Nature Podcast

This is a transcript of the 13th March 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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Adam Rutherford: Coming up, a special report on animal testing.

Lida Anestidou: The most important contribution of this report is to bring first of all the attention to the fact that laboratory animals actually do get distressed.

Adam Rutherford: And changing your position on the relation between science and religion.

Frank Wilczek: For many years I, like some of my colleagues and some recent best selling authors thought that active, aggressive debunking was an order. I've changed my mind.

Adam Rutherford: That's Nobel Prize winner Frank Wilczek on our podium. This is the Nature podcast, I'm Adam Rutherford. Kerri is on holiday this week, but before she left we sent her down the farm on the trail of a nasty parasite that infects cows and sheep.

Kerri Smith: Worms are a common problem in many animals and livestock are no exception. These sheep here at Kentish Town City Farm in London are worm free and healthy, but worldwide such infections cause substantial animal health problems and economic losses. And what makes the situation worse is that many of these nematodes are resistant to all the drugs we have to treat them. On top of that there hasn't been a new candidate drug treatment for 25 years. But in Nature this week, a team of researchers led by Ronald Kaminsky of Novartis Animal Health Research Centre in Switzerland puts that right. They report a new class of drugs called AADs or less catchily amino-acetonitrile derivatives that are able to eliminate these parasites. Before speaking to Ronald about his study, I popped down the road from the farm to the Royal Veterinary College in Camden to ask veterinary parasitologist, Mark Fox, just how big a problem these drug-resistant nematodes are. Nature 452, 176–180 (13 March 2008) Goat bleats

Kerri Smith: Hi Mark, nice to meet you.

Mark T. Fox: Hi there.

Kerri Smith: Now tell me first of all, what is the scale of the problem of drug resistance in nematodes.

Mark T. Fox: Well I'm afraid it's a growing problem, not just locally but on a global basis. It's a real problem particularly in farm and companion animals and particularly in gastrointestinal roundworms or nematode infections.

Kerri Smith: And what kind of problems does this actually cause for the animals themselves?

Mark T. Fox: Well depending on whether they are farm animals or companion animals, if it's a farm animal it will adversely affect their performance. In the case of companion animals such as horses, it may mean that animals lose condition and in severe cases have to be put down on welfare grounds.

Kerri Smith: So, welfare issue as well as an issue of livestock productivity?

Mark T. Fox: Very much so.

Kerri Smith: So currently then, what are the practices available for dealing with these worms?

Mark T. Fox: We have a variety of different classes of deworming drugs or anthelmintics available currently free are widely used in farm animals and companion animals, but of course with anthelmintic resistance becoming more and more of a problem globally and some strains of worms are resistant not just to one class but sometimes two or all three classes, control of the parasites can be very very difficult.

Kerri Smith: Now the new paper in Nature reports a novel class of drugs that seems to overcome that problem of resistance. What kind of impact might a new class of drugs such as the AADs have?

Mark T. Fox: Well it will certainly provide us with an additional tool in our armoury, it will give us another chemical class of drugs to choose from, but we shouldn't use that at the expense of other approaches to worm control. Parasitologists and veterinarians now like to adopt what is called an integrated approach to parasite control. The main aim behind that is we don't just rely on drug treatment of animals, but we use it in combination with pasture management and using worm-eating fungi selective breeding that has resistance and also of course vaccination against the parasites themselves.

Kerri Smith: Obviously resistance is a big problem in these nematodes. How can we ensure the continued use of this new class of drugs? How can we make sure that resistance isn't a problem here as well?

Mark T. Fox: This integrated approach to parasite control should be combined with measures designed to deny the parasite resistance to worms. So for example, farmers or animal owners should choose the right drug for the parasite. They should give the correct dose, use the minimum number of treatments and herein the knowledge of the parasites' epidemiology is important. Alternating the chemical group used on an annual basis is important. Check the effectiveness of treatment by monitoring faecal egg counts on a regular basis and try not to introduce resistance onto a farm by quarantining and treating or introduce stock and don't forget education; it's very important to increase awareness of the problem and to seek veterinary advice.

Kerri Smith: Mark Fox. A problematic parasite indeed, but there is hope. When I got back to Nature headquarters, I called Ronald Kaminsky to find out about their new discovery – a new class of drugs to tackle these nasty nematodes. I started by asking him how they discovered these compounds

Ronald Kaminsky: We screen various compounds and then we do after that when we have discovered molecules, we follow up in rodent models and finally we test those – the better compounds – we test them in our target animals in sheep and in cattle.

Kerri Smith: And these AADs, you found two particular molecules in this class of compounds that worked particularly well against these nematodes. How did you find that they were effective? How did you test how effective they were?

Ronald Kaminsky: Yeah! Well those two also belonged to more than 600 AADs we synthesized and out of those one they were quite a number which showed in the ex - vivo screen a very good efficacy and they were so good that we could not even differentiate them in the rodent model, so we were trying to evaluate their activity finally in sheep, so we tested about 40 different AADs in sheep to find out which were the better ones.

Kerri Smith: And how effective are these exactly?

Ronald Kaminsky: They eliminate all nematodes, all round worms including those ones which are resistant. So we have tested them against a variety of different species of round worms and against a whole variety of different isolates which are drug resistant and then in the end what you test is in your experimental setup, if the AADs can cure infected sheep.

Kerri Smith: That's quite a result. I mean, these are 100% effective, these two compounds, aren't they in sheep against nematodes?

Ronald Kaminsky: Yes.

Kerri Smith: So, why are they so effective when other drugs are failing?

Ronald Kaminsky: They appear to have a new mode of action, so we have evidence from studies in a model worm in C. elegans and from studies in our parasitic worms that the AADs hit a new molecular target which is nematode specific, so you don't find that target in mammals.

Kerri Smith: And I suppose that has issues for the toxicity or otherwise of these drugs then?

Ronald Kaminsky: Absolutely. That is a good explanation why we find those AADs very well tolerated by ruminants.

Kerri Smith: And so the paper has those two aspects of interest not only applicable to livestock in to its real world, if you like, but it's also got this basic science, this new finding of the new channel.

Ronald Kaminsky: That makes it so interesting because it covers basically the whole story from starting from the molecule, finally to the farmer who is hopefully at some point able to use one of the AADs as an anthelmintic.

Kerri Smith: When do you think that might happen?

Ronald Kaminsky: If it's for me, it could start tomorrow from the results I have and from the information I have, but it's unfortunately not only me who decides that. It's subject to the authorities, to regulators, who will approve hopefully one of the AADs at some point of time.

Kerri Smith: And now that would be approved first of all for use in livestock, but I understand that humans also suffer from these kinds of infections sometimes, could this be applicable to human use as well?

Ronald Kaminsky: Yes, in principle it could be applicable and as a matter of fact we are already in contact with WHO to discuss how we may proceed with the discovery of the AADs also for the human health.

Adam Rutherford: Ronald Kaminsky and before him Vet Mark Fox. Remember to listen right to the end of the show for your chance to win an iPod Touch. That competition is closing at the end of March, so you better get cracking. Now we are constantly reminded about reducing our carbon footprints, but an aspect of climate change that is often overlooked is deforestation, particularly in the rain forests of the Amazon. Nature reporter, Jeff Tollefson has spent a special two-part investigation into deforestation and how we can tackle its impact. I've got him on the line from our DC office. Published online 12 March 2008, Nature 452, 134–135 (2008), Published online 12 March 2008, Nature 452, 137 (2008)

Adam Rutherford: Hi Jeff

Jeff Tollefson: Hello there.

Adam Rutherford: Jeff, can you explain the significance of deforestation on climate change for us.

Jeff Tollefson: Well there are various estimates, but the general figures that get used are that, deforestation accounts for as much as 20% of the global emissions, so that is not a small number, the question for years has been how do you quantify number one and two, you know, how do you actually incorporate that into some kind of a framework within the international community?

Adam Rutherford: And I understand that it was discussed at length there, in the UN Climate Change Meeting in Bali. How did it fare?

Jeff Tollefson: That's right. In Bali, the UN negotiators basically agreed to put deforestation on the agenda for a future climate treaty that will follow the Kyoto protocol. This was an issue that actually came up in Kyoto a decade earlier and it was kind of left off the table at that point of time because people did not know if it would be technically possible or how difficult it would be to actually deal with this issue. So the UN negotiators in Bali did agree to, you know, put it on the agenda and now various countries are working out solutions for, you know, just how to actually handle it in the next treaty?

Adam Rutherford: And take us through some of those proposals?

Jeff Tollefson: They are kind of two main frameworks. The coalition for rain forest nations has a proposal that would basically involve setting a baseline at the national level and then countries that can reduce their deforestation emissions below that baseline; they could sell those credits onto the international market, whatever the international market is. This would be something like a trading scheme like the European Union Trading Scheme. The alternative proposal is to also set a baseline for where deforestation is today, but instead of putting credits on an international market to fund the deforestation programs, there would actually be an international fund, kind of a traditional international fund that, you know, major industrial nations would put money into and then the tropical nations would pull money directly out of that. This is an idea that's been pushed by Brazil.

Adam Rutherford: You just mentioned Brazil there, which is the subject of your second report and is the home to one-third of the earth's species and half of the world's rain forests? So how are they specifically going to deal with deforestation in the Amazon?

Jeff Tollefson: So Brazil is a unique case. Much of the deforestation that takes place globally actually takes place in two or three states in Brazil. They are actually in the midst of a big federal crackdown on deforestation as we speak. This is something – it was a bit of a surprise in January when Brazilian scientists announced that deforestation rates had actually gone up in the last 6 months of 2007.

Adam Rutherford: And that was based on satellite data, I understand?

Jeff Tollefson: Right, Right. So Brazil has probably the most advanced program for tracking deforestation from space. They've been doing this for a couple of decades and are kind of recognized around the globe for, knowing what they are talking about, on this issue. So their scientists put out the information saying that a three year decline in deforestation had reversed and it's now on the increase. So the government is now sending federal troops out into the forest and you know they're using this to help make the case but what they really need is more money to resolve the problem.

Adam Rutherford: Now in your article, you raise the question of whether we're actually beyond redemption with regards to the Amazon, whether we pass some kind of threshold beyond which it becomes impossible to reverse the cause. Could you just explain that and how likely it is if that situation will arise?

Jeff Tollefson: So, there are different theories on this and the scientists are still trying to figure out exactly where such a threshold might be, but some of the modelling results indicate that, you know, as far as deforestation goes, if you get to a point where 40 or 50% of the forest has been logged, then you might reach some kind of a tipping point where the forest no longer produces enough rain to sustain itself, in which case, kind of swamps of the eastern and south-eastern Amazon become Savannas, they become basically incapable of supporting a tropical forest, even if you would let them regrow. So that's one. Another one is with global warming itself, if it gets too hot, some of the weather patterns may change and some models indicate that there will be decreased rainfall and then the same effect happens, you get the Savannization within the south and the east portions of the forest, so you know it's a little unclear on when and if we might hit these points. The problems are fairly severe.

Adam Rutherford: Okay thanks Jeff. Those two articles plus comment are online at http://www.nature.com/nature.

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Adam Rutherford: This is the Nature Podcast. This week's Podium speaker is the Nobel Prize winning physicist, Frank Wilczek.

Frank Wilczek: I was an earnest student in Catechism class. The climax of our early training, as thirteen year-olds, was an intense retreat in preparation for the sacrament of Confirmation. Even now I vividly remember the rapture of belief, the glow everyday events acquired when I felt that they reflected a grand scheme of the universe, in which I had a personal place. But soon afterwards, came disillusionment. As I learned more about science, some of the concepts and explanations in the ancient sacred texts came to seem clearly wrong; and as I learned more about history and how it is recorded, some of the stories in those texts came to seem very doubtful.What I found most disillusioning though was that the sacred texts suffered by comparison. Compared to what I was learning in science, they offered few truly surprising and powerful insights. Where was there a vision to rival the concepts of infinite space, of vast expanses of time, of distant stars that rivalled and surpassed our Sun? Or of hidden forces and new, invisible forms of "light"? Or of tremendous energies that humans could, by understanding natural processes, learn to liberate and control? I came to think that if God exists, He or She, or They, or It did a much more impressive job revealing Himself in the world than in the old books; and that the power of faith and prayer is elusive and unreliable, compared to the everyday miracles of antibiotics and transistors.For many years, I, like some of my colleagues and some recent bestselling authors, thought that active, aggressive debunking was an order. I've changed my mind. One factor was my study of intellectual history. Many of my greatest heroes in physics, including Galileo, Newton, Faraday, Maxwell, and Planck, were deeply religious. They truly believed that they were discovering the mind of God through their scientific studies. Many of Bach's and Mozart's most awesome productions are religiously inspired. Saint Augustine's writings display one of the most impressive intellects ever. And so on. Can you imagine hectoring this group? And what would be the point? Did their religious beliefs make them stupid, or stifle their creativity?Moreover, debunking hasn't worked very well. David Hume set out the main arguments for religious scepticism in the early eighteenth century. Bertrand Russell and many others have augmented them since. Textual criticism reduces fundamentalism to absurdity. And modern molecular biology, rooted in physics and chemistry, demonstrates that life is a natural process; Darwinian evolution illuminates its natural origin. These insights have been highly publicized for decades, yet religious doctrines that contradict some or all of them have not merely survived, but prospered.Why? Part of the answer is social. People tend to stay with the religion of their birth, for the same sorts of reasons that they stay loyal to their clan, or their country.Beyond that, religion addresses some deep concerns that science does not yet, for most people, touch. The human yearning for meaning, our fear of death — these deep motivations are not going to vanish.Understanding, of course, is what science is all about. Many people imagine that scientific understanding is dry and mundane, with no scope for wonder and amazement. That is simply ignorant. Looking for wonder and amazement? Try some quantum theory!Beyond connecting facts, people want to discover their significance or meaning. Neuroscientists are beginning to map human motivations and drives at the molecular level. As this work advances, we will attain a deeper grasp of the meaning of meaning. Meanwhile, medical science is taking a hard look at aging. Within the next century, it may be possible for people to prolong youth and good health for many years — perhaps indefinitely. This would, of course, profoundly change our relationship with death. Freud's theories had enormous impact, not because they are right, but because they seemed to explain why people feel and act as they do. Correct, powerful scientific understanding of our motivations and emotions will have much greater impact.Debunking religion is a thankless task, perhaps we can transcend it.

Adam Rutherford: Frank Wilczek and you can hear Frank talking about the history and future of spin and spintronics on our special physics podcast. That's at http://www.nature.com/podcast. Now from one emotive subject to another. Animal experimentation remains a wholly necessary part of biomedical research, but draws much criticism. The principles practiced by the researchers include minimizing the numbers used and the suffering that the animals experience, but how do we actually account for that? Here's Kerri with the special report.

Kerri Smith: Do lab animals get stressed and how best to avoid causing them more pain and distress than is necessary? Challenging questions indeed and ones that the US National Academies of Science have been trying to answer. This week they published a report on recognizing and alleviating distress in lab animals, the first they've produced in over 15 years. At the AAAS meeting last month, I caught up with two people integral to the new report, Steve Niemi, chief veterinarian and director of the Centre for Comparative Medicine at Massachusetts General Hospital and a member of the report committee and Lida Anestidou, program officer with the Institute for Laboratory Animal Research with the National Academies of Science in Washington. I started by asking Lida to explain the need for this new report.

Lida Anestidou: The first report was in 1992 and it was a report that was going to address both pain and distress that is observed in laboratory animals but back then science and understanding of distress was minimal, therefore the report ended up being predominantly about stress and about pain. And when the request came into the academies to update their reports because its been a while since, of course 1992 we realized that a lot of scientifically based information was available this time around to address distress in its own right and therefore we decided to split the previous report into two sister projects. One, on the recognition and alleviation of distress that came first and the second on the recognition and alleviation of pain which is to follow and be released in December of 2008.

Kerri Smith: So we now have these two reports and the distress report is coming out this week. I wonder if you could tell us a bit about the kinds of findings that we have been making over the last 15 years that you have been able to build into this report which weren't in the 1992 report.

Steve M. Niemi: I think there were three fundamental conclusions in the new version, first that there is a difference between stress and distress and research over the last 15 years has allowed us to distinguish between those two where living organisms of all kinds experience stress on a regular basis and usually that's beneficial because it challenges the organism to adapt and evolve to its medium environment, but there's been a growing consensus on the definition of physiological distress where the animal can no longer cope and so you'll see a permanent or a long-term change in their homeostasis, whether it is keeping body weight, whether it is keeping their immune system up to par. The second element that came out of the revised edition is that we were still not comfortable with psychological distress as opposed to physiological distress. There was recognition that at some time in the future, we'll be able to define mental health and mental disease in laboratory animals with greater accuracy and understand the impact of that, but we're not there yet. And then the third conclusion was that there are still great needs for intended distress in laboratory animals. When we are studying models of human distress and whether that's depression or other psychiatric diseases or other mind-body relationships, there will be an occasion for animals to experience distress intentionally and so that needs to be appreciated and preserved, but the majority of cases these days are unintended distress situations and that's where we think this document can make a lot of positive contribution.

Kerri Smith: And now as an aside, I imagine that those kind of unintended consequences could change results of an experiment quite drastically. What kind of effects might this have on people's research?

Steve M. Niemi: Well, that's a very good question and again over the last 15+ years, we've been able to identify some of those consequences not only because the scientists got better but because the questions they were asking, if animals models has become more sophisticated and more specific and so when we look at genetically engineered mice for example that will be carrying a new gene or have a gene function eliminated, we're seeing behaviour or changes in their biology that were never predicted and so you have to be able to anticipate ways to overcome those either with better communication, so we can detect these sooner and in addition to that, be willing to go to what used to be considered unusual lengths to accommodate the animal, so that you can restore that biology back to normal without compromising the endpoints of the research.

Kerri Smith: Finally then, Lida we've been talking a little bit about the implications for experimenters of this new board. What would like the take-home-message to be for scientists working with animals?

Lida Anestidou: Well I think that the most important contribution of this report to the scientific environment today is to bring first of all the attention to the fact that laboratory animals against perhaps either conventional wisdom or current beliefs, actually do get distressed. I do not want to use the word suffer, but they do get into diseased state – this is a diseased state and as such it not only will affect the validity of the experiments and the data collected, but it also is a matter of animal well-being and welfare, so its also an ethical issue to address how well the animal is adapting to the laboratory environment.

Adam Rutherford: Lida Anestidou ending that report by Kerri. She's back in the studio next week, but that's all for this issue of the Nature podcast. I'm signing off with a wicked fresh rhythms of MC Hawking, that's astrophysicist Steven Hawking to you. MC Hawking a.k.a Ken Leavitt-Lawrence sets the professors voice box to fast hip-hop beats. Here he's explaining entropy.

(Entropy of MC Hawking plays) Defining entropy as disorder's not complete,'cause disorder as a definition doesn't cover heat.So my first definition I would now like to withdraw,and offer one that fits thermodynamics second law.First we need to understand that entropy is energy,energy that can't be used to state it more specifically.In a closed system entropy always goes up,that's the second law, now you know what's up.You can't win, you can't break even, you can't leave the game,'cause entropy will take it all 'though it seems a shame.The second law, as we now know, is quite clear to state,that entropy must increase and not dissipate.Creationists always try to use the second law,to disprove evolution, but their theory has a flaw.The second law is quite precise about where it applies,only in a closed system must the entropy count rise.The earth's not a closed system' it's powered by the sun,so f*** the damn creationists, Doomsday get my gun!That, in a nutshell, is what entropy's about,you're now down with a discount.ChorusYou down with entropy?Yeah, you know me!Who's down with entropy?Every last homey!

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Adam Rutherford: If you're all still listening here's your chance to win an iPod Touch courtesy of the Nature podcast.

Kerri Smith: First you need to listen to the following three sounds of science taken from the podcast archives from autumn last year and then go to our web site that's http://www.nature.com/nature/podcast and follow the link at the very bottom of that page. Here they come.[Music plays with three different sounds]

Adam Rutherford: So identify those three sounds and follow the link from http://www.nature.com/nature/podcast. This competition closes on the 31st of March 2008. Good luck and thanks for listening.(Music)