Transcript - Feb 2009
Gareth Mitchell: This is the official podcast of Imperial College London. And I’m Gareth Mitchell. Hello, everyone. I present the BBC’s technology programme, Digital Planet, and I’m a Science Communication Lecturer here at Imperial. Welcome to this month’s roundup of what’s happening across the College’s various campuses. Today, the £100 million molecule. That’s in just a moment. Also this month, how to make sure you’re found in translation. In this case making sure that computer software and games translate into whichever language people are using them in.
Daniela Ford: It’s not just about translating the product but it’s really about adapting it culturally so that the final audience has the impression that the software was actually written for them in the first place.
GM: So focalisation on localisation as a new e-learning course gets underway at Imperial. And how to save lives by generating new heart tissue. In the latest stem cell research one Imperial team is getting the bone marrow to help out.
Sara Rankin: What we found is a therapy that increase the release of these stem cells into the blood stream. So we’re boosting levels of stem cells in the blood. And these are a particular type of stem cells that are involved in tissue repair.
GM: And also this month, the simple surgical checklist that’s already prevented deaths after operations in hospitals. That’s part of our news roundup and it’s all right here on the Imperial College podcast.
Professor Steve Bloom on the quest for safe, effective anti-obesity drugs
Let’s get on with it then. And rarely could the phrase “putting your money where your mouth is” be more appropriate. A major US pharmaceutical company has just invested £100 million in an anti-obesity drug pioneered at Imperial. The compound, called TKS1225, has been developed by Imperial Innovations spin-out company Thiakis. The firm, Wyeth, is now preparing the drug for trials in humans after announcing its acquisition of Thiakis last month. The Imperial scientist who spent over two decades working on the drug is Professor Steve Bloom of the Faculty of Medicine and he’s been giving me more background to it all in his office on our Hammersmith campus.
Steve Bloom: As a bit of background, about 80 people die per day in the UK as a consequence of obesity yet the pharmaceutical industry hasn’t yet developed anything that’s very effective. Our research, which began actually 25 years ago in Imperial College so it just shows how long it takes to develop things through to a practical endpoint, was about why you feel less hungry when you’ve eaten lunch. There is actually a mechanism that the body has to regulate appetite. The gut releases a hormone. That hormone goes round the circulation, gets into the brain and you just feel less hungry. And we can prove that by infusing the hormone at the sort of levels that you have after you’ve eaten a meal and then just people don’t feel hungry anymore. The problem is that if you’ve shown it’s a good mechanism, how do you turn it into a drug? And that’s perhaps a rather important issue.
GM: And so massively important. Because that is the Holy Grail of treating obesity surely?
SB: Yes. I said there’s no effective treatment of obesity and that is right in terms of drugs. But there is a surgical procedure, the bypass procedure, where people lose 60 to 70 per cent of their weight and then they stay thin for the next 20 years. And this bypass procedure is great except that there’s a three per cent death rate. So it’s a bit like a roulette wheel. and personally I’m not sure I’d like to go in for it. And of course it’s pretty expensive and a big nuisance being in hospital.
GM: Now, this is a drug called TKS1225. So just tell us what this compound is and what’s behind it.
SB: Well, going back to the bypass surgery. How does it actually work? Well, it turns out that by bypassing the upper gut you fool the gut into thinking that it’s eaten a very big meal, because it gets down to the lower gut very quickly, and also perhaps that digestion isn’t working. So the gut sends out an emergency signal, hey, stop eating. And it’s due to a hormone telling the brain that the gut is in trouble. It actually only lasts about five minutes. Hormones are made to be rapidly destroyed so the gut can keep switching them on or off. But as far as our therapeutics are concerned, we want it to last all day. Because people don’t want to take something more frequently than that.
GM: And has that been the major challenge then, to have that durability of the effect?
SB: Yes. There are really two challenges. It’s a peptide hormone and it would be very nice not to have to give it by injection. But if you swallow peptides they’re destroyed by the digestive system. We haven’t got round that. We do have to give it by injection. As you say, the other problem is this short lasting effect of five minutes. Well, it wouldn’t be much use suppressing appetite for five minutes. So our big therapeutic challenge was to be able to have a once a day injection that lasted a full 24 hours. And that is what we succeeded in doing. And having done that we could then set up a company to test it in humans. Because there’s a very big gap between showing such a thing would work in animals to showing that it does work in humans and it doesn’t have any side effects.
GM: On the business side of things then. You had the molecule, there had been toxicity studies, Wyeth came onboard and now they’ve acquired it for £100 million. So apart from quite a transaction, giddy amounts of money there, what does this all mean?
SB: Well, to begin with it means that Wyeth is likely to do its very best to develop it as a practical drug. And of course Imperial College still owns the patent rights or the intellectual property. I should say Innovations, Imperial’s commercial arm, owns it. And this means that if it should eventually be an effective agent maybe the £100 million initial payment will be dwarfed by the eventual income stream as the percentage from the royalties, which could be very interesting for everybody in 10 or 12 years’ time.
GM: And that’s the serious side of things, isn’t it? This is a way of generating funding. When you’re a university or a research institution and you’re trying to get money for your research you either go to the research councils or I guess use this model where you develop an amazing molecule that somebody wants to spend £100 million developing.
SB: Yes. Universities are very rich in ideas but they do need money. So these two things should come together. In a capitalist society we should sell our ideas and use the income that we gain to be able to develop new ideas. Now, Imperial College has always had as its rubric to work with industr y an d that means that they’re particularly friendly to academics working commercially, or partially commercially, and of course have set up things like Icon which offer consultancy services and Innovations which handles the intellectual property and spin-outs and new drug development.
And I have to say that Thiakis was enormously helped by Innovations who were able to put in an initial sum of money to fund it and the venture capitalists, who provided quite a bit of the funding also, only came in because they saw that Imperial had confidence in the company and were prepared to put several million into it. So the trick that got Thiakis started in a difficult environment where borrowing money isn’t at all easy was Innovations themselves investing in us. So that’s what got us going. And I must say that Innovations has been nothing but very, very helpful in this entire process and we couldn’t have done it without them.
GM: And that’s the upside, £100 million, obviously speaking for itself. But on the other hand, universities aren’t here to make money. They’re not here to be businesses. They’re here to develop science, aren’t they? I just wonder if there’s a danger that scientists sitting at lab benches around Imperial will be thinking now I’m going to be under pressure to come up with the next new amazing drug when what they should be doing, surely, is just concentrating on maybe blue sky science that moves science forward. It doesn’t necessarily make hundreds of millions of pounds.
SB: Yeah, very interesting point, Gareth. I completely agree with you. Of course, if some people’s ideas are exploitable that helps fund everybody.
GM: And now that Wyeth is working on the compound, it’s going into clinical trials, what is likely to happen next? I mean are we going to see this available anytime soon? Or is it going to fall foul of the problems of many of the other similar attempts at this have suffered from? I think one drug was actually cancelled because it was associated with mental disorders. How close are we to it actually becoming reality?
SB: Yeah, interesting point. Of the 114 drugs that have gone into clinical trial of obesity only two are on the market and they’re both feeble. And basically obesity isn’t a disease of its own. It does cause hypotension and cancer and diabetes but it doesn’t actually do any harm just by itself. And so we have to be very, very safe. And it’s also possible that you’ll treat a 15 year old girl and she’ll still need an anti-obesity therapy when she’s 75. And this requires a very different order of safety than, let’s say, an antibiotic which you take for three days to treat your pneumonia and then stop.
So, yes, of the 114, 112 have failed. Is ours going to be the same? Well, maybe. But most of those other drugs were interfering in normal function in a way that’s artificial and I’m not surprised they caused trouble. Ours uses the natural mechanisms that you use after every meal you eat. And so there’s a hope, and I think quite a good hope, that it in fact will work and will work very well and will be safe long term. So, yes, it’s got to be very well tested.
GM: As a scientist, is this what you got into science for? You’ve worked on the compound. You’ve nurtured it. It’s become a business proposition and it looks pretty likely to end up going out there into the real world and treating people’s obesity. Reducing heart disease, all these other complications associated with obesity. People will live longer because of your science. How does that make you feel?
SB: Gooey. The danger of being soppy in one’s ideas. Actually that is exactly why one went into medicine and went into biological research in order to help people. If you go into the children’s ward and see all those children dying of cancer you can’t just sit back and watch it and say not my business. And in fact the British Diabetic Association, as it then was, had a stamp on all its letters which said it is unethical not to do research. And I think that’s very much true. Just to watch all these people suffering and not try and help is really bad.
GM: Definitely ending on a reflective note there. That’s Professor Steve Bloom.
Headlines from around the College
Well, in a few moments how to make sure that software and games aren’t lost in translation. They call it localisation and I’ll be finding out more. Before that though let’s have some quick headlines from around the College.
Surgeons at St Mary’s Hospital, part of Imperial College Healthcare NHS Trust, have been piloting a new technique that showed a 40 per cent reduction in inpatient deaths after operations. So was this some new surgical procedure or did it perhaps involve a novel state of the art drug? Well, no. It was much simpler than that. A safety checklist similar to the kind of thing that pilots work through before they take off.
As part of a study just published in the New England Journal of Medicine, Imperial was one of eight hospitals that trialed the Safer Surgery Checklist. It only takes a few minutes and includes simple things like confirming the identity of the patient. It’s used at three crucial stages. Before giving the anaesthetic, prior to the first incision and just as the patient is about to leave the operating theatre. During the trial the rate of major complications fell from 11 per cent to 7 per cent and now the checklist is being used across the NHS Trust.
And there’s been a fair bit of concentrating going on in our Physics Department as of late. In this case, concentrating the sun’s light on to a solar cell. It’s a bit more complicated than just waiting for a sunny day and getting a magnifying glass. The idea of concentrating solar energy on to a relatively small surface area isn’t new but the tricky bit is doing it efficiently. And that’s where choosing the right kind of material comes in.
The Imperial physicists have just been hailed for breaking the world efficiency record using so called luminescent solar concentrators. They’re coated with molecules that absorb light and then re-emit it through the material’s elaborate internal reflection properties. There’s a long way to go before these polymer solar concentrators are cheap and durable enough to be used commercially but the plan is ultimately to embed them in buildings, in windows for instance, as part of the shift from fossil fuel based energy to more sustainable forms such as solar.
And you can catch up with more news from around the College via our Press Office website and that’s at imperial.ac.uk/news.
Daniella Ford and Mark Shuttleworth on translating for computers
Okay, so software. Obviously a huge part of everybody’s lives these days and yet how do you make it work across cultures and across languages? Well, that’s the problem facing software localisers. And in fact here in the Humanities Department at Imperial we have Daniella Ford who is a professional software localiser. That’s quite a job title there, Daniella . And you’re behind a new e-learning course aimed at teaching people about localisation. They don’t even have to be here on campus at Imperial. The obvious first question is what exactly is localisation?
Daniella Ford: Localisation is all about adapting a product be it software, a game, to a local audience. That means it’s not just about translating the product but it’s really about adapting it culturally so that the final audience has the impression that the software was actually written for them in the first place. It’s not just about the language. It’s also about adapting potentially the colours, maybe the user navigation. Some cultures might be used to seeing certain parts of software in different areas on the screen. So it’s a whole range of aspects that need to be taken into account.
GM: What about games then? Because that’s part of localisation as well isn’t it? You know, the fun side of things.
DF: That’s right, yeah. Games are certainly a lot of fun to work in. Basically the rules for games apply the same way as they do for software applications. But on the games side you also have a lot of other aspects because you have the fun side to be taken into account. And that’s something you can only really do properly if you are a gamer yourself, which is one of the nice parts of being a localiser.
GM: So what kind of skills do you need to be a localiser? Because I must admit until I met you I didn’t realise these people existed. Are you a software person or a translation person or a linguist? How do you get into all this?
DF: At the moment there are not very many courses about to become a software localiser. So people who are already in software localisation have come into it by default more or less. They will be mainly translators who then start to work with developers who may go on programming courses as well and so really become a developer to some extent as well.
GM: Or you can do it through an e-learning course like yours. Now, we’re going to have a little walk-through it in a minute but just before then let’s set the ground work with Mark Shuttleworth who is the course leader of the translation MSc here at Imperial. What kind of students might be signing up for this e-learning module that you’ve made available?
Mark Shuttleworth: Well, as you say, it’s an e-learning module and in fact it’s an offshoot of an existing module on the MSc in translation which has been running for a number of years now at Imperial. We get people from all kinds of countries around the world not only the UK and the European Union but also quite a number from the Far East, China, Taiwan, Japan and also occasionally from South America. So we’re conscious that there’s an interest in translation technology and localisation all round the world.
GM: So Daniella let’s have a little look at how the module works itself.
DF: So once the students sign up for this course they’ll receive an email telling them how to log on to the course, which they can do from wherever they are. Once they have done this they than start with the first unit which is course material plus a quiz which they can answer. Once they have gone through the first unit they then have group tasks to complete. And the group task can be anything from finding a specific definition of a specific concept, like culturalisation or localisation, which is quite a new concept.
They will work together online as a team to provide answers and then a tutor will provide feedback on these answers. Tutors will also be live online at regular intervals to answer any questions that students might have so that no one gets stuck at any point. The course runs over 11 weeks which means we release one unit per week. So every unit, there’s a new topic to be tackled with specific tasks attached to it.
GM: So to get an idea of the tasks and the kinds of subjects that are covered, for instance, shall we look at the quiz? I know that you set a quiz fairly early on in the module, and I like the way that you don’t call it a test or an exam. Quiz sounds much more friendly. And I know that’s deliberate, you know, it’s a fairly informal way, I suppose, of making sure that people are engaging with the material. So it’s come up on the screen here. You’ve just clicked through a few links. And it’s a multiple choice question so what’s it asking?
DF: So we have the very first multiple choice question which asks what does localisation mean? And then we provide three possible answers. The student will then choose one of the answers and they’ll get feedback straightaway. If he chooses the right answer it’ll say correct. If he chooses the wrong answer it will actually tell him why this is the wrong answer and he can then try again.
GM: Now, to see if I’ve been concentrating during this interview I’ll see if I can work out which is the right answer to this. I thought it might be the first one: adapting a software application to a target audience whilst keeping the flavour of the original software. But I’m wondering if it’s actually the last one: adapting a software application to a local market. Which is right?
So we’ve clicked on the top one. This is the feedback coming back. It says: this is an approach which is sometimes taken when localising games rather than more serious software applications like imaging applications. Please try again. Oh, I was wrong. Notes to self: concentrate on what the person is telling me before I try doing multiple choice questions. But I can imagine students find this very useful but you as a tutor, I’d imagine, find this ongoing almost real time feedback useful too?
DF: Yes, that’s right. For these multiple choice questions we’re not actually recording the answers but we do tell the students to complete them because they are useful for their own benefit. However, we do get feedback from the students because we have an area on our course provided for questions. So students can either ask a question regarding a task or regarding a unit and that gives us instant feedback of the way maybe whether something isn’t very clear or whether we need to provide more instructions.
GM: And obviously the quizzes and the tasks get more elaborate as you go through. You’re easing people in with this one. I’ve fallen at the first hurdle here myself. So the time you get to unit 11 what kind of tasks are you doing then? It is like here’s a game, localise it then please or maybe something a bit less scary?
DF: Well, you’re almost spot on there. Obviously you have an excuse for the first question because you haven’t read the actual unit. The very, very last unit, unit 11, is about localising games and we are actually asking students to localise a part of a game. It’s actually an educational game for children but it involves a lot of localisation issues.
GM: And because of this e-learning approach the students are obviously getting feedback from you and the other tutors in an ongoing way. You’re getting feedback from the students as well. So can you build that into the modules so you can be tweaking it and refining it as you go along?
DF: Yes, I can tweak the module as and when we go along and so that’s really, really useful.
GM: Finally then Mark, how can people find out about this course and sign up to it if they want to?
MS: Probably the best way to do that is to go to the link on the Centre for Professional Development website at Imperial College. The url is www.imperial.ac.uk/cpd. And then if scroll down a little bit you get to the link for translation technology localisation and all the information is there.
GM: Well, it’s fascinating stuff. Daniella Ford and Mark Shuttleworth, thank you both very much indeed.
Dr Sara Rankin on speeding up healing and repair by boosting the body's stem cell levels
Okay, well now I’ve crossed campus, across the Queen’s Lawn actually from Humanities here into the Sir Alexander Fleming Building which is home to the National Heart and Lung Institute. It’s part of the Faculty of Medicine. And to finish this podcast talking stem cells with Sara Rankin here. We’re in your office Sara. And this is a story that was released some weeks ago. It’s had enormous coverage in the media but just in case listeners to this podcast haven’t heard about it just explain it to us briefly Sara.
Sara Rankin: So this research is about adult bone marrow stem cells. And what we’ve found is a therapy that can increase the release of these stem cells into the bloodstream, so we’re boosting levels of stem cells in the blood. And these are a particular type of stem cells that are involved in tissue repair. So these stem cells would promote tissue repair and therefore they’re going to accelerate the tissue regeneration and repair of damaged tissues.
And I suppose you’re taking it right to the beginning then? So stem cells, you know, these cells that can differentiate into lots of other kinds of cells in the body like tissue, bone or whatever. And our bone marrow then, so that’s a natural source of stem cells within our bodies then is it?
SR: Yes. So it’s been known for many years that bone marrow is a really rich source of stem cells and in particular the stem cells that make blood. So everybody is familiar with bone marrow transplants and this relies on stem cells in the bone marrow that make blood. More recently we’ve identified, or other people in the world have identified two different types of stem cells in the bone marrow. And these are the stem cells that contribute to tissue repair and it’s these cells that we’ve been able to release into the bloodstream.
GM: So the stem cells are already is it? Are you actually making the bone marrow produce more of these or have you just got a mechanism that allows them to be released more effectively and more efficiently?
SR: Yeah, we’re actually promoting that release process not production. So they’re sat there, we’ve got plenty of them, but we’re actually boosting release.
GM: And I suppose that’s the really important thing then so you can release these stem cells or you boost the release of the stem cells, as you put it. What, and that means then they’re available to differentiate into other useful cells in the body in a therapeutic context?
SR: Yeah. An analogy would be of having fire engines sat in a fire station and what we’re doing is providing the signal. So you’ve got a house on fire, we’re providing the signals to release fire engines from the fire station. We know that those fire engines, once they’re out on the street, they will naturally home where there’s a house on fire or to a damaged tissue. And obviously what we’re hoping to show is that 10 fire engines is better than one.
GM: And so to extend your analogy then what kind of house might be on fire here? In other words, what kinds of cells or parts of the body can you treat or regenerate using this technique?
SR: So there are two types of cells that we’re releasing. One type is very good at making blood vessels and so they would be able to provide profusion of tissues after ischemia. So the classic example of this would be the heart, so after a heart attack. The other type of stem cell that we’re releasing are ones that can differentiate into bone and cartilage. So these obviously are going to be important if you have damage to these tissues. So, for example, broken bone.
GM: And the obvious benefit for all this, I should think, is that you don’t have to introduce foreign stem cells, as it were, into the body. That gets over many of the difficulties and ethical difficulties associated with, say, embryonic stem cells and the fact that the stem cells are coming from the person’s own body.
SR: Yeah, you’re absolutely right. So this is a non-invasive process. We’re using drugs to simply mobilise cells that are present in somebody’s body. So it’s almost like promoting self-healing. And importantly, as you say, it gets over the ethical issues but also the regulatory issues that are associated with using stem cells from other sources.
GM: And in essence how does it happen? I’m sure it’s very complicated but what is it that’s triggering the enhanced release of the stem cells to where you need them in the body?
SR: We showed a few years ago, we identified some of the molecular mechanisms that are retaining these cells. So we found that there’s an active retention mechanism for these cells. And so what we’ve done is use drugs that actually interfere with that retention so in a way free the cells such that they can be released.
GM: Where are we at, at the moment? Have you just shown this as proof of principle in cells in the lab or have you tried it in mice or humans? Where are we at, at the moment?
SR: So our research has been done in mice and so we’ve shown that we can release these cells in mice. And obviously the next stage would be to take into larger animals, which is something that we wouldn’t do. We hope that drug companies would take that up. We have filed a patent through Innovations for the therapy that we’re using to mobilise these cells. So we hope that it will be taken further in that way.
GM: This story clearly captured the public imagination and imagination of science journalists around the world. You’re looking pretty encouraged by all this?
SR: I’m incredibly excited by it. Obviously we’re going to take this further and continue this line of research. We think it will be very fruitful.
GM: And in doing this we often like to think of these Eureka moments in science. Was there a moment when you and your team looked at this and thought my goodness this is actually working, and if so can you take us back to that moment or that day or that week or however it unfolded?
SR: I think this was something that had been in my mind for a long time so I’d been wanting to do these experiments for a long time. And is often the case it’s difficult to get the grant funding necessary to do the things that you want. I think we were very surprised at how striking the results were. Because we’ve seen very selective.
So what we have noted is that you can differentially mobilise different subsets of progenitor cells, or stem cells, from the bone marrow. So we can use different therapies to mobilise the blood stem cells versus the repair stem cells. And we didn’t know that was going to happen. But it makes sense and it’s very interesting and we hope it’s going to be therapeutically beneficial.
GM: And finally, and this is always the hardest question, you don’t even have to answer this one, but I mean can you anticipate when this might end up as a real therapy?
SR: Obviously a difficult question. And the standard answer to that question is roughly within 10 years. And that’s realistic. One of the drugs that we’re talking about has already been licensed by the FDA for use in man so it’s not like these are completely new molecules that we’re putting in. It’s just that we’re using a combination which would have to be tested.
GM: Sara Rankin bringing this edition of our podcast to an end. There will of course be more for you in March. And goodness me February is only a short month. I’d better crack on with it. This podcast grew from a stem cell that was harvested by our Press Office and combined with the life giving molecules from the Science Communication Group where I work. And more renowned for base lines than base pairs is Turkish composer Oscar Buldum who composed this very theme music. And telling me that the stem cell analogy is definitely wearing rather thin is producer Helen Morant. Oh, and hello, by the way, to Nick Caulfield and Mike Burton who both deserve bit fat mentions for saying very nice things about this podcast via our listeners’ group on Facebook. To find us there just type Imperial podcast into the search box. Otherwise, stand by your mp3 players in anticipation of our March edition. For now though, thanks very much for listening and good bye.