Nature Podcast

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Kerri Smith: Coming up:

Judith Campisi: Is it possible to keep humans healthier, longer and if so how can we possibly decide who will have access to this technology or not?

Kerri Smith: We will be grappling with those questions later in the show.

Geoff Brumfiel: A new theory on conflict within the genome:

Christopher Badcock: If it were to prove right, it would provide a completely new basis for psychiatric diagnosis and classification.

Kerri Smith: And you might think that steam trains are a technology of the past, but:

Alan Fozard: It's now possible to design steam locomotives, which have twice the thermal efficiency of steam locomotives that were built in the 1950s.

Kerri Smith: We look to the future of transport on the rails, roads, and water. This is the Nature Podcast. I'm Kerri Smith.

Geoff Brumfiel: And I'm Geoff Brumfiel.

Geoff Brumfiel: For the past few weeks Nature has been running a series of articles on new transportation technologies and this week we have three mini reports on the topic. We've got cars and ships coming up, but first off trains. Here's James Morgan.

James Morgan: The rail passengers here at London's Waterloo station, travelling by train is a green alternative to driving, but the vast majority of the world's trains are not passenger vehicles but haulage locomotives, running on diesel engines which produce a significant junk of the world's CO2 emissions. Steam power may seem an unlikely alternative for reducing those emissions but in fact, new second generation steam engines could provide us with a cleaner, greener alternative to diesel. So says Dr. Alan Fozard, Commercial Director of the 5AT Project. Published online 27 August 2008, Nature 454, 1036–1037 (2008)

Alan Fozard: Many people think erroneously that steam engines reached its full potential, in fact it didn't because it's now possible to design steam locomotives which have twice the thermal efficiency of steam locomotives that were built in the 1950s.

James Morgan: So although some people think of steam as part of the industrial revolution, you think that steam engines can actually help us in our current green transport revolution.

Alan Fozard: Well, there is one point in favour of steam locomotives which isn't generally recognized, it's possible to reasonably readily modify the locomotives to run on different types of fuel including, of course solid and liquid fuels, coal, oil of course, but also wood and other biomass materials.

James Morgan: So you are part of the Commercial Planning Team for the 5AT project. Could you tell us what the 5AT Project is and what it aims to do?

Alan Fozard: Well, the 5AT Project is concerned with the developments of a steam locomotive originally conceived by the steam locomotive engineer David Wardale. The locomotive design would be something like twice as thermal efficient as older steam locomotives developed in the 1950s. In fact although it's a relatively medium size locomotive it would be more powerful than any steam express locomotives that had been designed previously in the UK.

James Morgan: And do you think there are commercial markets today in Britain and elsewhere for steam engines?

Alan Fozard: What we are looking at it as, is a demonstrator for second generation technology steam. I think it's particularly suitable for niche markets, not particularly mainline in the developed world but in the developing countries where the shortage of fuel and high cost of fuel, we might say it for example being used to carry coal from mine to coast in those countries which have inland coal mines.

Geoff Brumfiel: That was Alan Fozard talking to James. More from him later, also coming up on this week's show why antibiotics might be bad for your immune system.

Kerri Smith: But before that how sharing can be good for society. In George Orwell's book, 'Animal Farm', the pigs go back on their promise of equality by painting a sign saying all animals are equal, but some animals are more equal than others, which seems rather unfair to the animals and us readers, but are we born with this sense of egalitarianism, or does it develop and if so when does it start to appear. That is the question that Ernst Fehr of Zurich University and his colleagues wanted to answer. We already know that our concept of fairness set us apart from animals, give a chimp the option of giving another chimp a candy at no cost to himself and he won't actively choose to, but how do young children do with this type of choice. Here's the aptly named Ernst Fehr. Nature 454, 1079–1083 (28 August 2008)

Ernst Fehr: Our main result is that at age 3 children are basically almost completely selfish while at age 8 strong forms of egalitarian preferences developed that distinguish human children from chimpanzees.

Kerri Smith: So, to do that then you enlisted over 200 children between, sort of, 3 and 8 to help you test that out. So take us through the three types of little games that each child would play and I am sure this version sounds to me like much more fun in the adult version, because instead of money the currency is jelly babies and things.

Ernst Fehr: The currency is jelly babies, fizzes and other sweets and each child plays three games for sweets and in game 1 which we called a Pro-social game, the child has as in any other game has two choice options. Choice option A means that the child gets one unit of sweet and the partner of the child gets one unit of the sweet. Choice B means that only the child gets one unit of sweet. So the child always gets one unit regardless of which option it chooses and that means it can without cost for him or herself benefit the other child. This is not costly for the child to be nice to the other person. Then we have a game we called envy game, choice option A is again one for me and one for the other. Choice option B is one for me and two for the other. So now here the question is, is the child willing to give the other child two units of the sweet without being hurt, him or herself and what we find here is that at age 8, we all have almost universally the egalitarian choice. So almost all children do not want to give the other child two units and finally we test for a strong form of altruism because in the third game, the child can again choose between one for me and one for the other and now option B is two for me and zero for the other. Now it's really costly sharing that is investigated. Is the child willing to give one unit away to the other child that's cost to the donor and a benefit to the recipient and what we found here is that about 45% of the children are willing to do this at age 8, but almost no children are willing to do this at age 3 and now what we find here over time is a very strong increase in egalitarianism.

Kerri Smith: Now you also looked at whether a child had siblings or not, so whether these were older or younger siblings had an effect on how much they cared about equality. Could you briefly tell us which children out of those groups were most or more bothered by it, more concerned?

Ernst Fehr: Well, we have one surprising effect and that's the only child effect. Only children turn out to be more altruistic, so they are more willing to share even when it is costly for them and then we have a youngest child effect, the youngest children in the family regardless at what age they are between 3 and 8, the youngest children are the most selfish ones. So we have an only child effect and a youngest child effect.

Kerri Smith: And how about George Orwell's idea that in Animal Farm that all animals are equal but some are more equal than others. Did that kind of thing apply to the children? Did they show more of a bias towards fairness when they knew the children were from the same school as them or the same playgroup?

Ernst Fehr: Yes, we had a very strong in-group, out-group effect. Towards the in-group altruism increases over time, so the willingness to share increases over time, but when the partner is an out-group member the willingness to share decreases over time even.

Kerri Smith: And I suppose that might be evolutionarily useful to have that bias.

Ernst Fehr: Well, we speculate a bit why is that? Why do children already at such an young age exhibit such a strong in-group, out-group bias and I mean some theories of the evolution of altruism put forward the hypothesis that altruism is just the other side of the coin of not being nice to out-group members. So basically, altruism develops towards in-group members but no towards out-group members. It's really an in-group phenomenon and it coevolves, so basically altruism and parochialism, that's how it's called in the literature, seems to co-evolve.

Kerri Smith: Ernst Fehr. Later on in the show, we will be finding out how fast science can get us in the quest to lengthen our lives.

Geoff Brumfiel: First though, Charlotte Stoddart sorts the good from the bad in the world of bacteria.

Charlotte Stoddart: Our bodies and in particular our guts are teeming with microbes. Most are harmless, but occasionally an infection of hostile bacteria makes us ill. We treat such infections with antibiotics, but as well as killing the target bad bugs these drugs deplete our good bacteria, know as the commensal flora, and this enables dangerous infections to take hold. In other words, giving patients antibiotics makes them more susceptible to nasty drug-resistant bacteria. To find out how, a team at the Memorial Sloan-Kettering Cancer Center in New York, exposed antibiotic treated mice to the hospital superbug VRE, Vancomycin-resistant Enterococcus. I called team member Katharina Brandl. Nature advance online publication (24 August 2008)

Katharina Brandl: So, we have in our guts the normal commensal flora which everybody carries and there is nothing dangerous about the commensal flora, but there are of course bacteria around which are orally acquired like VRE which can become dangerous.

Charlotte Stoddart: And we normally treat these harmful bacteria with antibiotics. But what are the side effects of using these antibiotics on the commensal flora, the good bacteria?

Katharina Brandl: What has been widely assumed is that if you treat patients with antibiotics, you basically eliminate the commensal flora and that can then open intestinal niches. So if you get rid of the commensal flora through the antibiotics treatment, you basically make space and provide nutrients for dangerous bacteria which can come in and thereby you enhance directly the survival and proliferation of, now for example, VRE what we were working with.

Charlotte Stoddart: And Katharina how did you get interested in antibiotics and the effects they have on gut flora?

Katharina Brandl: So, this work was performed at the Memorial Sloan-Kettering Cancer Center and we have a 450-bed hospital. So in 2007, we had 70 cases of VRE and every single one of them happened in patients under antibiotics therapy. So we wanted to understand why these hospitalized patients are so susceptible against these antibiotic-resistant bacteria and we were wondering if it's more than, if you kill the commensal flora and then just provide space and nutrient.

Charlotte Stoddart: Did you come up with another explanation then?

Katharina Brandl: So, we know from others that commensal microbes in the intestine induce the expression of proteins that restrict, for example VRE proliferation, thus where as commensals directly restrict VRE proliferation. We had this alternative hypothesis that commensal microbes also can inhibit, for example VRE indirectly by activating mucosal innate immune defences.

Charlotte Stoddart: What happens to the production of these bio-molecules when we add antibiotics?

Katharina Brandl: We found that when we test the mice on broad spectrum antibiotics then we get rid of our commensal flora and these stimuli are absent. So we don't produce anymore antimicrobial molecules and we found that if you get rid of these commensal stimuli, you basically can kill dangerous bacteria much less efficiently.]

Charlotte Stoddart: So, that sounds to me a bit like we need to stop giving people antibiotics and just let their own immune system get on and do the job.

Katharina Brandl: We certainly need antibiotics to treat dangerous bacteria, but I think our work suggests that we might use some molecules to fool the mucosa into believing that commensals are still around or still present and that we can then through the administration of these molecules induce the antimicrobial molecules.

Charlotte Stoddart: So you're suggesting that we give patients two drugs, the antibiotic plus an extra drug which stimulates our body's own antimicrobial defences. How difficult will it be to develop this new drug?

Katharina Brandl: I mean so far our study which was done in mice, we used basically oral TLR ligands which are ligands for these receptors which stimulate the production of antimicrobial molecules and we don't know so far which of these TLR ligands can apply to humans and I think our work can only suggest very carefully the science that is with the molecules which increase the levels of Reg3g or other intermicrobial molecules and thereby enhance the killing of dangerous bacteria in the gut.

Geoff Brumfiel: Katharina Brandl there. Coming up shortly, a theory on how conflict in the genome could explain a spectrum of mental disorders, but before that for the second of our transport mini series, we find James Morgan aboard a water taxi on the River Thames.

James Morgan: The shipping industry makes a major contribution to global greenhouse gas emissions, emitting more sulphur dioxide than all land transport combined. To make shipping greener, researchers are trying to design technologies which can help our existing vessels to glide more easily through the water. I spoke to Dr. Yoshiaki Kodama, Japan's National Maritime Research Institute to hear about his idea to inject a blanket of bubbles underneath boats. Published online 20 August 2008, Nature 454, 924–925 (2008)

Yoshiaki Kodama: Microbubbles is just air bubbles injected at the bottom of a ship running at sea and we are planning to apply microbubbles to a slowly moving ship which are usually very large and they have a very flat and wide bottom, so we though that if we inject air bubbles near the front they will cover the entire flat bottom very efficiently thus reducing the skin friction efficiently.

James Morgan: So instead of sailing on water the ship is gliding on air, how much fuel will that save, how much more efficient is that?

Yoshiaki Kodama: We hope to save energy by as much as 10%, but so far we have succeeded in saving as much as 5% and that was the value we obtained in our recent full-scale experiment.

Geoff Brumfiel: Yoshiaki Kodama of Japan's National Maritime Research Institute with his intriguing bubble boat concept.


Kerri Smith: We turn next to a peculiar group of genes and a theory on how they might be responsible for a wide range of psychiatric conditions. They are the so called imprinted genes. I went to see Christopher Badcock of the London School of Economics, who explained what they are and how he and his colleague Bernard Crespi think they might be responsible for disorders as different as autism and psychosis. Nature 454, 1054–1055 (28 August 2008)

Christopher Badcock: They are really the biggest surprise since Mendel. Because Mendel discovered that in sexually reproducing species, every individual gets complete set of genes from each parent giving them 2 sets and normally you use both and indeed need both, so it was a big surprise to discover in the 1990s that there are some genes which although you inherit them from both parents they are only expressed from one of them and this is deeply surprising because you do seem to be shooting yourself in the foot; I mean, it's a bit like somebody throwing away that backup copy of their manuscript, you know why, why trash the backup when you might need it and rely on one. With the exception of the placenta before birth, after birth more of these imprinted genes, genes that are only expressed from one parent, are expressed in the brain then anywhere else and that's very surprising given how important the brain is.

Kerri Smith: So the brain is important and there's lots of them there and they themselves seem to be so important that we are almost able to sacrifice, you know, this benefits of having one gene to cancel out the other. So what are they doing there that they are that crucial?

Christopher Badcock: Of course this is the big controversial question and the best answer so far I think most people would accept relates to conflict over the provision of resources. In mammals, the mother makes a vast contribution to the offspring, in fact all the contribution up to the moment of birth with the exception of a single sperm that comes from the father. So, the answer is that as far as we know the best theory we've got about imprinting seems to be that it expresses conflict between the mammalian parents over the size of offspring and their level of investment.

Kerri Smith: You have taken the conflict hypothesis one step further, haven't you and applied it to cognitive disorders, disorders of psychosis and at the other extreme of the scale, autistic spectrum disorders. Talk us through that.

Christopher Badcock: The important point to realize about this and this is the other big surprise about imprinted gene expression is that imprinted genes are expressed in different parts of the brain. The finding here is that in the mouse brain, maternally active genes are expressed in the equivalent of the neocortex and the underlying striatum and paternally active genes are expressed mainly in the hypothalamus. So what this suggests is that this genetic conflict we've been talking about between the mother and the father is built into the brain.

Kerri Smith: And how could that conflict lead to mental disorders.

Christopher Badcock: Here the idea is that if there's an overbalance as it were of paternal gene expression in the brain, you might get the so called extreme male brain and what the extreme male brain theory says is that autism is the consequence of taking typical normal male cognitive tendencies to an extreme. They certainly show deficits in understanding body language, people's frame of mind, stuff like that. Our theory suggest that it may be not so much of a question of an extreme male brain, but an extreme paternal brain in the sense that what may be happening is paternally active genes have been over expressed in an autistic and as a result, they have developed what we would prefer to call an extreme paternal brain.

Kerri Smith: So, if autism and similar autistic spectrum disorders are the results of overexpression of paternally expressed genes what about maternally expressed genes, what about when they are upregulated as we would say.

Christopher Badcock: What you would expect if this theory is right is that if autistics were kind of a caricature of male mentality, psychotics ought to be caricatures of female psychology and we already know that they are good at what I would call mentalistic skills, reading people's mind, respond to their emotions and so on.

Kerri Smith: What eventually could be the implications for diagnosis for treatment even of psychiatric conditions of having this theory?

Christopher Badcock: If it were to prove right, it would provide a completely new basis for psychiatric diagnosis and classification. Because you see one of the implications of this, is that if there is what we would call a mentalistic continuum ranging from extreme hypomentalism, too little theory of mind autism-spectrum disorders to extreme hypermentalism, too much theory of mind in psychotic spectrum disorders, normalcy sits in the middle, my own personal view is that there is no absolutely central point of sanity as it were. We are all off slightly disposed towards the autistic or the psychotic spectrum to some extent. But most of us get away without other people noticing too much. Our theory suggests a new way of looking at these kinds of diagnosis and also new kinds of therapies. For example, one implication is that psychoanalysis is probably the worst kind of psychotherapy you can have if you are on the psychotic side of the spectrum, because it encourages people to over mentalise, to think too much, to analyze too much. Our theory would suggest that will only make things worse.

Kerri Smith: Christopher Badcock and the essay that he and Bernard Crespi have written on their theory is available from

Geoff Brumfiel: James Morgan's water taxi took him indirectly to traffic choked King's Cross from where he sent us this report on the cars of the future.

James Morgan: As the world grows more and more dependent on automobiles manufacturers are under pressure to make existing engines less polluting. Ricardo, UK have designed an engine which they believe is 27% more fuel efficient than existing models. I spoke to Dave Greenwood, their project's director for advanced technology. Published online 13 August 2008, Nature 454, 810–811 (2008)

Dave Greenwood: Well, the challenge for the gasoline engine is in trying to deliver high efficiency in the way the diesel engine is able. Primarily then what we are trying to do to deliver that is to make the engine as small as possible, but still be able to deliver the power and the torque which is required to respond to the driver's input. And what we are doing with the 2-stroke/4-stroke engine is to try and take that trend to its extreme and look at the smallest possible engine that we can build which will deliver the driving requirements for the vehicle. So the 2-stroke/4-stroke engine operates in a 4-stroke mode like a conventional engine under normal low throttle driving conditions, but when you do need to increase the level of torque available especially at low speed, it switches into a 2-stroke combustion mode, so now we have 2 firing strokes in every 2 revolutions as opposed to one firing stroke in every 2 revolutions that you would see from the 4-stroke engine.

James Morgan: How much fuel would drivers save on the average journey by having this engine in their car?

Dave Greenwood: Well, by allowing the engine to run as a very small engine in 4-stroke mode or for the European drive cycle which is a typical mix of in city use plus some motorway in extra urban use, we are predicting a 27% fuel saving over a gasoline engine of the equivalent performance.

James Morgan: 27%, I mean that's a significant saving isn't it, on a machine's hands, hands on money and do you envisage in the future that you could go even further and approach the X Prize Foundation's target of 100 miles per gallon.

Dave Greenwood: To do that with just the combustion engine would be extremely challenging. We see this 2-stroke/4-stroke research is pushing the downsizing on its own about as far as we can. If we push the downsizing much well than this then actually the fuel economy can get worse again. That is the point at which you end up running a small engine extremely hard and you have to take measures to protect the engine which tends to cost in fuel consumption. So, I think to reach a 100 miles per gallon, with a purely internal combustion engine and no forms of hybridization or breaking energy recovery would be extremely challenging. I think if we are to meet the CO2 targets that we've laid down within Europe which are inline with Kyoto then by 2015 and beyond we will have to have an increasing level of hybrid vehicles in the fleet. I don't think it is the panacea which is going to be applied to every single vehicle in the fleet, but those which have a highly transient operating nature, so for instance those used in cities or mixture of cities and outside of cities, they will see significant benefits and in order to meet our CO2 targets we'll have to see an increasing penetration of hybrid in those applications.

Kerri Smith: Dave Greenwood there of Car Technology Company Ricardo, UK.

Geoff Brumfiel: Now while we are thinking ahead what about your future. Hopefully you're looking forward to a long full life but it might be that your life will be even longer and fuller than you imagined. That's because aging researchers are making great progress in understanding aging. Judith Campisi of Lawrence Berkeley National Laboratory has written about the future of aging research in this week's issue. I called her to find out what sorts of results scientists have been able to achieve. Nature 454, 1065–1071 (28 August 2008)

Judith Campisi: Amazing results, especially in worms. These little tiny nematodes they are about a millimetre in length, they live a couple of weeks and the record I guess now is to extend the lifespan of that animal 10-fold. So this is done by simple genetic manipulation, usually changing only one gene and so this was a surprise to the aging research community that single gene mutation could cause such very large differences in life spans in this simple model organism and I should point out many of the basic processes of life are conserved between worms and humans and so it was not unreasonable to assume that if you could change the life span of a worm 10 folds with a single gene mutation that similar genes of longevity might be possible in higher organisms.

Geoff Brumfiel: That's an amazing result, but it also brings up another question which is what exactly is aging, I mean, what does it mean?

Judith Campisi: Yes, that's a great question. So, first one of the things we tried to do in our article is distinguish lifespan from aging. Secondly, we do point out though, that for many of these long-lived mutant simple animals, both deaths and aging are postponed. So for many of the mutant worms when they are 3, 4, 5-folds out in their lifespan extension they are still healthy, they are still moving like a younger worm. So these single gene mutations postpone both death as well as the degenerative changes that we associate with aging and that's really what aging is, it's multi-system degeneration.

Geoff Brumfiel: What do you think needs to be done to, sort of, move the study of aging forward to get from, you know, what we are seeing in worms to ant and even in fruit-flies and mice to sort of really understanding the human system?

Judith Campisi: Some of the very large gaps that exist in our knowledge are first of all are the pathways that we have identified in simple organisms like flies and worms are they conserved in humans and I think the evidence is mounting that that's the case, but what we don't know is whether there are other pathways that have yet to be discovered and this gap in our knowledge can only be filled by the very inefficient and rather random process of basic research.

Geoff Brumfiel: When I was reading through your review here, I have to say I detected there was a little bit of an agenda that you seem to sort of imply although I am not sure you ever came out and said it. There's being a lot of promises made in this field right now, you see a certain amount of snake oil out there being sold to the public. Do you think that's true?

Judith Campisi: There has always been snake oil in the field of aging. It's much more so than any other major field in biomedical research and I don't know if there is any more or less of it now, but what has changed is that we really have the tools to begin to attack this problem on a scientific level. We should be cognizant of the fact that the scientific process can now start dissecting what is and is not possible and it should be done based on science rather than based on wishful thinking or fear.

Geoff Brumfiel: Obviously and sort of the naiver sense extending lifespan is good and living longer something that we all want quite instinctively but this isn't really going to get rid of the problem of death and if we live 10 times longer to curse me there's going to be a whole lot of other problems created by that. What's the point really? What are we trying to do here?

Judith Campisi: Well, we have already done it. Right! In the last hundred years, improvements in public health and biomedical interventions have extended lifespan quite a lot, extended quality of life quite a lot. I can even remember as a young child, 50 was old and it's just not old anymore. I think the important question is, is it possible to keep humans healthier, longer, than we already have and if so how can we possibly decide who will have access to this technology or not. We have to really extend it to all human kind. Now at times I am pessimistic but at times I am also optimistic that if humans really have to live more with the consequences of their actions, we might not have some of the problems we have right now.

Geoff Brumfiel: Judith Campisi there.

Kerri Smith: That's all from us for another week. Back next week 4th of September with more of the best from Nature. Must go or we'll miss that bubble boat. I'm Kerri Smith.

Geoff Brumfiel: And I'm Geoff Brumfiel. All aboard!


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