Fat Dinosaurs and the Descent of Man

23 February 2009
Presented by Ben Valsler.

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In this NewsFlash we find out how to build a tolerance to peanuts and beat allergies, discover how fat the dinosaurs were and how meningitis bacteria wear a disguise to evade our immune system.  Plus, why both fish guts and tiger nuts could be an economic stimulus in Africa, and we delve into science history on the anniversary of Darwin's 'Descent of Man'.

In this episode

Scientists crack Peanut Allergy Problem

Researchers have successfully treated four individuals with peanut allergies using an approach called oral immuno-therapy.

Close up of peanutsWriting in the journal Allergy, lead author Dr Andy Clark, who is based at Addenbrooke's Hospital in Cambridge, explains how he and his team recruited four boys aged between nine and thirteen with established allergic reactions to peanuts.  Blood tests on the children confirmed the presence of ciculating peanut antibodies, and injecting small amounts of peanut protein into the skin provoked signs of inflammation, proving that the boys were reacting to the nuts. 

The children were then given daily doses of peanut flour containg the nut protein to eat every day.  The starting doses were very small at just 5mg per day but this was doubled every two weeks until the participants were eating 800mg per day, equivalent to about four peanuts.

After a further six weeks at this top dose the volunteers were then "challenged" with twelve whole peanuts, which they were all able to consume without ill effects.  During the study the volunteers were equipped with antihistamines and adrenaline syringes in case of anaphylaxis, but apart from mild reactions the process was well tolerated by the subjects who have now been prescribed a daily peanut ration of five nuts per day to ensure their new-found "tolerance" for the food is maintained.

Both the patients and the researchers are delighted with the results but they do caution that it's a small trial and not something that should be undertaken outside of a properly monitored medical setting.

"Don't try this at home," says Clark.

Cervical cancer rates higher in poorer areas

Cervical cancer is in the news here in the UK as reality TV star Jade Goody has been diagnosed with the diease.  And this week researchers at King's College London have published a paper showing that rates of cervical cancer are higher in poorer areas than in richer ones - results hat have important implications for targeting cancer awareness and screening campaigns.

Cytological specimen (ThinPrep) from a patient who was later diagnosed with cervical adenocarcinoma in situ.Led by Dr Laura Currin, the researchers analysed data from over 2,200 women diagnosed with cervical cancer between 2001 and 2005 in London, Kent, Surrey and Sussex.  They then looked for any patterns linking the disease to social deprivation, and related factors such as smoking, teen pregnancy and cervical screening.

The team found that the rates of cervical cancer varied dramatically across South-East England, and in some neighbouring areas there was up to a three-fold difference in rates, with much higher rates of cervical cancer in poorer areas.

There's a number of reasons for this.  Firstly, smoking is linked to increased risk of cervical cancer, and rates of smoking are higher in poorer areas than richer ones.  Also, we know that women in poorer areas are less likely to take up cervical screening, which saves thousands of lives every year in the UK.  Last year alone, hundreds of thousands of women across the country failed to take up their invitation for screening.

The key thing about cervical cancer is that it's a highly preventable disease.  The national screening programme of smear tests picks up pre-cancerous changes, so women can be treated before the disease has even developed.  These new results tell us that healthcare providers and health campaigners need to focus their efforts more firmly on reaching women in poorer areas of the UK, encouraging them to be aware of symptoms such as bleeding between periods, and going for screening when they are invited.

And although Jade's story is a terrible personal tragedy for her and her family - as it is for any family affected by cancer - she has done a lot to raise awareness of cervical cancer among younger women.  Cancer Research UK have seen a big jump in the number of people seeking information about cervical cancer symptoms and screening on their CancerHelp UK website and Science Update Blog.  Hopefully we'll see a jump in the number of women going for screening, particularly from poorer areas, which could lead to lives saved in the future.

New way to battle opioid withdrawl

Scientists have found a drug which is highly effective at combating the symptoms of opioid withdrawal.

A pre-war bottle of HeroinWriting in the Journal of Pharmacogenetics and Genomics, Stanford University researcher Larry Chu and his colleagues made the discovery by studying how 18 different strains of morphine-addicted laboratory mice coped with going cold turkey.  When opioid-accustomed mice are given a drug called naloxone, which blocks the effects of opiates, they jump up and down, and strains that show more jumping behaviour seem to be worse withdrawers than animals that jump very little.

To find out why the team compared the DNA sequences of animals that jumped the most with the mouse strains that jumped the least.  The team were gratified to find a DNA hotspot in a gene called Htr3a, which is a brain receptor for the transmitter substance and chemical feel-good factor serotonin, also known as 5HT.  The strains of animals with the worst withdrawl effects seemed to have a different form of this 5HT3 receptor than the animals with fewer side effects, prompting the team to speculate that 5HT might be linked to at least some of the classical symptoms associated with drug withdrawal.

To find out they gave the mice doses of the drug ondansetron, which blocks 5HT3 receptors and is used to prevent nausea in patients undergoing chemotherapy.  Administration of the drug to the withdrawing mice produced a dramatic improvement, and since the drug is already licensed for human use, the team conducted a simple trial on humans volunteers.  Similar to the mice, 8 subjects received either ondansetron or a placebo before being treated with morphine and then put into withdrawal using naloxone.

Predictably, those given ondansetron first reported far fewer unpleasant withdrawal effects compared with their placebo-treated counterparts.  The researchers are pleased with the result, but caution that the drug isn't a panacea and addiction is a hard nut to crack.  At the same time, the findings offer encouragement that other receptor-systems responsible for the effects of physical addiction, which compel addicts to continue using drugs, will be found so that more effective treatments can be developed.

Fattysaurus rex

We usually think of dinosaurs as huge great beasts, roaring about and generally being terrifying.  Now researchers at the University of Manchester have used laser imaging to reveal whether our favourite prehistoric beasts were trim and fit, or big old fattysauruses.

Tyrannosaurus rexWriting in the journal PLoS One, Karl Bates and his team used laser imaging and 3-D reconstruction techniques to recreate the bodies of five dinosaurs of differing sizes as they might have appeared in real life.  They looked at two Tyrannosaurus rexes, an Acrocanthosaurus atokensis, a Strutiomimum sedens and an Edmontosaurus annectens.  Their results suggest that the smaller of the two T. rexes could have weighed anywhere between 5.5 and 7 metric tonnes, while the larger one might have weighed in at 8 tonnes.

They also think that Acrocanthosaurus atokensis, a big predator similar to T. Rex weighed around 6 tonnes, but the ostrich-like Strutiomimum was probably a weeny 04-0.6 tonnes, while Edmontosaurus weighed in at just under a tonne.

To get their reconstructions, the researchers used a laser scanning technique called LIDAR to image each dinosaur's skeleton.  They then used and computer modelling methods that can create a high-resolution 3-dimensional computer image of the skeleton, which they can use to investigate the potential mass of the living dinosaur, its internal organs, and its movements.

After making these reconstructions, the team then tweaked the sizes of the body parts and organs to find the maximum and minimum masses that the animals might have been.   Although we'll never be able to know exactly how fat or thin they were, this analysis tells us the range of possible body masses that are physically possible.  And because of the lack of cakes and telly in prehistoric times, the researchers think that the dinos probably come in at the lower end of heir predicted weight ranges, as there's no biological need for them to be fatties, as this would slow them down, making them less effective predators, or easy prey.

To demonstrate the accuracy of their models, the researchers applied their techniques to a modern-day ostrich skeleton, and found that their predicted mass measured up pretty well against the living bird.

The next steps - literally - for the researchers will be to use their models to make predictions about how the dinosaurs walked and ran, which will tell us more about their lives and evolution.

12:34 - Meningitis in Disguise

The bacterium Neisseria meningitidis, which is behind the most common form of meningitis, actually wears a disguise to stop itself from being detected by our immune system. Professor Susan Lea explains more...

Meningitis in Disguise
Professor Susan Lea, Oxford University

Chris - Professor Susan Lea has a paper in the journal Nature this week, explaining how the bacteria do this and manage to hide themselves.  Susan, how do they disguise themselves?

Purpura spotsSusan - Hi, Chris.  Well the work came to us in a problem that was brought by Chris Tang at Imperial College.  He'd been working with meningitis for many years, looking at the bacteria and trying to understand them in more detail, trying to generate therapeutics.  They'd noticed a couple of years ago that the bacteria somehow managed to mark themselves as human cells by coating themselves in a protein that circulates in our own blood, called factor H.  This protein is a very important part of how we regulate our own immune response in that we've got one arm of our immune system that essentially seeks to destroy anything it comes into contact with in the blood.  To protect our cells we develop a series of sugars on our cells that then bind a protein called factor H which turns off this part of the immune system.

Chris - How do the Neisseria meningitidis bacteria exploit that?

Susan - Neisseria can't make the same sugars that we make.  They don't have the machinery to make those sorts of chemicals.  Instead the Neisseria has chosen a different route and manufactures another protein.  Instead it uses this protein to essentially seek out and bind the factor H to coat the bacterium in factor H: the way our own cells have done but by using a very different chemistry underlying the reaction.

Complement factor HChris - Your work has been to discover the structure of that protein to work out how the bacteria grab this protective, this disguise factor H from the blood and then decorate themselves with it?

Susan - Absolutely.  We've worked with Chris to generate the structure of the actual complex between the proteins of the bacteria and the proteins from our cells.  In doing this it allows us to see how the bacteria uses the chemistry of proteins to mimic the chemistry of sugars that we have on our cells.  The interactions are actually very similar.  Some years ago we looked at the structure of sugars binding factor H.  We found the structure of this protein binding factor H mimics the same sorts of interactions that you use in protein-based chemistry rather than sugar-based chemistry.

Chris - And how, now that you've got that structure, will this help us to get a vaccine?  We've had a vaccine for the A strain of meningitis for a long time and that's helped in places like Africa.  We've had the vaccine for strain C which has made a dramatic difference for young people, especially people going to university.  B has always been the big problem.  90% of meningitis cases in Britain are down to group B.  How is this going to help us get a vaccine against this now?

Susan - Essentially the protein we've done the structure of is actually one of the components of the vaccines by both Novartis and Wyeth that are currently in phase through clinical trials are looking quite promising.  We think, from looking at our structure, we predict that  by altering a very small part of the protein we  can make a protein that will no longer bind with factor H and we suspect that  this will make a much better vaccine.  It won't have a large part of its surface covered up my factor H.  When you immunise somebody with the current versions of the vaccine trials that are going on - in fact much of the bacterial protein will be hidden from the immune system because it will be bound to factor H.  You therefore won't get as good an immune response against it as you might otherwise get.  We've made versions of this protein which are more than 98% - 99% identical to the natural form but they no longer can bind factor H.  We think that these will be much better candidates for targets in the vaccine.

23:14 - This Week in Science History - The Descent of Man

This Week in Science history saw, in 1871, the publication of The Descent of Man by Charles Darwin – perhaps not as famous as the Origin of Species, published 12 years earlier, it was still an influential and controversial book...

This Week in Science History - The Descent of Man
Sarah Castor-Perry

This Week in Science history saw, in 1871, the publication of The Descent of Man by Charles Darwin - perhaps not as famous as the Origin of Species, published 12 years earlier, it was still an influential and controversial book.

Cover page of Charles DarwinIn 1871, Queen Victoria was on the throne in Great Britain, photographs were in black and white, travel was by horse drawn carriage or steam train, Lewis Carroll published Through the Looking Glass, the Impressionist art movement was in full swing led by artists like Monet and Cezanne and slavery was abolished in the US during the Reconstruction after the Civil War.

After the publication of the Origin of Species in 1859, Darwin began working on another book that would allow him to discuss further how humans fitted in to his theory of evolution and also try to explain the process of evolution of traits that were purely for increasing success in mating, or 'sexual selection'.

The first part of the Descent of Man, in which he discusses man's place in evolution and his 'descent from some lower form', was the most controversial. Darwin had not intended to publish his writings on this subject, but as more 'young naturalists' showed enthusiasm for his theory, he felt he should see how far his 'general conclusions' on natural selection applied to man.

It is now accepted by most people that we are closely related to apes less closely related to other mammals, and even less to other vertebrates, other multi-celled organisms and so on, but this understanding has developed with over 130 years of research since the Descent of Man was published.  We have modern DNA evidence that Darwin did not, but a lot of the anatomical evidence that he presents is still relevant to comparisons today. Woodcut depicting the similar appearance of a human embryo (top) and a dog embryo (bottom), from Charles Darwin's Descent of Man (1871).Darwin suggests that the similarity of human embryos to those of other mammals, and the anatomical similarity of humans and apes, down to the fact that we can suffer from the same infectious diseases with similar symptoms, is strong evidence in favour of man being descended from other animals, not specially created.

In the book, Darwin also makes the comparison of mental characteristics such as tool use, altruism and kindness in humans, apes, monkeys and dogs, concluding that ' the difference in mind, great as it is, certainly is one of degree and not kind'. The idea that our mental abilities and moral ideas were merely one level on a scale that also included animals was abhorrent to many, and the debate over intelligence in animals is still going on today.

The question of whether natural selection is still acting on humans is one that Darwin and many of his contemporaries discussed, and in fact is still asked today - David Attenborough, for example, believes that humans have probably stopped evolving.

The provision of medicine, aid and asylums for the poor or sick seemed to Darwin to 'check the process of elimination' by natural selection, allowing these weaker members of society to breed. Although Darwin suggested that this might be bad for the evolution of the human race as a whole, neither he nor his cousin Galton, who argued in favour of eugenics and social Darwinism, would ever have supported the ends to which these ideas were put to by the Nazis and others in the 20th century.

Sir Francis GaltonThe second half of the book is a detailed collection of evidence for sexual selection - the idea that a characteristic might evolve because it gives greater success in mating rather than greater survival.  Darwin suggested that sexual selection could occur by two routes - through competition between members of the same sex for mates (leading to weapons such as horns and antlers), and through mate choice (leading to elaborate plumage or colouration in males to attract females).

We now know that there is a third way sexual selection can lead to the evolution of characteristics- male-female conflict, which can lead to deceptive behaviour to make your mate stick around to help rear young.

In 2009, we're celebrating 200 years since Darwin's birth and 150 years since the publication of the Origin of Species, but this second major work by the great naturalist also deserves recognition. It was a collation of a huge amount of information on sexual selection from mammals and birds to fish and insects, and also an in-depth view on the controversial debate over man's place in evolution from one of the greatest scientific minds of the age.

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