Cafe Scientific, Southampton, UK, past talks , end of 2016

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Some summaries etc of past talks held at the venue, The Southwestern Arms (upstairs room) , 36 Adelaide Rd, St Denys, SO17 2HW
Some hosts are not alowing remote linking now , so to view a "forbidden" picture you have to right click on the mouse and select "view". Not verbatim, and there will be homonyms, transcription, transliteration, typing and spelling errors and misattributions in the following write-ups. Q&A , grouped under one "Q" or ? terminator tend to be dialogue with / multiple questions from one enquirer. ? for unheard / masked words , ??? for phrases.





Monday, 12 Sep, 2016 Prof Nils Andersson Gravity Group and STAG Research Centre Mathematical Sciences University of Southampton Title: Catching the wave Synopsis: The breakthrough associated with the direct detection of gravitational waves is one of the biggest science stories of the last decade. It lays to rest nearly a century of discussion and speculation and opens a new window to the universe. In this talk, I will provide a general introduction to gravitational-wave physics, discuss the challenges associated with this area and describe what the detections have taught us about the universe. I will also touch upon what we may hope to learn in the future. 37 people, 1.75 hours This is one of THE science stories of the year or perhaps the decade, some people claim for the century. Almost bang on the day of fist discovery og GW, it was very close to 100 years since Albert Einstein predicted they should exist. If it takes a100 years for someone to prove its right , that tough going. Part of my talk is as to why it took 100 years , then what actually happened and then the future. How do we understand the universe we live in, how do stars work. Historically astronomers are looking at the sky with ever improving telescopes, trying to figure out what stars atre doing. O(r go back 50years and ask what happens when we get better and better telescopes looking at different wavebands. Snapshots of galaxy M81 from Xrays 10nm to radio at very long wavelengths. Looking at the different images, you get very different impressions of what is going on. As we've opened up more wavebands , after WW2 when radar was adapted to become radio-astronomy. We went through Xray revolution of the 60/70s , improved optical with Hubble space telescope etc. You still see the galaxy core in all these images but you can see there are diffwerent things going on . So more complicated today, than just loking through an old style backyard telescope. Over the last 50 years we've learnt the universe is not ths place where stars glide serenly across and nothing much happens. Evolving so slowly that no one really cares, because we don't live long enough. We've learnt that is plain wrong. The universe is a violent place where things go bang, crash together 3etc. Stellar evolution, born and die, they can end their lives in massive explosion supernovae. So they can have a more interesting afterlife , in some sense, than their actual life. Becaus ewe believe the most exotic objects that exist in the universe, are black holes that don't shine at all or neutron stsars the most dense objects you can imagine. Artist impression of Cygnis X1 a suspected black hole in the galaxy that is feeding off a partner blue giant star, into an acretion disc . The black hole in the centre and as the matter is accreting , then for some reason we don't quite understand , because numerical simulations cant quite reproduce it, matter is ejected in powerful jets. We think this is the archetypal black hole i nthe galaxy. We've learnt a lot bu the problem is , if we want to look to the dark side of the universe then from the fact of dark-side , trying to look at them with light is not so good an idea. Black holes don't shine, so how do you look for them. We think we see black holes presence by the imprint it leaves on matter surrounding it. One candisdate is the gigatic black hole at our galactic centre, something like 3 million times the mass of the sun. We know as much as we do about it , by the way that stars move in the vicinity of our galactic centre, still very far away from the black hole itself. Nothing tells us what is going on at its centre. If we want to test ideas about the dark universe , black holes etc, how do we go about it. I believe we need a different kind of telescope , instead of looking, listens to the sky. The topic of the talk, we need to start listening. We need to pay attention to the young Albert Einstein, when he did his best science, not the iconic pics of the older Einstein . Einsteins field eqation for general relativity. He spent 10 years up to about 1905 trying to understand the way things move and how the way they move , can be reconciled with the theory of electromagnetism of Maxwell , Faraday and others in th late 1800s. He formulated Special Relativity but it had 2 big flaws. It didn't allow things to accelerate , just uniform motion , uniform relativ emotion . It also did not allow for gravity. SR was in conflict with the theory of gravity at the time. Newton's theory that gravity is a force , that falls withthe inverse square of the distance. In SR there is a speed limit, you can't travel faster than the speed of light, whareas with Newton there was no such constraint, gravity propogated through the unoverse instantaineously. The 2 theories don't mesh. Einstein spent the next 10 years tryingt o resolve this. He generated General Theory of Relativity that celebrated its centenary last year. Mathematically complex, a lot of people don't like it for that reason, but then others like myself who think they understand it, like it. Not going inti the maths, we have to understand 2 things essentially. Gravity now is not a force , it is a statement about the geometry of space and time, the shape of space and time. You take some stuff, and that stuff disctates what the geometry of what combined space and time should be. Combining space and time came out of the first theory of SR. In the second theory gravity and acceleration , the general theory, you get the geometry. The object with stuff could be very complicated or very simple. On the other side you have a statement of the geometry. So gravity is this statement, the realm of mathematicians so in some sense why astronomers did not like it, they did not have the training in maths to the required level . Or we can look it from thre point of view of John Wheeler who led the reurrection of GR from 1940s onwards, creating the School of GR and astrophysicists thaty have dominated the era since the 1960s. He was the PhD supervisor of Kip Thorn who was the theorist behind film Interstellar . He was the driving forc ebehind the effort to detect GW , now crowned with success. The story goes that Wheeler got excited about GR when he moved to Princeton , where Einstein lived later. Wheeler invited his students to his home. The GR equation shows that on the right is hte matter that tellls the space on the left how it should curve and then because left equals right , the space on the left tells the matter how it should move and then there is balance. Move stuff around , change the shape of space, and that affects how things move. As a result you can explain how gravity works. It is a complicated theory to work with, but we won't worry about that now. This theory tells us one importsnt thing, space and time are not fixed concepts, it tells us they depend not just how you move as in SR but depends on gravity. A black-hole is now not just an object sitting here, simply not shining. It is an object tht has bent space and time, so much, that not even light can escape from inside it. So a completely different picture of how things work This explains why it should be so, wheras Newton's inverse square law simply says this is the law, I don't know why its the law- a powerful philosophical difference, in that Einsteins laws says why. This flexibility in space and time does something else. So set up a thought experiment. Take 2 stars, or the earth and moon , let them go round one another in orbit. As we see all the time in double-star systems then #ask , how does now the information about gravity changing from this configuration , to this configutration and so on. How does that move over to you observation p[oint over there. There is a speed limit, you don't see it immediately, takes some time fpr that to get to you. The information about how gravity changes, moves outward from the source as waves. Just as light moves out from a shining body. We know that because in the fundamental equation, there is a limit that we call weak field, where you say - there is no gravity, just some tiny little thing , then the equation can be written and looks like and describes sound waves , water waves, any kind of waves. That says there should be waves and Einstein realised that and he wrotr a paper saying that in 1916. The discussion started , there shuld be changes in gravity, moving at the speed of light as tiny ripples in space and time, stretching and squeezing everything they pass through, that comes out of the maths. The problem is, he was not quite convinced, and so following on a lot of other people were not quite convinced either. In einstein's theory you cannot measure the pressence of these waves at a given point. Imagine being a cork floating on a pond and we throw a big rock into the pond, water ripples. If you ride along with the cork , how do you know there is a wave. You say but I'm bobbing up and down , but here there is no up and down, its just the shape of space. There is no way of knowing. This conundrum took half a century to figure out. It was the late 1950s that people convinced themselves that these waves should be real although some people remain unconvinced still today. You hav eto put in 2 corks and simply measure how they move relative to one another. Now regardless of how they move relative to one anpther , there is some measurable relative motion. What gravitational waves do , are doing to you right now , all the time. They stretch and squeeze your bodies. In all sorts of directions, dependent on the polarisation direction of the wave. Luckily ths effect is not very strong. So it comes down to measuring distance. In the 1960s people set up a large resonant bar , tha t if the frequency of a wave coming in , disturbing the bar, it would resonate. This was not successful despit ethe measurements being very accurate, nothing seen that was convincing. In the 1970s they said why not use lasers, very precise, given one light frequency , very precise tool for measuring distance. You know the speed of light is fixed so bounce a laser light off a mirror at a distant point and back , you can measure the distance very precisely. So take a laser , shine it into a beam splitter , split into 2 , mirror at either end , bouncing repeatedly, and measur ethe distance. Form in plan an L shape , look at it from above , the maths tells you that the waves would come in 2 different flavours. Different polaristions, one squeezed and stretched into a + pattern and the other as an x pattern of deflections. In reality any such process would be a mixtur eof those 2. So we look for the tiny changes in the relative lengths of these L arms. The Einstein argument started in the late 1800s about the Ether, where the Michaelson-Morely experiment was based on an interferometer like this , a table top instrument , to prove ,or not, there was a particular direction that light moved faster or slower against the Earths movement through this Eather compared to perpendicular to it. Anothe rexperiment where they did not find that effect but it did lead to SR and onward to GR. Nice in a historical context that such interferometers go back to the very beginning, full circle, and are still now at the cutting edge of gravity research. How to detect GW. This is where people like me come in. Our job is to try and figure out, how strong are the waves from different realistic astrophysical processes. Stars explode, stars collide, stars are born, stars go round each other. So we apply the Einstein maths on supercomputers with modern understanding of nuclear physics etc. The answers always come out terribly disappointing , GW are extremely week. I'll give you a numbe r we call H , the strain, measuring the relative change in length beween both arms of the L interferometer, comp[ared to the total length. The answer, typically from all these calculations is 10^-21 . A fascinatingly small number, 1 with all those zeros between it and the decimal point. So how long is this interferometer . If I make it 1 metre, I have to change that 1m by 1 part in 10^21. The French metre rod is made of atoms , the six=ze of the atomic nucleus , it is the Fermi 10^-15m , so a millionth of the size of the atomic nucleus in 1m. How can I beat this impossible task. I can make the overall length longer , make it 3km , that buys me a factor of 1000, but I'm still a factor of 1000 or so short. There is one flaw in my statement of comparison of magnitudes. I said 1 atomic nucleus, but you have a mirror about .3m across anda large number of laser photons at any given time. So not a matter of comparing 1 guy, but looking at the statixtics of where that surface is. In reality we cannot make a mirror surface as precise as we'd have to , for one scatter. But with large amount of them it can be done statistically. So with 3km and our statistics in hand , it is at least conceivable thst you can do this , not beyond credibility now. In the 1990s the Americans stsrted working on the Laser Interferometer Gravity Observatory, LIGO. Nowadaysd a collaboration of 1000 people, a couple from Southampton. In the 1990s there was a proposal for a similar instrument in Europe , between Britain and Germany but that was not funded to 3km size. Only 600m but it did display an important role in later developement. Something like 10 years ago they fine-tuned and fine-tuned until they got to this magic 10^-21 number, whicvh is what they promised they would achieve. Ant they saw or heard nothing. So why do I keep saying listen rather than see. The current instruments measure the relative distance between the 2x 3km long arms. What comes out of it is just a wiggle. It is sensitive in hte range 100Hz to 1KHz, so you can listen to it. So the initial phase, the initial LIGO discoved nothing. A negative statement but some remarkable things. They did reach the claimed sensitivity , engineering-wise this is incredible. It told us some things about the universe, it told us our calculated numbers were not totally wrong, in reality it was weaker . We also knew there were rotating spinning stars in the galaxy, that are symetrical , neutron stars that are 10km in radius, 20km in diameter that are symetrical to the point of a fraction of a mm. We cannot construct an object i nthe lab that would have tht high degree of symmetry, but the universe apparently can. We learnt stuff despit no signals, but kind of disappointing. Built into this experiment was thinking if they were not successful initially. They had dard-wired in a stage2. While this instrument was being built , the Britissh-German collaboration led by people from Glasgow, kept refining the technology of the 600m one. Better suspension for the mirrors , a different kind of resonance of the laser light in the arm to amplify the signal. Then more powerful lasers which again would increase the signal. This is one of the largest vacuum systems on the planet a 3Km tube that people can walk through , before evacuating. I viited this site in Washington State just before they sealed it off, to start up the second phase. They switched it on and even before they officially started , they caught a signal. This is GW150914, a number not liked by the Astronomy Union as day,month,year, as they prefer different date order. They were trying tuniong up the detector as working fine , not officially started the data taking , but during tuning up you still take data . Something went ping , a young researcher thought something must have broken. He phones his supervisor about the pfroblem. Sudenly all hell breaks loose, a thousand people trying to keep quiet . This was annponced in February , the most secretive science operation we've seen in this area ,ever. There was rumours spreading . In reality it happened pretty much immediately . Why do we think it is what it is. These instruments are incredibly sensitive 10^-21 says so. They are sensitive to changes in gravity . Consider changes of gravity on the minute scale . The moon is a big culprit, the tides from the moon make a whopping big signal in this instrument, that you hacve to filter out. But thats big , so that s easy. Clouds in the sky , tumbleweed in the NW of west USA, people walking around i nthe lab, the phone ringing, rush-hour traffic but as in an old nuclear testing site not so near humanity. But even so rush-hour times are off the observation time slots. Al l very sensitive and a lot of noise all the time. So you are filtering out all this material , leaving something you are looking for, within this wall of noise. So you must have some idea of what you're looking for. So we predict a star will look exactly like this , then despite the whole sky being bright, you can find this type of star , because you said such a star would look like that. For decades we were told that would happen , the amplitude and frequency would both ramp up at the same time, exactly as predicted from whan 2 objects spiral togethe r, getting closer and closer together , faste rand faster and then crash together. So waiting a hundred years for this signal. Thats why they were so excited as thety knew there would be no discussion , about cheating via some filtering technique or whatever , as when it appeared it was clearly what was expected. They realised this had to be 2 black-holes colliding . From this signal you could read off the masses of the 2 objects and before the crash they were 36 and 29 times the mass of the Sun. Then after, there is formed a final object that is 62 times as much as the Sun . We don't know anything that weighs that much and doesn't shine, thats why they must be black holes. We don't even know of anything that massive that can get that close together without touching, thats not a blackhole. You know that 36+29 is not 62. The missing stuff , 3 times as much mass , or energy as we're talking Einstein here, as of the Sun has been radiated away as GWs. Three times the sun, a lot . But even back-of-the-envelope calculations give this sort of expected result, done half a century ago. So it all fits. It goes a little deeper than that. Since the 1970s we've tried working out what happens when black holes collide. It took to 2005 or so to successfully do this. Calculations run on the biggext superconputers on the planet. Why is it so difficult, there is a lot of dirty detsils. When I was a young researcher I was in a group where we tried to do this, in 1992 or so. We had a student in hte group who tried to simple move a black hole on the computer, but that didn't work. So tried moving the black hole and then calculating at some distant point , where the black hole was not. Calculate empty space of here while you try to move the black hole down there and the computer still crashed. The maths just did not work, we did not know how to deal with this at all. People now can do these things regularly, there is a trick , discovered in about 2005 and now it can be done almost on a desktop. As we are talking of really weak signals, the reason we know we are right as the two matched, the signal received and the simulated signal, the very slow ramping up in level and frequency and the final swift ramping whoop. They were incredibly lucky, it doesn't happen that often. You should have waited a long time before receiving a spectacular example of what you wanted to hear. eg the LHC ramps slowly up to the high energies, waiting to see a signature of super-symmetry and change the way we view everything, then stsart again . I think they were lucky, ther's bee nso much discussion, so much toing and froing and false starts, the community is not confident in announcing such success. With the signal v=being so spectacularly clear, they don't have to worry. A couple of months later they possibly had another black hole candidate but this one was not so strong, so not confident enough to announce it. 16th of December they saw the second one , the first with about 30 times the mass of the Sun, the second about 15 times. We did not know that black holes came roughly in size of pairs. So a spectacular success . So for strain H from about 10^-21 down to 10^-24 , 10Hz up to 1KHz. the outputs have a lot of spikes red and blue for the 2 detectors . You need at least 2 detectors as a very noisy systrem. You need to be able to say something happened over here and then something happened over there at just the right sort of time lag, so the signal could have travelled from one to the other, to give confidence that they look the same in both. The green trace, that may or may not be, the blue and green , how they move through the frequency space , as the chirp frequency increasded. This is not the end. People have talked for a long time about GW astronomy. First of all we have to convince astronomers that we are doing astronomy. If I need my supercomputer to show how all this works astronomers don't like it much, they like telescopes and pictures. So we need to go to where they can see the same stuff , their version of the same thing happening, like those different versions of Galaxy M81 . We'd like to hear something in grasvity that corresponded to seeing something at the same time, an electromagnetic counterpart, eg an explofding star. We are due a supernova since 1987. If we are lucky and one did go off , this instument should see it, in neutrinos and optical etc. That would tell us a lot, but there is the element of luck. What we're hoping to happen , when we are looking from the ground. Some things we'd hope to see , small black holes colliding , stars colliding but they'd have to be compact. We should see spinning stsars that are symmetric to some impossible level, if less symmetric than that, then maybe. For now we have impetus to ge to other bandwidths. We don't expect anything to happen over 10 KHz, in gravity terms that would be an empty zone whrere nothing really happens. At the othe rend , for LIGO, shutting off at about 1Hz, because at that point you hit Earth's gravity and everything is very noisey. The motion of the Earth's crust just destroys the experiment. If you want to go any lower you have to go into space. Since the 1990s there has been plans to launch a similar instrument into space, it was called the Lisa Project in 1992. An interferometer with 5million arm length in space, tracking behind the Earth. A beautiful prokject , developed and developed, the finance crisis hit , science funding went south, it was NASA + ESA, NASA pulled out . Esa decided there may be life in this , had a revue and ranked this as their top science target but people said the technology was not ready, and ended up being the second mission. Fly this anyway , with dodgey technology in 2034. Its such a long time away, thats how space projects work, they say. Fresh as of last week, a small experiment , flown last year, called Lisa Pathfinder, a great success, definitly demonstrating this technology is definitely ready, so thye can't say the tech is not ready any more. With the success of LIGO, the us is coming back into this project, which means we might scale it up a bit, compared to the ESA version and perhaps bring it a bit closer. It would be able to detect black holes up to a million times as heavy as the sun , perhaps 10 million times. And also nornal stars and galaxies viewed in a different way. There are experts in precision tracking of radio pulsars, acurate spinning stars. They thought they might beat Ligo to this first detection , but they might still succeed. They are looking at a time scale that corresponds to years. There might be GW imprinted on the Cosmic Microwave Background. Stare at those blobs, but not looking for different colours, but for swirly patterns. The Bicep? experiment, they made an announcement but it turned out not to be quite so. Its all an area where we're hoping to see stuff from the birth of the universe to merger of 2 compact neurton stars. It will be exciting because colliding compct neutron stars are thought to lead to gamma ray bursts that are seen wiht gamma ray instruments. So possibility of doing e-m astronomy and gravity astronomy there. As a mathematician, theoretical physicist I'm allowed to play with funky physics in modelling these, physics that we really can't test on Earth. The LIGO collaboration is just about 1000 people, so quite big for astronomy. Also a lot of other people doing relevant work. You need astronomers to piece together where these objects come from , physicists to build the detectors and engineers. You have to hand it to the engineers who built these instruments, amazing precision detectors. I didn't think they could do it , but they said they could, and they did. We need mathematicians to figure out how the equations work and then the biggest computers to play with. I'm not asking for much. Q&A If you have 2 super massive black holes, presumably they could do the same thing, circulate round each other , presumably getting bigger GW from that, could these instruments get swamped by that? The most massive black holes that we know are too low in frequency for any of the detectors we are likely to have. From the ground we are only likely to hear black holes of 1000 times the Sun mass, then the cut off in frequency, you cannot go lower. From space you might be able to see up to a milloin sun mass black holes. There wont be many of those. A game you can play - If I've got a space detector, they are directional . They hear everything goingt on all the time, like going to a party with a microphone , the cocktail effect, hearing everyone talking , clinking glasses all the time. You need to be able to filter out different things. You try to subtract out the strongest, listen to what is left, subtract out the next, until you hit this background noise. People did this for the Lisa experiment and the cocktail effect was not as severe as was thought. Its a legitimate consideration because , in a galaxy there are many double star systems , going aorond each other and many of them have typical timescales of hours. For those systems ther will be a point where you canot subtract off , and tell the difference between 2 systems any more, a noise barier, for detections in space. For the ground the signals are relatively rare, seeing 2 and a half in 6 months. The detectors wil lbe more sensitive when it comes back and so hopefully the rate will go up. But it will never be a problem, space it would be a problem. Were you able to measure the spin of the black holes and could you tell whether the Black holes were astrophysical or primordial? Spin yes. The first guy measurement , the best detection one of the BH is spinning at about 75% of what its allowed and the other one thought not to be spinning at all or at least not very much. They did not make much of that statement about 3/4 of maximum , with some error bar might be the most precise measurement of BH spin that we have. We have from Xray data statements some BH spin as near as fast as they can go , based on theory. The problem is that 2 groups are into this and they both completely disagree and no overlap at all. Each claims their error bars are small even so. Now where do BH come from. Before these detectioons people were not talking of coupled BH systems of these 30 times sun masses. They wer etalking of 10 to 15 as we see those from other systems. Now people are trying to figure out how do they evolve . There is a massive unknownm in astrrophysics . When 2 stars evolve together , one will evolve faster than the other and so at some point the fast evolver will swell up and swallow the other. They have to be close together as you cannot get BHs to collide on th etimescale of the age of the universe. That phase when one star is evolving inside the envelope of another we don't understand . Thyerre is a black magic button the theorists push at that phase and then something comes out. We need to understand this better. There are a couple of models that predict these kind of BHs . its easier to predict something when you know what you're predicting, so maybe wishful thinking, its not clear. Primordial - its not so easy to see how to build thsoe massie objects early on in the universe, but its not inconceivable. The discussion in terms of the effect of the waves is in terms of physical dimension ,ie space . But I presume the waves are actually in space-time . In my reading of this there has been no mention of correction for time and the passage of time on the long interferometer, it must have an effect? Correct. In my hand-wavy description I described it as mirroes wobbling in space . With a bit of maths what you actually calculate is the propogation of the laser light thru space and time and that is what you are looking at. There are 2 ways of doing this calculation 1/ I'm sitting with one of the mirrors , in the centre and measure the movement of the outer parts as I evolve wiht my clock. I have a clock and I don't move, I measure in space. 2/ Measure it in space and time , one mirror is at a given distance from me call it 1 unit of length, the othe rone is 1 unit of length and I hold them like that. I define these distances to be the length , then how do I evolve in time , holding these fixed and that leads to another way of doing that calculation. Ultimately it gives the same answer as the first, but that is the true space-time calculatio nthat you'ee asking about. You can do that but its harder to describe the concept of holding things fixed in location while they're evolving in space and time. People joke about this , because when you build these instruments on the ground, you don't need to worry about space and time. Do it in space and youi have to do exactly the opposite calculation. The people involving space kit say they understand Einstein better than the guys who work on the ground. Now the guys on the ground have the detections and the space guys don't even have any instruments, not so funny any more. Will they be building any more ground based instruments, to get a better idea of directions? One of the things these instruments don'd do well is direction, space location. With 2 you could see something like the view angle of the moon, with 3 you would do better . Not quite on line is the French=Italian detector in Pisa, I think later this year. Then the Japanese detector called Kagra? it is underground and cooled down to deal with some quantum effects. I think that is a couple of years away. The next after thsat is Ligo-India which will give a lot for space-resolving . The Americans said we need 3, so they agreed to box up one of their machines and ship it somewhere, settling on India, pehaps. Thn the initial detections happened and india then said yes definitely. Maybe for 10 years time. When I visited the Hanford Ligo the boxes were sitting on the floor , unfortunately they'd half-inched all sorts of bits off it , to keep the other Ligos going. So even 10 years off, there may be another 5 years until any space observers. At the moment people are excited and don't mind spending a billion . The next ground detecor would cost a billion or more. So we can't afford many, if one is 10Km laser arms, maybe underground and cooled, The Einstein Telescope. Do we have the will to proceede , I think it might happen. After 100 years of nothing , its suddenly very exciting. It promises to do things we cannot do any othe rway and happens at a time when the large energy conditions in the LHC will not be able to go any further. So what further can we look at for the big science. For the existing Ligo , to make another after making the fisrt one is much easier. But did they have to make the second one deliberately different, different detectosrs , differentr servo systems, just to avoid a glith being repeated in both at the same time, or a bug in a duplicated system being repeated in both at the same time? They are pretty similar . They were deliberately built using different strategies . One was put together in one way and the other was built almost the opposite way round, ordering things differently. I think there is merit in having them different and sobe able to say these are different experiments, but the reality is that you need 2 detectors to make a detection. You nedd to able to say that the same sort of pattern happened in both , otherwise you don't hve an argument, given all the noise. There are many noise sources that look pretty similar to what you are looking for. There is the Crab Pulsar from 1054 supernova that spins pretty near as dammit at 60Hz, which is the mains frequency in the USA. So you are looking at a periodic signal where there is the huge swamping signal of the 60 Hz mains. There is a merit to have identical technology , so you understand it from one site to the next, because the 2 together is one experiment. I alsio think its important that , like the Italians using a different suspension and the Japanese different again, to give confidence. I was thinking of the fly-by -wire control principle in planes, of having 5 comp[letely different systems and they poll the results in case there is an error in one that is offest by the otehr 4? up to today they've been pushing the technology as hard as they can , to get something. Either this area wil lexplode and next time of switching on see more and more detections or its game over. Either could happen , its technology limited. Now we no the technology works, its a big plus in confidence. We don't know how often these things happen in the universe. 14 billion year universe, the main recorded GW detection collided 2 billion years ago. Its possible to go much further with improved technology. the Lisa craft would see big BHs colliding through out the universe. I believe you cannot see GWs from symetrical explosions? correct So you would not see a supernova exploding? They are not symmetrical, there is a symetrical part to them , an explosion and a contraction but a lot of messy stuff going one. The question is are those asymeties strong enough. Look back at 1970s articles , supernova explosions were top of the list, they would see tons of these. They predicted exactly how much energy would be radiated. Then people did simulations and thpse numbers got smaller and smaller and now we are almost able to explode stars on a computer. Its difficult to get this process to take off in a computer. At the same time the predictions for these asymetries has gone down. A supernova in the galaxy is near enough that we'd hear it with these instruments. Go a bit outside the galaxy and it probalby would not be possible. In the galaxy a SN happens 3 or 4 times a century. A PhD student studying this may be very old by the time he is a awarded his Phd For the deltaL over L, of 10^-21 , presumably for time what is the corresponding stability of atomic clocks, based like your 2 corks going up and down, is that comparative to the lenght measurements? Not anywhere near. Can GWs tell us anything about the Cosmological Constant or even anything about so-called Dark Energy? For the CC, in my writing of the Einstein Equation I did not include that term. Essentially it makes gravity push instead of pull. Einstein put it in, considering it his biggest blunder, according to himself, although he never said that. He realised his equations predicted an ever expanding universe, so he put it in. That was at a time before Hubble discovered the red shift of galaxies, they receede. Einstein believed the universe was static, he put that term in to hold things back. That went out the window when galaxies red shift was discovered. Then it came back and forth, into fashion recently. When we found we thought we knew, and then didn't know what is going on in the universe in that 75 % of everything is dark energy. We don't knpw what that is , but one way of describing it is in terms of this CC. So either recorded energy and it sits on the right of the equations or on the left as the CC , but we still don't know what it is. I didn't put it in because if you look at a GW in Ligo its near enough to us in the universe, not to worry too much about cosmology. If you go farther out, say with the LISA detector, you will have to put in your cosmological history, so at that point, perhaps even with LIGO eventuially we will start being able to measure things like the Hubble Constant. So doing cosmpology is an independent way as compared to say the Plahnk Experiment. It is possible with GW, we have in effect an independent distance measure, you could do bettwer if you have both e-m and GW observations but we'll see. For Dark Energy, its a hard question as we don't even knopw what the idea may be other than we've named it. I think it depends on whether DE has an evolution to it. If it something that evolves in time and is an energy it will emit GWs in some sense. It could be something that evolves through cosmological history, different in the past to what it is today, that you might track by simply measuring the cosmplogy bettter. All a bit whacky, I have a problem here with a lack of understanding of the universeand our relative happiness to give something a fancy name and let that be it, because we really have no idea. We know stuff is there , because we can see it, we know there is dark stuff like BHs becaue we can hear them 2% of stuff. We no Dark Matter is there because we see gravitational lensing and then there is 75% missing, So either our theory is wrong or we do not know what the question is, a big issue there. Is gravitational lensing applicable to GWs? Exactly the same So its in the theory? GWs pretty much propogate , in the simplest version of the theory, exactly like light. So if light is lensed, then GW would be lensed. In principle that could mean that you could see some GW sources if the lens to be amplified, further away and at some point you need to worry about cosmology and will be missing? Doppler shifting or dispersion effects over great distances, is that there? Its pretty much the same as for light apart GWs don't interact with matter in the same way. Light essentially comes from individual atoms changing excitation levels, the light is bouncing off stuff like dust , but GWs don't care. So they come to us more pristeen than the light would. Its probably pushing things a bit but they're looking for perhaps the edge of the universe, perhaps where it bumps into another universe, like bruises in the CMB, would GWs travel across universes? We have come to the Brian Cox moment of the evening, I will stare wistfully into the distance. I don't know. There is an aspect of cosmology that was fashionable 10 years ago , 'brane cosmology. Where we live in 4D and the real universe is 5D or higher. The idea was that gravity could move freely in the other dimension. So we can only move in a sheet but gravity can move off the sheet, so GWs could also. Its hard to do any calculations or predictions. I think you'd have to do as with the CMB ,find anomalies that don't fit with your current theory. Its very fashionable to try and prove that Einstein's Theory is wrong, because you'd bring down one of the icons, a big thing. We know Einstein was wrong at some level, but we don't know at what level. So far every test thrown at his theory has been OK. So we know the theory is remarkably accurate, it achieves more than he could have ever believed possible. Because up to 1950 there were no real tests beyond his pen and paper 1915 tests. with all the advancing tech over the years , everything fits. So do the experiments better and do we get to a point where there is something missing. Numerical simulations throw up something but reality looks different. At that point we'd have to start asking questions. Would things like Cosmic Strings fall into that category? CS should leave some fairly typical imprints on GWs, one would be from kinks , the other would be an intersection between 2 CSs. People have tried to model that and its possible that you could see a background in CSs with a space based detector but its a bit speculative, quite speculative. There's no reason why CSs could not be there . Recent TV programme of Alan Goods? idea on space-time and how they were looking in the Arctic for small ? size . It was disappointing for him as it could have been down to cosmic dust. What is the status of inflation at the moment and have GWs anything to say with regards to polarisation? Its not my poison but its probably the case that a detection from GWs from the Big Bang would be the deepest pysics discovery that we could ever make. The rreason is that GWs from the Big Bang would merge a tiny tiny fraction after the BB itself. Whereas the earliest you can go back with CMB is 300,000 years. So this would allow to probe all the way back to the beginning. If you have that imprint, you should be able to track the cosmological expansion. In practise when people try to calculate this , it wuill never happne in a year with a million sundays, because they're too weak. There are models , where people may be a little over optimistic and they get things that could barely be detectable. Then others build graphs, and where this detector is sensitive here, the way this background looks there is a spike just where you are sensitive and then goes away again. That looks like a construction to me. It would be a very hard experiment but in principle , you know the BB was not perfectly symmetrical because the CMB is asymetric , so there were quantum fluctuations. Those would leave an imprint in GWs on very large scales. If you found something like that in the CMB. Is inflation still accepted ? If you don't have inflation you have huge problems in fine-tuning the various parameters thet we think we see. These parameters have huge dark energies, so it could be we are missing something. Are Inflation Expansion and Dark Energy similar? Inflation is exponential expansion of the very early universe, happening by magic. DE leads to a slow exponential expansion of the universe today, by magic. But it cannot be the same because , inflation expansion was much faster than today, something must have happened in between. So caused by different things, or the same thing with different incarnations or whatever, we don't know. There are many ways to achieve inflation expansion . Whenever you have something that can be explained , many different ways, so you cant tell the difference in the different explanations, you're in trouble. Whenever , with like DE, you put something in because must have to explain what you see , but also you don't know what it is , that's also problematic. The perfect science is GWs a prediction , a detection and they test each other. Cosmology is becoming a precision measurement science but I think the balance beteeen theory and experiment is not at the same level as say the LHC is now. We need better theory , to match the data we have, a hard problem. Would it be possible to enlarge the detectors by having mirrors on stable planets and moons? How much money will you give me. Not possible. The motion of the various orbits is not regular enough to do that with precision, too much accululated error. LISA is planning to fly in an empty environment, tracking behind the Earth in a very controlled fashion . Multiple lasers , at different locations? In principle yes, but each would need to be controlled. A free-floating spacecraft you've a chance of doing that, but on planets etc there is other stuff going on, earthquakes etc Orbital errors would not be deterministic? They would be but if you add in other things like local geology and things that can evolve, it becomes mighty complicated. You said the contrast between yourself and astronomers is they like to see things , do you see in LIGO or other technologies a resolution of this, in being able to see more than 1 signal? Yes. If you push hard enough you'll get to the point where things happen close together and overlap . I don't think the technolgy is avaialble to deal with that, unless they are at exactly the =same frequencies forever and that is unlikely to happen A few years ago, because they had no GW signals the group in Hanover decided to try to use GW technology , via crowd-computing, looking for signals in data. They used that on gamma-ray data from the Fermi Satellite. They found 30 or 40 new pulsars that the research group did not find. So using more sophisticated data algorythms , and putting them to play on other data is very successful. That is telling you , that we come from a problem where the signal is weaker than the noise and you know that from the beginning. Mainstream astronomy comes from looking at the sky, see the stars, stand out against the night sky. Its never the quaetion of looking for a black star on a black background, tha t we've trained ourselves to do. So astronomers looking for ever weaker things, need the thinking that goes into this area. I can see that happening more when mainstream astronomy moves to things like the square km array, it will be fantastically sensitive for radio observations. They will need better dat ahandling than they have today. We are moving away from the luxury of astronomy having strong signals. So the satellite is looking at only a small specific part of the sky, then the satelliste moving and looking at another specific part of the sky, wheras your array is looking orthogonally. Do you see any way of expanding the technology to be able to look directionally. ? Its very hard to do, apart from if you are looking for things that evolve very slowly, so you can use the Earth's motioon over say a year , that gives you a different level of ditrectionality. Things over and done in a fraction o f a second is very hard. We can only hope for several detectors to be able to pinpoint better. I don't think we'll ever reach the astronomy precision as far as sky location. Could I confirm that your community set upon the characteristic signal of interacting BHs as a chirp, before it was detected on LIGO? The first part of the signal was calculated by Einstein himself in 1918 or so. That part was refined in 1950s/60s , the BH merger part was done ,badly, about 1978 . We knoew how much energy would be radiating from 2 colliding BHs in about 1990. We knew how the final object settles down , we knew how much weight was to come off. We could do the simulation of the whole thing in about 2005. Those simulations took about 3months on the largest computers, come down now . The first signal , I could write the equations down on the back of an envelope , with enough precision , that we'd detect it. With 2 BHs merging , they presumably have to end up as a BH. Could 2 neutron stars merging , could they end up as a BH? It depends on the nuclear physics, which is one of the questions we don't know . How heavy can you have a star before it bwcomes a black hole. How much can nuclear physics push against gravity. We know we can build them up to about 2x sun masses. Take 2 of them then they will likely collapse to a BH. But how quickly does that happen, is not clear. When they come together , they spin quickly and centrifugal force also pushes out and that could hold the object up for weeks or months perhaps. So does not have to form a BH immediately, just eventually a BH. That intervening time gap will show us a lot about how exotic physics works. That would show up in the signal trace, after the chirp? Yes Energy deficit or mass deficit you measure and was predicted a century ago. Is that all accounted for in the measurements. Is there a strain energy in space, a calculable stiffness? It depends how you look at it. If you compare terrestrial material you can work out how stiff the space is. I'm not sure how meaningful it is, but there are othe reffects. Space-time has a memory, like materials with memory. So after GWs have passed thru there is an offset of space and time, quite small. Detecting that would teach us something about these questions about how space-time actuially works. Its the next level of difficulty, people are working on it. W49

Monday, 10 Oct, 2016, Dr Neil Gostling, Soton Uni :The Origin of Species in 45 minutes. 2.5 hours, 38 people The Origin of Species, OS , was published on the 24 Nov 1859. There was 1250 copies and they sold out on the first day, 13 chapters, the book has never been out of print, 500 pages. It was never Charles Darwin (D) plan . The abstract tells you of the ideas and results found, usually. His plan was to right a much longer book, 2 or 3 chapters of a much longer book, but he never finished it. He waylaid himself by othe rbooks, other tales to tell. So the OS was about evolution, does it say that in the book, no. That word appears once, thats it. Its about natural selection , his idea about how the world is , as we see it today. This is a pic of how we imagine D and we forget, he had led a rich and exciting life. This is a photo here when he was young, when photographs did not exist, aged about 28, after a 5 year mission of discovery , to seek out new worlds and civilisations. D was originally to be a doctor because that is what the sons of wealthy landowners did. A relative Erasmus Darwin, and his father was involved in medicine. As a young man ,16, D was send to Edinburgh to learn medicine. D was really squeemish and he didn't like it, so he retuned to his austere fathe rRobert D . So he would go into the othe rprofession for gentlemen. He went to Cambridge to study divinity. D's only qualification is divinity, somewhat ironic. He enjoyed Cambridge, not because of the theology but he got to do other subjects, like botany . He would go into the fens with friends and profs and would botanise. He would collect plants and document what he had, insectts, beetles etc. Aged 22 in 1831 he'd finished his studies , disappointed his father in not doing anything. His father got him a position on the ship , the Beagle . His job on it , was as gentleman's companion to the captain. For seemly discussion as the captain obviously couldn't spend time with rough men and coarse language. He required a man to have discussions with, but having equal standing. It disn't take long for them to realise that Robert Fitroy , the captain and D , they hated each other, they did not see eye to eye. To D's good fortune, after leaving Falmouth, goind south. Luckily for D , the ships surgeon , who would have the role of naturalist, was taken off the ship at Gibralta, ill. So D became the naturalist. Looking at the natual world, and documenting, not having to talk to Fitzroy who D considered to be very arrogant. When D got on board at Falmouth he was like most of the time a believer in creation. He spends as much time as possible off the ship , hiring donkeys to ride across islands, th eBeagle would sail round and pick up D on the other side. Collecting specimens of all sorts and having a good time. No one could do that these days, the financial support to take 5 years out , go round the world, and cllect biological specimens. We have this ides that when he got to the Gallapogos (G) Islands, 600 miles off Ecuador, there is a Eureka moment , and suddenly he understsands evolution. No, he got back on the boat with his many specimens , lots of birds, tortoises . He left G with questions but still much the same person as originally boarded. Pics of 2 tortoises, one with an arch around its neck. That one could reach higher up , to higher shoots, living on a dry island. Wheras the other lives on a wet island with lots of ground vegetaion . The one with hte arch has adapted to the new environment it finds itself in. The Voyage of the Beagle is like Ripping Yarns, adventures and all sorts. D , when no one was watching rode on one of these tortoises. Who amongst us , would not be tempted to ride on a tortoise. He noted different tortoises on different islands. Hood Island very dry , Isabella very lush and green. D's finches , we now know, are the product of a population of birds being blown in from mainland S America, finding themselves on different islands and having to survive. Different beaks, as a tool for eating. Robust beak on one type and very thin for another. We now know they are all finches , but all slightly different finches. When D found them and shot them, skinned them, and stuffed them and sent some back to Londion , it wasn't D who knew they were different. D did not realise at the time they were even finches. It was John Gould at the British Museum that recognosed they were all finches. By the time D gets back to England in 1836 , he writes the Voyage of the Beagle, he'd seen the different tortoises on different islands. He must have come back still much believing in Christianity, but he was starting the think. One of the things he could not quite understand was why was god so obsessed with putting different animals in different places. Why do we have some many kinds of the same thong. He makes comments about why is god so obsessed with so many beetles. The half million species of beetle. Over a million species of insects and half of those are beetles. Whats going on, why so many beetles, why so many finches. With voyage of the Beagle, 1836, he becomes overnight a celebrity. What does he do next, he has to make some decisions. He's made his name , what next. D sits down and a beautiful piece of work. He has to decide whether to get married or not. Litterally a pros and cons list. If I get married I'll not be able to do exactly what I like. If I don't get married I could go to Europe ? America ??? . If I do'nt get married , It is intolerable to think that spending ones whole life like a neuter bee , working,working and nothing at all. Emma D , who was his first cousin, the granddaughter of Josiah Wedgewood , Charles was the grandson of Josiah. Another observation, by D, of a wife, is something to be loved, something to play with and its better than a dog. In 1838 he got married on the 11 of the 11th and moved to Kent . To Down House , stayed there , and never left the country again. He settled down, had a n enormous family and started to think. In 1844 he wrote an outline of natural selection, that he sent to Joseph Hooker botanist, Charles Lisle father of geology and to an American botanst called Aisa Grey. Then sat on it. Around 1859 he got round to publishing, 23 years after the Beagle voyage. So why is that. This goes back to his wife, extremely devoutely religious. By this time D had lost his religious faith , he would walk his family to the church in Down on sundays , they would go in and he'd walk around the outside until the end of the service. I think the main reason for his loss of faith was the loss of his daughter Annie, at 10 years old. He could not understand why god would be so cruel. A god so purposefully make a caterpillar that sole purpose in life would be to receive the egg of a parasitic wasp , which would grow inside it. He thought that was extremely cruel. He could not imagine a universe, an existence , where there was such an evil god. He spent a long time putting his ideas together , but sat on it all. In 1858 , in Down, he received a letter fro ma young Welshman, Arthur Russel Wallace . He was in the Malay Archepeligo, in a malarial stupor and he'd come to exactly the same idea. Another area of the world where nature has its own laboratory and ARW had come up with the same idea. D felt he'd missed a trick, he thought he was ruined. Luckily for D, Charles Lisle , Asa Grey , Joseph Hooker came together and decided we can solve this. You can both publish , on the same day , at the Lineas society of London. Both papers were read there, but D had the primacy of the idea because he'd documented it in 1844, when ARW but a child. So why was D an absolute genius. Evolution was not a new idea. People had seen that things change through time. Fossils had been known about for 50 years. People like Georges Couvier , a giant of the biology world, in France explained how changes had happened. The founder of the Natural History Museum, Richard Owen, had documented dinosaurs . Bu tno one said how these changes happened. Ernst Mayer a famous evolutionary biologist late 20C wrote a book saying the OS is one long argument and thats exactly what it is. D is explaining evolutuion and the mechanism for it to people who don't understand science. Firstly the book was written in English when other science books were still being written in Latin. Written in a language for the populace to read. OK you had to read , but of those who were literate far more read English than Latin. He took examples of what we know, so he chose pigeons . In 1850s in England , people were still very much in touch with the land, where food came from. People bred pigeons including ridiculous over-feathered puffy , heavily muscled and heavily beaked , that they could not fly but looked spectacular. Al lthe different types of cabbage that we have, from the common wild mustard , we get cabbages, brussel sprouts , khol rabi, broccoli, kale . All these forms of cabbage are as to common mustard as all the breeds of dog, Chichua , Alstaians etc are as to wolves. They are artificially selected , people understood that. People could see how we ourselves had changed things, domestication had led to variationb. The world is not fixed. Not everything alive today is as it was 4,004 BC 23rd October , when god said , let there be light and everything happened. We could change things and if we can change things , maybe nature can as well. Chapter 1 - Variation under domestication, we can change organisms to suit us Chapter 2 - Variation under nature. D knows about the finches now, he can show they are all finches and selected to live and thrive in certain environments. The one with a large beak can eat large dry seeds. The one with a narrow beak can get into clefts in bark, for weevils #and beetles. Chapter 2 is a recapitulation , a replaying of rguments from chapter 1. We can change things, crudely, surely nature can do it even better. Not quite that straightforward. Clearly if you had elephants and elephants breed, and they do it succcessfully , why aren't we up to our necks in elephants. This is where D is very clever. Its where I'm envious of D . The fields now are so broad, we don't have time to study other things. The zoology that D had to know was much smaller than the zoology I have to know. I don't have time to read about economics and the words of Thomas Malthus, but D did and he understood it. Malthus had written about checks and balances. You can't have exponential growth for ever, in economics. At some point there ia a crash and things even out. D worked out that if you take a slow breeding animal , lioke an elephant , starting with 1 breeding p[air, forgetting about in-breeding. If all the offspring of that pair were to breed and so on and so on. After 500 years you would have 15 million elephants. We don't have that many elephants. He used arguments that there must be something in nature , a struggle for existense , some things survive and some don't. This is the genius part, because all the way up to now, 1859, noone tells you how it works, a mechanism. D does and that mechanism is natural selection. Not everthing that is born will survive to reproduce. And if there is variation in those offspring , those best suited to the environment they find themselvers in , will out compete the others, and survive to reproduce. One of the arguments against evolution is that its far too complex, if you took any bit of it away, it would not work, so the eye could not have evolved by natural selection. Can we find anything in nature where its simpler, yes. We can find in nature all the stagrs you need to get to , to get an eye thats as good as ours, including corrections for the aberrations of light. A little patch of photo-receptors on a surface, we see that on flat-worms, just a little spot, that can select light. It can tell which way is up or down. Then we have a little cup where the pigmented surface is dished , so we can tell the orientation from which lighr is coming. So if you're wriggling along the bottom of the sea, and there is a shaddow, you can tell which that shaddow is going and get out of the way of what is casting the shaddow. If you can get out of the way, you may just avoid being eaten and it means if you're still alive to find a mate, that trait will be reproduced. Natural selection does not have to be perfect , just be good enough . There are plenty of things in our supposedly beautifully designed bodies, are just good enough. Take knees, they are just good enough. For earlier times , and shorter life span , they were fine, but now in old age they become a problem. If you were living onm the plains of africa 1 million years ago, you will only live to 20 or 30 and your knees are then good enough. Unfortunately, Homo Sapiens has taken what its got , runs with it, and our knees fail quicker than we'd like. They don't wear out until after reproductive age. So we have babies, with our not so good kneees. Going back to eyes , if its good enough to just outcompete your local community, you're alright jack. All that is genius. This is the bit that D didn't get right, and pretty much the only bit D did not get right. There ar enuances that we've finessed later. This error is on the laws on variation , because for natural selection to hsappen , you have to have variation withon a population that is heritable, can be passed on from parents to offspring. D knew nothing of what caused variation. He was working under the ideas of Jean-Baptiste Comte leMarc ? born 1789, writing his stuff up in 1809 the same year that D was born. His idea was the inheritance of aquired characteristics . Say you are a tortoise and the vegetation you need is high up, then you stretch your neck and as long as you keep stretxhing, you'll pass on that trait to your offspring. LeMarc talked about giraffes, starting off as cattle like animals with normal necks, reaching up to get the lushest of leaves. Or you build up your muscles, your partner does likewise , get big muscly babies. We know thats not true. Another LeMarc idea is take some mice, chop off their tails and then breed them, tyhe offspring will have progressively shorter tails, a simple test would test that hypothesis . An Auguste Weiseman , cut the tails off 900 mice , he was thorough, it didn't work. There was science in the raw, a hypothesis, he tested it, proved it wrong, it was a falsifiable hypothesis, so utterly scientific. Laws of inheritance via LeMarcian process, don't work. On to Gregor Mendel , the father of genetics, a monk in Brno in what is now the Czech republic, writing in German , in the monastery scientific journal of all things. He was crossing peas to see how , what we now call genes, segregated . Something in the plants was being transferred , parent to offspring and he worked it out, the Laws of what we call Mendelian inheritance. One of the saddest parts of this whole story, when Mendel died , a copy of OS was found in his monk's cell, full of scribbles in the margins. He understood what D was saying . When D died in 1882 , there is a story that as his son was going through his letters. D was a prolific writer, up to 24 letters a day, often to his wife in the room next door . We know a lot about their relationship , loving and kind and beautiful , because he wrote about it, and sjhe wrote back . Also found was a still sealed letter, which when opened was a letter from Gregor Mendel, to D, which he hadn't seen. In that letter it said, I've read your book , very good, I think my theories on inheritance would support your ideas and explain things. D would have seen it and understood it. Evolution and genetics parted company end of the 19C . Genetics starts at the start of 20C , evolution was championed by Thomas Henry Huxley, D's bulldog . People accepted evolution , it was not a problem. Julian Huxley in 1940s ggson and he brings back together, a modern synthesis , but could have been 40/50/70 years earlier. D says some of you are not going to like this. Depending on what edition you buy, either 13 or 14 chapters, 13 in editions 1 and 2 and 14 in 3,4,5,6. He added that chapter , for the problem, but you don't need to worry about it. The arguments people today like Intelligent design creationists in north america or Portsmouth. There is an intelligent design museum in Pompey. Evolution is just too complex , it can't happen , our wonderful knees , flagella on bacteria. I'm an evolutionary biologist, if you believe things thats fine, no problem. In my classes I teach science. You can learn about other things but not from me. Their idea is that god does not make mistakes. If thats true , why is the eye built back to front. Light enters the eye , passing through cells , before it gets to the light detecing cells. I think it does down people's belief if they accept that god is a bodger. If you have a blob of jelly a bit of protein mixed with water , you can start to focus for a rough image, with your primitive eye you can tell whether to expend energy and move away from a predator. Then a pinhole in front of your eye , improves the focus , to get a camera like eye for perfect focus like ours. These aren't hypothetical imagined stages , we find all these eye stages in living animals today, they are all just good enough for the animal to survive . As long as you've lived long enough to spread your gametes, thats all you need to do. A quote from a piece of creationist literature, D disproving himself. "To suppose that the eye with all its inimitable contrivances , for adjusting the focus to different distance, admitting different amounts of light , for the correction of spherical and chromatic aberration , could have been formed by natural selection , seems i freely confess , absurd in the highest degree". You can go to any creationist website , that does not like evolution , you will find this sort of thing. D says its absurd, what they don't do is say the next bit, continues as the full quote. "yet reason tells me that numerous degrations of a complex item , or a simple one, each grade being useful ot its possessor , can be shown to exist, which we have. If further the eye ... ". Argument, sorted , you don't have to worry about eyes. D takes all the arguments people could possibly come up wiht and dismisses them . Dismiss in the sense of explainiong why not a problem. If you want to know about bacterial flagella , which D did not really talk about. The tail on an e-coli that makes it swim, we can demonstrate stages of developement. It is complicated , the only circular rotating structure in nature , beautiful and of course cannot possibly be formed by natural selection. Except it can and we can show each of the stages in progression to it. We can argue that , even if D did not. Chapter 8 - Instinct. He is talking about the material world , but instinct is clearly not material . How does a bee know how to build a hexagonal shaped comb. D uses bees in this argument. If there is something that is heritable , and there is no reason why it should'nt be . Bees make their comb and turn at a certain angle, because that is the way they move and make a 6-sided shape, do better . 6 sides is the way to go for a #strong structure. If you are programmed in some way to do that and it is heritable , you can pass on that ability , through natural selection , in the same way as big muscles, long tails etc. There is no reason why instinct cannot be part of the natural world. It does not have to be some ethereal thing of the mind. Everything about us is material, what we make of our lives is something different. Some would argue it is only governed by genes, you could argue this. All the characteristics, be they cognitive , physical , can all be explained by NS. The title of the book is OS. o we really need to define what a species is. There is still an argument today exactly what a species is. It depends on what you are . If you're a plant, the definition of a species is different to if you are an animal. If you're an e-coli, the definition for bacteria is different again. D makes a good stab at explaining what species are. Ernst Meir stated a species was a group of individuals that can reproduce themselves. As long as you can interbreed you are a species, the offspring are viable and they can breed as well. D defined what are hybrids. A hybrid is where one animal breeds with a closely related species , like the liger or tigon, which is sterile . Hybrids tend to be bigger, including plants. Mules are brilliant , horses and donkeys, very strong but sterile . D got stuck on the following, he could not explain it. If you look at the fossil record. In the UK we have a nearly complete geological record, from the present back a billion years. The eras are called Devonian after the county, the Cambrian from welsh hills . William Smith , canal engineer, bankrupted himself . He dug into the ground and recorded the rocks he saw. 200 years ago He produced an astonishing geological map of the British Isles. He took core drill samples and recorded the similarity of rocks across the country. Compare it with the survey map of 5 years ago and its the same, just tiny finessed differences. The problem for D ws that we have a record back from today to the Cambian, dated now at 542 million years. At that time all the things that are alive today , the major groupings, not species are in the fossil record. Before that there is nothong. Confusing, because how could he be saying that species evolved from simpler forms , when all the forms appear in 10 to 20 million years , in geological terms a blink of an eye. The complete geoplogical record is 5.4 billion years. We have a fossil record , D had a fossil record for what we now know ,being 500 million years, 1/9 of the age of the Earth. D sauid that as we move through the fossil record , we should find transitional forms , he did not use that term, but find forms that unite the great groupings. Like birds and reptiles . Thomas Huxley later explained that birds and reptiles are closely related. In comes Archeopterix Lithografica ? , discovered in 1863 , a transitional form, feathers so a bird (not quite as simple as that) , fingers with claws, teeth, long boney tail . A pretty good proxy for being half way bwtween a small running dinosaur and a chicken. A lot of specimens since. D was right there should be transistions. Another aspect about science, if you make predictions you should be able to find things. If evolution is true , we should find half-way forms. We now know pre-Cambrian fossils do exist. 2.4 billion year old stromatilite section from Australie, bacterial biofilm layers. A piece of cotton marble from Bristol . What we are seeing is not a sudden appearance of life at the base of the Cambrian , we are seeing the evidence of skeletons that can be preserved i nthe fossil record. But we do have soft-bodied forms from before the Cambrian, it wasn't just a sudden explosion of life. Life existed but suddenly there was an arms race , things developed eyes, and needed skeletons to chase things down and flee from others. The skeltons are then preserved. The fossil record is not perfect, it is biased towards things that will preserve. Another transistion exampe a type of deer through to swimming whales that we have today. On geological time. The idea was that the Earth was young , less than 10,000 years. Charles Layelle , most important idea was , uniformitarianism . The idea that if processes are slow today they've always been slow. If it takes an awfully long time for sediments to form in lakes, then thats always taken a long time to form. So the Earth is unimaginably old. One of the key things that D needed , for evolution to happen. Evolution is slow , you will not see it . Chapters 12 and 13 is probably just one large chapter he split in two. He is talking about geographical distribution . He is not justy the father of evolutionary thought but also ecological thought. He set out a grid in his back garden , counter the plants. He did quadrats, a 1m x 1m frame , randomly place it somewhere, via random generator . Do so many quadrats in a given area and count the species, work out the diversity , see succession, which D did. He laid out his quadrat and watched how the grasses and plants changed . He was a brilliant biologist. He was working out how to explain, we have similar fossil forms in different parts of the world unconnected. Plants and animals that simply cant swim , how can things be in Africa, America and Australia. D did not know about tectonic plates, that was not acepted until the 1950s /60s. 2009 there was a prog, David Attenbrough and the Tree of Life. He was at Cambridge in the 1950s, he asked his professor to explain about this new idea of plate tectonics. Prof said, if you can show me a force on this planet that can move a continent just 1 inch then I'll think about it . D thought maybe there were land bridges that moved up and down , he was thinking, trying to explain thongs with science for explanations, not super-natural. 500 pages, just one diagram, shows how lineages split and branch , new species arise from the old. He brings up the importance of comparing like with like. You cant compare the wings of a bat , with the wings of an insect. They are not the structure, but you can compare the wings of a bat with the arms of a human and the wings of a goose. They are the same structure, modified in different ways. He also makes brilliant insightful statements about embryology , developement. If as an adult we hav e a mutation , it tends not to be a good thing. Most developing embryos , eggs or uteruses , if it has a mutation it probably won't be good for it either. But if that mutation is beneficial , if that mutation means an arm grows longer , just one extra round of cell division in your arm, would mean it was twice as long, twice as thick . If the mutation is in the embryo then that is where you will see big differences , and developement where evolution is really working, not in adults. Extremely insightful. He also talks of rudimentary organs , loike appendixes. These things have a function but they are no longer functional. Why would you put that in there if there was not some reason , ancestrally, for it to have been useful. Thats the 13 or 14 chapters of the book, that tells you the science. Then the last chapter is recapitulation and conclusion. At the uni I run a reading group to read this book. i've read it 12 times now. Most people never pick it up, they know what its all about . I think its important to read it. One of the arguments people use , always by people who've not read it, its so turgid, dry and stodgey. If you've ever resad Dickens , you can absolutely get through D. Dickens is like wading through porridge. The last paragraph. "There is granduer in this view of life, its several powers having been originally breathed into one , or a few forms , that while this planet has gone cycling on according to the fised law of gravity , from so simpler a beginning . Endless forms, most beautiful and most wonderful have been and are being evolved ". That is the only time that word appears in the book. I taught evolution in small-town America and I survived. It was a close run thing, is how I can describe it. One edition includes the 1844 outline in it. If you like pictures, there is a graphic version, it is really good , well done. Thats the Origin of Species, I haven't done it justice . On Kindle its free to read. I tell students about the beautiful langueage that D uses , it doesn't lose any of its power. Q&A The idea of NS seems almost trivial , any rationale as to why it took so long for anyone to come up with the idea, even the Greeks could have thought it through, surely? Its so intuitive , it almost seems ridiculous that it wasn't found sooner. Science was not a dicipline in the sense that it is now, its ubiquitous now. D was of his time, he was not ahead of his time. The enlightenment in Europe had happened , people were thinking and talking about thongs , that they hadn't before. The church was extremely powerful. D was not the first, his own grandfather Erasmus wrote Zoonomia ? which talked about chjange in animals. You can pick up a fossil and see it is no longer around today, including dinosaurs. Change happened and we can see change. I do think that for freedom of thought , to blossom, you have to have space for it to exist. I think in the 1850s , the church was just loosing influence enough that people who were thinking and were brave enough to speak out , could do. I'm talking here of intelectually speaking out, speaking their minds. That was probably the first time this was safely possible. D was 200 years back from us, go back another 200 years and we wer eburnong witches. Witches were probably wise woment who understood the world they lived in. But mid 19C it was probably safe to say awkward things without being lynched. The pre-Socratic and post-Socratic philosophers considering metaphysics , really did try to consider ??? atoms, moving towards such things. Thern go to the 4C when Aquinas brought Platoinism into the church , they wer ethen in the situation where the authority said for the remaining centuries , Heaven is there, hell is down there and that is what you will believe , any other thought was wrong. With hindsight, it is probably easy for us to say well its so obvious surely. Yes it is , but in prior times it may have been obvious , but it was frightingly dangerous to say so? Yes, that was my reference to being burnt for being a witch. If the dark ages hadn't happened , we would probasbly be a lot more enlightened. Its all Aquinus fault and blame the catholic church for so much. I think doctrine holds you back , stops you from being able to think and explore, you don't step out of line. If you can't read , and my ancestors could only write Xs on birth certificates in 1850s, people were not reading. It sounds flippant and glib but knowledge is power. If you can read and find out about something, that is why D wrotr in English. Isaac Newton, genius, but he wrote in Latin for a scientific elite, a new priesthood, not writing for people down the pub. The father of European philosophy wrote in French . Yes How much do think the family of D, with their status, allowed him to do what he did? Alfred Russel Wallace did not have any money , but he did it. The trouble was ,Wallace had to speak to someone , who was lofty and knowledgable and a science hero, as D was, saying would you please promote my work. i think D's social status was absolutely key to allow him to do what he did. Wm Smith the canal engineer , he produced his map, he had no money. He spent a lot of time in pauper's gaol , owing people that had backed him, not easy . D's fear , spending an awful lot of time in Down House. In D's study at Down House, behind a screen D has a vomitarium. Where he could go and be ill, D spent a lot of his time being ill . He suffered from nerves, whatever that was. He probsbly picked up something on his travels around the world , some kind of tropical disease and suffered from it for the rest of his life. He wasn't confident in putting his ideas forward. It was Wallace who tipped the balance, and overcame his own concerns and pushed it forward. Did people know , at the time , of the genetic dangers of inbreeding? Yes they knew about it, but humans were considered different from anomals. D , letter to his wife. A book written by Keynes ? D's great grandson, called Annie's Box, about her treasure chest. It was turned into a film , the producers thought should be called Creation . It is a beautiful film , D's life in flashbsck , there are moments when he's talking to his dead daughter, dramtic licence, not he was crazty. Conversation with his wife , after losing his daughter about maybe our marriage was too close , maybe that was the reason behind her death. Certainly an awareness that it could cause problems, but not so much in comparison to the requirement to protect family wealth. There was no understanding of genetics as such , so no understanding as to what could underlie it. Do you think on his deathbed , he may have said, this is all a theory . Like myself he was agnostic , did he have a deathbed conversion? Theory is a very important word , because in science , theory means something different to colloquially. What commonly is called a theory , a scientist would call a hypothesis, something you've though up but have no evidence to support it. A theory in science is something you test , must be falsifiable fundsamentally important. This is why theories about intelligent design are not scientific theories because you cannot falsify that god did it, you cannot disprove a god. Evoliution you can absolutely disprove. Everyone i work with, are researching things, their hypothesis are falsifiable and if it is proven , that the evidence as a result of your observations doesn;t fit with the theory you are working with, you change that theory. Thats not being Procrustean , the Greek giant , and if you went to visit his house , he would offer you a bed for the night . If you were too short, he would stretch you , so you fitted and if you were too tall he'd squash you. That argument has been levelled at my PhD examiner , Dick Jeffries ?, for changing his ideas. It is absolutely right , that you change your hypothesis , change your conclusions , based on the evidence that you have. Evolution is testable , we can make predictions , make the observations, does it fit , yes, move on to the next thing. If it does not fit, what do we need to do . Genetics is a beautiful example. The idea of lemarcian inheritsnce , it does not work, so we throw it away. Do we need to throw away the whole idea , do we need to explain it better , ie move forwards. Theory is a perfectly good word to use. I do not believe in evolution, I have no requirement to believe it. I can accept it, based on the evidence. Its not a faith thing. You yourelf can believe whatever youlike. But when I'm doing my science , the books I have to use, the books that will inform me , tha tI will be able to build on , will be science texts, employing the scientific method and not 1 Corinthians. Natural selection relies on variation , can you talk about how those variations can happen, and how they propogate? Variation is where the random bit comes in. Some people say evolution is random, evolution is not random. Mutation is random , your DNA is a string of 4 different chemicals adanine, guanine, cytanine and thianine. Those 4 nucleic acid bases , they are arranged in groups of 3 and each group of 3 codes for an amino acid, strung togehter 3,3 3 and those amino acids form a protein. Proteins do stuff. Students think life is to do with a Beethoven Sonata or the works of the Spice Girls, not at all.Life is proteins interacting with proteins and reproducing themselves, not very romantic. Variation is just changing , by DNA not copying itself perfectly every time, just changing the order or 1 of the 3 bases. Delete it and everything moves back 1 space . So the entire amino acid code can change and so the protein that comes out. Protein itself is not just a long string, it folds up on itself, forming a 3D structure , and acts like a lock and a key. It will bind to something else and catalize areaction. If you change its shape , it doesn't bind so wil probably be functionless, gone and that organism with that mutation may not survive. Sometimes, and this is where the length of time is important , a mutation will not be negative , it will be a new novel form and conveys an advantage on that organism containing that protein. Thats where the random mutation comes in, and then the absolutely non random natural selection acts. A mutation can be something as simple a bacteria creating a protein which knocks out the function of an antibiotic drug. So we look at bacteria and antibiotic resistance as artificial selection. Artificial from our perspective but not from the perspective of the bacteria. It has evolved by NS to find itself in an environment , and now with a beneficial mutation , survives and reproduces. Where does that DNA have to be modified? in the sperm , egg or the first cell, or somewhere else? The modification occurs where it is dividing quickly, and so that is in dividing cells. But the first place a mutation has to be , for it to be passed on , is an egg or a sperm. If I have a muscle cell , that has a mutation in it , it won't get into the next generation . If I have some weird sperm , a mutation in a germ cell and its passed on , thats where the magic happens. Thats where NS can act in the germcells and the embryo itself. Whats your prediction for the future ? isn't NS over now? No, human beings are special, no we're not. There is something happening in the world at the moment , that I hope we can adapt in time for, global warming. Human beings wil lbe exposed to exactly the same selection pressures as everything else. One of the antiNS arguments is how cruel nature is, red in tooth and claw. Nature is only kind of cruel, because its not thinking about it, its just selecting the organism that fits an environment best to pass forward into the next geberations. D says clearly, paraphrasing, NS is not a nice situation and human beings should not live by its rules. So when people say D leads to Hitler, they've never read . Hitler was quite adamant that all the works of D were to be burnt, so not exactly a proDarwinian. The idea that Social Darwinianism, thats taken his name unfairly, crazy. We should not be trying to engineer ourselves, because we've not done a good job with dogs snub-nosed bulldogs etc, they're not healthy. The skull of King Charles spaniels is too small for its brain. We probably should not do similar to ourselves. However there is one aspect of humanity that is crucial and that is our compassion , our kindness to individuals that nature probably would not select. There are people with health conditions which are now perfecly livable with. I have acousin with Cystic Fibrosis , een 10 years ago he would not have seen out his 20s. Now you can have a relatively normal life. Its unlikely she will live to 90 but for every year of your life medical progress is made . This is a small number of people that this applies to , where left to nature would not have survived. Its not changing the population so drastically . When I was a boy , we would have all grown up to be a boy, transgender issues , artificial insemination, isn't it part of a process of selecting survivors? The people who will survive global warming are the people who could afford to? People move up hill, people in Bassett will survive. Yes, maybe. Transgenderism is'nt affected by NS. Just because you've had surgery to make youself , to live happily in your body and appear male or female, a different body to your chromosomes . You will not then have children , that is not changing NS because you are nt passing on your genes. The selection would not be natural anymore? There is no selection , because a man who becomes a transgender woman or vice versa, they will not reproduce. Only because we've nt solved that problem yet? There isa n amazing piece of science, I'me certain others will disagree with me. Recently scientists , have taken soma body-cells , somatic tissue , treated in such a way that they've made it become egg-like . So you can now , if a woman has lost her ovaries , you can now make an egg-cell . For the previous history, the only cell that could give rise to an embryo was an egg cell, sperm is secondary to it . We've now changed that, I don't see that as a big problem. I see it as a wonderful step forward . One of the big problems we will have to overcome , very quickly , and it will select extremely quickly , is the global fertility issue . There is a massive decline in human fertility across the globe. I'm not talking about people choosing not to but people being unable, not producing sperm, a male issue in the most part, sperm counts are dropping rapidly. If we can get around these things with science, I think thats a good thing. One potential cause for that , who likes using those lovely micro-beads , bad for you, made of plastic . If you buy something that is a biodegradable plastic , its not biodegradable, no such thing. What there is is plastic that break down , getting smaller and smaller until you can't see them . These tiny bits get into fish . We've entered a new geological era . We mark this new era , in one way, radio-active fallout since the 1940s, no , that will disappear. We'll not have in the rock record in 10,000 years a noticeable radioactive legacy. What will be still there is a layer of plastic . Plastic has a lot to answer for. Many of the breakdown compounds , from plastic, mimic a female hormone . Along with other chemicals such as Roundup , this feminises frogs, makes male frogs female. Its banned in many places but rivers and seas tske no notice of state lines. Evolution shows that we are extremely closely related to frogs . A worls full of females could be the answer to world peace. Some morphological questions. Convergent evolution where different species develop separately but their appearance is much the same. Why are they so similar, in that I could understand if one species developed eyes on its thumbs say. There seem to be morphological structures inherent in everything. ? Its just common ancestry. Evolution is great but you can only work with what you've got. You can develop such structures but it takes an awfully long time. Its quicker to modify what you've got . So if you find youself in an aquatic environment , the physics of water affects everyting that is 4 foot long , in the same way. If you're really tiny, the viscosity of water , for you, entirely changes, so you are driven down a different course. If you're a largish vertebrate , the selective pressures on you, if you are a predator . So sharks , tuna fish, dolphins and ichtheosaurs , they look fundamentally the same, long and thin torpedo like with a tail the flaps in hte same plane. The NS, the environment they find themselves in , drives them along that line , and onlt so many solutions , to be a fast active predator in water. With worms, its a perfect way for burrowing , so worms , snakes evolved to be burrowers, legless amphibians etc. Its a situation you find yourself in , only so many solutuions available to you. There is no desire in this, the way you are selected , if you're a burrowing organism , you end up with a long thin muscular animal , segmented along its body, it can thrust its toughended domed front end through the soil. I believe in the embry stage of humans and others, there is a stage where, I'm thinking of the formation of cleft-lip/cleft-palate, where part of the developement has to fold back on itself, which seems a horribly complicated process to go through and it does so reliably in the most part? It is truly remarka;be that so many of us turn out to be normal . What we have to go through . A book I would encourage people to read . Richard Dawkin and The Greatest Show on Earth, published for the D 200th , one of my favourite books. It talks about , and addresses alll the arguments of OS. A famous developmental biologist from mid 20C. He was challenged by a woman in an audience I can accept the great lengths of time, but how can you explain a single cell organism becoming so complex as a human being, evolving over time. His answer was simple, why madame you've done it yourelf. We've all gone from a single cell to the 3 trillion cells you have now. The difficulties, the complexities of your personal developement you have to go through to get here. That is works and so reliably well so many times , more than 99% of the time, is remarkable. When things go wrong its not surprising. Its purely a developemental problem for things like cleft-lip. We're cordates , we form in a little cup basically. Chickens and things that grow in eggs form as a flat disc on top of a yolk. Mammals form concave in a cup inside the uterus. The contorsions that you have to go through . Basically a flat disc although curved, through to a 3D animal is remarkable. One of the first stages we go through is the formation of alayer of cells and an ectoderm , an outer layer of cells. Then where those 2 cell layers interact you get cells moving in between and you get the mesoderm that form our muscles and skelton . The endoderm ,the first one, forms our guts . The exoderm forms our nervous system and our skin. in order to get our nervous system , the edges of the exocerm lift up , forming a ridge , it pushes down and as it does so the "lips" close over and you end up with a tube , underneath the skin . Along that very top crest, is the neural crest, where that closes perfectly, later on in developement , then no problems. When it doesn't close you get spina bifida. Assuming its all gone fine , then there are very special cells , that vertebrates have nothing else has , is the neural crest cells. They are migratory cells , from the very top of the closing tube, move away , move out and move into our faces, as very early embryos a couple of weeks old. It causes the farangial clefts , to grow round . If you are a fish those cells will create gills, if a human it forms jaws and a face. These tissues move around and where they move around properly , they knot up the front of your face, and the roof of your mouth. It makes sure you have 2 eyes , rather than 2 eyes in one hole , which does happen. A great many times all works perfectly but sometimes it does not work quite enough and you get cleft-lip , cleft palate is the precvious step back. We can remedy them surgically and you would never know. Is that a problem from the genes? No its a developemental problem with those migratory cells. 2 aspects to all this, there is your genes ,nature v nurture. Nature is the genes that you have, nurture is how the environment that youy find yourself in , also crucial. You are in a nice warm uterus and things are going well , then mum has a few drinks or smokes or there are problems such as being unwell. All sorts of things that can change the local environment of a developing foetus. So not so much your genes but the nurture that causes this issue. You could have genes to be the smartest person in the world but if you don't get nutrition at the necessary time for your brain to develop properly , then will no be so brainy. Thalidomide problems , was due to a drug that affected developement , a very tiny window, in the foetus developement. That time slot coinciding with the time that it was adminstered to stop you being ill. Thalidomide though is useful for Parkinson's and leprosy. So be male or don't get pregnant while being treated for leprosy. Beneficial evolutionary rationale behind nausea in pregnancy? A secondary effect of the hormones at the time probably. I can think of no reason for it. A lot of things that affect humans, don't affect wild animals. I can think of no evolutionary reason. Its only in the last 50 years that childbirth has become a much less life-threatening event. An Alice Roberts TV prog, took a human female pelvis and the skull of a full-term baby and matching size available. So many problems that can arrive if you go over just a few days, childbirth become dificult, beyond the normal difficulties. from the audience, I read a book The Genome an autobiography of The Species, Matt Ridley? he covers it in one of the chapters. The placenta, according to him, is controlled by DNA from the male and so the male is sort of overriding the female body to prioratise the baby over the female, so the female is putting mpre effort . If the female was in charge, then she would want to survive , and cut down on what I'm giving the baby , but the DNA from the male is taking over. He says if you have terrible morning sickness , then blame your husband. Not possible to test that hypothesis. Is that why we have a very long training stage, because we cannot have big brains at birth? Absolutely. If a baby is born at an extremely underdeveloped stage. If you are a new-born gazelle , you are born running or you are eaten by a lion. Luckily for humans we're not socially Darwinian , you are born weak, so you cannot run withthe pack, so we will leave you behind. It would be very negative for us as a species if we did that. There is a big trade off between having an intelligent adult and a baby that is developed enough not to be really rubbish for 18 to 30 years. Is there any reason for humans having menstruation , with all that leaking every month, a predator could run after you.? For early Kahlari bushmen women they would be pregnant or breastfeeding and supress menstruation. Male and female and sex for survival of the species, is that likely to be the only way on other planet lifeforms? We do have different modes of reproduction here on earth. There is the no males at all Bdelloid Rhotapers ? have no males. Bees. We have neuter males , eggs that are unfertilised , the half chromosomes of the females and develop into males. Then there is reproduction via one of those males mating with a queen . Aphids. Your tomatoes are going really well then ther are thousands of them. A female aphid has within her, a clone containing a clone etc , parthogenetically you have new females. The males are waiting in the eggs. Each one grows a bit then pops out the clone etc, a quick way of colonising. Ultimately there is no genetic variation as they are clones. If something like a virus affects one of them , it will affect all. You need sexual reproduction to mix the genes up to bring some variation , so that when something comes in and knocks out some of the population , some will survive. Bacteria bud, splits in half like yeast. Any higher lifeforms? London zoo recently had an unmated snake, produced parthogenetically an offspriing without mating Are there any examples of where it takes 3 sexes? No. Some people have argued that bees may be. Never 3 sets of DNA contributing? no. Someone has a faulty heart, whip that out, and transplant in another. But take out defective mitachondria from an egg , put in functional mitachondria , I don't see that as as big a deal as a heart or a liver. So prevcnting a mitachondrial disease. But , shock horror, 3 parent children , a no no. That child wil lnot have a mitachindrial disease when he becomes a parent. I don't see the problem of changing an organelle in a tiny cell , is comparable to changing a heart or a liver later on. They are not 3 parent children, you've taken a tiny structure that has its own DNA , but it does not contribute to the next generation. We have 2 parents and sometimes we can give an offspring a better chance by giving them a really tiny transplant. W50

Monday, 14 Nov, 2016, Dr Paolo Cipollini , NOC Southampton: The use of satellites to monitor sea levels. 18 people, 1 3/4hr It might sound asking too much to measure sea levels SL from way up there in satellites S, but we can do that. Is the sea really flat. And does SL remain constant. The sea is not flat, there can be big waves. Wind blowing over the sea surface creates waves but when it calms down, the level will flatten out to the average of the waves previously. Create waves in your bath and when theyy stop the water level is just the same as before. There are tides . The tides in Soton are 4 to 5m between minimum and maximum heights. Again the average of the tides is zero. A place like the Bay of Fundy in Canada, 16m of difference in height there. Again there, the average of the tide is zero. In the long term these changes don't count for much. There are other effects, bumps and troughs in SL , due to currents. Where you have a current there will be some signature of that current in the SL. Its not the simple case of where there is a current there is a bump. It relates to a slope in the SL. If you could look at the large scale of the sea surface of 10s to 100s km, you would see these bumps and troughs. Its the same concept of highs and lows in atmospheric weather maps, is what generates winds. Winds don't go from the high to the low , as you would intuitively think, but tend to rotate around the highs and lows. In the ocean , the same effect bumpsa and troughs are similar to the highs andlows of the atmospr=here. If I say the currents don't change, they may well do over long time scales, then the mean SL should not change. We've now been measuring SLs for decades if not 150 years or so in some places. When you look at the global picture of SLs, the regional SLs have been changing. If a current changes somewhere , then the SL in one place will tend to go down and in another associated place, go up by the same amount. But its also changing globally, the global level of SL, what worries us the most. Along the coasts we have tide guages, originally placed around, to study the tides. After a while , months or years, by looking at the data , the tide becomes really predictable. Essential for shipping and navigation. There isanother thing you can measure for tideguages set in one place for a long time , filtering out the daily up and down of the tide , and see over years whether an upward or downward trend in SL, or stays flat. So we can look at long term sea-level at these guages. NTSLF tidegauge network of the NOC , Liverpool site. There is a global network of tidegauges, GLOSS. The Newlyn gauge has 150 years of data, but some others , developing countries , perhaps only for 5 or 10 years. Trying to put all that together to find a global mean , has to be done with a pinch of salt , as different weightings for different stastions. For some of them there was a war over some of the period. A gap of perhaps 10 years and lack of cross-calibration of the new siting, a lot of practical problems in trying to assemble a nice plot. Where there are no islands, we can only use satellites. From tide-gauges we do see the SL changing. A map of Europe and N America , with up or down arrows along the coasts with gauges. They show the local trend in sea-level , measured wrt a local reference. Sweden has down arrows , the relative SL, in that region, since the end of the ;ast glaciation , all covered in ice, the Earth crust is still bouncing back. The crust does not flip back , with no overburden, in a few minutes, its taking hundreds of years to return. Trying to account for all the local land movements , which we can do with GPS coupled to tide-gauges. The GPS system works on an absolute co-ordinate system, so it can tell you whether the coupled tidegauge is going up or down in the longer term. We've seen over the last 130 years, using old tide gauges, new ones and plugging in S altimetry data in the last 25 years, we see a clear increase. Some people see an accelaration in global SL rise, still under discussion , but consensus is going that way. TRhis is worrying because you have to project this situation into the future for designing coastal infrastructure and defences. we nget , for mean SL for the last 110 years of about 25 cm. This is a global average. When you use tide gauge data from the past, perhaps old instruments, lacking calibration , or an operator taking readings only daily, there are errors, giving an uncertainty to the data. The error bars get narrower with modern equipment. Even accounting for the uncertainty , it is rising, perhaps 1.5 to 2mm per year in the 1900s and now more like 3mm per year in the last couple of decades. The launch of Sentinel3, by ESA in Feb 2016, that i work with. On board are different measurement instruments, particularlya radar altimeter, the data I work with primarily. Aeroplanes have altimeters for measuring height relative to the ground, similar principle for us. The altimeter measures the height from the sea surface to the S, quite accurately. It orbits the Earth and in one orbit the Earth will spin under it. The result of 10 days of orbits is like a mesh pattern. Interpolate the mesh points to produce a nice image. Filling the gaps with some maths filtering. In red there is the peaks and blue the troughs of the sea surface. The light blue depressions may be 10 to 20 cm and dark colurs 20 to 30cm. So a variation in SL of about .5m. This image shows the effect we call El Nino . So not just a rise in sea temp but even the SL goes up. With now 25 years of data we can see what local SL change has been in different areas. So we can produce maps of the rate of change of the heights. On one side of the Gulf Sea is going down , on the other side, its gone up. In the eastern Pacific the SL has gone down but around Indonesia gone up, over 20 years of dat aits gone up 7 or 8cm. Since 1992 we've had about 10 altimeters in orbit. If one stops working, and a new one is launched , we can cross-calibrate with the old data. Al ot of work inter-correlating all these mission data. ESA has 2 S, US navy , a couple of polar ones. There is an annual cycle in the data of about 15mm. A mix of the effect of snow and thermal expansion perhaps. The peak is in Sept/Oct, and thermal expansion effect should produce a mimimum then. It is due to water storage on land, as water or ice. Sept /oct is when most of the glaciers , mostly in hte north hemisphere offset by only a few in Chile and NZ. Plants taking up water in the summer months? That will have a signal due to tree canopy storage. Again most of the forests are in the North Hemisphere so you'd expect a minimum then. The signal that dominates is the land based snow and ice. So SL rise is due to accumulation of greenhouse gases from climate change and the Earth is warming up. There are 2 mechanisms there, 1 is thermal expansion of seawater , the other is overland ice has been melting proportionaly more going int othe sea. For that 20 to 30cm rise from the 1800s, these 2 effects have contributed about the 2/3 and 1/3 between them. For the future , extra increase from thermal expansion but the major problem will be from melting water over land. Melting from Antatica land and Greenland will be the major contributor in the next few decades. The IPCC assessing the science and reveiwing everything continuously for their reports on the state of the planet.They've been compiling the results of different reports based on different models. A precautionary approach is to run different models and describe the results in terms of probabilities. So we are not saying the like of SL in 2100 will be 87cm higher. It is a spread of values , giving probabilities. Another IPCC report is due June 2017. What SL rise will be in say 20 years is dependent on what we do in the way of burning fossil-fuels. So the IPCC quantifies a few differnt behaviours. Go for a totally green economy and not burning fossil fuels, something in-between taking a couple of decades to change our behaviour wrt renewables etc, and the other is continue as we are. Continue as we are scenario, by 2100 end up with 70cm rise. There are huge stretches of the world where people are living at the level of current SL. Think Venice or Bangledesh. All those people will have to relocate. They can currently cope just about with current storms but not those storms on a 70cm background rise. Bear in mind there may be an acceleration in the melting over Antartica and Greenland. So a non-zero probabilit yof over 1m in 2100 for that scenario. Lots of people around the world are working on this trying to perfect their models to hopefully converge on some figure. There are things we don't know well enough. One major thing we don't know well enough is the melting rate of Antartica and Greenland ice. We do know pretty well how much water is locked up in those locales i nthe form of ice because people have sounded through it and now where the bedrock is and is known to good accuracy. For more immediate concern it is the ice melt over Greenland. There is water enough there to increase global SL by 7m. The upper floor of this pub where we are nw is probably 3 or 4m above SL. Then 3 m on top of that and we've drowned. Along with all the other coastal cities of the world. For antartica there is about 55m of water locked up there. Loads of islands in the Pacific would completely disappear. Pu ta storm surge on top of current SLs can =be coped with but add a metre. Hurricane Katrina broke local sea defences. In the UK we had a bad storm surge 1 Feb 1953, which resulted in the Thames Barrier being built and has to be closed quite often to defeat storm surges 100cm of mean SL rise and Venice goes, a normal tide of 100cm and Venice floods, so that elevated water level all the time would be impossible. Amsterdam , Hamburg , the sea-front area of Los Angeles and San Fransisco is low 1 to 5m above sea level, so those would disappear. Most of New orleans is low, flooded with Katrina. London is a bit higher up at 8-9m , but if antartica starts melting then vulnerable then. SLs are rising , with great confidence. So we need to start acting now , for the sake of future generations. We need to mitigate the effects of our economies on climate and SL, so need to reduce fossil fuel use, increase enrgy efficiency, adopt renewables. But already we have to adapt in terms of building new coastal defences. We need to rethink how we use land, build away from the coasts and accept that we will have 1 to 2m of SL rise. A digression on the recent phenomenon of, for 35 years the Arctic and Arctic sea-ice global total for any day, compared to the long-term average for that day, was surprisingly constant, until the middle of October 2016 when it went totally off the scale and eventual record global minimum on 22 November 2016. A climate change tipping-point ? Everyone agreed geography, oceanography etc was very different at the 2 poles but no one could say why a fixed scale of +/-3 million sq km was sufficient for 35 years, in fact for 25 years +/-2 million was sufficient scale for this Dies Anno global anomaly metric . A different use of satellites , for remote sensing. using http://nsidc.org/arcticseaicenews/charctic-interactive-sea-ice-graph/ to plot https://icons.wxug.com/hurricane/2016/nsidc_global_area_normanomaly-11.17.16.jpg https://forum.arctic-sea-ice.net/index.php?action=profile;area=showposts;u=19 1:03 to 1:15 , I could transcribe if there is interest . Satellite altimetry - how we use it over the open ocean. At the NOC I like to push the techniques . We would not usually use it in the coastal zone, but it is important so we are trying to remove the technical obstacles. These altimeters don't work well over land , so no use for monitoring the recent NZ or Italian earthquakes. The basic principle of alimetry is you put a saltellite up there , it sends down a radar pulse , a ping of e-m energy to the surface of the sea. The signal bounces back and the satellite gets the reflection. Knowing the time and speed of light you measure the distance. If the sealevel is lower , it will return later. You know the orbit , precisely , from a numbe rof different technoques. One intuitive on is to have a GPS receiver on the satellite. So you then know how high the satellite is wrt to the centre of the Earth, take the difference , gives the sealevel. What makes it challenging, is we want it to be very accurate. The bumps or troughs on the surface may only be 10cm, I want to be able to resolve a cm of sea-level change over say 10 years. I want an accurate measurement from a satellite that is 1000km up there. So you have to account for every source of error, every strange effect. Send and receive signals have to go through the atmosphere, so there is water-vapour, different gases, free-electrons in the ionosphere, a ;lot of things that make the speed of light not quite the speed of light. I'm proud to say that with hte latest generation of altimeter satellite up there , I can measure a disc of just 5 km across, with an accuracy of 2-3cm. When you average all those millions of readings across the whole globe you get a really accurate measurement. Accounting for the error sources, you can get to mm precision, and you can observe a global sea-level change of 3mm per year, perhaps only 2 or even 1mm per year. We are down to that level of precision. We get those pings back to the instrument, and by somehow decoding those pings, we get extra information about the sea. We fit a mathematical model to the rise and fall of that waveform and from that can determine a number of different parameters. Looking at the location of the waveform in the time sense, I get the height of the SL. From the shape of the ping, if the sea is very flat, the ping rises very quickly. For a rough see it rises more slowly. So from the slope of this rise its possible to determing the significant wave heights all around the globe, just from the altimeter returns. The overall power, the amplitude of the peak response is related to the wind speed. So I measure 3 things with same instrument. Altimetry is long-tacks. Images from satellites we are familiar with. Altimetry is differnet , the S goes around a track and the measurement is beneath that track. So the data is just a file of the returns along that track. So in say 10 days , there is a mesh of results, but not in between. For a nice 2D image, then some interpolation is required. I'll highlight 2 missions, Poseidon 3 the name of the instrument on Jason-3 and Sentinel 3a. Those have been this year, plus the past ones and many more lined up for the future commissioned until 2030. We've been building up the data record since 1992. Its a mature technique now for oceanography.From altimetry you get maps with the bumps and troughs in the ocean surface. Varrying between + and - 30cm or so. For a complete world map the gathering time is 35 days. So these maps are used in combination with gravity measurements to build up the absolute dynamic typography, accounts for the major currents. The complete range of heights is about 2 to 3m . Where there is a major current like the gulf stream, or off South Africa, you have big changes , there are large changes in the height. But the current is not where the bump is, but where the slope is. Much the same conceppt that you see on weather maps. The winds are not where the highs or lows are, but where the isobars are closer and bigger slope in the pressure. The same effect in the ocean, called geostrophy, the balance between pressure gradient and Coreoleus Force, because both situations are on a rotating sphere. A complicated reference structure, the apparent force, everything that moves on a large scale, of > km scale will tend to steer to the right on the northern hemisphere and to the left in the south. At very large scales we can assume it is at equilibrium . With a high in one place of the ocean and a low in another place, pushing water over, and the Coreolus Force , means the water rotates around the highs and lows, moving where the slope is highest. So end up wiht a map of current, and flipping between the 2 images, highlights the major currents. So from altimetry we see the bumps and troughs and then the currents. In the 1990s , designing in the 1980s, that was the major objective. At that time there was less importance laid on knowing global mean SL. It worked very well and we measure the global SL rise as well. Movie of a current off Japan, the height of the sea as measured by the altimeter. One side is higher by about 1.5m , the other side 0, and in between is the Kuroshio ? Current , highlighted by arrows by looking at the gradients. We see the current , but also eddies and other things apparently moving back westward, as well as the mainstream with the meanders. This is anot a simulation but directly from the measurement data. In 100km there is a drop of 1.5m. The same effect with the Gulf Stream , over 100-200km about 2m and where the maximum slope is, there is the main body of the current, again real data from the altimeters. Excluding a few early missions, lacking requisite calibration, the later missions are quite consistent, giving 3.1mm per year as the mean SL rise globally. Within that you can look at the trend, region by region. Around Indonesia SL is going up fast, about 1cm per year. Around California, going up but not as much and changes in the currents. For the Gulf Stream , the southern side of it is going down and the northern side going up. On average the current is going slower, less transport . We are moving these kind of measurements closer to the coast, for a number of reasons. When the altimeter baem impinges on the coast , the return p[ings are not easy to interpret. They get corrupted, and when land intrudes on the footprint of the altimeter, there is more work to be done on interpreting this. Over the last 13 years we have a group of about 100 colleagues working on this around the world, working on coastal altimetry. Its a good thing we've 25 years of data to work with. There are many stretches of coast in remote regions that have no tide gauges, no instrumentation. Or if there is, then only placed there , in the last 5 years say. Altimeter returns start getting corrupted perhaps 10 to 30km from the coast. We always compare S and tidegauge readings , and there is good agreement , despite not measuring in the same place. Conventional altimetry stops 30km off shore but tide gauges are right on the coast. People will be using this coastal monitoring to explore coastal currents, for sediments emerging from rivers, or for disaster management such as will an oil spill affect land or swamp or tidemarsh areas. A killer use for it will be studying of storm surges, resulting in coastal flooding. Storm surges ,like Huriccane Katrina are among the most deadly of natural phenomena. Images relating to remote sensing observation of Katrina, the bathymetry , the shelving to the coast. There was an overpass of a Chinese altimeter , that evening showing flat until getting to the shelf and then from the altimeter data you see the big piling up of water. The S passed perhaps 100 Km away from New York itself, but the surge was apparent far away, about 1m where it was observed. Such a pass was adventitious unfortunately, not assignable. If lucky to have such an overpass then the profile of the surge becomes very obvious. very important for peiple that produce models for predicting storm surges, can check the validity of their models. Improvement in such models will give better warning for areas that will be flooded and those not flooded , evacuate people or not. In 2012 Hurricane Sandy flooded New York . In 2015 there was the Santa \claus storm over the North Sea. In the Danish Straits , we had an overpass of an ESA altimeter, where the surge was. The image shows the profile of the SL . You see the piling up of water for a storm surge of about 1.5m . Comparing this with the model result produced by Danish colleagues , for the same time, good agreement. Strong surge one side of some islands and lower on the other side, a good validation check. We can look at the finer scale of mid-ocean. So th eGulf Stream , sea-surface temperatures, chlorophyl from mid-ocean sensors. Fine scale details, important for biologists, from alitimeter data. There are interactions between the physics and the biology that are important for life in hte oceans. local upwelling of nutrient rich waters from the deep that stimulates growth of phytoplankton , the base of the food-chain in the ocean. Another image, off South Africa, sea surface temp , a chlorophyl map of interesting things close to the coast. Places where cold water is coming from below , near the coast , stimulating growth around it. Another mission , to be launched by Nasa in 5 years Surface Water Ocean Topography Mission. It has an alitimeter but also 2 long beams with antennas, using interferometry , also sending pulses to the same surface of the ocean . In a sense they get a stereoscopic view, giving a measure of the relief, the topography of tyhe ocean. Another clever technique we are moving to use GPS tomeasure SL. We put a GPS receiver in space and we receive the reflection of GPS signals off the sea surface. The GPS Ss are about 20000 km up. They are there already, the signals there already, all the time. They also bounce of the sea. So with a lightweight cheap receiver in spavce you get these reflected signals and also the original direct signals. From triangulation I can start estimating where the sea surface is, and its height. Not just for height but also has info on the sea state, for waves and wind. This is promising as its light, relatively simple receiver, it is passive just receiving what is already there. It does not have to generate its own pulses, so low power requirement. So 8 or 10 on the same rocket , spread them around in space, will get a lot of measurements. On 12 Dec 2016 Nasa will launch a constellation of 8 GPS receivers , the main reason for this Sygnus mission is to measure winds in huricanes. Hurricane forecasters need wind info , for near the eye of the huricane, to predict strenght and direction of travel. I have a personal interest in using Sygnus for doing SL measurement. With relatively low launch weight, relatively low cost mission, we hape to get a lot of measurements. So we can take the "pulse" of the planet , monitor the oceans for SL and climate change. Q&A What is the wavelength of the radar? For altimety we use Ku band 13.6GHz, which is not too affected by things in the atmosphere, but we still have to compensate for some of them. It allows good measurement precision , the return is nicely sensitive to the wind, so gives a nice estimate of the wind. One of the missions called Altika? , Ka for Ka band which is 36 GHz a French instrument on an Indian S. More precise in its measurement , it is likley to be more sensitive to rain in the atmosphere so trickier to use in the likes of the tropics. In practise we're stunned by this instrument, it works extremely well , we can compensate reasonably well for the problems we get. My guess is in the next decade or 2 , most altimeters will be using that range. Usually we make altimeters with 2 frequency ranges. By looking at the difference in return signals , you can compensate for the effect of the ionoaphere. The free-electrons there, have an impact , that very much depends on frequency , at 13.6G every few pulses sent down , youy send down a pulse at dsay 3G . By looking at the differences you can estimate the effectof the ionoaphere and correct for it. A lot of interesting radar aspects in altimetry. I can see with a swell going through an ocean that you radar, in a biased fashion, will pick up the concave troughs rather than the convex peaks? Yes we have to compensate for that. Another correction of the many that we have to apply. Its called the Sea-State Bias. Due essentially to 2 things, 1/ what we are trying to measure over the footprint of the altimeter for one of its pulses. We are trying to see the mean sea surface . The return signal is not really the mean but more related to the median of the sea state. So the half-point of the distribution #of heights. Because the wind-waves are not perfectly sinusoidal peakier with flatter troughs , swell tends to be. 2/ in pure electromagnetic ?, for the peaks , the energy is factored away so we get a lower intensity return, compared to the flat bottom of the troughs. Without compensating for that, the altimeter will over-estimate the range and a lower SL than actuality. In the error budget, error uncertainty, for altimetry the SSB , as of today is perhaps the most important in the modelling. Variability of temperature , humidity etc of the atmosphere are less of a problem? There is a correction you have to do for the gases in the atmosphere, O2 and N2 . In terms of range that correction is of order more than 2m . But we know how to model it very accurately , this correction is extremely sucessful and we can remove it almost completely, with a residual error of the order of mm. SSB effect is smaller in magnitude 10 to 20cm but we cannot model it to such good precision. The residual error for SSB of about 2cm is a major contribution to the error budget. The poster for this talk, shows the 200 yearold tide gauge record on Brest Peninsular in France. Could you explain , 200 years on the same spot , new gauges presumably ,but no one has messed about with datums. For the first 100 years its virtually flat. I know that in the last 30 years or so if you look at the BODC tide records for the UK, Lerwick shows 30mm of mean SL rise but Portsmouth shows 170mm , from the isostatic rebound effect. Lerwick rising and portsmpouth sinking, presumably for the UK the average is somewhere between those 2 numvbers, for SL rise. Brest is not that far from Pompey , and pompey has not suddenly started sinking presumably, so what does that flat bit of Brest tide record represent? I would say this plot is fairly representative of what has happened to the global ocean level. There may be local land movements for this particualar site. Then it starts increasing more rapidly. Interpreting a single tidedegauge is a work of art because , only recently have gauges been fitted with GPS. What was that gauge doing in the 1800s, you have to make a lot of assumptions. If in one area you have a rate of isostatic rebound, perhaps it was pretty much the same in the 18C, but then there are other things. Like in the vicinity of towns or indusstrial or agriculture areas, in the 19C coukd have been pumping out a lot of water from the watertable . In Venice there was a big problem in the 1940s/50s/60s because a huge petrochem plant , close to Venice, extracted a lot of water, used in the plant. Resulting in a lot of subsidence. Very few of the current crop of tidegauges have been calibrated with altimetry. Not used because of the cost and many would not have the land vertical data as accurate as you would need for multi-gauge site comparisons. We've looked inot this with accuracy and you still end up with discrepancies that are difficult to explain. Even if GPS is used at a gauge site, its only for the last 10 years and you don't know what was happening before. So altimeter based SL rise globally agrees with the tide-gauge records but when you look regionally its difficult to get a good match. With coastal altimetry we are trying to fill that gap, at the same time , our tidegauge clooeagues are getting more knowledge of local vertical land movement. Every country uses a different reference system for tides, usually a local reference. UK has one , Italy has one. It seems sensible to bring all these separate sytems into one international reference frame IPRF ? which we should do if we want a global comparison. B23,2/16/00 W53, 0/13/00

Monday, 12 Dec, 2016, Dr Catherine Mercier supported by Dr Frank Ratcliff , both of Wessex Academic Health Science Network, Southampton: The 100,000 Genomes Project , focus on rare disease and cancer. 1 3/4 hr, 27 people Wessex Academic Health Science Network is a facility for driving innovation forward into the NHS and DR Mercier is a clinical geneticist at the Soton General Hospital. The talk will be about The 100,000 Genomes Project and the wider question of whether you'd have your genome sequenced. Dr Catherine Mercier I believe we're in the midst of a revolution. If you think of thr industrial revolution, it did not happen overnight, taking about 100 years for the changes to come to the fore. I think there are similiraities with the genomic revolution. 1953 the structure of DNA was discovered by Watson , Crick and Franklyn. I believe a doctor in 2050 will still be looking at their medical records, blood pressure , what medications the're on but also on the screen info on the person's genetics or even their genomics , the entirety of the DNA, the coding and non-encoding parts in-between and how they interact. So in my career I believe genomic medicine will become much more main stream. We are made of about 3 billion cells and within the cell is the nucleus which contains 23 pairs of chromosomes. Take a single chromosome and unwind the DNA, and along the string is gene after gene. Genes are important as they encode for proteins , essentially we are all made of different types of proteins. The gene is the smallest unit of heridity , about 20,000 in the human genome. An onion has 4 times that number. I'm a clinical geneticist , I see individuals and families , who have a conditipn we believe to be due to an alteration in their DNA. Perhaps a mistake in a single gene. Perhaps a child with multiple congenital abnormalities , prhaps heart abnormality . Someone with absent thumbs I saw recently. I have to try an find an underlying cause why those abnormalities can be found together. I also specialise in cardiac genetics . I look after families with hypotrophic cardiomyopathy , abnormal thickening of the heart walls and heart muscle pump fails to work as well as normal and predisposition to abnormal heart-rythyms. The sort of cases where an apparent fit and healthy footballer collapses on the pitch. Often they are inherited cardiac diseases. So a family member says it happened to my brother, what is the chance of it happening to me. Will another child be affected in the same way as a first affected child. I think about DNA and chromosomes. A child might have a whole extra copy of a chromosome like trisomy-21 or Downs Syndrome. When I started genetics, the best way of looking at somebody's DNA was to look down mucroscope basically. If you look at a cell at an appropriate stage of division , you can see the chromosomes. You can see whether there is an extra one or one missing or even perhaps a chunk of one missing, causing the diagnosis. So to look at greater resolution, gene by gene I would have to look at the patient and think which of the 20,000 genes might have a mistake in it that is causing the problem. Thinking of them 1 by 1 and I'd send them off for Sanger sequencing. The answer might take 3 months and be a yes or if no then go back and rethink, which was the next best candidate. A very time consuming process and all the time families are waiting for an underlying molecular diagnosis. Recently the tech that allows us to look at DNA has changed unrecognisably. Insted of looking down a microscope at relatively little detail a twhat the Chromosomes look like or 1 gene at a time, I can now ask for the entire genome , all 20,000 genes and the DNA between, to be sequenced and done in about 48 hours. That is the same test that took the human genome project 10 years to do. The first sequencing was an international collaboration , nillions if not billions of pounds . We can now get that data overnight, that is why things are happening fast in the world of genomics, the tech has changed so much. The cost of sequencing the genome. 15 years ago - 100 million, we now talk of the 1000 dollar genome. I used to put out my rod and fishing line and ask for alterations in one specific gene and get 1 result back. Now when you sequence an entire genome , we've all got alterations in our genome that make us human. Part of my job now is to sort out which of these genetic variants are disease causing and which are just part of normal human variation, that makes each person unique. So in some ways my job is easier as we can sequence more, but also harder as there is much more interpretation. It does mean its an exciting field to be part of. My work at the hospital is with patients who have had years of investigations, perhaps initially as a new born. Some we've been seeing for 10 year sand we still don't know whats causing their problems. We know its likely to be genetic but not now exactly what the gene change that is to blame. There is a support group called SWAN, Syndromes Without A Name. They are parents of children of whom doctors can only say , I'm sorry I don't know what this is, I don't know the name of it, I don't know what the recurrance risk is. That is very isolating for a child with disabilities, for who no explanation can be given. With technology change and families out there who badly need a genetic diagnosis, in 2012 ther ewas the launch of the 100,000 genomes project in England. A government funded project through the NHS , its not research and its not as such, mainstream medicine. Its whats called a transformational project. We are working on having genome sequencing being incorporated in the mainstream of the NHS, hopefully as a legacy on completing this project. We're sequencing 100,000 genomes, its not quite 100,000 patients . The project is split into a rare disease arm , the sort of patients I see, but also a cancer arm. We bid at University Hospitals Southampton in a competitive bidding process and chosen as 1 of 15 hospitals to host a genome medicine centre,in 2015. As well as hospitals being involved, there are also industry partners as its realised that it won't be the NHS that goes on to drug developement for example . This will run parallel with all the extra data we are creating. The NHS is not resiurced for developing new medicines, so there are partners in private industry also. Its not just UHS area we are recruiting patiens, but around Wessex, Portsmouth, Basingstoke, Winchester and perhaps Bournemouth. The most important thing for me as a doctor is I'm hoping that many of my patients that I know to have an anderlying genetic diagnosis , but have not been able to find it. I'm hoping that for them , if enrolld in this project, they will get an answer. It is important that the process is transparent and involves a clear consent process. We spend about 40 minutes with a patient at the outset explaining what it means having your genome sequenced and chances to answer their questions. We are about the first healthcare system in the world going about this. I was talking to some colleagues at a recent German conference and they said they could never do this as their healthcare systemcis not joimed up enough, we could not get the right people to talk to one another. But with the NHS, the data would be stored centrally and hopefully the benefits will be huge. We hope to find some new gwnes along the way. Theyare always there , its just we don't know what they do. Every week the scientific literature gives the name of a gene and what it does. Is it a cause of intellectual disability or some unusual familial condition. Hopefully with all this data will come along a lot of medical insights. Its possible we will start to stratify patients , according to their genome. About 15% of hospital admissions have an adverse drug reaction involved at some point. If we could find out what it is about a person , that causes a bad reaction ot a drug, and not give them that drug. That would save significant morbidity and also save money. There is a particular HIV drug , 5% are super sensitive to , and if you have that sensitivity , that genomic signature, that medication is not used, so this is already happening. The project is also being used to stimulate the UK genomics industry. We are hoping for patient equity across the country. Every patient with a rare disease, or a particular type of cancer, has access into this project. Half the project is recruiting people with rare diseases . A rare disease is something that affects less than 1 in 2000 people. You may not think that is a huge health care burden but there 1000s of rare diseases, so many that 1 in 17 of us will have a rare disease of some kind. S oat least 2 people in this room. Look at rare diseases as a whole group, then they ar e pretty common, so an important healthcare burden. 80% of rare diseases have a genetic cause and genetic diseases are stil lthe largest cause of death in the first year of life. The other half of the project is enrolling patients with various malignancies. Cancer ,essentially, is due to DNA errors. We're born with our germline DNA , there are certain cell-lines that will continue to divide through life, such as skin or gut or lung cells. The instructuons telling the cells how to divide is in our DNA. But if you accumulate mistakes in your DNA , by too much sunlight or cigarette smoke or poor diet , then the instructuion manual is damaged and poorly regulated cell multiplication can result and a tumour. If we can learn the genomic signature of those dividing cells, we can much more exquisitly target treatment. Again this is already beginning to happen. Non-small-cell lung cancer , we routinely look for mutations in the EGFR ? gene and stratify treatments accordingly. At UHS we're including patients with breast, prostate , colon and lung cancer. We take DNA from their germline and compare it to the DNA in the tumour, with the mistakes in it. Thats why the 100,000 GP is not quite for 100,000 people , because people in the cancer arm of the project will have 2 genomes. If we have a suitable patient , see the patient in clinic, go through the consent process in detail, take DNA from the patient . If they appear to be the only person in the family affected and seems tobe a recessive disease , we take blood from the patient and their parents. Basically its a complex spot the difference puzzle. With dominently inherited conditions we want to get as many samples from affected family members as possible. Then spot the genetic change that tracks through a family withthat disease. For the cancer arm , a blood sample and a tumour sample DNA. We also need lots of patient medical records or data , because interpreting those genomic variants , is impossible without knowing what kind of job is done by the gene that has the mistake in it. So we have to marry up patient details and DNa samples . That involves inputing data about people's medical history. The DNA is all sequenced in a super-factory near Cambridge. The Sanger centre, the results fed back to our lab in Salisbury . Thenv the doctors involved with recruiting patients wil lbe involved in partial interpretaion of results and feeding it back to the families. We are hoping that the diagnosis rate will be about 25% of rare disease. That sis quite abig uplift as many of these patients have had numerous investigations before. The main piece of info back to a patient will answer the diagnosis question, such as why has my child intellectual disadvantage. We also give patients the option of additional findings fed back to them. Such as gene changes we know to be associated with other separate diseases but for which management is available. Such as if a high risk of bowel cancer gene or breast cancer gene. Feeding back such info , only if that is what the patient would like and only if its an actionable condition. So not incurable neauro-degenerative disease s , with no known treatment. If parents are considering further children , they can opt for carrier status of certain conditions fed back, such as CF or some X-linked conditions. This is determined in the consent part of the enrollment. Dr Frank Ratcliff. Prooject is about building a UK genomics industry, building on research so we can link medical records to genetics and outcomes. Its also about bringing improvements to patients. 2 videos of people as part of the project A family with a newborn child and they're immediately told that there is nothing we can do to help, serious medical issues and there is no help. But their attitude was that if you just have one day of this life , then plant a seed for others. So they joined the project to help research and the body of knowledge, even knowing that it would not help them at all. A survivor of aortic disection , but has the potential benefit of joining the project. Because if the gene behind it can be found then they can quickly and easily ask whether his sons carry the gene and if they do, then there is preventative action that can be taken. So a potential benefit within the family . A third story involving epilepsy. going round many hospitals and seeing many consultants and multiple tests often daunting, NMR, lumber puncture. At the end of the day undiagnosed and having doses of antiepileptic medicine to try and control the epilepsy for Jessica and that was not working. The only option going forward was to increase the dose, powerful medicines which have significant side effects. The family had the chance to join the 1000,000GP . The questions were can I get a diagnosis, can I get a treatment and for the parents, if they had another child , would that child have a normal risk of eplipsy or the same risk . A samll amount of blood taken from the child and the parents, whole genome sequencing of all 3 people. That produces an awfl lot of data. We have about 3 billion letters in our genome. 20,000 genes are about 2% of that , swimming around in there without any punctuation or paragraph marks . If we pick normal healthy caucasian males there would be about 3 million differences between us. In Jessica case about 6 million differences , something she has but neither parent has as both were healthy. Out of the 6.4 million differences, 700,000 were known to be rare , about 3000 would affect a protein , 67 were not shared with her parents and 1 was linked to a gene previously associated with Jessica's symptoms. It was a gene that encodes a protein which moves glucose across the blood and into the brain , a glucose transporter. If you can't move glucose into the brain , the brain does not get its normal energy source and so the symptoms of epilep[sy were symptoms of hypoglycaemia , as a diabetic would have. Only 500 cases of this gene known globally , so for almost any clinician they are unlikely to see 1 such case in their life. Certainly not 2, so without a large database, no clinician has any learning to go from . There is out there in the literature some evidence of a treatment. We can make our own glucose from fat , if you don't have a source of sugar. So she was switched to a low carbo, high fat ketogenic diet , which provides an alternative energy source for her brain and she is now a lot better. She has some symptoms from a brain starved of glucose for her fisrst few years . Somilar to Atkins diet but goes a step further. Her genetic changes are not shared with her parents. Perhaps they were healthy becasuse it was a recessive gene and both passed on that gene and so a 1 in 4 chance of a child haveing the same outcome. But not the case, it was a spontaneous arriving mutation, so now the parents are confident that if they have another child there is little chance of a similar epileptic symptom child. Not always such good news but shows what can be done. Do you think its an opportunity to take control of your health or play ostrich and hide your head in the sand. The clipboard passing round is Would you like to have your genome sequenced or not. No one has put down "No" in this outing for this survey. A printed volume for chromosome 21, one copy, the smallest chromosome we have. Printing is double-sided , narrow margin, 4 point font. Q: how do you know its right? The first time we showed one of these books, at an exhibiotion and someone turned up and looked at it and said there was a mistake, pointing to the precise place. .......... Its printed upside down. The printers had bound a page upside-down. That is called a DNA translocation , and that can also cause symptoms. The genes that encode for protein in this printing are in uppercase. If the whole thing was printed, in the same print size, it would be 130 volumes. This chromosome is the standard one, normal, for academic research purposes. Q&A So why do most people think having their genome is a good idea and why a couple of people do not. For If you have huge numbers of datapoints , it would be interesting to look at gene type clusters. One group of people who appear to be perfectly normal and another group also normal, but not quite the same. Could that show some kind of evolution ? So you would donate your genome for research purposes, to improve the knowledge about what is normal. I think a number of people join the project for that reason. If it costs 1000 dollars to get it done , then why not get it for free, assuming you're allowed to download the raw data.? You have to pay extra for the raw data but you can get it. No one has asked for it yet, so I don't know what the charge would be. The difficulty with that 3 billion bases on a disk, is having the bioinfomatics pipeline to interpret it. Aren't there sites out there to interpret in some , maybe limited , way? So if you have your genome on a disk, you could upload it somewhere to ask whare are the diffeneces in my DNA to everyone elses. The challenge then is the difference between you and me , there will be about 3 million differences. You'll find 3m changes , but how do you find out what maters. Thats where you need clinical skill and a bucketload of medical history and case notes. So perhaps a wikipedia type structure listing all the relevant changes? So what is relevant, without medical history. So SNIPS which are Single Nucleatide Polymorphisms , locatins in the genome where we know there are differnces between various populations. Some SNIPS are associated with propensiies for certain disease types , so 23andme is like that. Send a swab off to them and get a SNIP report. We don't use them in clinical practise at all. So its difficult whan someone says to us, can you interpret the data from 23andme, when its not a test we use. It can be interesting , but not enough knowledge around it to have proven clinical utility for NHS. On the nothank-you side I could go into a long spiel between the difference of the agenda of the patient compared to the doctor, which are very different. Essentially, the reason is , if I'm well , I've no interest in getting any investigations done, or even having anything to do with any doctors.? Personally I'm also not unwell and would take that view as well and say I'm not sure that I want to know that I will get cancer in 20 years time. Because I'd be eating well, not smoking , exercising regularly anyway. So it wouldn't change what I do. Its also the fact , that you get older, you will die from something and so don't worry about your health and wasting time going to doctors and spend more time getting on with your lifre? There is a balance, some conditions are so much more treatable than they were . I said no , partially to get a response because I'd quite like to know what could be useful to me. I'm not convinced at the moment that they are predictive tests, coming from genes. Which meant I could look out for the bowel cancer in 10 years time or become aware of an issue that I would suffer from? Many patients come forward because they are in a very different situation, they know they have something to be found, even desparate to find out. The people we talk to , who are not affected by rare disease, for them the concern is more paramount because the question is lesser. We probably do sonmething like a risk/benefit analysis but not putting it in those terms. If there is no benefit to you or your family then there is just anxiety. Will they discover a gene for anxiety. Will I get Parkinsons when I'm 50, do I want to know whether I'll get Parkinsons at 50. but if one of my kids was ill , then #all those such concerns would go out of the window. So many illnesses are a combination of genetics and interaction with hte environment, how far down that route.? There are a lot of conditions that we have a genetic risk and then its to do with the environment whether we actually express that condition. The project is not looking at the environment and we are looking for really strong genetic factors or absolutely causitive ones but a lot of work to be done on that. Would that be epigenetics? We're not looking at epigenetics Genes change throughout a lifetime , things turned on or off , so epigenetics.? Not just epigenetics. I only made this arm once , all the genes needed to make arms were active only once. Teeth I need twice and hair I need all the time. So different genes are switched on and off at different times and in response to illness a whole different suite of genes is switched on and that is probably a key part of the lower case text in this book. Between genes are the switches, some are on/off switches some are dimmer switches. But most of our genes are not used most of the time. I was also wondering about the spontaneous chenges throughout a lifetime, maybe you had a gene sequence as a child , would you want one when you are 60? At the level we are looking at the moment, we wouldn't find differences like that, apart from sequencing a cancer genome, which definitely would be different. I read something about a study of identical twins , presumably originally identical, but they had changed due to different lifestyles and environments? We accumulate mutations. If one twin smoked , then they would accumulate mutations in his lungs much faster than the nonsmoking twin. We would not sequence people at birth and then later but may sequance a tumor and tissue from the same patient, spot the difference. Are you suggesting you can resequence parts of our body ? The cell sequence of cells in my left hand should be the same as my right hand, but if I had lung cancer in one lung then the sequence of that cancer would not be the same as the sequence of the other lung, because cancer is a genetic change that causes undifferentiated cell division. Bu tin terms of medicine it is possible to get in there and resequnce the lungs? When you say resequnce , when we say sequencing we mean identifyig what the sequence is, we cant go back and change , we can't edit it. We can't set it back to zero. That sort of technology does not exist? It probably is coming , but not currently. With cancer there is multiple genetic changes in a tumour . Its not a question of a single mutation and then you get cancer. Cancers are dividing rapidly and accumulate additional mutations all along the way. Its a complex catch-up trying to keep on top of a cancer's mutation load. If it was a single mutation then that would be easier, but its constantly evolving. So another interpretation of the term mutation, is gene change? Exactly. I think I've heard that racial differences are in fact just due to very small differences in the DNA. So if we compare an Eskimo with an Aborigine , are there big difference, does it make interpretaion difficult.? The differences are genetic, why eskimos look like eskimos. If you took a rare disease family as an example . Go back to 100,000 genomes being sequenced , about 50,000 in the rare disease arm. That is something like 17,000 patients plus 2 close family members. So the comparison we are doing is between Eskimo child and Eskimo parent and then play spot the difference. Rather than comparing an Eskimo with a Glaswegan. The proportion of your DNA that reflects your appearance is a tiny proportion. I expect there is more to racial difference than simply appearance , but your saying that even so, the differences are relatively small.? Yes. And for the patients , the comparators are close relatives, so they'd be sharing almost all the genes and thwen saying, which genes are similar between patients with the same diseases , that are not present in patients without the disease. With cancer patients you took cells from the tumour and DNA from something else, bilateral or ??? You want germline DNA , DNA you're born with and that is in every tissue of your body, its just blood is the easiest one to get hold of. We use the DNA in white blood cells and compare it. Is there work to take non-invasive tissue samples? For the types of investigations of patients we are seeing , in the scheme of things, a blood test is relatively non-invasive. There is some work to see if you can use saliva , but the DNA from that is not so good quality. We sometimes try that if we have a needle-phobic patient. Or children , it is difficult to take a blood test from, we sometimes have a stored DNA sample. For the kind of tests I do , a sample is stored pretty much for many years. How much blood? We take 4 tubes with a few mL in each, so about a tablespoon each. Is this process limited to 1 to 1 mapping , 1 gene to 1 condition or is there perhaps a mathemtical limit on how many multiple genes apply to one particular condition? Primarily we are looking at conditions that are monogenic, one gene for the disorder. We are also learning that more and more conditions are pehaps polygenic in 2 or more genes. The work I do with cardiac genetics we're seeing that quite a lot. So 1 significant risk factor gene , then another gene variant and added together they may reach a threshold effect, whereby you get the condition in question. Is it possible to have say 10 genes affecting one condition, and you wouldn't actually pick that up? Absolutely, look at height, perhaps controlled by 100 genes and childhood nutrition as well to complicate things. But then mapping back which genes it is , to the height is too complicated withing the scope of this project. We know some genes, say classical achondroplasia or pescle? dwarfism , a single letter change in a single gene, you go from an adult of average height to someone with achondroplasia. But other conditions like Coronary Heart Disease ar edue to factrs in multiple genes that are additive and work together. different conditions work in different ways. Many common diseases are due to multiple variants in many genes . A slide covering peoples responses from other such talks as this. Would you want to know your risk to disease or would you like to carry on enjoying life. Would you want to be reassured , on the flip side, if the answer was you're to be healthy. How would you share the info with family, if you needed to ( I've got 2 kids but also 3 sfiblings , if I was sequenced and found out that I'm likely to get Parkinsons when I'm 50, what do I tell my brother and sister , because 50:50 chance they share it as well). Insurance implications Would it change your self-perception , your behaviour , your lifestyle and should it , as we all should be living healthy lives anyway. Have insurance companies started taking an interest in this? There is a moratorium at the moment and there has been for a long time . At the moment they all comply with the UK moratorium in that they will not ask if you have had a genetic test and they certainly will not ask for the results. But they can ask the simpler question, do you or your parents have any of the following conditions. So they can get genetic info , without asking about any sequencing been done. That is only a voluntary moratorium, its not statutory law , so they could decide not to follow it and call the government's bluff. Is that true around the world? We don't know the answer to that. How might primary care change? There will be some diagnosees that emerge , that will have a small impact on primary care, as many don't have rare diseases. In time with work on pharmo-genetics , then in primary care, this particular drug , normally prescribed 20mg , but this patient ,post sequncing , would require less drug . In the longer term there would be more tailored drug policy. Its not just sequencing us but sequencing the disease. A few weeks back I was holding a small DNA sequencer produced by an Oxford company , it fits happily in my hand, linked via USB to a laptop . Uses a tissue fluid sample , its not running whole human genome sequencing. They took that out to west Africa last year, and sequencing patients to assay whether this sample contain Ebola. In the situation there, someone would walk in and say I might have Ebola. Up to then, that person would sit in a tent and if your still standing up in 21 days , you didn't have it. If you did have it , then you're dead. With the sequencing , you can sequence for the infectious agent and in 2 hours you can say , positive or your free to go. Treatment situations go from the likes of Ebola to have you a viral infection , so take some paracetomol, or have you a bacterial infection then we'll give you antibiotics and by the way we know which antibiotics will work. What about long term conditions and things that are more multifactorial, you have a percentage risk of something ? There are some subtypes of diseases where the management will change. Diabetes, we used to think was type1,early onset, and type2, later onset associated with increased weight. We are now learning there are certain subtypes of type1 for which the treatment is different. We had a boy at 16 diagnosed with type1 , given insulin 4 times a day as his treatment. His blood sugar control was terible, a huge impact on his lifestyle. There was a family history of diabetes and eventually they had genetic testing and found out he has MODY or mature onset diabetes of the young. And the right treatment for him was not insulin , but sulphonoreas? an oral medication . So he came off 4 times a day injection , and his blood sugar control is much better. I thuink we'll be substratifying some common diseases. like this. Learning more about tailored treatments, and that would filter down to primary treatments. Is the project part of interfering with nature? Will the genome technology , is there a chance of it interfering with nature's natural processes? , ??? dilution? Elligible adults can choose to find out as a result of this project, whether they are carrying a gene that does not givbe them symptoms , because its recessive and if they are carrying the gene , they could also have a potential lifepartner carrying that gene also. They could then make reproductive choices , knowing of the 1 in 4 chance of a child having that monogenic trait. So yes it is possible to change natural processes. We have to accept that medicine is interfering anyway? There was a recent article about people having Caesarians , are interfering with nature, as there are now a lot more people with narrower birth channels, than there were before? So selecting against. With small handheld devices in the future , do you see a point where DIY home testing will become cheap and accessible enough for people to hack around sequencing? The Oxford Nanopore ? , I don't know the cost, but wouldn't it always be cheaper to just send your sample in. You could go around sequencing all sorts of stuff, ants , beetles? The Startrek Tricorder . There's bound to be people who'd like to mess around hacking this stuff, these biomes, a new hobby? It only tells you what's there, it doesn't enable you to change anything Garage biology. Prior to the genome technology, I never found out whether in the medic community or researchers themselves , whether there was ever a system equivalent to Google search engine , where with exact medical terminology for clinical expression of some condition , otherwise an unknown rare disease . Put in some database search engine and come out with possible diagnoses.? You go to a medical clininician , fully versed in all the correct terms, bung in the clinical features and out comes , perhaps ranked, possible conditions? There are a couple of databases , that are free to use. One called OMIM, Online Mendelian Inheritance in Man. Its not as refined as you were suggesting, but you can put features into that and it will give a list of a number of genes. In clinical genetics we use databases such as the London Database of Genetic Conditions and we can do just that, enter perhaps 5 features and get it to tell me all the syndromes that have those things linked to it , and a drop down list. They ar e under licence and expensive to use. That would contain all the medical literature , going back to the 1970s or 60s ? There is Pubmed available to the public. You can but in the searchbox , the relevant feature , and it gives a list of publications that have those keywords in. Extending on from that, is there a halfway house , for just ordinary people, a sort of reverse dictionary. Those facilities are great if you have the exact medical terms and specifics of clinical details to search on. Is there a haflway house , where an ordinary person can put in vague ordinary English terms and get out specialised medical terms for them? I'm aware of some specialised terms like subluxation , supination and pronation which Joe Public wouldn't know , but you could eventually zero in on those exact terms and then progress to OMIM and Pubmed? Part of my experience as a clinical geneticist , is learning which of those terms are likely , when confronted in a patient, could mean an underlying diagnosis. I'd talk to them and ask about features that I know to be related to that kind of disease. So a lot of experience and also the tools . There is a system trying to unuify the descriptive terms that are used, HPO Human Phenotype Ontology, terms and trying to standardise those across databases and websites, so the communication between doctors is clearer. The money alowing this project to progress, where dioes it come from and is there a chance of selling the data date derrived, to those , the NHS will be producing responses . So the economics? The project is funded by NHS England , in the region of 550 million. A lot of money, but the people with rare diseases have a long term condition and especially if you can impact them young, its not difficult to imagine the cost savings, saving the project eventually. 11 paharma companies have already paid for access to the data , a quarter of a million pounds each. Significant sums but not against 550 million. They've paid to see an anonymised version of the data and to run some analyses. They can't copy the data , they have to run their analyses on NHS England servers. So the model is that its a reading library , not a lending library. Then if they discover anything , they still don't own it . They will still have to buy anything that they then discover off NHS England. At a price that would reflect the value of that discovery. So not one price fits all . The aim of the project is not to make money , the aim is for patient benefits. The NHS is not in the drug dicovery game . I was just concerned the NHS could discover something very valuable and who would share those profits? The knowlege we accumulate will be exportable . We're leaders in genomic education and we're being asked , by others around the world, to teach and share what weve learnt. There may be a revenue stream there, but not the really big sums that drug companies make. So what happens to the data, who can see it. THe patient identifiable data , with a name on it, only comes back to the clinical geneticists who are looking after that particular patient. Anonymised data is visible to 11 pharma cos, but also visible to groups of academic researchers , registered to use that data, which is medical history and genetics but anonymised. So its not just drug companies that can make important discoveries. That data refers to one particular individual or a collation of loads of peolple? The anonymised data is all of it, so you can start doing comparisons between whole groups of people. If there is a disease that only occurs 500 times globally, you need to look at all those datapoints to find the commonality. How do the researchers approach this? The research groups are all based around a clinical disease, called GSIPS , Genetics Interpretation Partnerships. They will ,say, we're researching the genetics of asthma, they'll register as a consortium or collaboration , for access to do that , in order to research asthma. They cant then go off and research diabetes , which someone else ids registered for. Importantly, when patiens join the project, part of the consent process , the 40 minutes. Part of that is to give consent for academic and commercial research. If people change their mid=nd, they can withdraw later, even after being sampled and sequenced. After they're own personal result, they can then decisde to withdraw, everything would be withdrawn. ??? to make their results public and be exploited. I wondered if a similar thing with the NHS. Its in the public interest to make the info public ???. ? This dat ais not publically available. Its held on NHS England servers. You can't copy it out. If you want to make a discovery, you have to write programs that will work on thise swervers. Send your program to them , they'll run it and send you the results. But they know what your results were , they know what your program was , what your research interest was. The same whether you are an academic or commercial researcher. What they charge later, may be different. Could an academic group ??? could follow ??? They could be doing exactly the same thing. It could be a straight race. That means patients would get the discovery quicker . This seems to be a British database. How are we getting along globally, as presumably other than Germany, there are people doing this. ? There are big databases of normal genomes , like the EXACT ? databse . We often use that when we find a variant in someone's genome, we look there and see if its found in the normal population. The databases are being produced in a compatible , workable way? Ideally all this data would be shared on a central server and thats not happening. In this country there has been silos? of data about different conditions. The cardiac world that I know about, there was different research groups had their own silos of data. This project is about sharing the data because its so much more powerful if its shared. So you're saying we ought to be working towards it but we're not doing very well ? I say it ought to be universal , I think we're good at it in England and this project will improve that more. THe project is initially in England rathe rthan the UK. This project is a global leader. There are other projects, in the US , Canada and France which will do similar work but they're not so far advanced as this project. Hopefully they will use databases that talk to this database. What happened to the Icelandic database? This was Decode Genetics company formed about 10 years ago. The govt noticed they had a highly homogenous population , a lot of in-breeding . So they had very good medical records and births deaths and marriages going back 800 years in writing. The govt formed that company to analyse that data , find inherited causes of disease and very controversially , they set it up us an opt out system. So they said to all Icelandrs , we're going to commercialise your medical data unless you tell us not to. Instead of it being an opt in system which effectively thios project is, come and join if you want to. They had a high number of opt outs and I'm not sure that it got them very far. If anything perhaps a model of how not to do it. In the sequencing, you always get 2 letters per chromosome. Is there a technology that would sequence each individual strand and would that be helpful to identify diseases? You always know what the other one is, because they always pair. If you're reading an A then on the other side there will always be a T. Same C and G. And the reciprocals. So you only sequence 1 strand because you can always infer the other. But each locus could be twizzled round either way, so you don't know an individual strand, you don't know which letter belongs to which strand? You know what order they appear in and the orientation , where a gene begins and ends bedcause there are certain sequences in the DNA that always occur at the beginning. So if I got one change on 1 strand and another letter change, I would not know they were on the same strand or different strands? You also don't know which strand is the coding strand because the gene could be on one side or the other. When you get a DNA sequence , are you sequencing just 1 strand? Yes, but you can always infer the other, from the complementary nature. You have pair of chromosomes , sorry i should have said chromosome rather than strand, one of the pairs? So rephrasing. Each chromosome is 2 pairs , 2 letters , but can you figure out which letter belongs to which pair and wiould that be useful for picking out diseases? Yes , you probably can because we have about 3million differences between us , so with any particular family we are sequencing , you will be able to identify which chunks of chromosome have come from the mother and which from the father . The DNA of each parent is mixed , not totally randomly , but in random blocks And does that make a difference to disease progression, 2 mutations on one chr as compared to 2 mutaions on different chr? Some ar edominant so yes. If you think of a simple model of DNA encodes a protein that does something. We are all protein, we are either made of protein or stuff that isn't protein but was made by an enzyme which is a protein. So if you make a small change in the complete chr, the most likely outcome is that you've broken it. Its very difficult to make a change that mends it. But I've 2 copies of everything, one from mum , one from dad , so for a lot of disease , as long as I still have 1 working copy, I still have an enzyme that does something and you don't notice. So the only issue arises when I get a broken copy from mum and a broken copy from dad. So vthat's now recessive mutations , and if I pick up both of them, 1 in 4 chance , I then have no worjking copies at all and then I get the disease. I was thinking perhaps you needed 2 changes to break the copting process? They can get beastly complicated . So go home and talk to othe rpeople about this as it will change medicine, change how disease is treated and that'll only work if the public accept it. W56/1/40/10


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