How Cancers Form, Cancer Biology and Future Therapies

08 October 2006
Presented by Chris Smith, Phil Rosenberg.


Cancer biology goes under the microscope this week, as Gerard Evan talks about the causes of cancer and how cancer spreads around the body. Also on the show, and joining us live from the National Cancer Research Institute Conference, is Fran Balkwill who will be discussing cancer treatments and the development of targeted therapies, and Kat Arney, who will be talking about the latest news in cancer research. We also travel Stateside for a Sciencce Update from Bob and Chelsea, hear from Michael Halpern from the Union of Concerned Scientists about governments interfering with scientific research, and experience the deep freeze with a couple of balloons and some liquid nitrogen in Kitchen Science.

In this episode

Winners of The Ig Nobels

In a parody of the real Nobel Prize Awards the Ig Nobel Prizes are awarded for scientific achievements that make you laugh, then think. Ten awards were passed out this Thursday and this is my highlight. Francis Fesmire of the University of Tennessee College of Medicine and Majed Odeh of Bnai Zion Medical Center in Haifa, Israel share one award for independently finding a cure for severe persistent hiccups referred to as digital rectal massage. Essentially hiccups is caused by runaway signals travelling along the Vagus nerve. This nerve wanders all the way from your brainstem through your neck and chest, finally terminating in the abdomen. Along this path it is responsible for many involuntary actions such as heart rate, sweating, forcing food towards your stomach and also mouth muscles used in speech. A lot of the anecdotal cures for hiccups such as drinking, gagging or applying pressure to your eye sockets rely on somehow stimulating the nerve in other ways to sort of distract it from making you hiccup. When Fesmere had tried all these methods on a patient that had been hiccupping constantly for 72 hours he remembered a method of stimulating the Vagus nerve used to slow runaway heartbeats. Essentially the Vagus nerve was massaged with a finger stuck up the patients anus. However, Fesmere now recommends another method for curing hiccups. An orgasm floods the Vagus nerve with signals and also has the potential to cure hiccups. Sounds like much more fun than his earlier method! The late Philip May at the University of California at Los Angeles and Ivan Schwab of the University of California at Davis shared an Ig Nobel Prize for ornithology after their investigations into how woodpeckers are able to bang there beaks against trees so hard. If a human tried the same thing their brain would rattle around inside their skulls resulting in a severe concussion. May wondered why this didn't occur in woodpeckers. They found that the woodpeckers they studied had small brains that were more impact resistant and their skulls were formed of a thick spongy bone that helped to cushion the blow and hold the brain firmly in place a bit like packing something in rolled up newspaper. In addition to this the woodpecker has had to evolve a special mechanism to literally stop it's eyes popping out as it hammers a tree. It has membranes across its eyeballs that tighten a fraction of a second before it's beak hits the target holding them firmly in its head.

'GOOD BACTERIA' FIGHT OFF HIV Scientists have engineered one of the "good bacteria" naturally found colonising the human female genital tract to enable it to produce a chemical called cyanovirin-N, which has powerful anti-HIV effects. Just as some people take probiotic yoghurts as an aid to digestion, the researchers think that their modified bug could be added to the bacterial flora growing naturally in the vagina where it could help to protect the host from infection by the AIDS-causing virus. Cyanovirin-N is naturally produced by a type of blue-green algae called Nostoc ellipsosporum, and it has already been shown in primate experiments to be able to prevent HIV from locking onto and penetrating cells in the vagina. Now, Stanford University's Peter Lee and his colleagues have successfully added the gene for cyanovirin-N to the main chromosome of a bacterium called Lactobacillus jensenii, which naturally colonises the vagina. When the modified bacteria were added to the genital tracts of mice, the researchers were subsequently able to detect small amounts of cyanovirin-N being produced locally. This suggests that it might be possible to use these bugs to provide an effective yet cheap and simple additional line of defence against HIV. This would be especially useful in third world countries such as Africa where several million new cases of HIV infection occur each year, largely because women in these countries have little or no access to effective barrier methods of contraception.

Allergy Cure Not To Be Sniffed At

A Swiss company - Cytos Biotechnology - have produced a vaccine which they say can neutralise allergy symptoms for at least 8 months. Ironically it works by fooling the body into thinking that it is suffering from a bacterial infection. Known as CYT003-QbG10, the new vaccine comprises a piece of DNA from a class of microbes know as mycobacteria. This is delivered in the form of a fake virus-like particle that carries the DNA into dendritic cells, which orchestrate the immune response. The mycobacterial DNA fools the immune system into thinking it is fighting a bacterial infection, and as a result it activates what is known as a Th1 response. Th1 responses are strongly linked to fighting infections and also suppress Th2 responses, which are associated with allergies. In initial tests, ten patients with allergies to grass pollen were treated with six weekly injections of the new agent, and five of them completed the course before the pollen season commenced. Amongst those five, there was a marked improvement in allergy symptoms. And when the volunteers were exposed to grass pollen in the laboratory there was a 100-fold reduction in their sensitivity compared with their response before the trial started.

'Good Bacteria' Fight Off HIV

Scientists have engineered one of the "good bacteria" naturally found colonising the human female genital tract to enable it to produce a chemical called cyanovirin-N, which has powerful anti-HIV effects. Just as some people take probiotic yoghurts as an aid to digestion, the researchers think that their modified bug could be added to the bacterial flora growing naturally in the vagina where it could help to protect the host from infection by the AIDS-causing virus. Cyanovirin-N is naturally produced by a type of blue-green algae called Nostoc ellipsosporum, and it has already been shown in primate experiments to be able to prevent HIV from locking onto and penetrating cells in the vagina. Now, Stanford University's Peter Lee and his colleagues have successfully added the gene for cyanovirin-N to the main chromosome of a bacterium called Lactobacillus jensenii, which naturally colonises the vagina. When the modified bacteria were added to the genital tracts of mice, the researchers were subsequently able to detect small amounts of cyanovirin-N being produced locally. This suggests that it might be possible to use these bugs to provide an effective yet cheap and simple additional line of defence against HIV. This would be especially useful in third world countries such as Africa where several million new cases of HIV infection occur each year, largely because women in these countries have little or no access to effective barrier methods of contraception.

Liquid nitrogen

Experimenting with gases and liquid nitrogen

This week Derek is with Dr Chris Muirhead from Birmingham University and student volunteer Mary from Hills Road Sixth Form College in Cambridge. They'll be using liquid nitrogen, which is very cold and can be very dangerous. Chris has special liquid nitrogen safety training, and you should NOT do this experiment at home.

To do this experiment, we used:

- Balloon filled with helium

- Balloon filled with air

- Vat of liquid nitrogen

How we did the experiment:

1 - Chris took the balloon filled with helium and put it into the liquid nitrogen.

2 - We observed what happened and took the balloon out again, watching how the balloon changed.

3 - Chris the repeated the experiment with an ordinary air-filled balloon.

What's going on?

Firstly, we need to understand what liquid nitrogen is. 80% of the atmosphere is composed of nitrogen gas, and liquid nitrogen is this same gas cooled down to a temperature of -196 degrees Celsius. It then turns

from a gas into a liquid. When a balloon full of helium is lowered into the liquid nitrogen, it gets smaller. In fact, it shrinks to about a quarter of its original volume. Why is this?

Balloons are made of rubber, and rubber likes to contract. You can easily see this by stretching an elastic band - if you stretch it out and let go, it will contract back to its original size. The reason a balloon full of air doesn't contract is because it's being maintained at the larger volume by the pressure of the air inside. When you cool the gas down by plunging the balloon into liquid nitrogen, the atoms of gas inside move around less rapidly. This means that they bash against the walls of the balloon less hard and less frequently, and that produces less force on the walls of the rubber. When the force acting on the inside of the balloon decreases, the rubber is able to contract.

When the balloon is removed from the liquid nitrogen, the balloon begins to increase in size and start floating back up towards the ceiling. This is because as the gas warms up again, the atoms start to move around a lot more rapidly, the pressure on the inside of the balloon increases and the rubber is forced to expand.

Repeating the experiment with a balloon filled with air gives a slightly different result. Instead of contracting down to a quarter of the orignal volume, the air-filled balloon becomes much smaller and is pretty much flat. Inside the balloon you will see a small amount of liquid floating around in the bottom. What is it?

It turns out that the liquid is liquid air, and herein lies the reason why this balloon became a lot smaller than the helium balloon.

When a gas turns into a liquid, its volume decreases dramatically. In fact, the volume of the liquid air is about a seven hundredth of the volume of the gaseous air. The reason why the same result wasn't seen with the helium balloon is that helium doesn't liquefy until much lower temperatures. In contrast, normal air will turn into a liquid at about the temperature of liquid nitrogen.

It's possible to demonstrate how much more space is needed when molecules exist as a gas by putting liquid nitrogen into an empty Pringles container - it's not long before the lid pops off. This is exactly the same process of gas contraction and expansion seen in the balloons - when the liquid nitrogen evaporates it takes up 700 times its original volume. The reason we use a Pringles tube is that the lid is made of a light plastic and can blow off safely. You must never put liquid nitrogen into a sealed can, as it will explode. And it goes without saying - don't try this at home!

Want to find out more?

The science of the very cold and superconductivity are some of Chris Muirhead's specialities! If you'd like to find out more about this kitchen science experiment or any of his research, then you can contact him through the Birmingham Portfolio Partnership.

- Science Idol

The Naked Scientists spoke to Dr Michael Halpern, The Union of Concerned Scientists, Washington DC

Science Idol
with Dr Michael Halpern, The Union of Concerned Scientists, Washington DC

Chris - Now you've all heard of Pop Idol, but now meet the scientific equivalent. It's called Science Idol but it's not scientists strutting around with microphones, so much as pens and pencils. The aim of this competition is to produce a cartoon that will highlight how politicians in America are attempting to distort the conclusions and suppress the results reached by US scientists on issues about things like climate change and pollution. In all over 400 scientists and artists have put pen to paper, and joining us now from the Union of Concerned Scientists to tell us more is Michael Halpern. Why did you need to set this competition up?

Michael - We thought it would be a good idea to set a competition up like this because just like the Ignobel prize, you have the opportunity to laugh at political interference in science and learn a little bit about how important is to decisions.

Chris - But are politicians really meddling in science? Do you believe that?

Michael - We've seen that happen a lot in recent years. The people that lead scientific agencies here in the United States like the Environmental Protection Agency and the Centre for Disease Control have increasingly inserted themselves into the scientific process. I can give you a couple of examples. First of all, climate change. The Bush administration has consistently tried to downplay the threat of global warming and as a result, they've prevented scientists from talking to the press about potential links between hurricane strength and global warming.

Chris - How would you do that though? How would you stop scientists talking to the press? You're talking to us for example. How would they try and stifle the dissemination of the information?

Michael - These scientists that work for federal agencies work under a different set of rules and they are required to only speak to the press when they're allowed to by their superiors, by the political appointees, who are their bosses. If the political appointees don't like what they're going to say, they can tell the scientists not to talk. If the scientists talk then they risk getting fired.

Chris - Now obviously the UK often stands shoulder to shoulder with America. Do you think the same thing is happening here and further afield?

Michael - We haven't done any investigations into what's happening in the UK, but we do know that any sort of interference in the scientific process hurts the way science is done and decreases our capacity to respond to important and complex environmental and health problems.

Chris - Now whilst setting up a cartoon competition is a good way to raise awareness, is making light of the situation when it's actually quite serious the best approach?

Michael - I think it is a very good approach because it allows people to approach the issue in a very accessible way. They see a cartoon and the cartoon pretty much says everything about the issue. Once you've been introduced to the issue then you can really learn a lot more about it.

Chris - I'm just having a look at the winning entry and it's quite funny. It's got a scientist with his pen and pencil in his laboratory and it's got a politician or a bureaucrat holding a grant form. The politician is saying 'you're completely free to carry whatever research you want, as long as you come to these conclusions. This sounds like the mantra from Ford: you can have any colour you want as long as it's black.

Michael - Right, exactly. This is obviously an obsurd sort of practice. Scientists need to come to whatever conclusions the science says, not what the political appointees tell them to do. The artist who drew this cartoon, once he'd one the contest, started getting phone calls and emails from other scientists at his university saying that this is exactly how I feel sometimes and I'm not really allowed to do the research that I want to do.

Chris - So Michael, once you've got your press coverage and people are aware of the situation, how are you going to execute a change, so politicians stop meddling and scientists in America and probably elsewhere are going to stop getting this degree of interference?

Michael - That's a very good question. It's a tough problem to deal with and what we've done is brought a lot of scientists to meet with members of congress and other politicians here in Washington DC to talk about the problem and to educate their members of congress about how important it is to keep the state scientific progress free and unfettered. So we're promoting more protection for scientists in the federal government to be able to publish and speak about their research and just a better way for decision makers to access scientific advice.

- Science Update - Lasers for Train Tracks and Super Dishcloths

The Naked Scientists spoke to Chelsea Wald and Bob Hirshon from AAAS, the science society

Science Update - Lasers for Train Tracks and Super Dishcloths
with Chelsea Wald and Bob Hirshon from AAAS, the science society

Phil - We're now going to head over the Atlantic for some Stateside science. This week Bob and Chelsea reveal how lasers are being used to spot cracks in train tracks, and how a new kind of super dishcloth could see the death of deadly bacteria.

Bob - This week on Science Update, we'll talk about a new way to use lasers to keep trains on track. But first, Chelsea has this report about the latest advance in identifying biohazards.

Chelsea - Yes, a new technology could soon move biohazard detection out of the lab and into hospitals, food preparation facilities, and crime scenes. Cornell University fibre scientist Margaret Frey and her colleagues created a special fabric that anyone could wipe over a surface. The fabric has special sites that can hold antibodies to just about any biohazard, including salmonella, strep bacteria, and anthrax.

Margaret - So basically as long as there's an antibody available or some kind of biorecognition agent available, we can attach that onto the fabric, and then the fabric will collect that specific thing.

Chelsea - They're now working on ways to make the fabric change colour when the hazard's detected, so people will know immediately. Right now, the wipe must be put in a developer before it gives results.

Margaret - The goal is to have this super-simple and super - instant.

Chelsea - And so far, they can only collect one biohazard at a time, but they ultimately hope to collect hundreds at once, making it a powerful tool against all sorts of contamination.

Bob - Thanks, Chelsea. This tapping may sound like an old-fashioned news ticker, but it's actually a state-of-the-art laser system for inspecting train tracks. Structural engineer Francesco Lanza di Scalea of the University of California at San Diego is leading the development team. The system uses a trailer-like vehicle that glides along the track at up to 70 miles per hour, tapping the track with laser pulses at one-foot intervals.

Francesco - And this tapping is like a virtual hammer. Just like if you were to hammer on a rail, you'd hear a sound going through.

Bob - And distortions in that sound, specifically in the ultrasonic range, can reveal dangerous internal cracks that current technologies often miss. Repairing those cracks early could save millions of dollars and prevent derailments.

Chelsea - Thanks, Bob. That's it for this week. Next time we'll talk about the family tree of venomous fishes. Until then, I'm Chelsea Wald.

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

Phil - Thanks guys. If you want to hear more from the Science Update crew, then you can go to their website at

- The Biology of Cancer

The Naked Scientists spoke to Professor Gerard Evan, University of California San Francisco

The Biology of Cancer
with Professor Gerard Evan, University of California San Francisco

Chris - We've devoted tonight's show to the subject of cancer. Lots of people know about cancer because one in three people die of it, but they don't tend to know what it is. So what actually is a cancer?

Gerard - Cancer's probably the best example we've got of evolution in action. Cancer's what happens when cells manage to throw off the shackles that normally restrain them and start to expand. As they expand they evolve and they get worse and worse and eventually people die.

Chris - But why is it that it's so common as a condition and why hasn't the body evolved not to develop cancer?

Gerard - Well the first thing is that it's not that common. Although one in three people get it, cancers arise from single cells and the average human body contains about a hundred thousand million cells, any one of which in principle could become a cancer cell. So in fact, cancers occur in one in a hundred thousand million times in one in three individuals in seventy years, which is very very rare. The reason so many people get cancer is that there are so many cells and you live so long. Really, cancer is suppressed and we have lots of mechanisms to suppress cancer being evolved, but like all evolutionary selection, it only works until we get to reproductive age. Once we've gone beyond reproductive age, evolution doesn't care.

Chris - You say that though but grandmothers have an important role too. I know this because I've recently acquired a new addition to my family and I can tell you that grandmothers are actually quite handy, so there must be some degree of evolutionary pressure to keep grandmothers in the family.

Gerard - Yes it's absolutely true and I've thought about this as well. So maybe in millennia to come humans will get less and less cancer because they'll be selected out as we want granny around. But we're so close to other organisms that don't live very long, and for them the grandparent generation is pretty much irrelevant in terms of care-giving.

Chris - Let's look at why you get cancer though, because it's fair to say that it's a genetic disease, and we're going to be hearing about one of them from Kat Arney who's at the Cancer Research conference this week about a new gene for breast cancer. But why should genes cause cancer? What are the mechanisms involved? What's going on?

Gerard - The thing we have to appreciate is that cancer cells aren't doing anything that normal cells don't usually do. So every time you cut your finger, cells proliferate very rapidly, they generate a blood supply, they recruit other tissues, they rebuild and remodel and mend the cut in the finger. So you have all the machinery you need to become a tumour cell. The point is that it's very guarded and reigned in in normal cells. Cancer is a disease when the mechanisms for reigning in those processes get lost or eroded.

Chris - How does that happen?

Gerard - It happens through mutation and through cosmic rays and various nice things that you eat and who knows what.

Chris - Well even the air that we breath because oxygen causes cancer.

Gerard - That's right. We live in this nasty gas second only to chlorine for how viscous it is, but we've evolved to cope with it. But as I've said, we've evolved to cope with it to a reproductive age and no more.

Chris - We're protected from cancer up to a certain age and we have repair mechanisms to stop the damage from happening. How do they actually work?

Gerard - That's a bit of a mystery actually because as I've said, cancer cells are really only doing what normal cells are doing. You've got all these mechanisms that prevent cancer but how do they tell what's a cancer cell and what's a normal cell. This is actually a deep mystery and we don't really understand that. What we do understand though is when the DNA in the cell gets damaged, there are immediate repair mechanisms that come in and fix the damage - at least as best they can. The problem is that sometimes they make mistakes and that's when you get a mutation. So in some ways you could say that mending the damage is what causes the cancer because that's what's causing the mutations. We also have another response to DNA damage in many cells which is to just trash the cell. That's actually the best way of preventing cancer, but unfortunately if you did that every time you wouldn't have a body left.

Chris - So when we actually have a look at what's going on in a cell, can you just talk us through how a cancer begins? You don't just wake up one morning and have cancer. It obviously has to evolve from somewhere and changes have to accrue. How does that process happen?

Gerard - The clinical disease, of course, is the end point of a whole variety of processes by which time the individual cell that caused the cancer has multiplied and grown and started to erode your normal tissues. The initial events which cause cancer arise in individual cells and they probably happen thousands of times a day, but they never get very far because we have these powerful mechanisms that put the breaks on incipient cancer cells and stop them dividing very early on or kill them.

Chris - What about spread around the body?

Gerard - Why do cancer cells spread around the body? Well a lot of cancers don't, but the ones that bother us do. So the point is that cancers start in one particular site, and they erode the tissue around that site, and if they stay put they're an operable cancer. They're not the things we usually worry about. If they start to break loose and wander round the body and colonise elsewhere, just basically acting like and independent life form, that's when we have the problems.

Chris - You published a paper recently where you had some very interesting things to say about how we might be able to make chemotherapy and radiotherapy a bit more comfortable for people in future. How does that work?

Gerard - I think it goes back to why we aren't able to cure cancers. The truth is, we can kill any cancer that any person has ever had; we just can't keep the patient alive at the same time. We don't have drugs that are sufficiently good at discriminating between the normal cells and the tumour cells. One of the reasons for that is that many normal tissues in the body turn over very rapidly and they're just as sensitive to the cancer treatments as are the cancer cells, and sometimes even more sensitive. If we could preserve those normal tissues and turn down their terrible responses, then we could deliver higher doses of radiotherapy and chemotherapy to the tumour cells and probably kill more cancers. The work that we did recently was looking at what the relationship is between the mechanisms in cells that respond to damage to the DNA, and whether those are the same mechanisms that are widely thought as the mechanisms that prevent tumours occurring in the first place. The idea being that if you have a mechanism that responds to DNA damage by killing the cell, then it prevents it from accumulating mutations and becoming a tumour cell. But our data seem to indicate that the two are actually separate and very different, and you can dispense with the nasty bit, the DNA damage response that kills off all sorts of normal cells, and still retain the tumour repressor functions of this particular protein; a protein called p53.

- Treating Cancer in The Clinic

The Naked Scientists spoke to Professor Fran Balkwill, Queen Mary's School of Medicine and Dentistry, University of London

Treating Cancer in The Clinic
with Professor Fran Balkwill, Queen Mary's School of Medicine and Dentistry, University of London

Chris - Fran's from Queen Mary's School of Medicine and Dentistry at the University of London, and she's at this conference too. Fran's normal work is on what causes cancer and perhaps what we might be able to do about it. But we've heard from Gerard some of the mechanisms of where cancer comes from. Are we in the position to start unleashing some of our killer weapons against cancer?

Fran - The two big things that have happened to me over the last twenty years of cancer research is first understanding what cancer really is. We know that cancer is a disease of genetic damage. It's damage to DNA. When you know that and know there are certain types of genes, not all bits of DNA damage cause cancer, we know what kinds of proteins are altered when there is a problem and the cancer occurs, it gives us new targets. It gives us much more specific treatments and I think that if you understand the disease, that's the first step towards curing people or at least making a big difference to patients.

Chris - I want to just throw the cat among the pigeons for a minute Fran. For the last fifty years we've known about the structure of DNA, we've known about the genetic code and we know that cancer is a genetic disease. We even know of some viruses that trigger cancer. But we've still got record numbers of people who succumb to it. We're very good at diagnosing it but not terribly good at getting rid of it yet. Or are we?

Fran - I think that there are a whole load, and we're hearing about them at this conference, of new targeted treatments that will target much more specifically. The old treatments we have for cancer have been 'sledgehammer to crack a nut' kind of treatments. There are new treatments coming out, but it takes a long while. Each treatment has to be carefully tested in clinical trials, and we all know the kinds of problems that can arise during clinical trials. They have to be tested very carefully in clinical trials. In phase one with a few patients for whom there is no other treatment. In phase two you look for an effect in patients in a slightly better state and in phase three when you compare them with an existing treatment. This all takes a great deal of time. And remember, to develop any anti-cancer drug costs about a billion dollars. We heard just now about the amount of funding Cancer Research UK is putting into basic academic and clinical cancer research, but this wouldn't fund a single new drug a year. There are many many reasons and there is a long lead time between finding a disease and what would have to be a whole load of cures because cancer is a whole load of different diseases.

Chris - And a very varied condition. But what are the drugs people are trying to develop to get more targeted therapies?

Fran - What I was talking about today was slightly different and not hitting the cancer cell at all. One of the things I was talking about that has become more important recently is that cancers are not just made of cancer cells. They're not just made of those malignant, out of control evolved cells that take on a separate life form. What cancers do is corrupt other cells in the body that normally do a good job and help us fight infection, heal wounds and repair damage. They corrupt those cells and take them over to help themselves grow and spread. The way that happens is a process very akin to a very mild form of inflammation. So another way of adding to the existing cancer treatments and maybe improving their action is to maybe look at some of the ways that we target chronic inflammation and see if that has an impact on cancer. Many of the cells that you find in chronic inflammation and many of the chemical messages that pass between cells during chronic inflammation are also found in cancer. That's a sort of additional approach, and some of us think that it's quite an exciting one.

Pancreatic cancer with resident bacteria (stained for LPS)

- Cancer Research

The Naked Scientists spoke to Dr Kat Arney, reporting from the National Cancer Research Institute Conference in Birmingham

Cancer Research
with Dr Kat Arney, The Naked Scientists

Chris - Now we're going to join Kat Arney at the National Cancer Research Institute conference in Birmingham. It's the largest UK annual gathering of researchers who work on cancer around the world. Kat's there at the launch today. We're used to having you here in the studio so it's nice to have you out and about. What's this conference all about?

Kat - The National Cancer Research Institute is a virtual cancer institute that has brought together all the major funding bodies of cancer research in the UK. First of all we heard from Mike Richards, the UK cancer tsar, and he gave us a really exciting overview of what the conference is going to be about and how we're going to hear from so many different cancer researchers over the week. Already we're heard from Fran Balkwill, who's here in the studio with me, and she was talking about how we seem to be entering a golden age for cancer research. We also heard news from Mike Richards that we're going to see £35 million given this year for the establishment of seventeen new experimental cancer medicine centres here in the UK and that's funded by Cancer Research UK and the Department of Health. Tomorrow we're going to find out where these are going to be. We're currently sitting here in the back of the lecture theatre listening to the clinical trails showcase and we're going to have new results coming out; successes in bowel cancer and also in breast cancer. And finally, just today, scientists have discovered a new gene for breast cancer. This is pretty exciting stuff because new genes don't come along all the time. But this a new gene called BRIP1 and the researchers have found that this increases a woman's chance of getting breast cancer; roughly doubling it. So by the age of seventy your risk of breast cancer is about 1 in 12, and this found that if you have a fault in the gene BRIP1, you go to a risk of about 1 in 6. They found this by studying about 3000 women.

Chris - How can we have missed this for so long, Kat, given that it's implicated in so many tumours?

Kat - It's something that's known as a low penetrance gene. They think that faulty BRIP1 is found in about 30 000 women in the UK, but it doesn't mean that you're necessarily going to get breast cancer. They think that faults in BRIP1 actually contribute to around 100 cases of breast cancer in the UK every year.

Chris - And will this form part of the screening programme or is this something of academic interest but not clinical relevance?

Kat - At the moment it's very much of academic interest, but it could mean that we could potentially help screen women in the future and it will also inform the development of new treatments and it's important to know about this. The other thing that's really interesting is hearing Gerard in the studio. You might like to know that Gerard lectured me when I was an undergraduate.

Chris - It's a small world isn't it Gerard? Well Kat, I first met Gerard because I was interviewing him for something completely different but in a similar field when he was over in California and we got talking to each other a few months ago and said that you're so good at talking about your subject, you have to come to Cambridge.

Gerard - How could I refuse?!

Chris - So he very kindly agreed to come to Cambridge on his way to Germany to talk to us this evening.

Kat - Well it's absolutely fantastic to hear him back in the UK.

Chris - But you've also got some good news about cancer research in general haven't you, Kat?]

Kat - A couple of weeks ago Cancer Research UK released their most recent funding figures and in the past year we've spent more than £250 million on cancer research. That's entirely from donations from the public, so that's absolutely fantastic news. Also, Mike Richards has announced that there'll be new experimental medicine centres, so that'll be for testing new drugs, getting what we know academically about cancers and turning those into treatments to make a difference for cancer patients in the future. We've got Fran Balkwill here, who's hopefully going to tell us more about how we can use this knowledge and make some genuine progress in cancer research.

- What causes cancer to develop?

Fran Balkwill and Andrew Wyllie discuss what causes cancer...

What causes cancer to develop?
with Fran Balkwill, St. Bartholomew's Hospital, Prof. Andrew Wyllie, Cambridge University

Fran Balkwill and Andrew Wyllie discuss what causes cancer...

Fran - I'm interested in cancer and how it links with other things in the body, like inflammation. I'm also really interested in the fact that cancers aren't just made from cancer cells, but are made from some normal cells that help the cancer cells grow and spread.

Andrew - I'm interested in the way cells die. It turns out that they have to do this to be good citizens in the tissues they make up. You can think of a cancer cell as an un-dead cell; a cell that has failed to die when there's something seriously wrong with it.

Kat - What is cancer?

Andrew - It's a disease in which the internal programmes that tell a cell what to do, where it ought to be, what it should be secreting, and whether it should be moving or not go awry. This means that the cells get the wrong internal messages. The programmes are driven by genes. The genes are altered in cancer cells by a process we call mutation. In general, you need several mutations to add together to get the disordered behaviour we recognise as cancer.

Kat - Then what happens?

Andrew - It does a number of things. The most obvious is that it loses its ability to top growing and dividing. That means that you get clusters of cells that shouldn't be there at all. It also starts to break down the normal barriers that surround tissues. It starts to digest these connective tissues and move into the blood vessels that are surrounding it. It has the ability to call in blood vessels to bring in extra blood supply. In this way, the cancer manages to stoke its own fires. Sometimes the cancer cells managed to jump into the blood vessels and get circulated around the body. A small proportion of these can lodge elsewhere in the body and start growing in sites where they shouldn't be.

One last thing is that they also fail to respond normally to injury. The normal damage cells are exposed to is curiously caused by oxygen; the oxygen needed to drive the cells in the first place. Oxygen is a reactive molecule and it sometimes damages DNA. Cells have a very good way of either repairing that DNA or, for reasons we don't quite understand, it destroys itself. This process of throwing out damaged cells is a very significant part of the life of good tissues. So death is part of life. If you don't throw the cells away, you get persistence and growth of bad cells.

Kat - Fran, can you tell us some more about how the body responds to a cancer?

Fran - Andrew has just talked about cancer as a rogue cell, but in many ways, cancer is a rogue organ. It is full of the cells that Andrew has described, but in order to grow and spread, those cells bring in other quite normal cells. If you have a cut, a lot of cells come in to try and repair the damage. Similar cells are found in a cancer, but in this case, all these extra cells help the cancer to grow and spread. The process of inflammation is a very good thing in the body as it helps to fight injury and resolve the problem. In the case of cancer, the problem doesn't resolve and the cells that came in to help are all part of stoking the fire for the cancer. If the genetic damage to a cell is the match that starts the fire, this chronic inflammatory response feeds the flames. As many as half the cells ina cancerous lump will be normal cells.

Andrew - So if we had ways of interrupting that process, could we stop the progress of the tumour?

Fran - Yes, that's what we hope. Every year in this country around 220 000 people are diagnosed with cancer. Although many are cured, a very large number actually die. There are many drugs that are good at getting rid of cancer cells and surgeons are very good at getting rid of the lumps. What we find more difficult is to stop it coming back and stop it spreading. The approach of tackling the normal cells and blocking the messages that go between these cells and the cancer may be a complementary way of augmenting the very good treatments we already have.

Kat - So you're trying to find a way to harness the body's natural processes and shut them off?

Fran - Yes. One specific thing we are looking at in my lab is a series of drugs that block a molecule called TNF. Anti-TNF drugs are used for arthritis and Crohn's disease. They are anti-inflammatory drugs, and we are now doing clinical trials with them on cancer. It's the spreading of cancer that kills, not necessarily the cancer itself. If you can keep cancer under control for a long period of time, people can have a good quality of life.

Mandy - Are there any good cancer cells? Or is it just by the word cancer that it is automatically saying this is bad news?

Andrew - That's a very interesting question with about half a dozen different answers. I will offer one or two. There are cells which have lost control but haven't yet acquired the ability to burrow through the connective tissue or to spread. We call these benign tumours. Some of these have the capacity to grow into benign tumours, but in general they don't. This is why screening is so important because it gives us the opportunity to find these tumours while they are still benign. They can then be removed.

Mandy - It also gives us the opportunity for lifestyle changes like giving up smoking.

- What is the 21 grams postulate from 1907?

I'm researching the 21 grams postulate from 1907. What can you tell me about it or refer me to in order to prove or disprove this urban m...

What is the 21 grams postulate from 1907?

I actually had another email about this. It stems from 1907 and it comes from an American doctor, Duncan MacDougall, who tried to work out how much your soul weighs. People have thought for thousands of years that there's some life force or soul that makes us human, and when we die it leaves the body. As it exists, it must be made of something, and if it's made of something then it must weigh something. The easy way to find out how much it weighs is to weigh someone at the moment they die. What he did was to recruit six terminally ill patients, and selected ones that wouldn't thrash around too much at the time of death because that would obviously skew his results a little bit. He had this special bed balance made up and installed into his hospital. One patient lost, he says, three fourths of an ounce, which is twenty one grams. He then published this in American Medicine and it got picked up as 'the soul weighs 21 grams' and there was a massive splash about it. But actually it's wrong, because if you go and examine the rest of his results more carefully, you'll find that there's a little bit of a bias in how he's reported it. One of the people lost 21 grams; two of the people were discounted from the study for 'technical reasons'; a third person lost a load of weight and then put it back on again; and the final two lost a load of weight and then lost a load more, suggesting that they died more than once - I'm not sure! This is where this stems from, and it just shows that if you do careless research it can be quickly picked up and turned into a massive urban myth.

- Do mitochondria produce free radicals?

I've just been reading Superhuman by Robert Winston this week and never realised that mitochondria, the power houses of our cells, produc...

Do mitochondria produce free radicals?

There's no doubt about it, the best way to stop cancer would be to stop breathing or live in an oxygen-free environment. But it's not a good recipe for a lifestyle. Human beings, all organisms, are a compromise. We live in this very dangerous gas that does us a lot of damage, but it also happens to be the way that we generate energy, and mitochondria do indeed generate a lot of these oxygen radicals and they cause a lot of problems for us as we get older.

- Why don't they use radiation for brain tumors?

If radiation is so dangerous to cells, why don't they use it more for brain tumours?

Why don't they use radiation for brain tumors?

Radiation is everywhere so there's nothing you can do about it. But radiation is bad for cells because you get these high energy particles shooting through your body and through the cells. They damage the DNA directly and they generate these reactive species which further damage the DNA and cause mutations. Most mutations don't cause any problems, but very rarely you'll mutate a gene that's fundamental in regulating cell growth, survival, or where the cell moves and spreads, and then you're on the way to potentially forming a cancer. So in the right places, radiation is good because it can be used in the right places and the right doses to destroy cells. Radiotherapy is used for a variety of cancers, including some brain cancers. Part of the problem seems to be that a lot of the cancer cells, by the time they're presented as a clinical disease, pretty much don't care how much damage they have anymore. In order to become the tumour cell they have, they've had to throw off all the responsive mechanisms that would normally curtail the cell from growing, and you end up with replicating glass beads that you can't do very much about.

- Does radiotherapy or chemotherapy make hair fall out?

Upon-Tyne - My mum is currently having chemotherapy and radiotherapy. What makes her hair fall out, and is radiotherapy worse if it's dir...

Does radiotherapy or chemotherapy make hair fall out?

The reason that chemotherapy makes your hair fall out is that the current chemotherapy treatments we have are very aggressive drugs. They kill cells that are growing fast. This usually means cancer cells, which grow quickly, but also your skin cells, your hair cells and your gut cells are all growing quickly. They are also affected by the drugs, and that's why you get side effects such as feeling sick and your hair falling out. Hopefully some of the new treatments that Fran and people are working on are going to be much more targeted and only hit cancer cells and not the other cells.

- How can I get bladder cancer at 24?

I'm 24 and I was diagnosed with bladder cancer earlier this year. How did this happen? I'm only 24?

How can I get bladder cancer at 24?

It's very difficult to talk about individual cases, and in general it's very hard to say. I just hope that he has very good treatment. It's extremely rare in someone so young. Most cancers in that age group are skin cancer, melanoma and testicular cancer, so I think that it would be very difficult to pin it down on any particular thing.

- Why does cancer kill you?

Gerard said earlier that all cells want to expand and grow and live. So why does cancer kill you? Why don't you just end up as some massi...

Why does cancer kill you?

That's actually an important question and one of the questions I ask my students when I'm teaching: why does cancer kill? It's not simple. I think what it tells us is that if cells don't grow in the right way and they start mucking up the blood supply and the nerves and the normal function of tissues, your body can't cope and that's what kills you. So cancers basically erode the normal functions of your organs and your tissues, and that's why it kills you, although different cancers kill in different ways. In fact you can keep cancer cells growing forever, you can take them out of a patient and put them in a petri dish and off they go forever and ever. There are some cancer cells that have been around for so long that they mass of cancer cells in the world is something like a thousand times that of the original patient. So in principle you could live forever as a large lump, but I wouldn't want it.

- Could we cure cancer with blood transfusion?

A while ago I was in an experiment where we were told that some people's blood fights cancer. Her idea was that once you've had an operat...

Could we cure cancer with blood transfusion?

The idea is that your immune system, which normally fights infection and bacteria, can also respond to any tumour cells that arise in your body. It's something that people have been thinking about for about 50 years. I started my career off as a tumour immunologist, as it's called. I think the jury's still out. There's no doubt that you can raise antibodies and cells that kill enemies; you can raise those against cancer cells. Whether you can do that naturally or whether we can make it happen by manipulating things is still not clear, but it's a very promising area. So in principle the idea is sound; we just don't know how effective it's going to be.

- How are stem cells being used in cancer research?

How are stem cells being used in cancer research?

How are stem cells being used in cancer research?

Stem cells are being used in many ways. One idea, and it's still an idea, is that cancers actually arise from stem cells. These are the small number of cells in the body that are capable of reproducing indefinitely. Most cells in the body don't. They are usually either differentiated or can only go a few times and then they cop out. The idea is that cancer cells, because they can propagate indefinitely, arise from a stem cell compartment. This is still a new idea and there are a lot of good arguments going on about it, but we really don't know. The other idea is that if you expose a patient to a severe therapy and you start to kill off normal tissues, if you could keep the patient alive and repopulate those normal tissues, then the patient will make a full recovery. To do that you would need to propagate the stem cells in the patient in those tissues.

- How does mRNA get from the nucleus to make proteins?

I'm an A-level biology student and I'm interested in knowing how mRNA from a gene gets from the gene in the nucleus out to the right plac...

How does mRNA get from the nucleus to make proteins?

We don't really know in detail, but what we know sort of happens is that as soon as the messenger RNAs are made, they are complexed in this protein particle. That particle is then transported in a system that requires a lot of energy through special pores in the nucleus and out the other side. It then attracts via a chemical reaction and congregates with various machinery for activating synthesis of those proteins. If you're asking me how each individual particle is moved around, that's the big mystery. How do cells know who they are and what they are and how do the bits themselves know who they are and what they are? I wish I knew!


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