Flu Vaccines from Tobacco?

In a show not to be sneezed at, we look at the evidence that coughs and sneezes are linked to heart attacks.& We also probe the Flu Survey, a new citizen science initiative to...
13 November 2011


In a show not to be sneezed at, we look at the evidence that coughs and sneezes are linked to heart attacks. We also probe the Flu Survey, a new citizen science initiative to gather data on the incidence of influenza-like illnesses in the European population; we talk to the company who are mass producing flu vaccines in tobacco plants and catch up with the Columbia University scientific adviser on Contagion, Hollywood's latest infectious offering. Plus, why babies don't tie their umbilical cords in knots and news of a new fat-busting injectible that selectively destroys adipose, evidence that only single strains of HIV are transmitted between partners and the discovery of two pristine primordial gas clouds produced by the Big Bang...

In this episode

White spruce tree

- Warming Earth not so good for Arctic tree growth

A group of researchers from Columbia University publishing in the journal Environmental Research Letters have found that the growth of white spruce trees on the northern treeline in the far...

Warming Earth not so good for Arctic tree growth

A group of researchers from Columbia University publishing in the journal Environmental Research Letters have found that the growth of white spruce trees on the northern treeline in the far north of Alaska has shot up over the past 50 years. They've also managed to put forward an answer to the so-called 'divergence problem', where tree ring widths stop correlating with increasing thermometer-measured temperatures from the mid 20th century, and a possible alternative measurement as a solution to the problem.

Most people will be familiar with the use of tree rings in measuring time passing - with one ring for each year. But the width of the rings can also be used to estimate climate at the time when those layers of cells were laid down, known as a 'proxy' for when temperature measurements aren't available. The area where the researchers carried out their research is in very far North of Alaska, where tree growth is limited by temperature - so an increased average annual temperature would allow for a longer growing season and therefore wider tree rings, and also an increase in the maximum latewood density of each ring. White spruce tree

Well, the team, led by Laia Andreu-Hayles and Rosanne D'Arrigo from the Tree Ring Laboratory at Columbia University's Lamont-Doherty Earth Observatory, have shown that in white spruce, while the tree ring width does indeed stop tracking the instrumental temperature increases seen after 1950, the maximum latewood density measurements do continue to follow the increased temperature. They suggest that this is because we have now reached a stage where temperature is no longer having a positive effect on growth. If you imagine a curve with temperature along the bottom and growth up the side - at first as the temperature increases, so does the growth, but after a certain point, although the temperature is still increasing, the graph levels off because growth is no longer responding.  This could be down to the increased temperature actually stressing the trees, if there isn't also an increase in water availability. This is the situation the team found - the ring widths are larger post-1950, but their growth no longer correlates with temperature.

They suggest that using measurements of maximum latewood density might be a more accurate proxy for temperature measurements where temperature is 'no longer the primary factor controlling tree growth'. This would be a useful tool, especially in the face of criticism of the lack of correlation of ring width and temperature.

Two hands forming a heart shape.

01:49 - Influenza virus and heart attacks

Looking at whether flu can trigger heart attacks in vulnerable people

Influenza virus and heart attacks
with Dr. Charlotte Warren-Gash from University College London

Charlotte -  Well we've been looking at Influenza virus and heart attacks.  We're interested in looking at whether flu can actually trigger heart attacks in some vulnerable people because some of the people who have heart attacks don't have any risk factors and it's not clear why they have their heart attack.

Chris -   You mean, people who have a heart attack usually have some kind of antecedent problem like high blood pressure or high cholesterol and you're seeing people who have heart attacks have none of those risk factors but they do have flu potentially.3D Model of an influenza virus particle.

Charlotte -   Well possibly.  It's still a grey area.  We're really not sure whether there's a strong link or not, which is why we've been doing this research.

Chris -   So how did you do it, what did you do?

Charlotte -   We used the big general practice research database that contains records of over 5 million patients in the UK.  These are all anonymised records but we could see when people went to the GP with a flu-like illness and we used linked data from a heart attack registry database also in the UK, and that gave us detailed information on people who had heart attacks.  And so, by linking these two datasets together, we pulled out a group of people who had both the heart attack and had been to the GP with a flu-like illness.  And then we began our analysis, and our analysis was looking at something called the self-control case series.  So what that means is you take people who have had heart attacks and you look at whether they were more likely to have their heart attack in the time period just after visiting the GP with a flu-like illness compared to other times in their lives.

Chris -   That's neat.  So in other words, each person is their own control, aren't they because if they're not having a heart attack when they haven't had a flu-like illness, then they're controlling from the time when they have had a flu-like illness.

Charlotte -   Yes, that's right and it makes this type of method quite efficient because you don't need to find control patients to compare them to because when you look at different cases and controls, sometimes there can be other differences as well so you can introduce bias that way.  But here, as you say, everyone was acting as their own control.

Chris -   And - the million dollar question, what did you find?

Charlotte -   Well, what we found was that in the first few days after having a flu-like illness or a respiratory infection, people were nearly four times more likely to have their MI (myocardial infarction - heart attack) than in other time periods.  We wanted to look really though whether this was a specific effect of the flu virus or whether it was more of a general effect of any old respiratory infection.

Chris -   Did you know they actually were flu cases though?

Charlotte -   Well, no.  This is one of the problems with using this type of data.  It's GP data and you rarely have - these people have rarely been tested for flu, so we had to use various proxy measures for what we thought might be flu such as the codes that GPs use to classify the illnesses or looking at the amount of flu that was actually circulating in the community.  When we use those different proxy measures, we actually got very similar results when you compared those illnesses more likely to be due to flu compared to other respiratory illnesses.  So to summarize, this didn't seem to be a specific effect of flu.  It seems that any sort of respiratory infection that we found in Two hands forming a heart shapeour study could actually have this triggering effect in vulnerable groups and it seem to be the elderly that this was happening in, mostly people over 80.

Chris -   How big is the effect?

Charlotte -   It's basically a four-fold increase that we saw in the first few days immediately following a respiratory infection and the effect gradually tapered off over time, so about a month after your infection, there was really no increased risk at all.  But having said that obviously, most heart attacks are not going to be triggered by respiratory infection and most respiratory infections are not going to trigger a heart attack.  So this really was just a very small proportion of people, but quite a significant effect in those particularly vulnerable groups.

Chris -   How do you think that having an upper respiratory infection might cause someone to then go on and have a heart attack in that risk window?

Charlotte -   I think it's a bit unclear at the moment. Flu is an acute inflammatory event - and when your body is subjected to acute inflammation, particularly something like flu that can affect all parts of your body it's not just the lung, it can cause muscle aches and fever.  So it can cause symptoms affecting the whole body and it's suggested that it can cause a systemic inflammatory response, so an inflammation all around the body that might then also include the coronary arteries and might in that way, trigger a heart attack.  But I think it's still unclear and there's quite a lot of research going on about potential biological mechanisms at the moment.

Chris -   Given you found this then what should we do about maybe raising awareness of the link or is there anything we should do?  Is the effect so trivial that it's not actually worth worrying about?

Charlotte -   No, I think it is important particularly because we have a good flu vaccine to help prevent flu and this vaccine is quite underutilised particularly in people with some chronic conditions, and the recommendation is that people with chronic diseases such as chronic heart disease should have the flu vaccine every year, so I think it's important to raise awareness in those groups, and amongst their GPs as well so that they do encourage people to come forward for the flu vaccination each year.

Chris -   What about also telling GPs, "Look, there is this association that I've found between respiratory infection and then heart attack afterwards.  So if you see someone with symptoms that might be an evolving heart attack, maybe have slightly higher index of suspicion, maybe do something about it more than just writing it off as indigestion"?

Charlotte -   Yes, I think that definitely true.  We wouldn't just take this one study in isolation as evidence.  We need to gather evidence from a number of sources.  But absolutely, I hope that this study will contribute to the evidence available for GPs and other practitioners.

Chris -   Is that what you're going to do?  You're now going to say, "Let's go and look at some of the individual viruses and see if there are any particular viruses that are more of a risk than the others"?

Charlotte -   Well that would be nice to do.  I think it's important though to make sure that this does have some practical applications and I think flu is really one of the respiratory viruses for which there is an effective prevention, so that's why we focused on flu at the moment.  But yes, potentially in the future, we could look at other viruses as well.

Map of Europe

08:19 - Flu Survey - Tracking Influenza Across a Continent

As we enter “flu season” in the northern hemisphere, to help track the spread of seasonal flu here in the UK and throughout Europe, researchers at the London School of Hygiene and Tropical...

Flu Survey - Tracking Influenza Across a Continent
with Professor John Edmunds , the London School of Hygiene and Tropical Medicine

John - Well we know surprisingly little about the details about how flu spreads through the community and just how much the burden of flu really is out there in the community because our traditional forms of surveillance are monitoring people going to the GPs.  The GP records if they see somebody with flu-like illness, but we know that that's just a very small fraction of the total amounts of disease that there is out there. So what we want to get a handle of is just how much there is out there, how quickly it spreads, and we also want to get to know a bit more about how well a vaccine works.  We know that a vaccine doesn't always match up terribly well to the circulating strain, so we want to get a very early indication of that, and our survey can help us do that.  And we can also get some indications about simple questions you think you might know the answer to but actually, you don't.  So going by public transport, is that actually a risk for flu? And if so, how much of a risk?  So these are the pandemrix flu vaccinekinds of questions we're trying to address.

Chris -   Gosh!  I hope it's not a risk.  Otherwise, we're all going to be in trouble, aren't we?  So how are you collecting this data because it sounds like you're going to be collecting quite a bit of data in order to answer some of those questions?

John -   Well, we're trying to ask the public to collect the data for us.  So, we've set up an online survey called the 'flu survey' and it's at
www.flusurvey.org.uk and what we're asking people to do is just to log on and just to tell us whether they're ill or not, and the first time you log on we ask some background questions about your use of public transport and so on, and whether you've been vaccinated.  And after that, all we're asking is that people just log on and just let us know whether they've got any symptoms or not, and actually, we're really interested when people don't have symptoms as well.  That's as important to us as when people do have symptoms and if you don't have symptoms, it really takes just two clicks of a mouse and it's all over in a few seconds.

Chris -   But of course, those people could have had flu and had no symptoms or equally, they could not have had flu and have no symptoms, so how will you discriminate between the two?

John -   It's the difference between when people have got symptoms and when they haven't got symptoms.  Your
previous speakerwas talking about a case where individuals act as their own controls and we're trying to do the same really.  So, if you log on and tell us that you're fine and then you log on and tell us that you have a bit of a sniffle or something then we can see the difference in the incidence- that allows us then to start to track the spread.

Chris -   And once you've got all this data, how will you begin to decode it? How will it inform our understanding of what flu does in the community and how it spreads?

John -   Okay, so there's lots of different ways that we can do it.  So first of all, we're asking about where people live and so, we can get some idea about the geographical spreads. Some of the geographical information is up there on our website so there's a map that you can see.  And if you log on and report, or even if you report that you're fine, you can look to see the incidence of flu in your locality so we can give you an idea about how many other people around you might have flu at the moment.  And then we also are looking to do what's known as - well, a matched cohort study.  So, what we're going to do is we're going to match people - so for instance, we're going to take people who've been vaccinated and match them with a group who are otherwise epidemiologically similar, so match them with people who are the same age for instance - if they're adults, whether they live with children or not because that's an important risk factor. We match them, and then we'll track to see the incidence of flu in those two groups - so the vaccinated group and the unvaccinated group, and we'll be doing that online live as the epidemic progresses this winter, so you'll be able to see immediately the difference in incidence in the two groups.

Chris -   Which will be useful to get an idea as to exactly how good the Euope mapvaccine is, but how will you confirm that those people who your system reports have had flu have really had flu compared with people who have had a very bad cold, or some other influenza-like illness that wasn't really flu, it just felt like it?

John -   At an individual level, that's rather difficult to do.  So, each time someone reports, we can't really tell whether they have flu or they have some other virus that's similar to flu.  But on average, we can tell whether people have flu.  One of the ways we can do it is actually to see whether the vaccine works.  Last season for instance, we could monitor the effect of the vaccine and by doing that, we can see that actually, what we're recording, a lot of it actually must be flu.  If the vaccine works against it, then it must be flu.  One of our sister studies - so we're now doing a study which is identical to a study done in nine other European countries from this moment onwards where we've linked all of our different systems together so they're identical.  And one of our sister studies in Belgium is actually going to be doing some testing of the cases that they've observed there in Belgium this season, to see whether they genuinely are flu.

Chris -   What's the trajectory of flu both across Britain but also across Europe because historically, we always say that it arrives in Scotland first and then makes its way south?  What about the rest of Europe?

John - Yeah.  We don't really know and part of the problem is our existing surveillance systems are GP based surveillance systems, so those are the systems that everyone has across Europe and we can't really make comparisons between them because there are differences in the way the GPs records illness, there are differences in the way that people go to see their GP.  So there are orders of magnitude differences in flu rates across Europe which doesn't make any sense and we don't really think that if you live in say, Belgium, you're a hundred times more likely to get flu than if you live in Holland.  That doesn't make any sense but the system records 100 times higher rates and so, by having this - from this moment onwards, the flu survey and our sister surveys, now that they're absolutely identical, the only difference is they're translated into the local languages, we can now start to see just how quickly it really does move across Europe because we're now all measuring exactly the same thing.

Willie Greeninge checks on his tobacco plants at his farm in Chatham, VA.

14:24 - Flu vaccines from tabacco plants

A new biotechnology company called Medicago have developed a technique for quickly and cheaply producing vaccines using tobacco plants. Genes from the flu virus are added to the plants...

Flu vaccines from tabacco plants
with Professor Brian Ward from McGill University

Brian -  So my name is Brian Ward.  I'm a Professor at McGill University in infectious diseases and I'm serving as the Medical Officer for Medicago.  The platform that's used is a transient transfection in a tobacco plant.  What that means is that pretty much all of the cells of the leaves of young tobacco plant are infected transiently by a bacterium that's carrying a little bit of DNA that we instruct the bacterium to deliver to the plant cells.  As a non-plant biologist, one of the coolest things about this entire process to me was the fact that you get the bacteria into all of the plant cells by literally turning these young tobacco plants upside down in water and then sucking the air out of the plant with a vacuum.  It's called "Vacuum Agroinfiltration" but it's fantastic because what happens is when you suck hard enough on the root of a plant, the leaves collapse like sponges.  You submerge them in a bath of these bacterium and then when you release the vacuum, every cell in every leaf of the plant sucks the liquid in containing the bacteria and every plant cell is infected simultaneously.pandemrix flu vaccine

Chris -   So you get little seedlings of tobacco plants which are making proteins from the genes that you've added with this bacterium.

Brian -   The bacterium contains the genetic information in a plasmid and that plasmid directs the production of the viral protein within the cytoplasm of the plant cell.  So that single viral protein then migrates to the surface of the plant cell and it auto assembles into these small virus-like particles that look from the outside like a virus, but have nothing on the inside.  They're empty.  They don't contain virus genetic material.

Chris -   But critically, they can behave as a virus in terms of their immunogenicity.  You can put them in, the body thinks they look like a virus so it makes an immune response against them.

Brian -   Yes, these virus-like particles essentially trick the body into believing that there's a viral infection and so, the body makes a response that it would typically make to a virus that's infecting them.  But in this case, it's just a response to the surface haemoglutanin protein, and so, you get the benefit without much of the risk.

Chris -   How do you get the virus-like particles out and not end up with the whole other plant glup going with it?

Brian -   So that's another really interesting thing that the company has done.  Initially, they did grind up the plant cells.  As it turns out, these virus-like particles collect between the cell wall that surrounds each plant cell and the outside membrane of the plant cell.  In these pockets essentially that contain large numbers of virus-like particles.  The cell wall can be digested with enzymes that are directed against plant wall but not plant membrane.  As a result, you can put the plant mass, just slightly ground up plant material, into a vat with enzymes and the cell walls are digested away because the virus-like particles are between the cell wall and the outside membrane of the plant cell, they are simply released into the liquid in which you're doing the digestion, making the purification very easy.

A field of tobacco plants in Chatham, VAChris -   Now when we make flu vaccines in egg, you get roughly three doses per egg.  So how many doses do you get per tobacco plant?

Brian -   It's highly variable.  The production facility in North Carolina works with batches of about 15,000 plants.  15 000 plants translate into about 30 kg of plant material - so it looks green - and then that green material can yield about 5 million doses of vaccine.

Chris -   So quite a bit and presumably very fast to make.

Brian -   That's one of the huge advantages of this platform is that the tobacco plants are young, healthy, growing, they're transfected.  When they're harvested between 5 and 8 days later depending on how much sun there is, they look perfectly healthy, and so, you harvest and then process so that the cycle of production is actually very, very fast.

Chris -   No risk of people getting hooked on flu vaccines?

Brian -   I don't think so.  No risk of people getting hooked on flu vaccines.

Chris -   But being more serious, when you put the vaccine material into a clinical setting, what have you done with this so far?  Has this just gone through animals?  Have you just done this in terms of demonstration?  Where are you in the sort of approval process?

Brian -   So far, the company has done the standard work pre-clinical which means animal studies and toxicity studies, and in fact, two of the products have gone into human trials.  One of the products, the H5 monovalent vaccine has gone forward into a phase II study.

Chris -    It's against bird flu - H5 N1.

Brian -   This is against the bird flu.  So that's the product that's furthest advanced.  The total number of people involved in those studies is about 300 so far - phase I and phase II, and the seasonal H1 vaccine which is again a monovalent vaccine that targets the circulating H1 virus now, that's gone into 100 people to date.

Chris -   Have you actually got to the stage where those people have been challenged with flu so you know that they're making a protective response?

Brian -   So, one of the options for testing a flu vaccine is to do a human challenge study, but we haven't done that yet.  Right now in phase I and phase II trials, what you're looking for is safety, how well the vaccines are tolerated, and what kind of immune response they make.  And so far, these vaccines are very well tolerated, very similar to the kinds of responses that you get from a standard trivalent vaccine.  But they also elicit really quite strong immune responses.  The H1 vaccine certainly meets all of the criteria for licensure for the trivalent vaccines.  So clearly, that's the next step for the company, to actually move from the monovalent H1 vaccine, to incorporate an H3 containing vaccine, and a B type virus to make a trivalent virus-like particle vaccine made in plants.

Chris -   And the timeline for that?

Brian -   Can I say soon and get away with it?  I think that there's a hope that by the end of 2011, that there will be a candidate trivalent vaccine that can be tested at least pre-clinically.

Chris -   What about costs?

Brian -   That's one of the huge advantages of this platform.  Using plants as the bioreactors instead of stainless steel vats in a high production facility allows the cost of goods to be considerably lower.  And so, these vaccines can be produced for less than the standard vaccines that are produced in eggs.  Furthermore, the facility itself, because it's not based on incubation of eggs and supply chain of high quality eggs, and so on, is also considerably less expensive than the investment in an egg based facility.

Excess adipose tissue around a male's mid-section.

22:40 - Chemical liposuction: fat-reducing injection success in primates

A fat-reducing drug that can reverse obesity in monkeys has been successfully tested by US scientists...

Chemical liposuction: fat-reducing injection success in primates

A fat-reducing drug, Adipotide, that can reverse obesity in monkeys has been successfully tested by US scientists.

The agent, which was injected daily over a four week study period into a group of naturally obese baboons, macaques and rhesus primates, contains of a short string of amino acids that cause the drug to lock selectively onto the walls of blood vessels that supply adipose tissue. Linked to this short, blood vessel-targeting protein sequence is a further chemical signal that causes cells that are exposed to it to commit suicide. This it achieves by triggering structures called mitochondria, which are essential energy-generating components inside cells, to break down. In this way the agent causes the chemical equivalent of liposuction, culling fat cells and causing weight loss.

Compared control animals, the treated monkeys showed weight reductions of Excess adipose tissue around a maleup to 14% and an average fat mass reduction of almost 40%. This translated into a body mass index (BMI) reduction of up to 20% and, just as overweight humans develop an insulin-resistant state that often leads to diabetes, the treated animals showed significantly lower insulin levels afterwards.

Surprisingly, the treated animals showed no signs of altered blood cholesterol or fatty acid levels while receiving the new agent, and there were no obvious behavioural side effects or evidence of altered eating behaviours during the study. The only thing that was picked up during the trial was a trend towards increased urine output and dehydration in animals receiving higher doses of the drug, although the relevance of this finding remains to be shown. The results offer a promising lead in the development of treatments to combat global obesity, which now affects up to one in five adults in many developed countries and carries a cancer risk elevation equivalent to being a regular smoker.

According to co-author Renata Pasqualini, "Development of this compound for human use would provide a non-surgical way to actually reduce accumulated white fat, in contrast to current weight-loss drugs that attempt to control appetite or prevent absorption of dietary fat." The team are now about to commence a human clinical trial involving a 28-day administration of the agent to patients with prostate cancer to determine whether their disease improves alongside the ensuing weight loss.

Diagram of the HIV / AIDS virus

27:12 - The HIV transmission bottleneck

Researchers have found that the strain of HIV virus most common in the genital tract of a chronically infected person is not necessarily the strain that infects a new sexual partner.

The HIV transmission bottleneck

Researchers have found that the strain of Human Immunodeficiency Virus most abundantly present in the genital tract is not necessarily the strain that infects a sexual partner.

Unprotected heterosexual sex is the most common way that the HIV is transmitted, particularly in developed countries and Debra Boeras from Emory University in Atlanta and her colleagues studied heterosexual couples in Rwanda and Zambia who were 'sero-discordant' - i.e. one was HIV positive, and the other was only just diagnosed as HIV positive.

An HIV positive person can carry many strains of the virus present in their genital tract, as it mutates so rapidly (which is one of the reasons we're having a hard time trying to figure out a vaccine). But previous studies have shown that a single strain of HIV establishes infection in the new host, known as the 'transmission bottleneck', and through studying vaginal swabs, and semen and blood samples from 8 heterosexual couples the team confirmed that this was the case. If the infection was random, you'd expect that the strain of the virus that was most common in the genital tract would be more likely to cause infection in the sexual partner.

But when the researchers compared the gene sequences for proteins on the outside of the virus that vary between strains, they found that the strain in the blood of the newly infected partner was not the same as the most common strain in the genital tract of the chronically infected partner.

HIV Viruses

The team suggest that this is due to selection of the viral strain best suited for successful transmission rather than just the most abundant strain. So, many virus particles may be transmitted to the uninfected sexual partner, but most of them will not be able to infect the person. It is only the strain with the right attributes, such as more efficient binding to receptor proteins on host cells, that are able to infect a new host.

This finding is important, because we know that transmission of the virus is via the genital tract, but if the strain that actually manages to infect the other partner is not the commonest one in the genital tract, then there must be a mechanism at work that could affect our strategies to treat the virus and reduce onward infection rate.

Cold Gas Flows of Primordial Gas

30:05 - Pristine primordial Big Bang gas discovered

Two gas clouds containing pristine samples of the gas spawned by the Big Bang has been spotted by astronomers.

Pristine primordial Big Bang gas discovered

Two gas clouds containing pristine samples of the gas spawned Cold Gas Flows of Primordial Gasby the Big Bang has been spotted by astronomers.

Using the powerful, Hawaii-based Keck I telescope, University of California Santa Cruz graduate student Michele Fumagalli and his colleagues focused on two distant quasars, called J1134+5742 and Q0956+122. Quasars are intense light sources produced by superheated matter falling into massive black holes at the centres of galaxies. To reach Earth, the light from them has to pass through any clouds of gas that are in their paths.

By looking at the light that arrives, researchers can work out what is in the gas because different chemical elements absorb discrete wavelengths of light, producing a unique chemical fingerprint. But prior to now all of the gas clouds that have ever been reported have always shown signs of significant contamination with metals. These can only have come from early stars, which produce heavier elements by fusing lighter substances, like hydrogen, together.

This means that the compositions of these contaminated gas clouds cannot be relied upon to test theories about the Big Bang, and the sorts of elements and in what ratios, it produced. Current models of the Big Bang suggest that, after about 8 minutes, the newborn Universe cooled from a sizzling one billion Kelvin to about 500 million Kelvin, which is hot enough for new elements to be born and yet cool enough for them to be stable.

The result, theoreticians think, was a mixture comprising mainly hydrogen and its isotope deuterium, together with a bit of helium and a trace of lithium. Yet without some of the resulting gas to study, the model remained unsupported by experimental evidence.

But the new findings, which are published this week by the journal Science and reveal gas clouds that date back to about 2 billion years after the Big Bang and are devoid of any metal contamination, change all that.

"The lack of metals tell us this gas is pristine," says Fumagalli. "It's quite exciting because it's the first evidence that fully matches the composition of the primordial gas predicted by the Big Bang theory."

Apart from validating existing hypotheses, the new findings also shed light on how the early galaxies were forming. Theoretical models predict that these nascent galaxies were growing by pulling in massive streams of cold gas, but these "cold flows" as they are known, have never been seen. Fumagalli is speculating that the pristine clouds he has spotted might just be them...

 This 2005 photograph depicted a female Anopheles albimanus mosquito while she was feeding on a human host, thereby, becoming engorged with blood. Like other species in the genus Anopheles, A. albimanus adults hold the major axis of the body more...

33:35 - Malaria Vaccines, Looking but Seeing and Nanoscale Electric Cars!

A new target for Malaria vaccines, How seeing and paying attention to things uses separate parts of the brain and the world's smallest electric car...

Malaria Vaccines, Looking but Seeing and Nanoscale Electric Cars!
with Julian Rayner, Sanger Institute; Masataka Watanabe, University of Tokyo; Paul Weiss UCLA; Karen Williams, Staunton-on-Wye Endowed Primary School

New Malaria Vaccine Target

A protein interaction on red blood cells could be a prime target for an Anopheles albimanus mosquitoeffective Malaria vaccine.

Symptoms of Malaria only begin when the plasmodium parasite causing the disease infects red blood cells to replicate.

Publishing in Nature this week, Julian Rayners team at the Sanger Institute have identified a crucial interaction needed by all strains of the parasite to get into the red blood cells, which if blocked could stop the parasite in its tracks and preventing the onset of disease.

Julian - So the interaction is between a parasite protein called RH5 and protein that's present on the surface of the red blood cell called basigin  That if we block that interaction, we can completely prevent invasion down to undetectable levels, so it seems to be an essential interaction, the parasite needs it in order to get inside their blood cells.


Looking but not Seeing

fMRILooking at an object and paying attention to it involve separate regions of the brains visual system.

Working with human volunteers, Masataka Watanabe's team from the University of Tokyo monitored brain activity in the primary part of the visual cortex, where information is first processed. By changing the visibility of images seen by the volunteers the team saw no different in activity when the images were visible or invisible, meaning their awareness and perception of the images must happen elsewhere in the brain.

Masataka - Even if the visual input is actually there into your brain, when you don't see it there's no modulation in the primary visual cortex. So we need like extra experiments to look where exactly awareness modulates your neural activity.


A Molecular 'four-wheel drive'

The world's smallest four-wheel electric car has been created by scientists molecular motorat the University of Groningen.

Ben Feringa's team have developed a molecular motor using a single molecule, which can move in a chosen direction after the injection of electrons, by using four attached rotary units, The units change shape in response to the incoming electrons propelling the molecule forward along a copper surface.

Paul Weiss, Director of the California Nanosystems Institute comments on the discovery.

Paul - We're really just getting the first glimpses in this field.  Single molecule motion is something we can now do, With this beautiful work by Feringa, the excitement there is this four motors and different parts of one molecule around working together in concert to move a structure forward.  If we can understand motion at these scales where we know everything about the system, we hope to bring that to bigger systems.  So for instance the motors that we have running our automobiles now don't work very efficiently.  We may be able to make motors that are more efficient.


The Rolls-Royce Science Prize

And finally, The Rolls Royce science prize was awarded this week to Staunton-on-Wye Endowed Primary School in Hereford and Mulberry School for Girls in London.

Beating over 2000 schools across the UK who had all developed science teaching projects that helped meet particular needs in their school, the two winning schools were awarded for their excellence in science teaching. Staunton-on-Wye winner and teacher Karen Williams on their winning project.

Karen - The children built quite a large playhouse in our school grounds and they had to reach a joint decision about what materials they were going to use to build the walls in the rough of the huts.  During the project, they were very engaged so we had 5-year-olds talking about the pros and cons of different types of roofs and 10-year-olds grilling the architects about the merits of different types of vinyl and rubber as a building material.  So it was combining practical science with a commitment to look at how we can make good decisions about what we're using.

Joint winners Mulberry School had developed a hydroponic greenhouse powered by renewable energy. More information on this years entries and runners up can be found online at science.rolls-royce.com.

The Cotte dé Saint Brélade

37:49 - Jersey's Neanderthals - Planet Earth Online

Richard Hollingham visits St. Brelade in Jersey to talk to a team of archaeologists who’re reappraising the caves to learn more about the Islands Neanderthal history...

Jersey's Neanderthals - Planet Earth Online
with Matt Pope, University College London

Chris -  the more that we learn about Neanderthals, the more fascinating they seem to become.  Much of our understanding comes from a remarkable site on the south coast of Jersey called La Coq, St Brelade.  Here, archaeologists have found piles of butchered bones suggesting that animals were literally driven over cliffs to kill them.  Planet Earth Podcast presenter Richard Hollingham has been to see it.

Richard -   Now I'm just clambering over the rocks and it's a spectacular Flint arrow headlandscape.  Over to my right it's almost a white long sandy beach that runs right across the bay out to the headland and then behind me these enormous granite cliffs, almost like towers coming out straight from the rocky shoreline, and Matt Pope is here from University College, London.  Now, Matt, this is world class really.

Matt -   Yes, this is one of a very limited number of sites in the prehistoric world that document long term occupations by ancient humans.  It's part of a wider pattern that we see over the world sometime after 600,000 years ago where humans start on a long term basis to colonise fixed places in landscapes and usually that means caves.

Richard -   Now we're looking out over the English Channel under very heavy cloud today.  Now if we go back, I don't know, 60,000 years, 100,000 years this wouldn't have been water here.

Matt -   No, if we're going back into the last ice age into the Devension, the sea level would have been much lower and what we would have been looking at is not a flat featureless plain, but a landscape of granite bluffs, steep sided granite ravines all feeding into a river valley system that ultimately feeds into the large English Channel river that would have run down the middle of the land under the sea today.

Richard -   The caves can only be reached at low tide and even then it's a difficult scramble across the rocks.  At the top, Matt and his colleagues are scraping away at the ground with small archaeologists trowels.

Martin -   My name is Dr Martin Bates.  I'm from the University of Wales, Trinity St. David in Lampeter and I'm a geoarchaeologist.

Richard -   So what is this we're looking at?  It looks just like a piece of flint.

Martin -   It's a piece of flint that has been chipped off a core.  That flat surface on the top there is where somebody has hit down there is it's broken off.

Richard -   So this is only about the size of your thumb nail, here Martin.  And how do you know it's not just a little bit of flint?  How do you know that's been made?

La Cotte dMartin -   Flint doesn't occur naturally here, any bit of flint that's on this site must have been brought in by somebody

Karen -   My name is Karen Rubens and I'm a PhD student at the University of Southampton.  La Cotte a St Brélade is a site that everybody learns about as an undergraduate, everybody knows it, it's such an important site for mega fauna hunting.  The story that the Neanderthals used to drive mammoths over the cliff here and they have huge bone heaps under the arch. If you come here and you have to walk on the beach, on those pebbles, you have to climb around then you come around the corner and you can see the scale of it and the massive amount of sediment and rubble that is still here.  It's very impressive and it's very difficult to describe because even if you see pictures you can't imagine the scale.

Matt -   Of course the thing that is really captivating about the sites are the piles of fauna, piles of mammoth and piles of butchered rhinoceros and trying to envisage what the site was like then.  Now we're pretty sure it was still enclosed, or at least partially enclosed, at that stage and also the site would have been much fuller and so, you're within a cave environment with a solid roof, they're bringing, we think, in these elements of mammoth skull, mammoth ribs into the site and they're carrying Wooly Rhinoout knapping there.  We also know that there's ash and burnt bone as well.  So, at this stage if you're imaging it, we're in a very cold environment, we know there's a lot of ice flowing around, so it's quite arid, sea levels are very low.  They found an area of shelter here that they're using for the sharing of meat, for the butchering of animals and for making flint tools and also burning material, potentially bone.

Richard -   Just being here and just talking to the three of you, you could sense the excitement and you're finding things.  You've been here between the tides, three hours or so and yet you've found a couple of pieces of flint, you've just found a little tooth, you know, it's exciting stuff.

Matt -   Well it's an incredibly rich site and that's why our excitement, we hope, can now translate into preserving it for future generations and that's going to take a lot of work and this is just the first stage in stabilising the site and working with the site owners to affect a long term preservation solution here.

 This 2005 photograph of the Centers for Disease Control and Prevention’s Dr. Terrence Tumpey, one of the organization’s staff microbiologists and a member of the National Center for Infectious Diseases (NCID), showed him examining reconstructed 1918...

43:18 - The Power of Pandemics - The truth behind contagion

Ian Lipkin discusses the science behind the film Contagion which depicts the series of events that unfold with the outbreak of a new strain of flu...

The Power of Pandemics - The truth behind contagion
with Ian Lipkin, University of Columbia

Ian -   The most important advance in the past few years has been the international health regulations to which all of the major countries that have represented the UN have signed up to.  The International Health Regulations' mandate is not only their requirement for improving health surveillance in your own country, but also supporting the improvements in the developing world as well.  So, this means that assuming that we follow this through to it's logical conclusion, we will have high quality surveillance all over the world and that people will report in a timely fashion.  There are a number of assumptions there of course and one is that there are resources are available to enable this and that's not clear right now and it's become obviously more difficult with the global economic crisis.  But nonetheless, there is a firm commitment on the part of the major industrialised nations to make certain that this does come into place.

Sarah -   I suppose it'll be a combination of observing at internal, nation wide, Ebola viruslevels, but also working between countries at an international level to keep an eye on things and track the movement of such a pandemic.

Ian -   That's correct and of course, one of the things that we would like to do would be to prevent or interdict the pandemic by recognising the potential before something moves from animals into the human population. Fully three quarters of emerging infectious diseases originate in wildlife and then either move through domestic animals into people or move into people directly, and there are many examples of these - HIV, SARS, influenza virus, West Nile virus.  So one of the things we're trying to do is to extend surveillance from the human community and to the animal community.  So there are a number of efforts that have been allowed in the UK, and probably the most support has been found from the Wellcome Trust.  In the United States, it's USAID and all these groups are collaborating and trying to support one another in these efforts to identify potential pathogens of humans and animals.  Sometimes we focus on gorillas and chimpanzees because we're thinking about the HIV,  and so on but over the past four or five years, people are focused on bats.  Bats appear to be tolerant to infection with many of these exotic and highly virulent viruses.  So examples rabies, and SARS, and Ebola, and Marburg.  And the bats don't seem themselves to be affected by most of these pathogens.  They seem to be able to coexist with them quite happily until somebody eats some of these bats or there is some sort of transfer of infectious material from a bat to a human.

Sarah -   And so, once we know more about the potential for animals like bats and other vectors to carry these infections and pass them on, what can we do with that information?

SneezeIan -   There are several things.  First of course, you can monitor wildlife for the presence of these infectious agents.  They're not all infected and they're not always infected.  And by tracking the movement of these infectious agents in wildlife, you can understand the risk that might be associated with humans.  In addition, you can develop specific measures to address these, so people are trying to develop vaccines against many of these agents.  There can be drugs which can be developed and once you know that a particular agent has a potential to move into humans, it becomes a much larger risk and you're able to focus investment of resources.  I'm trying to address those risks.  One of the things that we've been trying to do as a field in public health is to try to find ways in which we can streamline the process for creating vaccines for new infectious disease threats.  When the pandemic H1N1 influenza virus surfaced in the Americas a couple of years ago, it took us fully 6 months to develop a vaccine, to validate it, to be sure that it was safe and efficacious, and then to begin to distribute it.  And using modern molecular techniques, we have the capacity to make many vaccines more rapidly from that and we're trying to find ways in which the regulatory science can be brought up to speed.  By regulatory science, I mean the ways in which it will ensure that a vaccine or a drug, or an antibody, or any of the sort of biological intervention is safe and effective.  We need to find ways which we can streamline that process and also of course, make it less expensive.

Sarah -   So it seems like there's an awful lot of sides to addressing obviously something that is extremely problematic.  There's modelling, looking at potential vectors, there's the sequencing of new viruses that come up.  When you were approached to do the film, were you really keen to make sure that it addressed the different sides of a potential pandemic?

Ian -   Well to be honest, the most important thing was to figure out whether or not these guys were sincere about making a great film.  The screenwriter approached me initially,  Scott Z. Burns was a very serious guy and he said, "Look, I want to make something that's real.  I want to make something that's important.  Obviously, we need to fill theatres, but when we're done with this, we want to feel as though we've made a contribution."  So we ran through a series of different scenarios - which viruses were of interest, where might a virus originate, how would it spread, and you know - I got sucked in quite frankly because it was a lot of fun thinking about the ways in which we might be able to convey this message. 

I think they did a very good job.  I mean, there are a couple of points where I think things might have been done a little bit differently, but by and large, the film is accurate and it's timely, and it has had an impact.  Not least in its drawn attention to the people who do this kind of work day in and day out.  Many who don't receive much in a way of accolades for the work that they do.  Some of them die in the course of doing this work, but we try to emphasize the fact that everyone is at risk.  You can't hide from infectious diseases and it's important that everyone be protected.  I'm very proud of the film and it was a great deal of fun to make, I have to say.  I didn't anticipate it was going to be as much fun as it was.

What is the difference between a cold and the 'flu?

John - It's very difficult to say. Many different viruses cause flu-like symptoms and on the other side, flu causes a range of symptoms. So, without testing somebody serologically, we can't really tell whether somebody has got flu or not.

Can people spread the 'flu without getting the symptoms themselves?

John - Yeah, that's an interesting one. So probably about a third of people who get infected with flu don't display any obvious symptoms. They may display something very mild that they might not even notice it themselves. And they have the potential at least to spread the infection although to be honest, we really don't know whether they genuinely do or not and I'd love John in Peterborough to log on to the flu survey and tell us more about his illness and the spread because he just seems like a fascinating person.

How is the 'flu caught in the first place?

John - Again, we don't know in a great detail. I mean, clearly of course, if you sneeze, then you're producing a lot of virus into the immediate vicinity of you. So, coughing and sneezing -being symptomatic - those symptoms probably do aid the spread of the infection quite a lot. That's why you know, blowing your nose in a tissue and disposing of it properly is a good idea. But in detail, we don't know. It's incredible that we don't know very well but we don't.

Do men really suffer more when they catch the 'flu?

John - Well obviously, when we set up the flu survey, that was the first thing that we wanted to look at and what we found is, in fact, it doesn't seem to be the case. If anything, women seem to report slightly more flu than men probably because they have more contact with children. Maybe we men like to moan about it a bit more.

Chris - Who knows? I certainly think it's true. I think men probably - if they're not in contact with children as much probably don't get as infected as often. It's certainly true for things like Noro virus isn't it and that kind of sort of gut rot type bug. You often get far more female cases of that just because of contact with the kids.

John - Exactly, kids are a big reservoir for many of these source of infections. Not just the flu but many of them.

Do umbilical cords get tangled and knotted?

Christoph - My name is Christoph Lees. I'm a Consultant in Obstetrics and Foetal Medicine at the Rosie in Addenbrookes at Cambridge. It's a really interesting question and a lot of women do ask us this specific question. The umbilical cord is about 30 to 60 cm in length at term. So at 36, 37 weeks it really is quite long. The important thing about it is, not only is it long, but it's really thick. So it's up to 2, sometimes 2 Ã?,½ cm thick, and not only does it contain two arteries and one vein. But it also contains a lot of jelly-like substance called Wharton's Jelly that protects the blood vessels. So it really is encased in quite a thick covering and then the blood vessels have jelly around them. So that stops them getting twisted or occluded in any way. Now sometimes you can have a knot in the umbilical cord, so babies obviously move around. They jump up and down, they turn over from head down to bottom down sometimes. Why doesn't that cause the umbilical cord to knot? Well the answer is that sometimes it does, but it's very rare in fact, for a knot to cause a problem for a baby. So, because the umbilical cord is so thick, it tends not to knot itself easily and even if it does knot itself, there is so much protective jelly around the blood vessels that it's very rare that it causes a problem.

Diana - Umbilical knots do happen occasionally when a foetus swims through a loop in the cord, but the structure of the cord makes it difficult for this to have any adverse effects. There has to be a great deal of tension in order for the knot to compress the cord with any significance, and therefore, impede blood flow. CliffordK on the forum found us an article from Paediatric and Prenatal Pathology Associate in Louisville in the US. And they estimated that around 3% of preterm still births occur due to cord knots.


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