Transcript March 2007
Gareth Mitchell: From Europe’s leading science university this is the official Podcast of Imperial College, London.
Hello, I'm Gareth Mitchell, presenter of the BBC's Digital Planet and a lecturer here in Imperial’s Science Communication Group. Well, there are plenty of science podcasts out there but this one brings you the very latest from the heart of one the world’s most prominent centres for research and innovation. This month the controversial researcher who’s taking on the might of the pharmaceutical industry.
Sunil Shaunak: I think the lives of poor people in developing countries really shouldn’t be a commodity that is dependent upon their ability to pay for medicines that can cure infectious diseases.
GM: That’s in just a few moments. And an Imperial geologist tells us why he thinks that Martian rocks could tell us how life came about on our very own rocky planet.
Randall Perry: All of the latest missions have shown rocks that look like they have these sort of black shiny coatings and it would be something that may be able to last over the billions of years since Mars lost its atmosphere.
GM: That’s all to come right here on the official Podcast of Imperial College, London.
Sunil Shaunak and 'ethical drugs'
Well to begin, Imperial College often finds itself in the news and rarely more so than in recent months with one story in particular. An Imperial academic says that he’s found a novel treatment for Hepatitis C, one of the world’s deadliest diseases. And what’s more, he says that his approach can be marketed and sold for a fraction of the price of the existing treatment already distributed by one of the world’s leading pharmaceutical companies. In so doing he’s calling it an 'ethical pharmaceutical’. And it hasn’t been without controversy. He is Sunil Shaunak. He’s a professor of infectious diseases at Imperial College London at Hammersmith Hospital, in London of course, and I’m in his office with him now. Professor Shaunak, before we hear about your approach just tell us a bit about Hepatitis C. Because it’s a serious blood-borne disease and I think it affects something like 170 million people worldwide.
SS: Yes. Hepatitis C causes an acute infection. If you make enough of a natural protein called interferon you can cure yourself of the disease. But a very large number of people don’t do that and then they get a chronic liver disease which can eventually lead first of all to the disability and then eventually to the death of a patient. It’s a very big global epidemic second only really to the AIDS epidemic that we already know lots about.
GM: And the key to treating it then is a molecule called interferon?
SS: Yes. If your body makes enough interferon you can actually cure yourself of the disease. What we found about three years ago is that if you take interferon and put a big sugar molecule on the outside of it, it’s a fantastically good medicine. And if you combine that with an antiviral called Ribavirin you can cure the disease in half the people that you treat. The problem with that is that the cost of treating one patient is £7,000.
GM: So how does your approach differ from the standard approach and the one that’s very expensive of coating the molecule in sugar?
SS: Well, Steve Brocchini at the London School of Pharmacy and I had become concerned about what has happened in the AIDS epidemic. A very large number of people have died simply because they couldn’t gain access to drugs. What we wanted to do was to look at the whole question of how interferon could be pegylated, have these big sugar molecules put on it, without simply just copying the existing technology, but developing a second generation technology in which we would also make the medicine cost affordable. So on day one we set out to be inventive and creative, and to do good research, but also said that the technology that we would use would have to be cost effective in terms of the product that was made available to poor people in developing parts of the world at the end of the day as a medicine. Because currently there’s something like 150 million people who have access to no medicine at all purely because of cost.
GM: And as for the approach, obviously it’s quite hard to explain but I know that one way that you have put it across is that it’s a bit like using a door to enter the molecule, if you like, in order to pegylated it, to coat it, with this sugar molecule. How does that contrast and how is it novel compared to the existing way that I think Roche, the company that already manufactures a treatment, how it opens its door?
SS: What Roche and Schering-Plough have done is to say if you put the sugar molecule anywhere on the outside of interferon that belongs to them. So we had to find another way of putting the sugar molecule on to the interferon. Now, what we said is proteins have disulphide bridges which are a little bit like the belts and braces that keep up your trousers. And what we’ve done is to gently open one of these disulphide bridges and put the sugar on the inside of the protein. And that has enabled us to write a new patent, publish our work in Nature and then say that the patent we’ve developed ought to be used to make cost effective medicines. If you think of Hepatitis C as a room with three doors into it, and where each door is a cure, Roche and Schering-Plough have found the first door and they’ve bolted that down with a patent. We’ve found a second door and our patent attorneys tell us that it’s new and original and inventive so that allows us to write a patent. But we’re insisting on rules about how that technology is used to make cost effective medicines. And I’m sure there’s going to be a whole bunch of clever doctors out there listening to this who will think, ah, I can think of a third door into this room. And I’m sure there is a third door of doing this and they in the fullness of time will be able to create that door, invent it and write their own patent.
GM: But isn’t there a danger that the patent lawyers for the existing pharmaceutical companies are going to say, well, we’re the first people to find our way in through the door. The fact that you’ve found a different door isn’t actually that novel.
SS: Well, this idea that, you know, the big pharmaceutical companies do all the hard work and we’re simply getting on their bandwagon is just not true. I mean, all a patent really does is record at the moment in time in a legal document what the observations are. Fantastic advances that we have in biology, in medicine and pharmacology mean that there will be incremental advances leading to second and third generation drugs. And I think it’s much better to think of this as academics contributing to second and third generation drugs rather than simply copying. Because actually copying is the concept of generics and I think the world is moving on from that now.
GM: So you’re absolutely firm that this is novel research and the next stage is to take it to clinical trials?
SS: Well, I think so. I mean, we’ve written thr ee papers in nature research journals so our peers feel that it’s original. The patent att orneys charge a lot of money and they tell us it’s original. We have to wait and see what the patent examiners say. And we’re at a stage now where we’ve convinced sufficient number of people in the biotechnology industry that they’re prepared to invest the money so that the clinical trials can start next year.
GM: Professor Sunil Shaunak with details of that new treatment for Hepatitis C. But producing an experimental drug is one thing. There are still clinical trials to get through and figuring out how to market and manufacture the treatment. It’s ambitious but is it doable? Well more on that and some tough questions later in this podcast in Part 2 of our special extended interview with Professor Shaunak.
Headlines from around the College
Right now though let’s have a quick look at some of the other stories making the news from around the College.
Imperial researchers say they’ve found a mechanism by which carbon dioxide given off by power plants can be trapped deep underground in porous rocks saturated with salt water. It’s the latest idea in the quest to stop emissions of the gas getting into the atmosphere and causing global warming. The main hitch with the idea has always been the risk of the CO2 seeping back up to the surface. But now researchers from the Earth Science and Engineering Department here, working with colleagues at MIT and Stanford, have identified a mechanism by which salt water deep in those porous rocks would close in around the gas trapping it indefinitely, even when the power plant has gone out of operation.
And we’ve identified the most important genes involved with developing type 2 diabetes, so say scientists at Imperial’s division of medicine collaborating with teams from around the world including McGill University in Canada. The researchers say it’s the most detailed genetic map of any disease allowing doctors to predict with greater accuracy than ever before the likelihood of a person developing type 2 diabetes.
But it’s not all science here on campus. There’s culture beyond those Petri dishes you know. And for an all-singing, all-dancing week in February it came in the guise of Imperial College Union’s art fest. Twenty four of the Union’s more arty societies banded together to put on a rich programme of events, screenings and demonstrations culminating in a grand finale concert in our great hall. Naturally, the show was followed by the customary after-party orchestrated in the Union bar. And who knows, perhaps they’re still there.
Anyway, you can stay up-to-date with news from the college on our Pre ss Office website at imperial.ac.uk/news.
Randall Perry and rocks on Mars
Well, now then, you don’t need to be a planetary scientist to work out that Earth and Mars are very different. One has an atmosphere; the other doesn’t. One has liquid water; the other doesn’t, as far as we know. One has Starbucks and the other probably doesn’t. But if you do happen to be a geologist then you might well be placed to spot some of the things we have in common with our planetary neighbour, especially if you’re Randall Perry, a Fellow of the Royal Society and a senior research scientist here at Imperial. He, along with his fellow geologists here in South Kensington, is interested in how the rocks of Earth and Mars relate to each other and what they reveal about how life formed here on Earth.
RP: Mars and Earth formed at about the same time about 4.5 billion years ago or 4.55 billion years ago. But early on Mars would have had an atmosphere and the Earth didn’t really get an atmosphere until approximately 3.5 billion years ago, so about that same time Mars was losing its atmosphere. So the very early part of Mars, 4.5 billion years to maybe 3.8 billion years, had a similar atmosphere to what the Earth started getting when life started forming on Earth at approximately 3.5 billion years ago. So it’s likely that life formed much earlier than it did on Earth.
GM: And so if you take fossils from Mars then you get an insight as to what was going on in those early days of Mars’s existence, when it had an atmosphere, which can then in turn give you clues about what might have been going on very early on in the Earth’s life as it began to form an atmosphere?
RP: Well, that’s true because on Earth we have a really dynamic system going on still. We have the creation of new rocks and we’re destroying fossils and evidence of early life rather quickly. And on Mars, when it lost its atmosphere, it’s then maybe fairly static and so we’re not really having new life forms eating the old things up or we don’t have geological processes that are destroying the geology on Mars. So we could have good preservation. But I think the question really that’s interesting in that part is, is if life did form on Mars is it the same as it is on Earth or is it actually quite different? And if it’s quite different how is it different? A group of amino acids, for instance, than proteins and biological systems? Living entities on Earth do? Then it would be really unique to be able to study that and even see that they did.
GM: I suppose for, what you might call yourself, an astro-biologist it’s a win-win situation because Mars really is effectively like a time capsule? We assume there’s some kind of life frozen forever in the icy wastes of Mars and it may turn out that this life is very similar to the precursors of what became life on Earth. Or maybe it’s very different. And either way you’ve got a fascinating bit of science to investigate.
RP: Oh, absolutely. Because if it’s the same then we could say, well gee, maybe life always evolves along the same way. It’s the same mechanism. Maybe life as we know it always requires the same group of chemicals such as, say, the 20/21 protein amino acids that are in all proteins and living systems on Earth. So that’s an interesting concept. It also might be that we still have living things on Mars. They could be under the edges of the polar ice cap sub-surface. There’s a projected sub-surface ocean on Mars 10 kilometres or so below the surface. And any of those places could house actual living things. Now, not little green men but probably likely to be bacteria if there is something. On the other hand, there may not be anything living there at all now. That’s also possible. And if that’s the case though there could be lots of evidence that life did exist there early on. In that way it might actually be really quite interesting too because we could see what the early origin of life chain of events was chemically because it may be preserved in the rock record there.
GM: And you’ve got an idea of where you’d like to go and look on Mars, and also the kinds of features that you’re trying to look out for, by looking at geological samples on Earth. And you’re particularly interested in a kind of rock formation that you see in deserts on Earth.
RP: In the 70s when I first started graduate school we were looking at remote sensing on Earth because we were trying to predict what the geology on the moon was at the time using satellites. And we couldn’t do it on Earth because we were looking at desert regions and all of the rocks were covered with this black shiny jewel like substance and we didn’t know what it was. About the mid-70s the question became how did this stuff form? And it’s called desert varnish and it was described by Darwin, lot’s of people originally. Darwin had it analysed by a Swedish chemist and it came up that it had a lot of manganese in it, which is what gives it its black colouration. So we were really interested in how this formed. It hasn’t really been figured out until last year. The best idea that I have right now is that it’s actually a silica that forms. It’s like opal actually. A nd so that’s the title of an article that we did called, “Baking Black Opal in the Desert Sun”. It’s always been thought that it was a biological process that formed it. And all or our research shows that in fact it’s not biology at all. It’s an inorganic but it does contain all of the bits and pieces of dead biology. It’s kind of like varnish or sticky paper or sticky glue and whatever lands on it gets kept there whether it’s pollen or whether it’s lipids or amino acids or genetic material.
GM: And if you can find some of this desert varnish on Mars then and bring it back and have a look at it, then it’s going to give you a really good opportunity to see if there’s any remnants of life stuck underneath it?
RP: Yeah, it would be a really good way. All of the latest missions have shown rocks that look like they have these sort of black shiny coatings. It would be something that may be able to last over the billions of years since Mars lost its atmosphere. And if that’s the case you could complex either with silica, some of these things, particularly like amino acids or lipids. The amino acids are really important because, like I mentioned before, there’s 20 or so main amino acids and proteins and they’re all actually of one type, L-amino acids, which are left handed amino acids. In meteorites, another place, you have most of these amino acids that are in life but there are 50 per cent left handed and 50 per cent right handed and it’s just a mirror image idea. They can’t overlay them but they look like a reflection in a mirror. So if you were to go to Mars you could have all D-amino acids rather than L-amino acids like you do on Earth, for instance, which would be really unique. So I think the desert varnish can tell you a lot, potentially, if it’s there. That’s a big question. We won’t know that till we go.
GM: At this stage we don’t actually know if those kinds of geological formations are on Mars but if they are there you’d love to have some in your lab?
RP: Oh, absolutely. And I think a lot of people would like to have anything from Mars. And it’s going to be the European Space Agency that’s likely to have the first Mars Sample Return mission.
GM: So if the European Space Agency says, all right then Randall, we’ll send up some kind of robot to gather these samples for y ou, where should we look, what would you tell them? How would you direct them?
RP: Well, it’s a really interesting question because I sat in on some of the designing of where the last mission to Mars was actually going to land. And the places that we want to look are often places that are kind of dangerous to land any kind of rover at all. Near the polar caps where you might have more water. In steep canyons, fluvial valleys. So NASA, having just had a failed mission to Mars, wanted to ensure that whatever they did they landed in a nice safe place. That’s along the equator because it’s just easier physically to get something in along the equator. And so it’s going to be quite a difference of opinion among, say, people like myself that say, well, let’s risk it and maybe go to a place where we’re going to get the best samples and other people saying that it’s too risky and we want to go to a safe place. But I think you could find potentially rock codings any place on the surface. So that’s one good point. And the other one would be like in obvious areas where you have had recent water or things that look like ancient hot springs. Because hot springs are made of silica or opal, and it’s opal-A, which is one that just doesn’t have crystal structure. And that’s where these organic compounds are sequestered, is in the opal.
GM: So some good news for the rover designers then is that they can go to some safe places, but equally you’d love them to go into a cave. And I guess that’s the kind of thing that gives robot designers complete nightmares given that most of these things tend to be solar powered and there’s not a whole lot of light in a cave.
RP: Yeah, it would be interesting to get one in a cave. Likewise, on Earth in deep soil you have microbes living three miles below the surface in these really inhospitable areas like in nuclear waste places like in Hanford in Washington State in the United States. So they’ve drilled three miles down in these really toxic areas and found lots of microbes. And a really good place to find something living would be potentially in a cave. And also because the caves are not directly exposed to the sun, as you mentioned, there’s not also all of the solar radiation and stuff than can also destroy organic compounds. Because remember there’s no atmosphere so you have a lot of UV light and other things that are really destructive to biological things unless they’re protected somehow.
GM: So potentially there could be all these biological organisms living or dead sheltering in caves on Mars?
RP: Could be. But there’s also a good friend of mine, Vernon Phoenix, who’s at Glasgow University who just came back from the high altiplano in Argentina and in hot springs they have bacteria that seem to coat themselves with silica or opal and that protects them against the UV light. At least that’s the general idea is that they do survive better because they have this opal coating them and then they don’t get destroyed by the ultraviolet light.
GM: Randall Perry there, Fellow of the Royal Society and a senior research scientist here at Imperial highlighting some of the pitfalls and promises of searching for life on the Red Planet.
Second part of Sunil Shaunak interview
But back now to the very real problems facing the poor here on Earth. And earlier we heard from Sunil Shaunak about his 'ethical pharmaceuticals’, specifically his plans for a Hepatitis C treatment vastly cheaper than those already on offer. But taking on big pharma isn’t for the faint hearted. In the second part of my interview with Professor Shaunak I wanted to know how well equipped is Imperial, admittedly a well resourced and powerful university, to drive new drugs along that tortuous and expensive road from the lab bench to the bedside?
SS: We’re trying to suggest that there’s an opportunity here for a paradigm shift for people to actually recognise that they may be able to take some of the work they do and turn it into molecules in bottles using resources and using opportunities which don’t put profit at the top of the agenda. We’ve done it once for Hepatitis C. We’re just about to start doing it for Leishmaniasis with Medecins San Frontiers and the Drugs for Neglected Diseases Initiative. And I think the Gates Foundation is also trying to put forward the concept that we can make medicines that are available largely at cost or just above cost to large parts of the world. So something is changing out there. We just happen to be a small component of that wave of sentiment that’s beginning to recognise that we live in a global community.
GM: But making a cost effective medicine is really just solving the first part of the problem. The next one is obviously getting the pharmaceuticals out to the people who need them. In developing countries where infrastructures are compromised some people never even see a doctor.
SS: But, you know, I’ve travelled quite a lot around the world and I’ve worked in Africa and I’ve worked in India and Asia. And the thing that strikes me constantly when I go and visit these places is I go to the deepest, darkest jungle in Africa and a little boy comes up to me and he’s holding a bottle. And guess what it is? It’s a bottle of Coca-Cola. So if I can go to deepest, darkest Africa and a bottle of Coca-Cola can be provided to me I simply don’t understand the logistics of wh y we can’t get drugs out to these sorts of communities. There isn’t really a logistical problem. We know how to do it. We need to ask questions about why supplies get impaired and why supplies get held up. And I think in the context of many infections you don’t need large infrastructures. There’s a lot that can be done with locally trained healthcare workers in certain communities. That’s not to say that the problems of implementing large scale change in health in poor countries are small. There are very, very real problems but I think those are public health problems requiring public health agendas, and even logistical agendas to be addressed. What we’re trying to say is that in situations where simply the cost of the drug is a huge impediment to anything happening we can make a difference to that.
GM: And can we explore this notion of an ‘ethical pharmaceutical’? Mark Henderson, the Science Editor at the Times newspaper wrote, “For you to tout this as an ‘ethical pharmaceutical’ is obviously saying through logic that conventional pharmaceuticals through the drugs companies are unethical. And we might not like the drugs companies very much but just because they make a profit doesn’t make it unethical if the results of their, albeit profit motivated, labour are curing people of diseases all over the world.
SS: What we’re talking about is the provision of the medicine to the patient in the clinic. Okay? That’s what we’re defining about ‘ethical pharmaceuticals’. Look, I think the lives of poor people in developing countries really shouldn’t be a commodity that is dependent upon their ability to pay for medicines that can, in my case, cure infectious diseases. We have an opportunity to make cost affordable medicines for patients who currently receive no treatment at all. Millions rather than billions of pounds can have a major impact in parts of the world where big pharmaceutical companies have very little interest. Saving the lives of poor people in developing countries shou ldn’t be this complicated.
GM: And what next then? Clinical trials presumably? I’m assuming you’re optimistic about the outcomes of those trial s but, I mean, do you have any fears that for whatever reason the drug may not be practical? It might be difficult to deliver. It might have side-effects.
SS: We’ve said for every disease that we’re interested in we want to do the scale-up manufacturing, the clinical trials, in countries where the disease is very common. So the Hepatitis C, we’ve gone to India. That means there’s charitable and government money available to do those trials. We’ve also made sure by working between Imperial and the London School of Pharmacy that we have addressed a lot of the issues about drug stability, potential toxic side-effects. So we are very encouraged that really since the interferon is a native protein, and the peg has previously been in people, the chances that this will work and work well are very, very high indeed. Of course there’s always the unexpected possibility that something may go wrong. But I think what happens in the situations where you get an unexpected result is that you can actually go back to the laboratory and try and correct the problem and then go back into the clinical trials.
GM: And is there a message for researchers in similar positions at Imperial or elsewhere that they too maybe able to wave the flag for their institution rather than this kind of work disappearing into the pharmaceutical companies?
SS: Well, I think academics, scientists and clinicians have got very good and are very successful at doing research and writing it up in major journals. It is possible to go the extra few miles which enables you not only to write up the work in good scientific journals but to take that work and turn it into something tangible in terms of a product that can have an impact in many parts of the world. It’s not easy. It’s not impossible. But it’s worth the extra miles. And the opportunities and the doors it opens are marvellous.
GM: So you think this is something that Imperial College and I guess the academic community at large can be proud of?
SS: Imperial College and Imperial College Innovations will now proactively encourage the development of technologies into cost effect medicines for parts of the world where people currently get no treatment. So what our work has done is that the College has changed its philosophy not simply from saying we should be making high value products for high value profit but where there is an opportunity to use that technology for the benefit of people in poor parts of the world that will now be done.
GM: Sunil Shaunak there. And that’s a story that we’ll definitely be covering on future episodes of the official Podcast of Imperial College London.
That pretty much wraps it up for this edition but we’ll have more next time with the Imperial researchers who are unlocking the secrets of the Solar System courtesy of some very valuable space dust.
This podcast is updated on the first working day of each month so I hope to see you for the April edition. Thanks for listening. And thanks to Ozgur Buldum, the composer, who’s very kindly let us use this rather fabulous tune called Layla as our podcast theme music. You can hear more of his work at ozgurbuldum.com
Well, this podcast is a co-production of the Science Communication Group and the Imperial Press Office. The producer is Helen Morant and I’m Gareth Mitchell. I’ll see you next time. Until then, goodbye.