Combating Cancer

A large coal-fired power station can pump out up to one hundred thousand of tonnes of carbon dioxide per day, making it hard for countries like the UK to meet their obligations to cut greenhouse gas emissions.

There are ways to remove or scrub CO2 from what goes up the chimney, but they're very expensive to operate.

Now a research team in America have come up with a way to make this scrubbing process much more economical. They've found a bacterium that makes an enzyme, which is a kind of biological catalyst, that can turn carbon dioxide into a soluble chemical called bicarbonate.

By introducing random changes - or mutations - into the genetic instructions that tell the bacteria how to make the enzyme, they've been able to come up with a new super-powerful version of it, that might save us millions on our power bills.

Science writer Mark Peplow spoke with Naked Scientist Chris Smith about what this enzyme can do...

Mark -  It's called carbonic anhydrase.  This is an enzyme that's normally found in your body where it helps to transport carbon dioxide out of your tissue.  It does this by combining carbon dioxide with water to make soluble bicarbonates and a hydrogen ion.  Now enzymes are proteins and they'd normally be destroyed at the high temperatures and the harsh conditions that are normally used in carbon capture systems.  Just think about what happens when you put an egg in a frying pan.  The albumin in the egg white gets completely broken down and it goes solid and white and rubbery.

Chris -  So, when you would be applying this technology, you're saying that this enzyme would have to tolerate the flue gases coming out of a power station or something.  So, this can be really high temperatures.

Mark -  Well, that's right.  So, what happens normally when people are trying to set carbon capture systems on a fossil fuel power plant, it uses special solvents called amines.  They grab hold of carbon dioxide molecules before they fly up the chimney.  You then pipe the solvent away, carrying the carbon dioxide and you heat it up to release the carbon dioxide into a storage container so that it doesn't escape.  The solvent then gets cooled down and cycled around to do the same job again.  The trouble is that all this heating and cooling, and the equipment that you need to do it is really expensive and it potentially adds hundreds of millions of pounds to the cost of a powerplant which makes the electricity more expensive and it reduces the plant's power output as well.  That's been a huge barrier to widespread use of this system.  This is where the carbonic anhydrase comes in because it can help to capture the carbon dioxide and make this process much more efficient.  The trouble is that in the past, enzymes, because of their sensitivity, couldn't stand up to the hundred degree conditions and harsh alkaline conditions, of this heating and cooling of the amine solvent.

Chris -  So, where did these American researchers come by this super enzyme?  How did they make it?

Mark -  Well, they got have a bacterium and then they introduced random mutations into the enzyme to see if they could make it tougher in a process that's called directed evolution.  So, you get lots of the random mutations and...

Chris -  These are genetic changes aren't they?  You're adapting the DNA of the organism just by making mistakes if you like, spelling mistakes in the DNA.

Mark -  Yeah, you make deliberate spelling mistakes in the DNA and lots of different types of mistakes.  That gives you a whole pot of new mutated enzymes.  Most of them are rubbish but a few will be a bit tougher.  They did nine rounds of this directed evolution and each round, they picked the toughest enzyme that they got at each stage and then they made more mutations to that particular enzyme.  In all, it meant that they tested more than 27,000 different mutated enzymes.  At the end of that process, they end up with one which is the superman of all of these enzymes and it can withstand more than 100 degrees of temperature and a pH greater than 10, so that's almost as alkali as household bleach.

Chris -  That's almost the enzyme equivalent of the indestructible or invincible man, isn't it?  I mean, really, really tough.  So, have they actually got evidence that this can work?

Mark -  Well, this is the exciting thing about this paper which came out this week in the proceedings of the National Academy of Sciences.  They haven't just done this in the lab.  They tested this enzyme in a pilot carbon capture unit attached to a coal-fired plant.  They found that it improved the carbon dioxide absorption of the amine solvent system by 25 times.  It allowed it to remove about 60% to 70% of all the carbon dioxide from the plant's waste stream and they ran it for about 6 days with no loss in performance at all.  So clearly, the enzyme is working and it's really robust.  This faster absorption that it can allow you to do means that you could have much smaller processing units running at lower temperatures.  And that could potentially make carbon capture a lot cheaper.  They've done a cost estimate in fact and they think that if you scale this up, it could knock more than $100 million off the cost of a full scale unit.  That might sound like a huge figure and they're extrapolating quite a lot.  But it's important to say that the researchers that had been doing this, they're pretty big hitters.  They're involved big Industrial enzyme developers like Codexis and Novozymes, and they partnered with BP Biofuels on this.  They've been backed by research funding from the US Department of Energy.  All of that I think makes it quite promising that this is going to go forward for further development.

Science writer Mark Peplow.

When bats swoop in darkness to catch their dinner, they emit high-pitched sound waves and then listen to the echoes that come back. They use this echolocation technique to find food AND also to avoid crashing into things.  Now scientists have discovered that they also use the sounds for more nefarious purposes: they can JAM the echolocation of other bats. Jade Lauren Cawthray works with the Wildlife Trust; she's also a bat enthusiast and takes groups on night-time bat walks. She's been taking a look at this new study and Ginny Smith spoke to her to find out more...

Ginny -  Jade, can you tell us a little bit about how echolocation works to start with?

Jade -  Yeah.  So, with echolocation, a bat literally does this very, very big shout and the soundwaves travel through the air and then bounce off the environment and they come back to the bat, giving an idea of the shape and the textures of its environment.  So, objects that are really close to the bat, the sound will come back to the bat nice and quickly.  So, it knows it's not very far away, say, a moth for example.  But if there was a tree much further away, the soundwave would take a longer amount of time to come back to the bat so it knows it's much farther.  So, they get an idea of distance and the shape of their environment.

Ginny -  So, you say the bats are shouting, but when I go out at night, I can't hear a load of noise coming from the sky.  Why is that?

Jade -  So, bats do shout and they shout very, very loud.  They shout at about 110 decibels which is equivalent to a jet flying low overhead.  So, it's a really, really loud noise.  But the shout is actually a different frequency.  A frequency above that which we as humans can hear.  So, we can hear up to about 20 kilohertz but the bats, their echolocation can be anything from 20 to 200 kilohertz.  So, it's just a frequency above what we can hear.

Ginny -  So, it's just too high pitched for our ears.

Jade -  Yes.

Ginny -  But you've got an example of some bat noise that we can actually hear that I think you've brought with us.

Jade -  Yeah.

Ginny -  Do you want to play that for us?

Jade -  (bat noise).  So here, what you can hear is a slowed down version of bat echolocation and you'll hear these little shout points and they're getting faster and faster.  And they get faster and faster as the bat gets closer to an insect.  So, as it gets closer and the insect is moving around, it needs to be able to pinpoint where the insect is more accurately.  So, it does more and more shouts to get more and more information of the location of the insect.

Ginny -  But now, some researchers have found out that bats are doing something completely different with their echolocation.

Jade -  Yeah.  So, this piece of research that has been released this week, it's quite exciting because it's the first time something like this has been recorded.  Basically, what they found is in Mexican free-tailed bats, the bats are actually interfering with each other's echolocation.  So, one bat will make an echolocation call, trying to capture an insect, but another bat will come along and send a different type of sound, a different type of call that actually interferes with the soundwaves of the first bat.  What this means is that the first bat isn't able to judge the distance of the insect as accurately and actually misses the prey.

Ginny -  I think we've got a recording of that one as well.

Jade -  (bat noise).  So, you can hear that like we had before and then in a second, you can hear like a whistly up and down noise.  This is a kind of jamming tone that they're doing.  They're making this very different call around about the time that the first bat is increasing the speed of its echolocation.  So, as it's starting to hone in on that insect, the other bat starts to send a different frequency which stops it capturing the insect.

Ginny -  It sounds quite different so it's not just that that bat is also echolocating to find that insect.  Are they really trying to prevent their fellow bats from getting food?  I thought bats are quite a social species.

Jade -  Yeah, so the report suggests, they look very carefully at this.  They wanted to know, was it that the second bat was trying to disturb the first bat by sending the sound towards the bat or were they trying to capture the insect and sending the noise at the insect.  And they seem to be sending it at the insect to interfere with those soundwaves.  So, they're definitely trying to prevent the other bat from getting the food.  The Mexican free-tailed bats are quite famous particularly in the States because they roost in numbers of a million or more individuals.  And so, what could be happening here is that because there are so many individuals, the number of insects available per individual is much lower.  So, there's actually more competition between them for food.

Naked Scientists Tim Revel and Georgia Mills have some quick fire facts and misconceptions about cancer...

Tim -  There are over 200 different types of cancer.  But genetic research suggests that every cancer may be unique to the individual.

Georgia -  Cancer causes your cells to divide abnormally which then starts spreading around the body.

Tim -  Abnormal cell division leads to the extra cells building up in a clump, which is called a tumour.

Georgia -  But not all cancers make tumours - for example, leukaemia.

Tim -  There are over 14 million cancer cases worldwide each year, causing around 8 million deaths.

Tim -  Often, the cancerous cells prevent healthy cells from doing their job correctly.

Georgia -  Radiotherapy, chemotherapy and surgery are three of the most common cancer treatments.

Tim -  And they are often used in combination.

Georgia -  Surgery has the best overall success rate.

Tim -  This method aims to directly cut out cancerous cells from the body.

Georgia -  While radiotherapy involves precisely firing high energy rays at cancer cells and eventually causing them to die

Tim -  And chemotherapy uses drugs instead of radiation to achieve the same effect.

Georgia -  Now, for some myth busting:  fact or fiction...

Tim -  Cancer is a recent man-made disease.

Georgia -  Fiction.

Tim -  Cancer was described by the ancient Egyptians and the ancient Greeks

Georgia -  And has been detected in mummies, early skeletons and even in dinosaurs.

Tim -  Cancer is on the rise, but that's mostly because we are living longer.

Georgia -  As well as smoking, drinking and eating too much.

Tim -  Super foods prevent cancer.

Georgia -  Fiction.

Tim -  There is no such thing as a super food.  It's a marketing term, not a scientific one.

Georgia -  A diet rich in all kinds of fruit and veg will help to reduce your cancer risk.  But eating a few trendy berries on top of an unhealthy diet isn't going to be much help.

Tim -  Cancer treatment kills more than it cures.

Georgia -  Fiction.

Tim -  Now, it is true that a lot of people die after cancer treatment.

Georgia -  But this is usually because the treatment just didn't work or came too late and people succumb to the disease.

Tim -  Cancer treatments are not without their risks, but new treatments and earlier diagnoses have increased the number of survivors.

Georgia -  Many cancers still have poor outlooks, but there are some success stories.

Tim -  96% of men diagnosed with testicular cancer are now cured...

Georgia -  ...compared with only 70% in the 1970s.

Tim -  Three quarters of children with cancer are now cured...

Georgia -  ...while only a third were in the '70s.

Tim -  It's still a big problem, but we know more about cancer now than ever before.

New chemical treatments that selectively target cancer cells and leave the healthy ones intact. 

Chris Smith spoke with Dr Neill Martin, Chief Operating Officer and Co-Founder of Mission Therapeutics. They're trying to trigger what they call "synthetic lethality" in cancer cells by deactivating certain critical systems that cancer cells rely on to grow and remain alive. Healthy tissues have backup systems, but cancers don't, so switching off these systems makes the cells self-destruct.

Chris -  Tell us first of all, what's going on in a cancer cell genetically.  Why does it have this Achilles' heel that you're plugging into?

Neill -  So, a cancer really likes to be genetically unstable.  It likes to be very mutational.  So, what it does is it tries to switch off a number of these genes which protect a normal cell.  By switching those genes off, it actually becomes mutational and therefore, it creates the sort of environment that cancer likes to grow in and force the sort of growth of that cell.

Chris -  So, what you're saying is that in order to be a nasty cancer, it's a sort of a self-fulfilling prophecy. If it turns off a lot of these genes that normally keep cells in check, it makes itself able to gain lots of other properties of a cancer, but at the same time, the downside is that it's more vulnerable.

Neill -  That's right, exactly that.  So for us at Mission, what we do is we study the DNA repair processes and within the DNA repair processes, a normal cell has about 5 or 6 of those.  A cancer cell will try and switch some of those off because it wants to actually increase its mutational rate.  DNA repair protects the DNA.  So, when it does this, it then actually creates that sort of environment.

Chris -  Isn't that roughly how current therapies against cancer work?  They're exploiting the fact that cancer cells are actually quite weak and they're very easy to damage.  And so, when we give these drugs or radio therapies and things, you're actually making more damage to the DNA which in turn makes the cell fall apart.

Neill -  That's it, correct.  But the big problem with that is it also damages the DNA of a normal cell and that's where you get the problems and that's why a lot of patients suffer from this sort of chemotherapies that are given.  What we're now trying to do is actually, use that Achilles' heel, understand it a bit more, and actually tailor the treatment to that cancer cell and rather than the normal cells and therefore, protect the normal cells but kill that cancer cell.

Chris -  You're going in and finding which of these systems have been disconnected in the cancer so that you can hit the one that it is the thread it's dangling by genetically.  But isn't by definition cancer a sort of mixed population?  If we go and look at a cancer, we'll see, because of all these mutations and genetic changes, we're going to see lots of cells that are screwed up in lots of different ways.  So, is there just one Achilles' heel?

Neill -  What we're finding I think is that for a number of cancers that there's a very early switch and therefore, that you do get heterogeneity in cancers and different types of genetics that are evolved from that, but there'll be a very early switch.  We're starting to see that for example, the DNA repair processes are one of those early switches that change the environment.  Therefore, all the tumour cells that then evolve from that tend to have that same genetic background.

Chris -  So, they're still inheriting that nonetheless.  So, if you go in on that, that is the one thing that is consistent and constant throughout all of the tumours.

Neill -  Yes, exactly.

Chris -  What would you do then?  Do you go and say, "Well let's have a sample of someone's tumour and let's unpick it genetically and see what these areas are that it's deactivated" or what it's still using, so you know how to go in?

Neill -  Yes, exactly.  So, the way that we will be evolving this is by creating the sort of genetic test to go with the therapy so that you can actually then diagnose or take a biopsy or as Ian was saying, some sort of biomarker even from the blood, get to understand what that tumour type is.  And then because we actually know that it might have this genetic defect, actually tailor the treatment to that cancer.  That's really the personalised healthcare that we're looking for now within the sort of cancer field.

Chris -  Well, let's look at how you do that then.  So, you look at a tumour, you find what its genetic mechanisms are and you say, "Right, we're going to target this particular mechanism."  How do you then go about that, making a treatment for a person to do that?

Neill -  Well, because we know that, what we can do is we can actually take that right back to the fundamentals, so almost back to the Petri dish within the lab.  So, we then can actually start to look at, "Okay, this is what's actually been switched off."  We can then look to see what's actually remaining within that cancer cell and then look for the drugs that switch those mechanisms that are remaining within the cancer cell.

Chris -  But do those drugs exist?  Are there chemicals already that you could put your cancer in a dish and ask, "I want to turn off that particular gene and there's a drug that'll do that"?

Neill -  We're actually starting to see within the sort of clinical trials, a number of those drugs which are actually personalised and actually targeting certain tumours and different tumours in a non-cytotoxic way.

Chris -  In other words, not killing other cells in the body.  So, they should be very, very discrete.  It should just go through the tumour because your other cells in the body have all their other systems intact even if you disable temporarily with your drug, one of them, the other 5 strands are going to keep it together.

Neill -  Exactly, that.  

Chris -  Where are you in terms of the progression towards a market with this?  Are you at a clinical trial stage yet?

Neill -  We are.  Previously, we've created a number of products which are now in clinical trial.  At Mission, we're still quite - our labour is still in the pre-clinical.  What they call a pre-clinical, the sort of testing phase.  And we're probably about 4 or 5 years away from clinic in terms of being able to try these products out.

Chris -  What sorts of diseases are you going for?

Neill -  Well there are a number of diseases, but we don't know now, that diseases such as what's known as BRCA of which there was a high profile case of Angelina Jolie recently. Those diseases really are genetic diseases, and if you can get the right treatments, for those types of diseases you can actually selectively kill the cells.

Chris -  She underwent a double mastectomy, didn't she, as a preventative measure. She didn't have breast cancer but she does have that gene which we know is linked strongly to premature development of breast cancer at a very young age. . are you saying that had she pursued your approach, given the option of course, I mean it wasn't a choice at that time, she would potentially have the option not to have a mastectomy but she could have what you're offering instead?

Neill -  That's correct, Chris. Where we would like to get to is to have the sort of toolkit of drugs where we can actually offer these patients an alternative to surgery. And I think that will come, I think it's just a matter of time, because once we actually design the right drugs, we can use them then in those sorts of settings. And that'll give the alternative and therefore they'll hopefully be able to just live off rather have the surgery, the drug. 

Chris -  Does she have to wait, in Angelina Jolie's case, until she gets breast cancer and then has your treatment, or could it be used preventatively in anticipation of getting the disease?

Neill -  For us, we would like to get the point where its use is preventative in a prophylactic setting where you could actually treat these patients prior to them getting any symptoms and what'll it do is any cancer cells that actually come through at an early stage. And it might be that you need to do this sort of 20's or 30's when the possibility of those sorts of tumours starting to grow. It would be a preventative measure.

Chris -  Neill Martin from Mission Therapeutics, thanks very much.

Over time, more and more people are undergoing treatments for cancer and many are now being cured, largely thanks to advances in modern medicine. But how does the diagnosis affect a person's mental state, even if they are cured, and are we paying enough attention to the problem? Emma Cahill is a Cambridge neuroscientist and spoke with Ginny Smith about the issue.

Ginny - Emma, are mental health issues, are they a serious problem for cancer survivors?

Emma -   Well, it seems that they're going to be more of an issue in the future because as we heard earlier, more people are surviving from cancers.  So, it's going to be important to actually consider this.  In the past, until like the late 1990s, a chronic illness wasn't even one of the criteria that they included to diagnose people with posttraumatic stress disorder which originally was called shellshock and it was typically associated with war veterans. 

But research groups that look into cancer like McMillan, their Report in 2013 found that of the 500,000 people living with cancer in the UK today, about 248,000 will develop mental health issues.  So, these include depression and anxiety but also posttraumatic stress disorder.

Ginny -   That's a huge number and is this the same kind of posttraumatic stress disorder that you see in war veterans and that kind of thing or is it a distinct kind of disease?

Emma -   Well, that's hard to know because there's been a lot less research done on PTSD in cancer.  But what we know is when it's being diagnosed, the same criteria are used.  So, in the first instance, they look that the symptoms are actually persisting for more than a month since the traumatic event occurred and the symptoms they look at are a heightened sense anxiety.  This can lead to poor concentration, trouble sleeping, and importantly, with posttraumatic stress disorder, something that's different from depression, is that they'll also have flashbacks or intrusive memories that are associated with the traumatic event.

Ginny -   So, with a traumatic event such as being in a war, being shot at, you can kind of see that there'd be one trigger.  But I guess with cancer, it's a long period.  How would those flashbacks - would they be different?

Emma -   Yeah, but it's hard to know.  It could be coming as the forms of memories or nightmares and something you see quite often with posttraumatic stress disorder is an avoidance behaviour in the people suffering it.  And that's why it's a particular concern in the case of cancer patients because they could be avoiding treatments or seeing doctors or seeing people that they associate with their cancer symptoms.

Ginny -   Do you think it's something specific to cancer or do you think it's something about any kind of chronic disease that people may have recovered from?

Emma -   For the moment, we don't know if it's going to be anything specifically associated to cancer.  It's beneficial to think of it in this context because it's a new way of looking at posttraumatic stress disorder.  The way it's conceptualised at the moment as a mental health issue is that it's a disorder of memory.  And particularly, memories that are emotionally intrusive and they cause a state of anxiety in the everyday life.  So, that could come from a traumatic event such as war, but also, from the pain associated with cancer treatments.  One thing we can see across different types of cancers is that a common feature that leads to posttraumatic stress disorder in a certain percentage of patients is the duration of treatment.  So, the longer treatment has gone on, further more likely they are to develop posttraumatic stress disorder.

Ginny -   So, are there certain types of cancer that are more likely to give you posttraumatic stress disorder than other types?

Emma -   That's not known at the moment.  So, people are looking into this most of the time by focusing on a specific cancer.  In certain cases, it's been suggested that childhood cancers might be more prone to posttraumatic stress disorder.  But that's also because the survivors obviously are younger, so they're surviving for longer.  So, you've got these confounding issues.  But as I said, one common feature is the duration of treatment seems to be key.

Ginny -   Now, you actually work on posttraumatic stress disorder itself and perhaps looking at treatments.  Is there anything we can do to help people who are suffering with mental health problems after surviving cancer?

Emma -   Definitely.  Well, the first thing that is positive about being aware of PTSD in the context of cancer is that it's going to provide more research avenues, so people will be looking at this with a more open view. 

At the moment, treatments include behavioural therapies, and meeting with therapists.  What they regularly try to do is to make people remember or relive their traumatic experience in a safe context, and to lose the sort of emotional potency that they associate with this.  That's also something that we look at in the lab as basic fundamental neuroscientists.  We look at how fear memories can be reactivated and then we try and find what brain chemicals are involved in that, and see, can we block them with specific drugs to try and neutralise the emotional part of the memory.  We don't want to ultimately wipe these memories, but just dampen them down so they don't have this emotional component that's the problem.

Ginny -   So, I imagine that's probably the last thing a cancer survivor wants to do, is relive those memories.  Why is that important if you are going to dampen down the emotions?

Emma -   Well, it' important because we've known for a number of years that memories, once acquired by the brain are not just resistant and stored away like files in filing cabinet.  Once a memory is recalled, it's actually opened up again and what we call 'de-stabilised'.  So, in this stage, it can integrate new information and be updated.  So, by retrieving your fearful memory, you de-stabilise it.  in that instance, if you have interfering therapies, be there behavioural therapies or drugs, one of the ultimate goals for a lot of research right now is blocking the persistence of those damaging or fearful memories.  So, you'll retrieve them, they become de-stabilised and at that point, you use a therapy which will prevent them from persisting.

Ginny -   Quickly, you mentioned a drug that might be useful for this.  How long is it going to be before we have one that we can actually use to help people or is it already there?

Emma -   At the moment, there's no real drugs that can target the memory sides of PTSD.  Most people are treated with antidepressants or anti-anxiety drugs.  But research is really striving on to try and find particularly balance of the chemicals involved in the stress system such as adrenaline which not only has act on the body, but acts in the brain as noradrenalin.  So, there's a lot of focus on blocking the receptors for noradrenalin in the brain and trying to understand how that might be able to be a future treatment maybe.

Ginny -   Lots of promising ideas then.  Thank you.  That was Dr. Emma Cahil from Cambridge University.