that note it's time to say that's all for this week and thankyou very much for listening. Next time I shall be wrestling with the formation of the early Universe but, in the meantime, if you'd like to find out more about any of the reports in this week's show, they're all available on our website at http://www.nature.com/nature. And if you're in the mood for more science, this week's edition of the Naked Scientists explores the origins of the giant red spot on Jupiter and its smaller cousin, Red Spot Junior. That's the Naked Scientist podcast which is freely available from http://www.thenakedscientist.com. This week's show was produced by Derek Thorn and Anna Lacey, and I'm Chris Smith. Until next time, good-bye.AdvertisementThe Nature podcast is sponsored by Bio-Rad, at the centre of scientific discovery for over 50 years, and on the web at http://www.discover.biorad.com.