LN: This is an MRC podcast and I'm Laura Nelson. - And of course you know, what we have to bear in mind is that even when a disease doesn't kill you, if it causes extensive morbidity, if it makes people sick, then they can't work. - I'm going to tell you about a disease that affects 500 million people worldwide every year, mostly in sub-Saharan African, most of them children. - What seems to be generally agreed is that the numbers are somewhere about a million and 3 million people dying per year from falciparum malaria.
LN: In the time you take to listen to this podcast, 30 people will have died from malaria and it's getting worse. I'm inside a laboratory at The National Institute for Medical Research in Mill Hill, London, where Dr Mike Blackman worked on a potential new treatment for malaria. I spoke to him.
MB: There are lots of economic as well as humanitarian reasons for working on malaria and I think that there's no question that it's, altruistic factors aside, it's in our best interest to ensure that major diseases like malaria are not the threat that they are at the moment. LN: If the current trend continues, the death rate from malaria could double in the next 20 years. Countries are getting poorer; in the worst affected areas in the developing world, malaria may account for nearly half of public health spending.
Quick question, I'm from the Medical Research Council and we use tax payers' money to fund research into malaria, which is a disease that's affecting people mainly in Africa. What are your thoughts on spending UK's tax payers' money on this kind of research? - I think it's much more worthwhile than many other things that tax payers money is spent on. - A lot more people are dying of malaria so I do think that everybody should do something to help.
LN: So why is malaria such a deadly disease? Once a person has been infected by a mosquito, the malaria parasite hides away in a person's red blood cells, coming out from time to time to cause infection. Dr Blackman explains.
MB: It's been recognised for a long time that one of the primary pathogenic mechanisms used by the most dangerous malarial parasite, plasmodium falciparum has to do with the fact that the parasite has the capacity to what's often referred to as to sequester, it has the ability to bind endothelial cells in the deep vasculature, so in the spleen, in the brain, in the placenta in pregnant women. And this somehow enables the parasite to avoid clearance by the spleen.
LN: Different proteins on the surface of the malaria parasite mean that the body's immune system never gets a chance to recognise it as something it should get rid of. Another scientist at the National Institute for Medical Research, Neil Brown, discovered this disguise more than 30 years ago.
MB: And so parasites that can bind to the endothelial cells and escape being circulated in the blood, manage to survive better than those that can't and this is something that falciparum manages to do. LN: Because the immune system is so bad at getting rid of malaria we need drugs to treat it, but recently resistance to drugs has spread.
MB: Perhaps the most successful drugs against malaria or most successful single drug is Chloroquine which has been around for some considerable time now. What's happened over time is that resistance to Chloroquine has spread across the world to the degree that in fact Chloroquine now in large parts of the world is useless. LN: Scientists at the National Institute for Medical Research have been studying the life stages of the parasite, because every point is a potential target for drugs .
MB: And so we need new drugs. So we either need derivatives of Chloroquine that do the same job but better or we need completely novel targets, completely different parasite targets.
LN: Dr Mike Blackman is trying to find a drug, His group has not only identified potential targets, but has found compounds that could be developed by drug companies as treatments.
MB: So what we've discovered is I think a kind of conceptual step forward and we've shown a compound that attacks this process, but to then take that into drug development and create a drug; that's something that we hope that our work will enable, will facilitate, will trigger, but we ourselves are not in a position to do that. LN: New malaria drugs come onto the market very rarely, one every five to seven years. The compound identified by Dr Blackman's group is still many years away from being a marketed drug. So what about a vaccine which would prevent the disease in the first place? Scientists at the National Institute for Medical Research have been trying to find one of those too. The parasite multiplies itself by releasing spore like particles called merozoites. Dr Tony Holder isolated a protein on the surface of merozoites and he succeeded in making this artificially in the laboratory. He found that this protein had potential as a vaccine.
MB: So what Tony did in his early work here was clone the gene for a protein called MSP 1, now when I say clone I mean actually identify and establish the sequence of this gene and it turns out that MSP 1 is probably abundant protein, the major protein if you like, on the surface of the merozoite. So there are several trials that have been performed using components of MSP 1 and at the moment in the US these kind of trials are going, I think they're so far phase 1 trials still, so early stage trials. But the question of how long we have to wait, it's very difficult to say. LN: A scientist in Oxford, Professor Adrian Hill who is the director of the University of Oxford's Jenner Institute is leading clinical trials on another vaccine. I asked him why his work is important. Can you start Adrian by telling me a little bit about the impact of malaria worldwide and give me some idea of the scale of the problem that we're tackling? AH: Well malaria's the most important parasitic disease in the world. It kills far more people than any other parasite, over a million children a year are said to die of malaria in Africa and that's a huge global public health problem because it's not just Africa that's affected; in Asia there are hundreds of millions of cases of malaria causing disease every year and also in other parts of the tropics, in South America malaria's an important problem too. LN: I understand you've been working on a vaccine and there aren't many vaccines around today, so it looks promising. Can you tell me exactly how promising it is and what we can expect from the work?
AH: It's been extraordinarily difficult to produce a vaccine against malaria; people have been trying for about 40 years now and a whole lot of different ideas and approaches and types of vaccine have been explored. But only a few of those have actually shown any efficacy at all in humans and one of those is a vaccine that we've developed at the University of Oxford, which is a novel type in that it uses not a part of the parasite as most vaccines, but a virus, to encode a gene of the parasite that then is expressed after vaccination and gives rise to both cellular immune responses and to antibodies. So we're trying to use this fairly new technology to produce effective immunity against certainly the liver stage but also in some of our new vaccines, against the blood stage of malaria. So we're aiming for a multi stage, multi component vaccine. LN: So this vaccine is currently in trials, how long would it be until we can expect to see it on the market?
AH: So what's very exciting is we've got to the stage now with our latest type of vaccine where we've just been able to show safety in small numbers of individuals and we're aiming to move on soon to an efficacy trial where we actually administer mosquito bites to people who've been vaccinated, to test the vaccine and that should happen in the next six months. So it's getting to a really critical stage of asking do we see this vaccine doing anything in humans or not and if it passes that test and we see a substantial efficacy in people, then there'll be a great push to get that into trials in Africa as quickly as possible and particularly tested in young African children which is the population we really need a vaccine to work in. LN: And if this works will it be the first vaccine?
AH: No, there are several vaccines around being tested. The problem at the moment is that none of them work very well so we have no vaccine that say gives 50% protection against malaria. But there is one in field trials in Mozambique that has given 30% protection in one trial and there are a lot of efforts to look at that and hopefully to try and combine that with other vaccines to produce a multi component malaria vaccine that many people think will be the best approach to malaria vaccination.
LN: A vaccine for malaria would be the ideal solution to the world wide problem. Education and mosquito nets are also crucial. How do all these methods of dealing with malaria fit together and why should we be interested? I spoke to Peter Dukes, he's the head of the Infections and Immunity section at MRC head office. I asked him why we fund research on diseases that affect the other side of the world.
PD: I think the most obvious answer to that is that in a world with increased travel and increased mobility, health is mobile, diseases are mobile, so HIV, TB and flu are all examples of where the infectious agent, the bug, can travel with a person on an aeroplane and find themselves here in the UK. My second point is that the UK Government, both under the current Prime Minister and the last have shown a great deal of interest in the health challenges, particularly of Africa. There was the Africa Commission under Tony Blair a few years ago and the relationship between improving health, lifting people out of poverty and if you can lift people out of poverty it helps sustain secure countries. So good health is good economics, is good security.
LN: And here's Adrian Hill again, this time on where the MRC fits in. AH: The MRC has a very, very broad role in malaria, from the sort of molecular work that is done at NIMR by Mike Blackman and Tony Holder and others, through supporting vaccine development, so the MRC are supporting our current trial of one of our most exciting malaria vaccines. Then on into field work and very important programmes for example at the MRC laboratories in The Gambia and then with an interest in more global control and intervention strategies and how you develop those. So the MRC is unusual in funding right across the spectrum from very basic molecular studies to large scale intervention studies in Africa and there are very few agencies that do that.
LN: This is an MRC podcast and I'm Laura Nelson. LN: Laura Nelson MB: Dr Mike Blackman AH: Professor Adrian Hill
