Venoms and Toxins - Natures Arsenal

05 August 2007
Presented by Chris Smith, Kat Arney.

This week, mind reading children, scientists find a new gene in the lung cancer cocktail, and satnav or map-nav - what's greener? Plus we become biological weapons inspectors and explore nature's arsenal of venoms, poisons and toxins, including a scorpion's sting that can highlight cancer, how funnel web spiders are helping farmers fight off insect pests, the marine cone snail that harbours a painkiller ten thousand times more powerful than morphine, and how a snake bite can help to prevent a heart attack. Meanwhile, in Kitchen Science, Ben samples a more everyday toxin - by making stinging nettle tea.

In this episode

Can your kids read your mind?

As a new dad, Dr Chris may feel like his baby can read his mind. And now researchers in Italy have shown that he may actually be right.

One of the unique characteristics that makes us human is our ability to "mind-read", or represent in our own heads what someone else might be thinking. Experts think that this is at the heart of human understanding and communication. But nobody really knows at what point in life we develop this ability - some people think we acquire it around 3-4 years of age, while others argue that babies have the ability from birth.

Luca Surian, a psychologist at the University of Trento in Italy, and his colleagues have just published a paper in the journal Psychological Science showing that 13-month-old babies are able to "read our minds", and figure out what someone else is thinking.

The scientists made the babies watch an animation of a caterpillar searching for either an apple - the caterpillar's dinner of choice or cheese hidden behind two screens. In some scenes, the caterpillar could see a human hand pointing to the apple, but in other scenes there was no such clue. The caterpillar was either successful finding their preferred food, or went to the wrong screen.

When the animation showed the caterpillar doing the "wrong thing" - going to the other screen even when a hand was pointing to the right one, the babies tended to stare at the animation for longer. The scientists conclude that this means the babies were puzzled about the caterpillar's actions.

They suggest that even at this young age, babies have the capacity to predict how others might behave in response to the available information - effectively "mind reading", however simple. So watch out next time your baby stares at you with a puzzled look - they might be reading your mind!

Satnav receives environmental thumbs up

What's best for the environment, a well thumbed map and some common sense, or a satnav? To find out, Tiawanese researchers Wen-Chen Lee and Bar-Wen Cheng from the National Yunlin University of Science and Technology recruited 32 drivers and asked them to navigate to a series of pre-determined locations; half of them were asked to get there by satnav, the other half had to use a map. The team monitored the progress of the drivers and clocked the distances they travelled. In all cases the Satnav triumphed. On urban routes journeys were on average 7% shorter than when the driver followed a map, and even in the open country routes remained 2% shorter. Since shorter trips on average use less fuel, they are more enviromentally friendly. But satnav may also improve driving safety, Lee points out, because the map users consistently changed course more times per journey than their satnav-guided colleagues. More course changes can be a sign of frustration, which can lead to dangerous driving.

Key gene in lung cancer cocktail

Lung cancer has a very poor survival rate, which is often due to the fact that the disease isn't diagnosed until it has spread around the body, making treatment difficult. Now a team of researchers in the US have found that faults in a gene called LKB1 may be responsible for causing lung cancer cells to spread aggressively.

In experiments published in the journal Nature this week, the scientists took some mice carrying faults in genes that are known to increase the development of cancers, and bred them with mice carrying faults in LKB1. These double-fault mice developed highly aggressive lung tumours that quickly spread.

In healthy cells, LKB1 acts to protect us from cancer - it's a type of gene known as a tumour suppressor. In order for cancer to develop, cells need to pick up faults in several different genes - a bit like mixing a cocktail of genetic mistakes. But it seems that faults in LKB1 act like the "vodka in the cocktail", causing the cancer to spread.

Although it's still very early days, the researchers hope that their research may help to shed light on what makes some lung cancers grow so aggressively. The new mice they have created are a good model for human lung cancer, and will help to accelerate research into urgently-needed cures.

It is also possible that LKB1 may become a future drug target, if scientists can find some way to reactivate its function. And it could also be used as a prognostic tool - to predict how a person's cancer might progress, or how best to treat them. The team is now carrying out experiments to test this idea in cancer patients. But work like this needs to go hand in hand with better ways to pick up lung cancer at an earlier stage.

Of course, we don't need to tell you that the best way to avoid lung cancer is to quit smoking - a habit that causes more that 9 out of ten cases of lung cancer in the UK.

A rash of new anti-HIV drugs

A cluster of new anti-AIDS drugs are expected to be approved for general use later this year, giving hope to patients who have developed drug-resistant forms of the virus. This is because the new agents hit different parts of the virus compared with existing anti-HIV drugs, which means that there should be very little initial drug-resistance. The new agents include two "fusion inhibitors", maraviroc, made by Pfizer, and vicrivoroc, which has been developed by Schering Plough. These drugs block the ability of HIV to lock onto a molecule on the cell surface called CCR5, which the virus needs in order to penetrate and infect. The other agent, raltegravir, is made by Merck. It locks onto a viral protein called integrase and prevents it from inserting a copy of its genetic material into the host DNA, which is a critical step in the viral lifecycle. When both of these approaches have been combined (a fusion inhibitor given together with the integrase inhibitor), in patients with drug-resistant disease, the viral load in the bloodstream fell to undetectable levels, indicating good disease control.

Why are there so many chemicals in cigarettes?

The main thing that smokers are addicted to is nicotine, which is a drug that your brain starts to crave after you've been exposed to it. There's more than 4000 chemicals in cigarettes, and they come from a variety of sources. Some of them are in the tobacco plant itself, absorbed from the air by the plants including chemicals such as polonium. Some chemicals are produced when the tobacco is processed, some are added in when cigarettes are made. The most dangerous chemicals in tobacco are actually created when you burn a cigarette; the chemicals of burning are produced by the act of lighting a cigarette and inhaling something that is burning.There are a few extra chemicals added during the process of making a cigarette, and so smoking straight tobacco would lack these, but the important chemicals are created by the simple act of burning the tobacco.A lot more information is available from Cancer Research UK's smoke is poison campaign, www.smokeispoison.com.

What are the main components and causes of household dust?

Dust is mainly human skin cells. The average person loses between 50-100 thousand skin cells every minute. Those flakes of skin accumulate in carpets and furnishings, dry out and then are lifted into the air by drafts or air currents.Because dust mainly consists of skin cells, it's nutritious and there are some things that will eat it. House dust mites are a microscopic organism which eat these skin cells -asthma sufferers are often allergic to their poo, which is carried into the air, and can irritate the lungs.

17:01 - Scorpion's Sting Help Fight Cancer

Jim Olsen and his team from the Fred Hutchinson Cancer Research Centre in Seattle have found a way to use scorpion venom to make a ‘paint’ which shows up cancer cells. This means that...

Scorpion's Sting Help Fight Cancer
with Jim Olsen, Fred Hutchinson Cancer Research Centre

Jim Olsen and his team from the Fred Hutchinson Cancer Research Centre in Seattle have found a way to use scorpion venom to make a 'paint' which shows up cancer cells.  This means that surgeons can be more certain that they are taking out an entire tumour, which can limit the damage to healthy tissue.

Chris -   Tell us about your technique, how does it work?

Jim -   We took a peptide which comes from scorpion venom, called chlorotoxin, and we linked it to a molecule called Cy5.5 which is a little molecular beacon; it lights up.  The scorpion toxin binds to cancer cells, but not to normal cells, so our idea was to inject this into the veins of a mouse that has cancer and see whether or not the chlorotoxin could carry the molecular beacon to the cancer cells and make them glow.  Indeed, when we inject mice that have tumours and wait about a day or two, we can put the mice under a camera that picks up near-infrared light, the type emitted by the molecular beacon, and it's really easy to see the tumour compared to the normal brain around it.

Kat -   So you can see the tumour even inside a mouse?

Jim -   The light waves that are emitted by the molecule that we made have a very short path length.  This is developed mainly for surgeons who want to see whether they got all of the cancer while they were doing their operation.  So the point is that the whole tumour when they open up the cavity will be glowing, and then as they take more and more of it out, the pieces that are still glowing are where the cancer is left behind.

Kat -   And how sensitive is this technique? Part of the problem with cancer is it only takes a few cells to start the cancer growing again.

Jim -   Well that was one of the big surprises of our study; we initially started working on this for brain cancer, and when we tested it on other models such as prostate cancer and colon cancer we found that it was sensitive for picking up these kinds of cancer as well. In one case we had an instance where it picked up a cancer as small as 2000 cells, and that's 5000 times more sensitive than an MRI.

Kat -   That's really tiny.  Tell us a bit more about this toxin, this chlorotoxin, how does it recognise cancer cells and not target healthy cells?

Jim -   We believe that it's binding to a component of the matrix metaloproteinase-2 complex, and in easy to understand terms the matrix metaloproteinase-2 complex is what cancer cells use to eat away normal tissue to make space for the cancer to grow.  For that reason this complex is expressed in cancer cells but not in normal tissue.

Kat -   And do you think that this paint might also be useful for spotting cancers that have spread throughout the body, or is the wavelength not strong enough to get it out of the body again?

Jim -   Well, in some cases yes.  For example, if a person has breast, prostate or testicular cancer and the surgeons have the cavity open, and they're interested in seeing whether the lymph nodes are involved, the wavelength is long enough that they would be able to see whether the lymph nodes are involved.  You really couldn't do that in a scan, and be able to see things that deep in the body.  We're really talking about superficial cancers or cancers that are surgically open.

Kat -   So what's the next step for this?  Are you going to start testing in patients soon?

Jim -   Yeah, there are two directions that we're going.  One is to test it in patients and we're working with a company in Cambridge, Massachusetts, to advance this as quickly as possible to human clinical trials.  Because this company has already brought cholortoxin into humans there's a lot of safety data already available and we think we could be in clinical trials within 18-24 months.  The other direction we're going with this is to see whether it could be used as a cancer screening method, so for example people who are at risk for skin cancer, would they be able to take a dose of this tracer and then go to their dermatologist and have a scan to see which moles or which areas of their skin should be biopsied.  So we're thinking about that for the more superficial cancers, like skin cancer or colon cancer.

Chris -   Jim, just to finish off, are you confident that this scorpion venom based marker will bind to all kinds of cancer cells? One of the things we've learned about cancer is that they're a very heterogeneous cell population, there are stem cells in there, there are mature cancer cells.  Will it bind to everything, or are we going to miss some cells?

Jim -   So far we've tested it in six different kinds of cancer, and it has lit up all of those tumours.  Within an individual tumour, it looks as though in certain types of cancer it's lighting up almost every cell, and in others there are some cells that are lighting up and some that are not.  But they are so intermixed that at the level of surgery the ones that are not lighting up are entangled with the ones that are lighting up, so you can take that whole group of cells.

22:56 - Science Update - Sea Levels and Foxy Foxes

This week, Susanne and Bob look into the sex lives of Arctic Foxes and the effect of melting Polar ice sheets.

Science Update - Sea Levels and Foxy Foxes
with Susanne Bard & Bob Hirshon, AAAS

Bob -   This week for The Naked Scientists we're going to talk about why melting polar ice sheets may not be the biggest contributor to a sea level rise in response to global warming.  But before we get too serious, our new Science Update reporter Susanne Bard's going to tell you about how some foxes are mixing it up in the high arctic.

Susanne -   In foxes, wolves and coyotes, males and females often share the parental duties, bringing in food and protecting the young.  And for many years, researchers thought these species were monogamous.  But a recent study of arctic foxes on Bylot (Bye-Let) Island in Canada suggests otherwise.  University of Alberta biologist Lindsey Carmichael and her colleagues took DNA samples from 49 arctic foxes.  Carmichael analyzed the DNA fingerprints of the babies and found that some of the furry canines had different fathers from their siblings. 

Lindsey Carmichael (University of Alberta) -  What we found was that in 75% of dens the foxes were monogamous but in the other 25%, they were not.

Susanne -   Carmichael thinks that increasing the genetic diversity of a mother's litter in any given year could improve the odds that one or more of her pups will survive.

Bob -   Thanks, Susanne.  On a more serious note, we know that sea levels are rising because of global warming.  If they rise by just a few feet, it could devastate or even submerge coastal cities.  The best-known contributor is the melting polar ice sheets.  But according to a study by University of Colorado geological scientist Mark Meier and his colleagues, 60 percent of the world's ice melt actually comes from glaciers and smaller ice caps scattered across the globe.

Mark Meier  (University of Colorado)  -  And we also project to the future that this contribution will be greater than that of the ice sheets, at least to the end of this century.

Bob -   He adds that glaciers and ice caps melt faster than polar ice sheets, because they're smaller.  And what's more, melting ice can lubricate glacier beds so they slide more quickly into the sea. 

Susanne -   Thanks, Bob. We'll be back next week with more amazing science from across the pond.  Until then, I'm Susanne Bard...

Bob -   ...and I'm Bob Hirshon, for AAAS, The Science Society. Back to you, Naked Scientists!

25:13 - Deadly Snails Kill Pain

Chris talks to Dr Bruce Livett about using the venom of cone shells to cure pain.

Deadly Snails Kill Pain
with Bruce Livett, University of Melbourne

Bruce -   What I've been doing is exploring the potential of animals that live in the great barrier reef for production of novel painkillers.

Chris - Specifically what are you been looking at?

Bruce - Well we've been looking at venomous cone shells. These creatures developed just after the death of the dinosaurs and in the 500 million years since, they've developed a very sophisticated venom apparatus. They go out each night and they hunt down their prey. They do this by injecting them with a cocktail of very small molecules called peptides that make up the venom. One of those peptides is of particular importance to us, because its a very potent analgesic and we hope the develop this for the treatment of some very painful conditions, like neuropathic pain. That's the kind of pain you would have if you were to lose a limb-you may have heard of phantom limb syndrome? Where people have had an accident, lost a a limb, can't get to sleep at night because of the pain in their so-called phantom limb, which is very real to them. Another really painful condition, which happens mainly in older people, is shingles. Once again a very painful condition and a large unmet need with existing medicines not being very good at curing the pain.

Chris -   How does the cone shell actually use this? Why does it actually want to use a painkiller to kill something?

Bruce -   Well I think it perhaps doesn't need the painkiller, but it uses something like 200 other components in the venom. It uses these components to put its animal to sleep. That means the animal is not going to thrash around and they can eat it quite quietly without it feeling apprehensive, and maybe thats where the painkiller come in.

Chris -   What do these shells actually look like then and how do they catch things?

Bruce -   Well they're very pretty. There are over 500 different varieties of cone shell and they've been collectors pieces for hundreds of years. In fact, everybody in the 1600's who had a curiosity cabinet where they kept biological specimens wanted a cone shell. They were highly prized because they came mainly from the Indo-Pacific region and that meant they were quite expensive to buy. In fact, some of these cone shells sold at auction in the Hague for more than a Vermeer painting. These day, you can still pay up to $1000 for a very rare cone shell, but mostly you can get a very good collection, such as the one I have behind me, for 5 to 10 dollars a piece.

Chris -   But how do they actually catch stuff? How do they use this amazing example of overkill, these toxins, to catch things?

Bruce -   It's amazing that they need this overkill. I mean one of the toxins would probably serve the purpose well. I think the variety of toxins is there because their prey changes and they have to adapt their venom to the prey. So they make thus suite of toxins in the hope that one of them will kill their prey. Cone shells are marine snails, so like a garden snail, they're pretty slow moving and they need some benefits. What they do is they lay and wait, then put this long tongue out of their mouth, called a proboscis, and on the end of the tongue they've loaded it up with a modified, hollow, tooth, called a Radula. That tooth is stuffed full of venom, and they actually make a whole quiver of these arrows, harpoons if you like, they make the in one of the sacs in their internal digestive system, and they move them into an adjacent sac. They put their tongue back and pick up, with the muscular end of the tongue, they pick up one of these arrows stuffed full of venom and then they impale their victim with this. Now the victim, it depends on the kind of cone snail involved, but there are basically three kinds of victim. There are 'fish', some of these cone snails hunt fish, and they're the ones that are dangerous to us. There are 'others', the majority of them hunt marine worms, and then there's still another group that hunt other molluscs.

Chris -   Say I was to go near one and it stuck one of these things in my foot, what would I notice then?

Bruce -   Well if it was the kind that hunt fish, you could be in trouble. There have been thirty deaths from cone shell in envenomation worldwide and there's no antidote to it. The first hint that you would have would be that you would have blurred vision, and then your respiration starts to slow and then you would die from asphyxia up to 7-9 hours later. The things that interested us was, in the descriptions of such envenomations, that they said the patient dies a painless death. So I thought, I know what kills the person, but what is component there that acts as an analgesic? We went out on purpose  to look for the analgesic component.

Chris -   Have you tracked it down?

Bruce - Yeah, there are actually a number of different components but the one that we tracked down we got from a cone shell from Broome, in Western Australia. Conus Victorii  its name is. Named after Queen Victoria but in fact its not in the state of Victoria, its in western Australia. This component is a small peptide of 16 amino acids and that acts as a very potent analgesic between 1000 and 10,000 more portent than morphine.

Chris -   How do you know its going to work in us?

Bruce -   We don't. We know that it works in animal models of pain and we're current in phase 2 clinical trials, testing it on people who have painful sciatica. The results of those studies will be known mid-year. At this stage everything is coded, so the patients don't know if they're receiving a placebo or the real drug. And the results will be analysed and well the results will tell us if it's going to be an effective medicine or not. We've got out fingers crossed, as you can see I've got both fingers crossed and my legs crossed.  We're hoping for a good result because there's really a big unmet need of patients for whom conventional analgesics are not working and they need something else. We hope that the cone shell has the solution to their problems.

33:23 - Snakes - Venom, Antivenom and Medicinal Uses

We spoke to Gavin Laing, of the Liverpool School of Tropical Medicne, about why snake venom is so potent, how we could use it as medicine and how to make antivenom for those who do get...

Snakes - Venom, Antivenom and Medicinal Uses
with Gavin Laing, Liverpool School of Tropical Medicine

Chris -   Snake venom, we're lucky in this country in that we've only got one poisonous snake, Ireland and New Zealand don't have any!  But why do snakes produce this venom and how does it work?

Gavin -   Snakes, over millions and millions of years have evolved a very complex array, like an arsenal, in order to defend themselves or immobilise their prey before eating it.  We're only just discovering the complexity of a lot of the venoms present in certain snakes because they seem to have a very specific role; either they can immobilise by inhibiting the action of the nerves or they can immobilise by causing a complete thrombosis of the haemostatic system.

Chris -   But snakes don't need to bite us do they?  If you look at cobras they spit venom in people's eyes.  Is that effective or do they do that to blind you and then come in to bite?

Gavin -   Spitting cobras have this wonderful adaptation where they have holes in the front of their fangs, so you can get a plume, like an aerosol plume of snake venom, and if you get it in your eyes you can get a chemical conjunctivitis.  It's very painful but it won't envenom you in that way, the reaction is purely local.  These spitting cobras can also bit with these fangs and can immobilise because the venom is neurotoxic, can paralyse a patient in the worst case scenario.

Chris -   You don't seem to need much venom to see a pretty bug effect on a person who gets bitten.

Gavin -   That is true, the most toxic of the venoms is probably the inland Taipan of Australia.  It's got a very low LD 50, which is the standardised unit of lethality.  You 're right, you only need a very small amount of circulating snake venom in order to cause a huge disturbance in you, and if you survive you can become a cripple for the rest of your life if it's left untreated.

Chris -   I've got an email here from Arjan Hoek, who's listening from Delft in the Netherlands and he says:  "I think your show is one of the best podcasts in the world" (That's his opinion, of course.)  "When I heard that you were going to talk about venoms and toxins on this week's show I was wondering how you produce antivenom?"

Gavin -   Okay, antivenom has been around for at least 100 years, but the techniques of producing antivenom have not really altered a lot in that time.  What normally happens is a very large animal is immunised over a long time with very small amounts of snake venom, so it won't harm the animal; traditionally they have used horses.

Chris -   So what you would do is milk the snake, get some of its venom and then inject that into the horse.

Gavin -   Yes, in very small quantities, so the horse will not be affected at all, it's only a tiny amount.  The horse will then raise antibodies against this antigen that's been injected in the same way that humans immunised with smallpox would be raising antibodies against that.

Chris -   So the horse gets antibodies in the bloodstream.

Gavin -   That's correct, and over a long period of time, say eight months or so, the horse will then become hyper-immune.  Every so often, some serum is then drawn from the horse and immunoglobulins are purified from that, and from that you can split the immunoglobulins into smaller components such as the FAB or the FAB prime-2.  And these would then be infused intravenously to a person who presents themselves in hospital who has been envenomed.

Chris -   And so the antibodies would, in that victim, lock on to the venom and neutralise it?

Gavin -   They would.  They would seek out the circulating venom in the patient and immobilise it.  They would form an immune complex and would be completely harmless and would then be flushed away normally.

Chris -   Just to finish off then Gavin, you are also using the way in which these venoms work in people for clues about the way in which our own bodies work.  What have you flushed out from doing that and how does that process work?

Gavin -   Well there's a lot of proteins that have been isolated from snake venoms that have been seen as very useful over the years.  Particularly in our kind of work, we've isolated proteins that have inhibited or activated platelets.  Now these are very important in clotting and we've seen various signalling events that happen in the course of activation and inhibition of platelets.  These could be perhaps exploited as a therapeutic targets which could be explored in the future, if only we had far more research income or pharmaceutical companies could pick up on this.

Chris -   So better ways to make the blood not clot in people who have clotting illnesses such as heart attacks, strokes, or other hypercoagulable disorders.

How do you make anti-venoms?

We put this question to Gavin Laing, of the Liverpool School of Tropical Medicine:Okay, antivenom has been around for at least 100 years, but the techniques of producing antivenom have not really altered a lot in that time. What normally happens is a very large animal is immunised over a long time with very small amounts of snake venom, so it won't harm the animal; traditionally they have used horses.Chris: So what you would do is milk the snake, get some of its venom and then inject that into the horse.Gavin: Yes, in very small quantities, so the horse will not be affected at all, it's only a tiny amount. The horse will then raise antibodies against this antigen that's been injected in the same way that humans immunised with smallpox would be raising antibodies against that.Chris: So the horse gets antibodies in the bloodstream.Gavin: That's correct, and over a long period of time, say eight months or so, the horse will then become hyper-immune. Every so often, some serum is then drawn from the horse and immunoglobulins are purified from that, and from that you can split the immunoglobulins into smaller components such as the FAB or the FAB prime-2. And these would then be infused intravenously to a person who presents themselves in hospital who has been envenomed.Chris: And so the antibodies would, in that victim, lock on to the venom and neutralise it?Gavin: They would. They would seek out the circulating venom in the patient and immobilise it. They would form an immune complex and would be completely harmless and would then be flushed away normally.You can read the whole interview with Gavin here, or listen to it as part of the podcast.

39:13 - Spider Venom on Apples - Natural Insecticides

Robyn Williams, from ABC Radio National's 'The Science Show' speaks to Glenn King about finding natural alternatives for insecticides - in the venom of deadly spiders!

Spider Venom on Apples - Natural Insecticides
with Glenn King, University of Queensland

Robyn Williams -   Hello, I'm Robyn Williams, presenter of The Science Show on ABC Radio in Australia. It's a program similar to The Naked Scientists, but they don't let me go naked. But enough of me!  Scientists in many areas are looking to the natural world for solutions to problems which in some cases have been solved already. An example is the area of insecticides.  Spiders have been making molecules which kill insects for hundreds of millions of years. So why not isolate and copy these powerful molecules?  This is the work of Glenn King at the University of Queensland...

Glenn King - We started thinking about this about ten years ago, and we thought, well, where could one look for molecules that would kill insects? And we decided that the best insect killers on the planet were spiders, and we figured that if anyone would get away with killing insects it had to spiders since they'd been working on it for around about 400 million years, you'd figure they'd have probably come up with a solution or two by now. And so we started looking in their venom. I think most people have a fairly poor appreciation, at least non-scientists, of what venom is.

Going into this project I mistakenly thought that spider venom might contain 10, 20, a few dozen compounds, but it turns out to be an incredible chemical cocktail of hundreds and hundreds of different components. Our job was to pick through and try and find the ones that just killed insects and had no toxicity to vertebrates. So even though some of the spiders we work with are toxic to humans, it's just one of those thousand or so compounds in there that's toxic to humans and many of the others are completely harmless, and of course they're the ones we're really interested in.

Robyn Williams - Yes, it's bad enough with all the substances in the venom, but which spiders?

Glenn King - We chose the Australian funnel-web spider, which may sound like an odd choice given it is one of the four deadly spiders in the world. Again, I should put this in context that there are about 40,000 characterised spiders now, there's a website you can go to and look up all the names of them all, and of those 40,000 there are only four families of spiders that are potentially lethal to humans; that's our own funnel-web spider, the red back spider, the recluse spider in North America and the Brazilian armed spider in Brazil. All other spiders are completely harmless. They might give you a nasty bite but they're not going to kill you. So what that tells you of these thousands of compounds in these tens of thousands of spiders, most of them are going to kill insects and be harmless to vertebrates.

A group at Deakin Research led by Merlin Howden about ten years ago had looked at a whole bunch of Australian spider venoms and said; which one of those is best at killing a really refractory agricultural pest, the cotton bole worm, which most people have probably heard of. It turned out funnel-web spider venom was the best, and so we knew there were good compounds in there and that was the reason we chose that spider.

Robyn Williams - Narrowing it down from all the hundreds of ingredients, how did you do that?

Glenn King - We have to fractionate out...we use a process called chromatography. It turns out that that process is not enough to fractionate out what we now know are 500 to 1,000 compounds. So what we've done now is gone back and made DNA libraries from the venom glands so we can look at the DNA and sequence the whole profile of all the compounds that are in there, and then we just make those compounds in bacteria and test them individually. And so from these 1,000 or so compounds we've narrowed it down to only 10 or 20 that we're really interested in.

Robyn Williams - And what did you do with that 10 or 20? Get insects and do a trial run, see how they react?

Glenn King - We did, and the good thing is you don't need ethics approval to kill insects, which makes the process a lot easier.

Robyn Williams - It will come!

Glenn King - Yes, probably. We actually usually use house flies or crickets that we can just buy from the pet shop and we inject compounds into those and see what effects they have.

Robyn Williams - And is it effective?

Glenn King - Yes, it is, it's very effective. The compounds that we're using as are as effective as any like compounds that people have purified from other venoms, whether they be scorpions or cone snails or anything else. We were thinking originally that these things are peptides, so they're little tiny proteins, so what we like about them is they're natural compounds. We were concerned initially that these natural compounds weren't going to be orally available to insects, so if they ingested them they'd get broken down in the digestive system of the insects and they wouldn't work. But it turns out that a lot of these are quite potent when insects ingest them, and so we think these natural compounds could be very effective insecticides in their own right.

Robyn Williams - What happens when you actually use these? Because obviously there are some insects which you want to preserve like dragonflies and butterflies and many others, are they selective in that way?

Glenn King - There's some selectivity, and so you may want to choose your particular compound for your particular insect that you're trying to kill. Another way around it is to...because these things are just proteins, they could be used to make genetically modified crops, and then the only insects that would be affected would be anything that preyed on those crops, so that's one way of confining the range of insects that are targeted.

Robyn Williams - And then there's the problem of human sensitivity, I suppose, because whatever you said about insecticide, if I see a wonderful piece of fruit there and I think it's got the residues of spider poison on it...

Glenn King - Yes, and that's certainly an issue we're going to have to deal with in terms of commercialisation and what we're going to have to get people to realise, as I said, is that spiders for the most part are completely harmless to humans and we've injected these things into a whole bunch of different vertebrates and they run around doing what they normally do without any ill-effects. So I agree that's an issue that the marketing people will have to deal with.

Robyn Williams - But the commercialisation, has it reached that far yet? Have you got some sort of spider venom, one that you're offering to companies?

Glenn King - Not yet. So while I was in the United States, from which I just returned recently, we spent at a company from the university I was at based on this research. The application that we're thinking of first of all is for controlling ecto-parasites, and by that I mean fleas, mosquitos and ticks on pets. Insecticides on pets are actually very harmful to young children, and so it would be nice to have something that was more environmentally friendly, or at least that kids were less sensitive to.

Robyn Williams - What about the anopheles mosquito?

Glenn King - Yes, these things are really, really effective against mosquitos. In fact, mosquitos and flies are the things they kill best, and again they're orally active against mosquitos, we've been testing it against one that's really important in Queensland Aedes aegypti which is the dengue vector and carries a number of other nasty diseases. It's very effective against that, and so we think there could be applications in terms of treatment of environmental situations to control mosquitos.

Robyn Williams - I can just imagine a factory full of funnel-webs milked like crazy.

Glenn King - Yes, people often conjure up that image in their mind but the truth of the matter is we make these things in bacteria so we don't even have any funnel-webs in the lab most of the time.

Robyn Williams - Well, that's okay then.  So next time you eat an apple, think of the spiders who kept it in such good condition for you!

46:11 - Kitchen Science: Making Tea from Nettles

Ben finds out how to avoid being stung and make a great cup of tea at the same time.

Kitchen Science: Making Tea from Nettles
with Dr Beverley Glover, University of Cambridge

Ben - Hello and welcome to Kitchen Science. This week we are looking at natures arsenal and we thought that probably the part of natures arsenal you're most likely to come into contact with will be stinging nettles. So I've come to Cambridge University's department of plant sciences to talk to Dr Beverley Glover about exactly what they are. So Beverley, why is it that nettles sting?

Beverley - Well they sting you in order to try to protect themselves. It's a mechanism to stop being eaten by rabbits, by cows, by things that would normally damage a plant out there in the wild.

Ben - What advantage does stinging offer over say just tasting bitter?

Beverley - There are all sorts of different ways plants defend themselves, some taste bitter some make poisonous chemicals, some make cyanide even. And some go about it by having a combination of physical defense, say a sharp hair and a chemical component in it. So they really do put things off and they're very successful as a result.

Ben - So the way a nettle stings is by effectively stabbing you with a really sharp hair and then injecting a bunch of poisons in. What sort of chemicals are they're using?.

Beverley - Well its not a straight stabbing mechanism. The hair is very brittle its got silica in the cell wall. What actually happens is that when you brush against the nettle you break the hair, leaving a sharp edge to the silica wall which scratches you and then the chemicals flow up the hair and into the scratch. It doesn't stab you so much as scratch you. The chemicals it's using are an interesting question, people used to think it was formic acid because the sting feels like the sting you get from an ant or bee and that's formic acid but it turns out it's not. It's a mix of acetylcholine, serotonin and histamine. So it's basically the neurotoxins in there that are hitting a nerve and making it sting.

Ben - So you mention that it's good to defend them from cows and that sort of thing. Are all animals effected equally?

Beverley - I'm not aware of anybody having tested a whole batch of animals but there is some interesting data out there that says that rats aren't that effected by them. They tested some of the chemicals from the nettle sting on cell cultures and while human cell cultures respond by producing various chemicals in response, rat cell cultures were apparently not affected at all. So it seems rats are immune. But certainly if you watch rabbits they'll graze around them and cows will as well.

Ben - So they sting in order to defend themselves, to stop themselves being eaten, but is there actually anything in them worth eating?

Beverley - Yes, very much so. Well all plants are full of sugar because they photosynthesize, but nettles grow in places that have got a lot of phosphate in the soil so thats why they grow round farms and around human habitation. They grow on run-off from agriculture. Phosphates are expensive for plants to acquire, the fact that nettles have got a lot of it in them makes them interesting for most animals to eat. But apparently they are also quite high in Vitamin C and Vitamin A which is why people eat them sometimes. You can make nettle tea and nettle soup and they were apparently used a lot in the Irish potato famine as a standby food source when things got really bad.

Ben - Is there any way to avoid being stung?

Beverley - Well there's lots of different ways. The theory goes that because the hair breaks as you brush against it, then if you actually grab it and press it quite firmly then you'll bend it over and it won't break, won't be able to scratch you and you won't get stung. Another way is to choose your nettle carefully so theres a lot of evidence to say that the frequency of the stinging hairs increases in fields where theres a lot of grazing. If you're looking at a nettle in a field full of cows chances are its pretty spiky but if you go somewhere there aren't many cows or rabbits around the nettles will be less stingy, and so you might actually find it's easier to grab them. In my experience, if you go down to to the base of the stem and actually grab the nettle down near the roots as close to the soil as possible there are very few hairs usually down there as well.

Once you've got your nettle the way then to stop it stinging you is to heat it in some way because heat denatures the chemicals in the sting.

Ben - Fantastic. If you have been stung and its itching and stinging is there anything you can do to stop it?

Beverley - Because one of the chemicals is a histamine then applying/taking an antihistamine will stop the sting happening fairly quickly, but usually it only stings for about 20 minutes so anything to take your mind of it, a nice ice cream or something, will probably do the trick.

Ben - Beverley Glover, thank you very much.

Beverley - It's been a pleasure. Thank you.

_______________________________________________________________________________

Ben - Now, armed with Beverley's advice I'm going to try and make myself a cup of nettle tea without getting stung. I have come somewhere where there's no grazing and that's my own garden. I don't keep rabbits or anything like that. I need to find a nettle and grab it from near the root, just down near the soil there and grab it really hard and pull.....this is a success. I have myself a nettle, I'm going to take it inside and see if I can make some nettle tea.

Ok, I'm on my way into my kitchen now, so the first thing I need to do is to rinse these nettles off. So now that I've got my nettles all rinsed, the next thing I need to do is to cut the leaves off, I don't really want to use the stem in my cup of nettle tea.

Now I'm going to take a hand full of my nettles and put them in my kettle, [Agh!] thats strike one for the nettles. I'll put them in my cup and set the kettle boiling.....

Now while the kettle's boiling, I'd just like to say if you do want to do this at home feel free to try it out, but if you want to you can wear rubber gloves, they will keep you safe from the nettle stings but I thought I'd just give this a go with no protection whatsoever.

The kettle's boiled now so lets pour my tea.....already that smells very plant-like, like a herbal tea. I'm going to leave it to brew for a bit and come back to you later when I'm ready to drink it.

It's now been about 10 minutes, I've let my nettle tea brew and cool down. I'm now going to scoop out all the nettles, I don't want bits of nettles getting stuck in my teeth... There we go, nows its just time to drink it I guess....

(SIP)

Ooh, well it tastes quite good really. A bit like green tea, its got that fresh leafy flavour but its a bit more bitter and I've actually heard that if you add lemon to nettle tea it will change colour, a bit like a pH indicator, but I think I will save that for a different kitchen science.

So there we go, you can make your own nettle tea and you can avoid, almost avoid, being stung if you follow some simple rules:

1. Try and find your nettles in a place where there's little grazing so the nettles have developed fewer stings.

2. Grab the nettles firmly so you just push the spikes away instead of breaking them into your skin.

3. Try and grab them at the base where there should be fewer spikes.

4. Heat them up. It's the heating stage that's really important as it denatures some of the proteins in the poison, it denatures the proteins that makes those spikes so it stops the nettles from being able to inject that into you.

54:04 - Octopus Arm Control?

How does an Octopus keep track of all eight arms? Does it have one brain for each arm?

Octopus Arm Control?

We put this question to professor Scott Hooper, of the University of Ohio

A 2001 article in Science by Sumbre, Gutfreund, Fiorito, Flash, and Hochner has the answer. Octopus arms contain a very large number of neurons. To show that these neurons generate arm movements, Sumbre and her co-workers amputated octopus arms and then electrically stimulated nerves in the arms that normally carry information to the arms from the brain. This stimulation induced normal arm movement and, importantly, in many cases the movements did not begin until after the stimulation had ended. These experiments thus showed that signals from the brain trigger arm movements (they give the command to move), but it is the peripheral nervous systems (one in each arm) that calculate how to actually make the movements.This is clearly a very efficient way to do things, because it means the brain can concentrate on the environment and responding to it, not on boring calculations about what muscles to activate. This same efficiency is present in human nervous systems. When we walk, it is spinal neural networks, not the brain, that calculate in what order and how strongly the leg muscles need to be activated to produce walking. The higher parts of the brain are thus free to do other things such as looking for predators, thinking, and talking on radios.

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