Nature Podcast

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Kerri Smith: Coming up this week, we are a step closer to Star Wars style 3-D holographic phones.

Geoff Brumfiel: And you may remember that scene where R2-D2 plays a holographic recording on princess Leia to Obi-Wan Kenobi. Well in this week's Nature, a team of researchers have built a system that can write a hologram, erase it, and write a new one in its place.

Adam Rutherford: And we gear up for a special birthday.

Kevin Padian: What he understood about the natural world, the things he observed, the way he re-thought everything, no one has ever done that in biology.

Adam Rutherford: A celebration of all things Darwin, coming up later in the show. This is the Nature podcast, I'm Adam Rutherford

Kerri Smith: And I'm Kerri Smith


Kerri Smith: First, new information about how Alzheimer's disease affects the brain. As the disease progresses, a protein called amyloid builds up in the brain, but it hasn't been clear whether these protein aggregations, known as plaques, are a cause or a consequence of the disease. This week in Nature Brad Hyman at Harvard Medical School in Massachusetts and his team use a new microscopic method that allows them to film these plaques appearing. They were surprised to find them emerging super fast over the course of 24 hours. After that, the other signs of degeneration start to occur. Here's Brad Hyman. Nature 451, 720–724 (7 February 2008)

Bradley T. Hyman: The Alzheimer patient develops in their brain, deposits of a protein called amyloid and for years there's been a debate in this scientific literature about the effects of amyloid on the brain, by using some genetically-engineered mice and novel microscope called a multiphoton microscope, we've been able to actually observe the deposition of amyloid in the brains of the mice while its happening and found several things that were quite surprising to us. At first that the amyloid deposits occur very very quickly so that even though the disease process can take decades, the individual amyloid deposits can occur as rapidly as in a day. Second, once we could see the amyloid deposit get deposited, we could sort out cause and effect to some extent, so that the changes that occur in the neurons that surround the amyloid or in the astrocyte and other cells that the brain uses to protect itself around the amyloid could be determined. So we have sort of a birthday for each individual plaque and then can see what happens to that plaque over time.

Kerri Smith: So I wonder if first of all you could take us through the current theories of what happens to the brain in Alzheimer's disease.

Bradley T. Hyman: If you look at the brain of a patient who has Alzheimer's disease, there are many changes. One of the changes is deposition of the amyloid plaques and other change is the evolution of a different kind of pathology called neurofibrillary tangles, there's neuronal death, there's loss of synapses which are the connections between neurons, so lots of things happen in the course of the disease as might be expected from a disease that takes decades to play out. Sorting out which of those is the primary phenomenon has been very difficult because all of them are happening more or less simultaneously and the new technology that we brought to bare on this question, the multiphoton microscope, really let us get at the very fine detail of what events occur in what temporal orientation, so that we can see a plaque form and then see what the consequences of that amyloid plaque formation on the brain.

Kerri Smith: Okay and as I understand that then you wanted to test in this paper whether these plaques, these protein deposits, are causing the degeneration you see in the brain or whether it's the other way round.

Bradley T. Hyman: Exactly!

Kerri Smith: And what's made it difficult to do that until now. What does your new technique allow you do that you couldn't do before?

Bradley T. Hyman: Before we would have to look at pieces of tissue under the microscope and of course and that happens only once so that you can see a plaque that is present, but you don't know how long it's been in the tissue. It might have been there from the day before, it might have been there a month ago; it might have been there for 5 years. The new microscope allows us to essentially look at the same types of things, but in a living mouse, so that we can look at the mouse on the first day and say "No! No plaques there" and on the second day say "Oh! There is a plaque," and on the third say, "Oh! That plaque that was born yesterday, what effects has it had on the brain" and so forth for weeks to months on end.

Kerri Smith: Wow! So you've got some really high temporal resolution here, you're able take effectively snapshots of the same bits of brain at different time intervals.

Bradley T. Hyman: So it's exactly the difference between taking a snapshot and taking a movie, so instead of having a series of pictures that we then have to, sort of, figure out what order they should have gone in to make the movie, we actually have a video of it.

Kerri Smith: I see. And what did your movies, your results, reveal.

Bradley T. Hyman: The surprising thing to us was that the plaques which we had assumed would form quite slowly in fact deposit very rapidly in the course of about a day, at least in the mice and also that once the plaque forms, a variety of responses to that plaque that evolved something that looks like we've looked at under the microscope for years occur in the subsequent days to weeks.

Kerri Smith: And if these plaques are appearing so fast, I mean, a day is incredibly rapid, how come Alzheimer's disease in a human brain or in a mouse brain even is comparatively so slow in its progression.

Bradley T. Hyman: It's a really good question. In a human brain, there are literally millions of these plaques scattered all over the brain. The appearance of each one of them is a rare event. So we had to take essentially hundreds of hours of movies to see 16 plaques appear, so at any given moment it's unlikely that a plaque happens and for million plaques that sort of accumulate it would take a lot of moments, but each one of those phenomenon is a very rapid event.

Kerri Smith: And so I suppose if you know that these plaques are preceding the other neuronal changes, you have really strong evidence that they are the cause of this.

Bradley T. Hyman: Certainly we have strong evidence that they are a substantial cause of the problems that occur in the brain and also it gives us some ideas about how to not only stop the plaques, but how to stop the subsequent changes that occur.

Kerri Smith: Interesting, that was going to be my next question. If they are genuinely then the cause of these other neuronal changes that are occurring, can anything be done to get rid of them and therefore slow the progression of the disease?

Bradley T. Hyman: Well of course there is a lot exciting work going on now throughout the world and clinical trials already with drugs that hopefully are targeting plaques and the amyloid that makes up the plaques and we're all excited about the possibilities that as that works goes forward, we'll have ways to stop the progression of the disease and potentially even to prevent it.

Kerri Smith: This is basically stronger evidence that people are looking in the right place.

Bradley T. Hyman: Exactly right.

Kerri Smith: Brad Hyman of Harvard Medical School.

Adam Rutherford: Hyman's results relied heavily on a new and fast pace technique for imaging the brain as plaques develop. Another article this week focuses on images of a different kind, which may one day offer even more rapidly changing pictures in the form of 3-D holograms. Here's Geoff Brumfiel. Nature 451, 694–698 (7 February 2008)

Geoff Brumfiel: Let's face it! If you're listening to this podcast you've probably seen the first Star Wars movie and you may remember that scene where R2-D2 plays a holographic recording on princess Leia to Obi-Wan Kenobi. Well in this week's Nature a team of researchers have taken the first step towards making a 'holophone' a reality. They built a system that can write a hologram, erase it, and write a new one in its place. I called Savas Tay at the University of Arizona to learn more about how holograms work.

Savas Tay: A hologram actually is a piece of material, but more important thing about the hologram is that it contains the optical information that would usually come from an actual object and the optical information is recorded into the hologram using laser lights and when you shine a reading beam which could be daylight or another laser light onto the hologram, you can read it out and it will produce the image of that true object.

Geoff Brumfiel: People have been interested in updatable holograms for a while now, why?

Savas Tay: There are certain reasons, the first one is there are certain applications which require updating of the images. The good example is Star Wars obviously, in that movie you see a holographic videophone and obviously as the person moves around you want to be able to see it in real time, so that's the ultimate goal obviously, but in other scenarios you need updating of the information, for example if you're doing surgery and you want to visualize, say the brain of the patients, then as you change things you want to be able to visualize those, you want to be able to update the holograms and the static hologram will not allow that.

Geoff Brumfiel: So how do you sort of go about creating an updatable hologram then?

Savas Tay: I think that the main thing that we bring into table is using new materials that allow dynamic recording of holograms and erasing of holograms. Previously, holographic 3-D displays have been shown using a variety of materials, but unfortunately these materials did not allow erasing of the holograms, so they were permanent therefore updating of the images were not possible. Now we use a type of material called photorefractive polymers and this is the first time that these materials have been used for TV displays, although they have been around for a while and these materials allow dynamic recording of holograms and storage of holograms and you can erase the hologram as you wish, so this erasing capability allows you to record new images onto the same area, therefore you can update, you know, the real time video-type holographic display.

Geoff Brumfiel: From what I've seen in the paper, it seems like it takes a little white to erase an image right? It takes about 120 seconds or so?

Savas Tay: Well photorefractive polymers are capable of real time response and by real time of course it is not immediate, but as long as the response time, it starts with, the so called video rate, that is 33 Hz, it is quite considered to be real time. Now we could have came up with photorefractive polymers with real time properties, but then there would be other problems that would prevent us from generating these, you know, real time holo displays, where the first is you have a certain area and you want to be able to scan the whole area, record it and that takes sometime, so we have realized that real time is rather a long shot, so we go with near real time that is updatable holographic displays, so we came with our photorefractive polymers and tuned their properties so that they have a response time around fraction of a second and it has a persistence time of several hours.

Geoff Brumfiel: So is there any practical application already to even having something that's in between static and real time, are you looking at any uses for this?

Savas Tay: Certainly, the reason we started this whole program is to create 3D displays – updatable 3D displays for command and control centres for military purposes and there is a significant need for that because obviously the battlefield is a very complex and dynamic environment and the changes that are induced in the battlefield are, although they are in real time, it is impossible to report these in real time, so there is always a delay and near real time displays can play a big role in these kind of applications. Others are industrial and architectural imaging and also advertisement and entertainment.

Geoff Brumfiel: So do you think that you're ever going to get a sort of a holophone on princess Leia type communication device, is that somewhere down the road for you guys?

Savas Tay: Yes, obviously that will be real nice and I think the materials are capable of doing that, I mean, photorefractive polymers are already capable of some millisecond response times, but there are other things also that are involved in these kind of displays that is the optics, the mechanics of the display and also computation is the important mission, because 3-dimensional images involve a huge amount of data and processing these data in real time is a big problem.

Kerri Smith: Savas Tay there talking to Geoff Brumfiel - and the idea of bringing Princess Leia to life in any form is sending ripples around certain factions of the Nature office I can tell you.

Adam Rutherford: Hadn't even crossed my mind.


Kerri Smith: Coming up shortly, we resurrect some ancient proteins, but first the current issue of Nature has a set of dispatches from the future. Here's Editor-in-Chief Phil Campbell, from the podium. Nature 451, 643 (7 February 2008)

Philip Campbell: In 1992, I was the Editor of the magazine, Physics World. I commissioned an article from a young computational scientist at CERN. It described how a new system called hypertext might give researchers access to documents anywhere. He wrote, "Let me assure the cynical that to a certain extent this exists and where it exists it works, it seems to be taking off." Whatever physics has done since at CERN or elsewhere none of it has had such a dramatic and unpredicted impact on humanity as what became the World Wide Web. So it is with some humility that this week Nature offers a suite of forward-looking articles under the rubric Horizons. These represent the visions of expert and yes experts can get things horribly wrong, especially when they assert what's not possible as Arthur C. Clarke said. But when experts say what is possible they can be inspiringly right. In that spirit, my colleagues and I commissioned 5 experts to give us their sense of what should happen over the next few years. This collection of visions is not comprehensive. We wanted a mix of fundamental and applied science, about topics that could make a major difference to research and beyond. We asked the writers to articulate their particular un-refereed agendas for their disciplines. Tom Kirkwood for instance champions the advantages of one approach to researching human aging. Taking the example of human skin cells, he shows how a systems biology approach predicted an unexpected role of mitochondria in cellular aging. Other authors describe how exploring nanomaterials and biological material structures should furnish us with batteries to power the computers and transport of the future and how tailoring interactions between light and matter can help deliver the supercomputers of the future. And Georgy Koentges shows how the marriage of fossil evidence, genomic sequencing and molecular developmental biology promises to reveal more about how we came to evolve. The vision that chemist Peter Murray-Rust articulates is at one with that of Tim Berners-Lee, the young researcher from CERN who I published all those years ago. Peter writes about the next generation of the web in which computers can make as much use of information as humans can and indeed more. To attain this requires an enormous amount of community cooperation as he explains, but the gains for chemists and for everyone else will be enormous. I hope that you will read these visions and be inspired by them, perhaps even adjust your research ambitions accordingly. Meanwhile we at Nature will continue to scan the horizon to bring you more dispatches from the future.

Adam Rutherford: Phil Campbell there, those Horizon articles are on our web site along with all the papers featured in this week's show at

Kerri Smith: Turning the clock back rather abruptly we whiz back over 3 billion years to take the temperature of the early oceans and the hardy bacteria that lived there, Charlotte Stoddart reports.

Charlotte Stoddart: Working out what condition to alike in the ocean around three and a half billion years ago when life began and how they have changed as life as evolved, is pretty tricky. Geologists tackle this subject by digging around in rocks to find out about the chemical composition and temperature of the early ocean and atmosphere, but now a team of molecular biologists have entered the field delving into genomes of bacteria to rewind the tape of life. Eric Gaucher and his colleagues reconstructed a family of proteins that assist protein synthesis, they're called elongation factors, to find out how their structure changed as millions of years passed. By figuring out the temperature at which these proteins worked best, they are able to estimate the temperature of the environment and they found that the ancient ocean was a scorching 75 degree Celsius, similar to today's hot springs and then cooled by 30 degrees or so over the following 3 billion years, a finding which matches the temperature trend inferred from the geological record. Eric explained his approach to me. Nature 451, 704–707 (7 February 2008)

Eric A. Gaucher: We have adopted the concept of ancestral gene resurrection, the typical analogy that we offer is that of historical linguistics determining the relationship of spellings of what is in modern languages you can estimate what a spelling or even a pronunciation of a word was in an ancient or extinct languages. So we did the same thing, instead of studying words we studied genomic sequences and tried to resurrect ancient genes.

Charlotte Stoddart: And the words, or genes, that you resurrected code for family of proteins that facilitate protein synthesis in cells, so why did you choose this protein?

Eric A. Gaucher: So our research attempts to describe the evolution of early life ideally to the last common ancestor of bacteria, which probably lived at least three and a half billion years and so we resurrected a gene whose property in modern form reflects the environmental temperature surrounding the genes organism or host, so this means that for an organism that lives in a hot environment the protein we study is only functional at hot temperatures. The conversely found organism growing in a cooler environment, this protein is functional only at cooler temperatures, so on a sense then our genes family only served as a thermometer not only for modern life but potentially for ancient life as well.

Charlotte Stoddart: So you traced 2 bacterial lineages back to their origin about three and a half billion years ago and at various points along the way you've worked out the structure of this gene what did you discover?

Eric A. Gaucher: Well from the resurrection at different time points in the geological scale, in total we resurrected more than 20 ancient proteins and what we found was that all this resurrected proteins were the most thermal stable or heat tolerant and they could function around 75 degree Celsius. The ancient proteins representing a time point of about 500 million years ago however functioned at much cooler temperatures and were thus heat intolerant and these were stable about 40 degree Celsius and the remaining ancestral proteins had intermediate temperatures, so when we plot these results as the function of temperature versus time we discovered a slow progressive 35-degree cooling trend for the ancient proteins and this trend overlaps remarkably well with the palaeotemperature trend inferred for earth and ancient ocean based on the isotopic composition of sedimentary rocks deposited at the bottom of the ancient ocean and then that geologic evidence suggested the same 35- to 40-degree cooling trend across the same 3 billion year timeframe of our study.

Charlotte Stoddart: So if we assume then, that life evolved in an ancient ocean that was very hot and then cooled progressively over time, what does this tell us about the evolution of life on Earth, I guess life has had to adapt to a changing, cooling environment?

Eric A. Gaucher: That's right, so one of the interesting additional conclusions of our work is that we can kind of tie in the temperature trend to the rise in oxygen in the ancient atmosphere. Our current understanding of the temperature limits of photosynthetic microbes called Cyanobacteria suggest that photosynthesis can occur above temperatures of about 65 or 70-degree Celsius and based on our results in conjunction with the geologic records, it seems like these temperatures around 65 or 70 or below tend to occur until about 2.5 billion years ago, so this is roughly 200 million years before the great oxidation events. So life's ability really to produce oxygen as a bi-product of metabolism may have been prevented by high temperatures in the early Earth, so it was not entirely environment cooled, but the biochemical pathways of some bacteria were able to adapt photosynthetic machinery and therefore release oxygen into the environment and thereby potentially paving way for multicellular life forms.

Kerri Smith: That was Eric Gaucher from the University of Florida. Now February the 12th is the 199th birthday of Charles Darwin. We at Nature have begun gearing up for next year's bicentennial celebrations and the 150th of his masterpiece, 'On the Origin of Species'.

Adam Rutherford: And to start the party we asked evolutionary biologist, Kevin Padian, to write about Darwin's endearing legacy, not just his revelation of natural selection but the many other aspects of his work that remain crucial to the study of evolution and life. I spoke to Kevin and I asked him how you can top a theory as robust as natural selection. Nature 451, 632–634 (7 February 2008)

Kevin Padian: It is really hard to trump natural selection but you know he did it in his next big book, The Descent of Man with sexual selection. He said, "Look there's got to be a balance here sometimes when competition for resources isn't always coming down to who's got the biggest ability to compete and fight and sometimes it's who gets the mates and leaves their traits in the next generation. You know, he knew that it was just as efficient from times as battling it out and so this whole idea of sexual selection, which revolutionized another great piece of biology that's something that we think about everyday but we don't realize that this comes from Darwin.

Adam Rutherford: And what about Darwin's other ideas that natural selection relies upon?

Kevin Padian: One of the things about Darwin is that he knew that he required a whole lot of time in order for his ideas to work. He knew there were lots of variations, he knew that they didn't really, in most cases change populations very quickly and he understood the fossil record very well. He knew that he would have to have vast eons of time for this to happen and the physicists at that time like Lord Kelvin said, well there is enough time to do that but of course his model is a little bit off and Darwin was irritated by that but he knew what the rocks told him and he just kept on working out his ideas and okay, you know, some of his numbers were off but some of his numbers were uncannily correct. This is a man who really thought things out very well. And the other thing to say, I think it's really overlooked is his concept of what I would call selective extinction. It is a kind of a sorting and its one reason why many of the organisms we have today are very difficult to look at and say "oh! That's obviously related to this." We know today that crocodiles and birds are each other's close relatives but we wouldn't know that if it weren't for say DNA studies, we wouldn't know this if it weren't for finding lots of forms in the fossil records that are connecting these things including all the dinosaurs and many other things from the Triassic and even earlier. This is a kind of a selective extinction that proves the tree of life in ways that makes things very difficult to discern the relationships and Darwin understands this and he knows this is an impediment to classification and he knows the fossil record. In his time, it is not complete enough to solve all the problems but he couldn't have foreseen how things like DNA and genetics and various other kinds of molecular techniques would help as well, I think if he were alive today, he would just be thrilled.

Adam Rutherford: And of course he did all of this without any sort of knowledge of genetics which didn't come till several years after The Origin was published. It reads like a great work of humility; it's almost as if he is apologizing for how strong his theory is.

Kevin Padian: Some Darwin scholars would claim that he really didn't need genetics at all; that his world-view is the world-view that makes sense. It doesn't matter whether you are talking about gemmules as he did or any other kind of mechanisms; what counter the effects of genetics which other characters of heredity that pigeon fanciers and farmers and breeders of his time and for centuries before him no less than Darwin understood very very well. Okay he didn't understand heredity in the same way that we understand it today with all the sorts of mathematical probabilities that we can use for various combinations of things and this is actually with the great revolution of the modern synthesis of evolution which comes up in the 1930s where people start to use mathematics to make estimates of population genetic changes. These were the people in 1930s, who resuscitated Darwin's idea of natural selection which had been really pretty much abandoned in the decades before that.

Adam Rutherford: So after almost 150 years, how is The Origin of Species holding up?

Kevin Padian: Well I think that you can take any work and look at it, objectively no matter when it is published and say is this stuff still holding water, does it make sense or the fact is still right, for example are the lines of evidence cogent, is the argumentation valid and with Darwin you're looking at you're going to, well I mean this guy had it in a way that the other people who wrote books in those times don't anymore; not Owen, not Huxley, certainly not Buffon or Lamarck or anybody like that who wrote about biology. That's really the proof of it. If it still reads well, it still makes sense, then it is a great book and when you strip it down you realize that he is not a man writing in 1930s or 1980 or 2008, he strained before Victoria becomes queen essentially. He is a pre-Victorian and yet what he understood about the natural world is things he observed, the way he rethought everything no one has ever done that in biology.

Adam Rutherford: Kevin Padian's article is online at and incidentally he recommends that the best form of celebration for Darwin day would be re-read his original and still watertight Origin of Species. Happy Birthday Charles!

Kerri Smith: And instead of singing happy birthday, our sound of science is a premiere from a new oratorio called 'The Origin' by Ian Assersohn. This clip is from a movement called "Over all the causes of change" as performed by the Leatherhead Choral Society and conducted by the composer. I am Kerri Smith.

Adam Rutherford: And I am Adam Rutherford thanks for listening.

[Sound of Science]


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