Nature Podcast

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Charlotte Stoddart: This week, a major step forward in Huntington's disease research.

Anthony W.S. Chan: This animal does present the clinical feature, which is comparable to human patient that we haven't been able to see in other animal models such as rodents.

Adam Rutherford: And, what a pushover. There goes not one, but a pair of supernovas.

Alicia Soderberg: During the two-hour observation, I actually watched another star exploding in that very same galaxy, which is extremely unlikely since every galaxy should produce just one supernova every 100 years.

Charlotte Stoddart: Plus we'll be rounding up this week's controversial UK stem cell legislation. This is the Nature Podcast. I'm Charlotte Stoddart.

Adam Rutherford: And I'm Adam Rutherford. Kerri is on holiday this week, but before she left she spoke to researchers who have developed a new animal model, which gives an important insight into a terrible inherited disease.

Kerri Smith: When it comes to studying human disorders like the debilitating neurodegenerative disorder, Huntington's disease, mouse and rat models are far from perfect, which is why a team of researchers led by Anthony Chan of the Yerkes Primate Research Centre at Emory University in Atlanta have developed a monkey model of Huntington's. They inserted the gene that causes the disorder in humans, HTT, into monkey embryos and when these monkeys were born, they showed many of the symptoms of the condition. I first asked him why it has been difficult to develop transgenic monkey models of disease before. Nature advance online publication (18 May 2008)

Anthony W.S. Chan: First of all the first transgenic monkeys was made in 2001 and the reason it took such a long time to get to this point is because having to develop a Huntington disease model will take a lot of effort I think, from many different expertise. Also we need to make sure we develop an efficient way to make a transgenic monkey such that we won't use too many monkeys. We tried to minimize the number of animals that we need to achieve our goal here.

Kerri Smith: What are the advantages of transgenic monkey models of Huntington's disease specifically and other diseases over non-genetic models or transgenic mice models of the same disease.

Anthony W.S. Chan: I think it's very important especially for Huntington disease as well as other neurodegenerative disease, each related to the cognitive decline as well as some other brain function impairment. So, with the monkey, I think, we know the brain function as well as the cognitive tests available for monkey is far more sophisticated than what we have for rodents. In fact I think, most of the tests we used for monkeys, also is very similar to what we used to test human, so these animals allow us to understand the process of how the disease is developed because I think, they do develop a similar feature compared to human patient that no other animal models had been able to.

Kerri Smith: Now tell us briefly then next how you produced these monkeys?

Anthony W.S. Chan: Based on what we learned from the human patients as well from the rodent models, we know that the Huntington's disease was caused by mutation in the Huntington genes. So by introducing this mutant Huntington gene into a monkey oocyte using an antiviral factor, after about 150 to 160 days, the monkeys were born. And then we confirmed that these monkeys that were born does carry the genes that we introduced and we also confirmed the expression of the mutant Huntington protein and the most important, I think the key is, I think, this animal does present the clinical feature which is comparable to human patients that we haven't been able to see and observe in other animal models such as rodents.

Kerri Smith: How closely did they resemble the symptoms of Huntington's disease in humans then?

Anthony W.S. Chan: For example, in human patient we can easily see the things like dystonia which is being like the involuntary movement or contraction of the muscle that cause the body to twist in a very strange posture, as well as the important facial movement that I think like some of the facial muscles constantly is contracting as well as that we are losing weight, not capable to gain weight, but in rodents it was very difficult to observe this kind of feature, but I think in monkey we observed this feature and we noticed that it is very comparable to what we have seen in human patients.

Kerri Smith: Now of the five monkeys that were born, two survived for I think, less than a day and one for only a month. So this is due to the gene and if so, isn't that quite poorly reflective of the late onset of Huntington's disease in humans?

Anthony W.S. Chan: You are definitely right. I think Huntington's is also a complex disease. It's not just simply caused by a single mutation or defect of the Huntington gene, but it also depends on dosage which means, the more of this mutant protein is produced the phenotype is more severe. So that's exactly what we've seen in those animals that were born and lived only for a short time, because they expressed a very high amount of mutant Huntington protein, which is I think is consistent of what we've seen I think in rodents models and also we understand that, I think, people are concerned with the disease, the late onset Huntington disease, but in fact there are early onset Huntington disease, what we call a juvenile-onset Huntington disease, it also affects the people.

Kerri Smith: So this model of yours is more reflective of that early onset form of this disease perhaps.

Anthony W.S. Chan: Yes. I think we actually have the early onset form of the juvenile Huntington.

Kerri Smith: Now for many people a primate model of a human disease, is more ethically problematic than such a model in a rodent, for example. How would you answer those criticisms?

Anthony W.S. Chan: Well, I agree that the thing is there is always a dilemma there. We believe developing a primary model which allows us to learn better about the diseases and which will eventually help to cure the disease.

Adam Rutherford: Anthony Chan talking to Kerri and you can get more neuro news from Kerri on the latest NeuroPod show, which is available now at

Charlotte Stoddart: Back to the Nature show, next Geoff Brumfiel looks to the skies for some extremely unlikely explosions.

Geoff Brumfiel: Every now and then a scientist gets lucky and an author in this week's Nature is just such a case. Alicia Soderberg was doing observations on a nearby galaxy when a star in that galaxy just happened to explode into a massive supernova. Soderberg is a post doc at Princeton and she knew right away that she'd hit the jackpot. Her first of a kind, observations may tell us more about the deaths of stars as she explained to me over the phone. Nature 453, 469–474 (22 May 2008)

Alicia Soderberg: The actual explosion itself, the light that the explosion produces at first can be very brief, and so in order to actually catch the supernova exploding, you have to be, sort of, at the right place, at the right time. It only lasts a few minutes and it's very difficult to catch that signal, since supernovae are fairly rare

Geoff Brumfiel: What were you trying to look at, when you saw this thing?

Alicia Soderberg: So, that's an interesting point. What I was actually doing is I was studying another supernova. It was a bit older, it was probably a month old at the time and I was studying it with the swift gamma ray burst satellite, which has an x-ray telescope on board and during the 2-hour observation, I actually watched another star exploding in that very same galaxy, which is extremely unlikely, since every galaxy should produce just one supernova every 100 years.

Geoff Brumfiel: So, do you feel like you had sort of won the astronomical lottery?

Alicia Soderberg: I definitely won the astronomical lottery. The probability of this happening to me was I think one in ten thousand, so I got very, very lucky but I also knew what to do?

Geoff Brumfiel: What did you need to do?

Alicia Soderberg: Well, I needed to first of all alert the entire community. As soon as I saw that there was this really exciting very very bright object in my x-ray observations, I immediately triggered observation that all telescopes I could get my hands on and at the time we didn't really know it was a supernova, but I knew it had to be exciting.

Geoff Brumfiel: This of course is a very serendipitous discovery and exciting all by itself, but you've actually been able to figure some things out about supernovas from it. May be you can tell us a little about what you've learnt?

Alicia Soderberg: Sure, so it's been predicted for decades that we should see this really strong pulse of light when the star explodes, at the very moment of the explosion, but no one had ever seen it. If you can actually detect that emission, it sort of, has a signature of the properties of the explosion embedded within it and so by studying that emission you can sort of go back in history and understand what that star was doing just before it died?

Geoff Brumfiel: Just describe to us a little bit about what was happening to the star right before it went?

Alicia Soderberg: There are of course huge explosions and you'd think that the star would have some sort of notion of what was going on before it comes to its death, but what's really interesting about the star is you can tell, we've been able to show that the star actually didn't know it was about to die, you know, like a very good athlete, it was just sort of going strong until the last minute, when it exploded, it really had not indication on the outside, you couldn't tell that it was about to go.

Geoff Brumfiel: And what happened to it?

Alicia Soderberg: Basically the star ran out of fuel, the stars need fuel to support themselves and this star being a very, very massive star ran out of fuel quite quickly and basically the star just collapsed upon itself under its own gravity and following the collapse, it then exploded because it could only collapse matter to be so small, before it has to rebound.

Geoff Brumfiel: I suppose the only other question I have is what's next for you? What sorts of things do you hope to be working on next?

Alicia Soderberg: So this is, as I said, a serendipitous discovery, so I didn't expect to be working on this now, but its really exciting in a sense that it is the confirmation of a long-known prediction for dying stars and what's really interesting is that future x-ray machines that are being built now and getting ready to be launched in the next 5 or 10 years, we now know that supernovae are going to be one of the number one things they detect. Those x-ray satellites are going to go up and they are going to be finding supernovae instead of these optical amateur astronomers, which is how things are currently done now. So, the whole field of supernovae is really going to change and I'm really excited to be a part of these x-ray satellite machines, which are going to uncover these huge populations of supernovae that was never seen before.

Charlotte Stoddart: That was Alicia Soderberg taking to Geoff. This week's PODium is on an altogether more earthly theme. Here's science writer and broadcaster, Simon Singh on the dangers of bogus science degrees.

Simon Singh: Last year a letter in Nature alerted readers to the alarming fact that several British Universities offer Bachelor of Science degrees in fields of Alternative Medicine. David Colquhoun a quack-busting pharmacologist at University College London strongly argued that these subjects have no grounding in science and therefore they should not be at the heart of a science degree. Although I was shocked by the revelations in the article, the reaction from the universities in question was somewhat disappointing. Several of them failed to respond at all. Consequently, last month, I teamed up with Professor Colquhoun and Professor Edzard Ernst, the world's first professor of Complementary Medicine, to take another look at the problem of bogus degrees in Complementary Medicine. I say 'bogus' because what can be more bogus than teaching a form of medicine based on nonexistent entity such as "Chi" or based on unscientific premises such as those that lie at the heart of Homeopathy. Together, we ranked UK universities according to the number of unscientific degrees offered in Alternative Medicine. Top of the bogus lead table was Westminster University in London offering six degrees, closely followed by Greenwich and Middlesex Universities. By casting the problem in the form of a lead table, the idea was to embarrass the worst offenders and hopefully encourage them to rethink their policy towards teaching bizarre therapies. In Britain, the table was published in several national newspapers. By the way, this is not just a British problem. Many other universities in many other countries are guilty of the same problem. So, if you are based in another country, where bogus degrees are on the rise, then you might want to repeat the exercise and highlight the problem in your own country. But why am I encouraging you to get involved? Why is this a problem worth confronting? When I studied for a degree in physics I incanted a body of knowledge that had been proposed, tested, and established by previous generations of scientists. The problem with degrees in Alternative Medicine is that they teach information that is outdated and dis-proven. As such, these degrees undermine the integrity of a university education. Moreover degrees in Alternative Medicine mislead the students into thinking that they are learning something that has a solid scientific basis. And it's unhelpful for patients in the future, who have an unjustified confidence in a therapist, just because that person carries a badge of a B.Sc. Importantly, this is not just an academic issue. It's a medical issue. It can have serious implications. In the most extreme cases we know that some homeopaths make outrageous claims about their ability to treat HIV or prevent malaria. Hence, it's not so surprising that some patients treat these claims seriously, if they learn that Homeopathy is being taught at a university level. If you care about evidence based medicine and hate bogus science, then this is an issue that you should care about too. And if your own university teaches bogus degrees, then why not get your colleagues together, raise a petition, and write to your vice chancellor. Bogus degrees are on the rise and the problem would only get worse unless someone starts pointing out the absurdity of such causes.

Charlotte Stoddart: Simon Singh on the PODium. His latest book, 'Trick or Treatment?: Alternative Medicine on Trial', co-authored with Professor Edzard Ernst is out now. Remember if you've got any feedback, then you can write to us, the address is

Adam Rutherford: Now to a molecule that is present in every cell, in everything from yeast to humans, which is why they called it ubiquitin.

Charlotte Stoddart: Protein's the products of our gene participate in every process in our cells. They form structural elements, they catalyze biochemical reactions; they facilitate communication within and between cells and much more. In order to regulate these processes, cells must control the quantity of these different proteins and they do this by breaking down surplus molecules. Another protein called ubiquitin mediates this process by tagging redundant compounds and shuttling them to the cell's degradation machinery, the proteasome. Two papers published in Nature this week, revealed more about this important process and lead author, Ivan Dikic is with me in the studio. Welcome Ivan. Nature 453, 481–488 (22 May 2008) & Nature 453, 548–552 (22 May 2008)

Ivan Dikic: Thank you.

Charlotte Stoddart: Now you've been looking specifically at how ubiquitin binds to the proteasome and what do we know about this process before your recent study?

Ivan Dikic: So ubiquitin is a very exciting signalling modifier in our cells. This entire concept of ubiquitination of proteins was discovered by 3 scientists and they have received the Nobel Prize for this discovery. What these scientists have shown is that ubiquitin is attached to a protein, which needs to be degraded in the proteasome and in that way marks it for degradation. So the open question in the field has been for many years now: how the proteasome recognizes this ubiquitin on the target protein and how then the protein gets unfolded and understands the core machinery of proteasome which is in fact the shredding machinery. And that is the part of the beauty of the discovery. We know today for one receptor on the proteasome and our study now shows the second one, and we believe that these are the two major ubiquitin receptors of the proteasome.

Charlotte Stoddart: So tell me about this new ubiquitin receptor that you've found which you call Rpn13.

Ivan Dikic: So, Rpn13 is a part of the regulatory particle of proteasome. We identified it by using the screening method called yeast two-hybrid system, to bind to ubiquitin. This was immediate excitement in our lab, because we realized, well, that could be another ubiquitin receptor on the proteasome and indeed we confirmed it four years later in this publications. However, I want to emphasize again that from this original excitement to publication, it was four years of hard work and not work on our lab only, but also work of other specialties.

Charlotte Stoddart: And one of the striking things that you've found is that the way in which this receptor binds to ubiquitin is quite different from what you expected and from the other receptors that we know about?

Ivan Dikic: This is another beauty of science. You can never predict what you will discover. Once we solved the structure of this domain, which binds the ubiquitin, we were surprised to see it as a pleckstrin homology like domain, well known domain in other proteins and then the second surprise came out when we solved the structure of the ubiquitin in complex with this domain and then the new mode of binding was mediated only by loops, which were connecting the secondary elements of the structure, and that is the first time from all known more than 20 familiar ubiquitin binding domains, first one that binds with loops has a very large surface and for that reason has a very high affinity as well. It's a champion of all affinities up to now.

Charlotte Stoddart: Can these findings tell us something a bit more generally about protein breakdown in the cell?

Ivan Dikic: This findings are exciting both in terms of basic science but also in potential translational medicine, and we are hopeful that by discovering the atomic molecular details, how proteins are degraded and how receptors on proteasome recognize the misfolded proteins that we will be able to design the new methods by which we would be able to block those interactions. I think its very challenging, we need the new chemistry, but the details, the resolution that we have provides us with hope that this will be doable in the near future.

Charlotte Stoddart: And so what kinds of practical applications might this have, what kinds of patient for example might this benefit?

Ivan Dikic: So, proteasome is a cleaning machinery of a cell. So many proteins in a normal life of a cell need to be removed because they have performed their function. If this removal of protein is not accomplished, the proteins aggregate in cells and lead to several disease and among the most well known are neurodegenerative diseases like Alzheimer, Parkinson disease. We also know today that the cardiovascular disease is also caused by dysfunctions of proteasome, cancer development as well and so on and one of the therapies which is already used to block the function of the proteasome is used at the moment for treatment of multiple myeloma. It's a specific haematological cancer, which is treated by inhibitors of proteasome. So I think the applications are numerous because ubiquitin is involved in so many functions and also the proteins and the cleaning of proteins from our cells is a function of all cells in our body.

Adam Rutherford: Ivan Dikic of Goethe University in Frankfurt.


Adam Rutherford: Now in this week's Nature, we've got some new papers on important aspects of stem cell research. More on that later, but the last couple of days have also seen some rather significant political developments for stem cell scientists. After much heated debate, the UK parliament has decided to go ahead with legislation that allows the creation of human-animal hybrid cells for the purpose of research. Mike Hopkin has been following the story for Nature. Mike, you reported on the pod last week from parliament where a rally was being held in support of the new legislation. Can you set the scene for us? What were the new proposals and why have they got so many people in a rage?

Michael Hopkin: Well, the subject of the demonstration last week as I reported was the creation of hybrid human embryos created from animal material and that's got people annoyed because a lot of the religious groups were campaigning against the use of human cells in this way; equally the scientific groups were saying that its going to lead to potential therapeutic benefits through this, sort of, research, and the MPs in the House of Commons in Britain have been debating that for the past few days and they have now had a series of key votes on some of the most controversial aspects of this new legislation including the hybrid embryos, which they voted in favour of. So it's good news for research community, who are hoping to do the work here in Britain.

Adam Rutherford: And what were the other issues up for debate in the legislation.

Michael Hopkin: The other issues were things with more, sort of, social implications, they were voting on whether or not it is okay to use pre-implantation genetic screening of IVF embryos for saviour siblings. So this is, couples who have a child may be with an existing genetic condition that will now be allowed to select IVF embryos, so that that child will be able to donate stem cells to its older sibling to try and cure that disease. The other things on the slate, which have all been voted through now and approved by MPs, are a change to the rules governing, who can have IVF. So now they've removed the need for a father, as it was called which opens the way for single sex female couples to have a child via IVF and they've also voted to keep in place the abortion limit in Britain. The limit is currently 24 weeks and some people who have a negative view of abortion and some people who don't think it should be allowed at all had been campaigning for that to be moved earlier, so that once babies past a certain stage, they couldn't be aborted, but that has been rejected by MPs, so the limit is still 24 weeks.

Adam Rutherford: And how does this roll in specifically on stem cells, how does it compare to policy with the rest of the world?

Michael Hopkin: Well, Britain has been setting itself as a progressive government in terms of how it regulates human embryonic research and then I think, it is fair to say that once this legislation is finally passed then it will put Britain probably at the, head of the pack, in terms of what embryologists can do in research terms with public money. Also in places like America where the stem cell research is fairly restricted, in fact researchers are only allowed to work on a certain number of stem cells that have already been derived and they're not allowed to derive more, but within the private sector it is pretty much described as, the wild west, and it is, 'a free for all' there if you can get the funding to do it. So Britain, I think, in terms of public money is leading the way, but other governments in Europe are looking at whether to regulate this sort of work and not many governments in Europe are talking explicitly about banning it, although a few of the smaller countries have.

Adam Rutherford: And back to the research itself, Nature has got some major stem cell papers in this week's issue. What is your pick of the bunch?

Michael Hopkin: Well I've been looking a paper from Austin Smith group at Cambridge University, which is talking about how to maintain cultures of embryonic stem cells. It is obviously important for researchers working with stem cells to be able to maintain a population of them without them differentiating into all sorts of different specialized cell types willy-nilly. You need to be able to study the embryonic stem cells in the totopotent state as it is called and that's always being maintained using a whole cocktail of different growth factors and serum media and then things taken from cows and all sorts of complicated ways of effectively stopping the cells from going off on their developmental pathways and what this new research shows is a much easier way to maintain the cells in this state, in this embryonic stem cell state, by just giving them certain chemical inhibitors which stop their signalling pathways and therefore utilize the cells own mechanisms for staying in this embryonic stem cell state.

Adam Rutherford: And is it a case that this type of research would not have been possible if the bill had not been passed.

Michael Hopkin: It would have been possible but of course what the legislation in the bill is looking at is improving the supply of embryonic stem cells, so this is a way of working with stems cells. What is bothering the stem cell researchers at the moment is that they're relying on donated human embryos from IVF as their supply and that is obviously, in short supply. So what the new legislation will allow them to do is to create these animal human hybrid embryos as a way of improving the supply of the embryonic stem cells and then that's where this technique by Austin Smith's group then comes in for maintaining that supply.

Adam Rutherford: So a good week for stem cell biology overall. Okay thanks Mike. There is a special web focus on regenerative medicines and stem cells, that's at That's it for this week, I'm Adam Rutherford.

Charlotte Stoddart: This is the Nature Podcast. I'm Charlotte Stoddart. Thanks for listening.


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