This week, medical uses of cannabis. What’s the hype and what’s the reality? We hear from the people who grow it, and the people who want to use it.
Plus in the news, scientists grow replacement lungs in a lab, why a knock on the head can lead to dementia years later, and the very tiny thing that elephants are terrified of - and no, it’s not a mouse!
In this episode
00:56 - Scientists grow lungs in a lab
Scientists grow lungs in a lab
with Joan Nichols, University of Texas Medical Branch
Thousands of people die every year on transplant waiting lists. There just aren’t enough donor organs to meet the demand. Which is why the announcement this week, by scientists in the US, that they’ve managed to grow - in a culture vessel called a bioreactor - new human-sized lungs that can be implanted successfully into pigs, is a huge step forward. Joan Nichols is at the University of Texas Medical Branch at Galveston…
Joan - There are never enough donor organs for people who need to have a lung transplant and that’s people with severe lung disease who we can’t do anything for. People that do go onto transplant lists have long waits for organs and many people even die before they ever receive an organ, and that’s been an issue overall in transplantation since the process began.
Chris - So the issue is one of organ shortage? We just don’t have enough donor organs so what can we do to surmount that?
Joan - One of the ways that we have talked about in my research team is finding a way to make lungs for somebody who needs them. And right now that means using lungs that are discarded, that can’t be used for transplantation and finding another use for them, as either a source for cells to create a new lung, to bioengineer a new lung or as a source of a scaffold, and that’s the other part of this process that we need. We need both a source of cells and a source of a lung scaffold, and we’ve developed procedures to produce scaffolds from lungs that can’t be used for transplantation themselves.
Chris - So that’s the aspiration; that’s the goal where we want to be. We can grow someone a bespoke lung, or at least a lung that’s going to be compatible with them and we can overcome some of these shortcomings of the present situation. What have you got to do in order to make that possible?
Joan - I would start by making a human scaffold, by taking a lung that’s been very damaged and has no live cells left in it. Treat it with a special solution that removes all of the cells but leaves behind the proteins that are the structural support proteins that give it the strength and elasticity that a lung needs to have.
Second step is we take another lung. Again, not suitable for transplantation but has live cells in it this time and remove the cells from all the parts of the lung that make it a lung. And then we prepare to put them together to produce a new lung.
Chris - So you, in summary, get the donor lung; get rid of all the cells just leaving behind this protein scaffolding, which is going to show the cells which is going to be incoming where they need to go; put it into this bioreactor which contains nutrient solution - I presume you’ve got a supply of oxygen there to keep these cells alive and to feed them and then you just slowly add the cells onto this scaffold in order to encourage the right cells to take up residence at the right place?
Joan - That’s exactly what we do. And on a regular basis we add in cells or factors that help support this. Just like a recipe for making a cake, every time we did this for the study we did it exactly the same way to prove that using these procedures we could consistently develop tissues that were lung tissue.
Chris - How long does it take to grow a whole lung of the sort of size a person would need?
Joan - It takes roughly 30 days at this time to produce something that’s still immature, that will continue to develop once it’s transplanted.
Chris - What animals have you done this on, because people have tried to grow lungs in a dish for small animals in the past?
Joan - Those studies with small animals were critical to what we’re doing now. We’ve done it in a large animal model; we’ve done it in pigs. And, by the way, we’re giving the animal one bioengineered lung; they still have one lung that they can survive on that’s there own natural or native lung.
Chris - How many pigs have you looked at and what happened to them?
Joan - Of the four pigs in the study that received bioengineered lungs, they all survived for the length of time that we had wanted them to, so that’s ten hours, two weeks, one month, or two months.
Chris - Does it work? Does the lung actually appear to be exchanging oxygen and carbon dioxide as it should do?
Joan - That’s a huge step, so let’s start with a small step. The tissues survived. The animals didn’t show any respiratory distress or have any fluid development in the lungs or any problems associated with it. The part about oxygenation is a little bit harder because the way that we did this process we were not going to be able to see gas exchange.
But in our next pilot study we will actually go for a long term survival of animals where we bring them back after being back in the farm for maybe a year. We block off their ability to breath from their native lung and we let them breathe on the bioengineered lung alone.
Chris - If the lung is continuing to grow when it goes into the recipient, does this mean then that you could take say a child with cystic fibrosis - a chronic lung condition because of a genetic problem - fix that condition in the new lung that you give them, and then that lung would grow with them?
Joan - That’s what our hopes are. Even before dealing with something like cystic fibrosis, looking for a compassionate use, which just means that somebody cannot survive unless we provided them with this therapy. Perhaps a child that has something called Diaphragmatic Hernia, where the diaphragm doesn’t develop and that blocks development of the lung. These babies cannot survive without some intervention and that’s what we’re looking at in terms of first use for this kind of procedure.
06:17 - What is the Fields Medal?
What is the Fields Medal?
with Bobby Seagull, Cambridge University
Now you may have heard of the Nobel Prize, but the Fields Medal might be less familiar to you, but it’s the equivalent of a Nobel Prize for mathematics. This week, the efforts of four mathematicians were recognised with Fields Medals. To explain, Izzie Clarke spoke to Cambridge’s favourite mathematician, University Challenge mastermind, and friend of the show, Bobby Seagull. So what is the background to the Fields Medal?
Bobby - The Fields Medal is awarded for outstanding mathematical achievement for existing work. However, unlike the Nobel Prizes, it’s only awarded every four years at the International Congress of Mathematicians for between two to four mathematicians that, I guess, represent a diversity of mathematical fields.
However there is a catch, there is a condition and medalists cannot be aged 40 at the start of the awarding years, you’ve got to be 39 or under at the start of 1st Jan. And this is because the medal also recognises the promise of future achievement. the prize fund isn’t relevant, there is a 15,000 Canadian dollar award - that’s about 9,000 British pounds.
As you know I’m a quiz fan, so for those of you who are film buffs I have a maths related University Challenge style starter for ten quiz question. Are you ready?
Izzie - Oh, of course.
Bobby - Fingers on buzzers. My best Paxman voice: which 1997 Oscar nominated best picture film has the actor Robin Williams introducing an unrecognised maths genius to his Field Medalist’s university friend?
Izzie - Oh ding, ding, ding. That is Good Will Hunting - Matt Damon.
Bobby - Ten points.
Izzie - Yes!
Bobby - If anyone’s ever seen the film they actually mention the Fields Medal there. So definitely go and watch that film.
Izzie - Okay. So who has won it this year?
Bobby - This year they’ve awarded four. They don’t always have to award four. I think in 2002 they awarded two winners but since then they’ve sort of been encouraged to give four. The youngest person this year is Peter Scholze; he’s only 30 from Bonn University. Then second we have the Italian Alessio Figalli; he’s 34 and works at ETH Zurich. And then third we have a 36 year old Australian who researches in America called Akshay Venkatesh. And then the fourth winner is someone a bit closer to home…
Izzie - Now I’ve heard that this person is at Cambridge University, so what do they work on?
Bobby - Correct. Professor of Maths in the Department of Pure Maths and Mathematical Statistics is Professor Caucher Birkar. He was raised in the Kurdish region of Western Iran and moved to the UK in about the year 2000, and I think he did his PhD at Nottingham before moving to Cambridge. And his work showed that it was possible to bring order and find connections between apparently unrelated algebraic equations.
So just as a reminder, I’m putting on my Mr Seagull teacher hat back on so mathematical equations can be depicted as shapes so, for example, Y = 2X + 3 is a straight line. Another one, X squared + Y squared is 9 - that’s a circle. You still with me?
Izzie - I’m still following yeah.
Bobby - Algebraic geometry is about studying the shapes that can be described by these equations. And as mathematicians, we try and put an order to this variety of equations. As a normal person, if you looked at an animal and you tried to classify them you might think oh, some of these have wings like a seagull, or some of these are carnivorous like a cat eating mice.
But Birkar, his work was trying to understand one of three generic categories and these are called Fano varieties. But, unfortunately for Birkar his original medal, the Field Medal, was stolen after he left the medal in a briefcase with his mobile and wallet on top of the table, and they found the briefcase but not the medal. So this sounds like a sad story but it has a fairytale ending, he was given another medal, and he says he’s become more famous because of this. And actually the Fields Medal has had a bit more attraction in the media because of this. In a way, the theft has worked out well for mathematics.
Izzie - Not that we’re encouraging theft at all!
Bobby - Not at all, not at all.
Izzie - What did the other three work on?
Bobby - Peter Scholtz, he’s a young 30 year old, his research is something called P-adic Geometry. P I think basically stands for prime numbers. And Scholtz’s main innovation was on something called Perfectoid spaces - and that is a real word. This is a class of fractal structures and he’s essentially built a new bridge between arithmetic and geometry, so he’s is the first one.
Then the Italian, Alessio Figalli. His results actually provided a refined mathematical understanding of things that, for example, the shape of crystals or the weather patterns, and even the way that a block of ice might melt. Many of his results actually rely on the use of a technique called Optimal Transport. And curiously enough, this originated in the 18th century when a mathematician was working for Napoleon - and it is the Napoleon in the Abba song. This mathematician was trying to find out an efficient way to build network fortifications, and Figalli essentially - the optimal transport problem is about finding the cheapest way of transporting a distribution of maths from one place to another.
Then we come to the final person, Akshay Venkatesh. And he wasn’t awarded for one specific thing but more profound contributions to a broad range of subjects such as building connections from number theory to something quite distant such as algebraic topology or dynamical systems.
12:03 - Sustainable food: Munching on maggots
Sustainable food: Munching on maggots
with Miha Pipan, Entomics & Cambridge University
We waste 1.3 billion tonnes of food around the world every year. But now a company in Cambridge, called Entomics, has found some hungry individuals who are not bothered by sell by dates to feed it to. These diners are maggots; or more accurately, fly larvae, which will eat just about anything. And when they’re well fed, they grow quickly and turn into a rich source of fat and protein, which makes ideal fish food for farmed salmon in Scotland. So far so good. But now, the Entomics team think that their maggot-based meal could find favour with a host of other animals too, helping to recycle wasted food safely. Marika Ottman went to the Entomics laboratory to speak with Chief Scientist and cofounder Miha Pipan.
Miha - We're currently in our biological R&D lab at the Department of Veterinary Medicine in Cambridge, and this is where the magic happens. Food waste, things that come off farms, packaging and sorting plants, it’s blended and the insects eat the food waste, they will fatten up. We’re starting with the insects being sub-milligram range - really tiny things that you can barely see and they can grow up to about 300-350 milligrams even, and that is almost like a thousand-fold increase in weight. The insects are then taken aside and processed to create a meal that can be then blended into a final feed for any particular animal.
Marika - Can I see a sample of this meal that you’ve developed?
Miha - Sure. I could show you a few that we have here. Actually, they smell really good surprisingly.
Marika - It smells like dog food!
Miha - Dog food, chocolate, you know. But it’s not probably as bad as you’d expect given that it’s maggots feeding on food waste. Not the most glamorous of work.
Marika - It looks like dirt, honestly. It doesn’t look like much.
Miha - No, exactly. This is some of the processed samples. I’m also going to be a crazy worker over the past three years. I would say there’s a hint of coffee in there.
Marika - As you’re the connoisseur I see there’s a lot of variety in these samples. Are you specialising them? What’s the next step in this process?
Miha - This is really what our process is all about it’s taking the samey sort of substrate that the maggots particularly what we’re working with at the moment is black soldier fly larvae. And then from them deriving essentially a variety of tailored meals for particular animal species, and one could even say going to the level of tailoring these formulations to particular stages of those species: juveniles, adults or senior animals. They obviously have slightly different nutritional requirement but, ultimately, quite a lot of it is linked to performing the feeding trials with the animals. Only then can we really realise is all the signs that’s been done to date, and all the expert opinion going into this. is that actually right. And that really comes down to being good at collecting samples and asking the right questions.
Marika - Possibly the most important question: do the fish like this?
Miha - They haven’t complained yet.
Marika - Five star review.
Miah - I’m not sure if it’s a five star review but the results have been quite favourable. We kind of want to really try some pets soon - cats and dogs. From the human side of things being the person who actually tries these, I would say there’s still some room for improvement.
Marika - You’ve eaten it?
Miha - Someone has to. And if I’m not going to do it myself then how can I expect someone else to do it - right? Currently it’s focused on animals but you could easily change it to humans as well.
16:00 - How head trauma leads to dementia
How head trauma leads to dementia
with Willie Stewart, University of Glasgow
People who receive repeated knocks on the head, like sports players, or individuals who get head-injured in car accidents and falls, are at higher risk later in life for a form of dementia similar to Alzheimer’s Disease. Why this happens though, no one knew. But Glasgow pathologist Willie Stewart has been studying the brains of patients with a past history of head trauma. He’s found deposits of a protein called tau throughout their nervous systems. And by studying animals with similar brain injuries, it looks like the initial trauma provokes the formation of tau aggregates at the injury site, which then alarmingly promote their own formation elsewhere around the brain, spreading along nerve pathways, damaging nerve cells and triggering dementia. The good news is that now scientists know this, it might be possible to develop a way to stop it, as Chris Smith found out...
Willie - In many of the studies that have looked at people surviving brain injury they report that there is an increase in the risk of of Alzheimer's disease. But we’re also getting better at recognising that in many of these cases it’s a distinct form of dementia different to Alzheimer's disease and it’s one that we call Chronic Traumatic Encephalopathy or CTE for short, and it used to be known as Boxer’s Dementia.
Chris - How long after the injury do you tend to see these manifestations?
Willie - Well, patients who turn up clinically with problems it’s often several decades after the injury and the problem is what’s happened in that time from when they were exposed to brain injury to the development of dementia. What we were doing in our study was looking at people with a shorter period of survival to try and get a picture of that timeframe in between.
Chris - So what did you actually do?
Willie - We did two things. Firstly, we looked at material from patients who’d survived a brain injury. On average about five years after brain injury and looked at what their brains looked like compared to normal ageing brains. And what we found in that was that they had a deposition of an abnormal protein in their brain which we then went on to look at in an animal model to see if we could replicate that and figure out what was happening in these patients.
Chris - What was the protein that you found there that shouldn’t be?
Willie - What we found was an abnormal protein in the brain, or abnormal form of a protein in the brain called Tau. Actually it’s a protein that we’d normally have in our brains to kind of hold the structure of the brain together. It’s a very important protein but sometimes, for reasons we don’t understand, that protein can become abnormally processed or abnormally folded, and it’s that abnormal protein that causes problems down the line. So that’s what we were looking for and we saw this in greater quantities in wider distribution in patients who’d had a brain injury than in normal ageing.
Chris - So when you say it’s in a wider distribution, so rather than just seeing it where their brain was worst affected, you’re saying it’s everywhere or in more places than just the primary injury site?
Willie - Again, we were looking at patients who’d survived quite some number of time after the original injury, and what we found was that tau protein was throughout their brain. In normal ageing it can just be in tiny spots here and there as part of an ageing process, but we found it was spread throughout the brain more like you might see, again, in patients with Alzheimer’s disease or CTE.
Chris - Was the buildup of the protein associated with some kind of other damage to the brain, as in, can you say that where you see that tau protein there’s also evidence that the cells are dying or the brain is changing in those areas?
Willie - Certainly we can say that that abnormal protein is toxic to the neurons in the brain and causes further problems, but also there are other things happening too. I think what we do though is take those observations in our human material, which is really important and we take that back into a stripped back animal study where we can look at specifically what’s happening to the neurons at that point.
Chris - How do you know the tau protein is there and it’s damaging the brain in that area rather than some brain was damaged in that area and it left behind some tau protein?
Willie - Well, that’s a brilliant question. And that’s really what we tried to set out to do. Because we can see this in Alzheimer’s disease, and we can see this in CTE, and we can now see it in our patients after a single brain injury that they have this abnormal tau protein. And our question was did that protein appear as a result of some other process in the brain so that other damage that the injury had done had caused the tau protein to be deposited, or is the tau protein actually the real problem?
Chris - Which do you think it is?
Willie - That’s what our research has probably uncovered here - at least part of the story. Because what we can do with the animal model is that we can create a similar injury to what our patients had - a thing you might get with a car crash, and we can follow the progression of that tau pathology over time. And what we found is that it’s that abnormal tau protein that appears to migrate through the brain and appears to infect, if you like, the rest of the brain.
Chris - So there’d be an injury which is centered on say one brain region. The injury would trigger the formation of some of this abnormal form of this tau protein and it would then propagate along the nerve pathways that the injured areas connected to and begin to deposit tau in other areas that are anatomically linked?
Willie - That’s exactly it. That’s certainly what our evidence strongly supports. Obviously, this an initial study showing very strong evidence suggesting that that’s what’s happening. Now what we need to do is start to do the really clever stuff and figure out exactly what’s happening at the cellular level. More importantly, if we can figure this one out, we might actually have a way of trying to treat patients and avoid people getting dementia in this way.
Chris - Do your findings inform how we should manage head injury better in the future?
Willie - Yeah. That’s the really exciting thing that we’re taking forward from this research is that here we have a potential target, an abnormality that develops at the time of injury that seems to be partly responsible for driving later disease. So this abnormal tau protein formed at the time of injury seems to then go on and propagate through the brain, so if we can in some way figure out a means to stop that happening potentially what we could do is prevent the dementia developing later down the line.
22:17 - Elephants, buzz off!
Elephants, buzz off!
with Agenor Mafra-Neto, ISCA Technologies
While we may get exasperated by the plagues of wasps that inevitably arrive alongside summer, here in the UK most of our wildlife is relatively easy to control. But if you’re a farmer in some parts of Africa you might have a much bigger problem to contend with - elephants. But how can farmers fend them off without harming them? The answer is to prey on their fears… Georgia Mills spoke with Agenor Mafra-Neto, CEO of ISCA Technologies.
Agenor - One of the biggest problems that Africa has with the population of elephants is that they basically bulldoze. They are animals that reshape the environment… What is going on right now is that the elephants don’t necessarily respect fences and they invade those areas and they cause problems and elephants raid crops. When a herd of elephants get into a farm it can be the destruction of that family’s or that village’s whole year crop.
Georgia - And this destruction of crops leads to increasing tensions between people and the elephants which can escalate…
Agenor - Sometimes the elephants get killed.
Georgia - With elephants already in danger from poaching and habitat loss reducing this conflict is important for everyone involved. So how do you get an elephant to respect a fence?
Agenor - One of the ways that people started playing with was looking at what elephants are afraid of.
Georgia - And it turns out there is something that even the mighty elephant is afraid of… bees.
Agenor - They are aggressive protecting their beehives and they sting the elephants in very very sensitive areas, especially the trunk and around the eyes and into the ears. So the elephants hate that and it seems like it works, like they are really afraid of bees. They are not afraid of elephants or rhinoceros or anything like that but they are afraid of bees.
So what people in Africa started doing, especially the growers, they started putting beehives on the fences and they found out that the elephants were respecting those fences now.
Georgia - Right. It doesn’t sound exactly practical to line your fence with bees then, so what have you done that’s different?
Agenor - One of the things that a bee does when she stings you is that she leaves an alarm pheromone that this chemical induces the other bees to come and sting you. The elephants they smell that so this study that we did showed that the elephants no only can smell the alarm pheromone but the respect the area that has this alarm pheromone.
Georgia - How do you isolate this pheromone? Are you sort of squishing alarmed bees down together? How are you isolating it?
Agenor - The alarm pheromone of bees is something that people have studied before, and they published the composition of this pheromone years ago. The problem here is that the alarm pheromone has dozens of components and it was important that we used components that were inexpensive and make them readily available. So we needed to come up with a simplified blend so we decided to go with a couple of components that were simpler, easier to make and we thought that could convey that chemical message to the elephant.
Georgia - The team tested out this “elephant bee gone” in the field spraying the formula onto socks on fences. And 25 out of the 29 elephants that approached the pheromone socks turned and left.
Agenor - When we started having success with the response of the elephants it was really really great because it allows us now to have a formulation that is extremely inexpensive that is affordable for these growers and parks, and anyone that is trying to contain the elephants, so they can create this chemical fence.
Georgia - Do we have any idea what affect this is going to have on the rest of the ecosystem? Is it going to confuse the bees maybe?
Agenor - I’m not sure if it’s going to confuse the bees necessarily because they usually respond to the alarm pheromone when they are close to the beehives. So maybe if these alarm pheromones are close to beehives we are going to have an affect, but otherwise I don’t see a problem. In relationship to other animals, I’m not sure. I don’t think so and that’s something that in some places is important to determine if there are any other species that is being affected by something like this.
Medicinal cannabis in society
with Gary Potter, University of Lancaster
This week, we’re putting the medical use of marijuana under the microscope. Chris Smith and Izzie Clarke hear from Faith, a mother who is keen to try cannabis oil to control her daughter's epilepsy. Plus Gary Potter, a Senior Lecturer in Criminology at Lancaster University, explains the history of cannabis.
Faith - I saw around one years old that she had started to have some seizure activity. Eventually they got worse as she got older. When she got to two years old she was having 130 seizures a day. The seizures continued and we tried numerous medications but, unfortunately, they left her with lots of side effects. And at that stage, with Addenbrooke’s, we decided all together that we would stop trialling drugs. Obviously, this was quite a shock to hear at that stage and realising that we’re actually going to live our lives with epilepsy.
She generally is a happy child. She’s loving but, obviously, she’s having these blackouts every few seconds that stop her retaining the information. She did actually start to say a few words when she was younger. It was garden and baby brother, but then her epilepsy got so bad and we never heard them again, and now she only says yes and no. So that’s what we’re left with.
I feel that her world is very unsafe and confusing for her and I just feel that if cannabis was available to us, and we could at least try, then we could see if it works. It would be nice to do it with full medical support so that we don’t have to be doing something illegal. We should all be entitled to the treatment that is available. None of us should have to live with epilepsy when there is a treatment there for it.
Izzie - Faith, describing what’s happening to her daughter, and how she’s keen to try cannabis oil to control severe epilepsy.
And in this half hour we’ll investigate the story of cannabis, find out how it works, talk to the people who are growing it - quite legally - in Britain, and hear why it might be able to help people like Faith’s daughter...
Chris - Now cannabis, or marijuana, comes from the Cannabis sativa plant, usually in the form of dried leaves, flowers, and stems. There are hundreds of different chemicals floating around in cannabis, and we don’t actually know what most of them do...
Izzie - ...but the ones that are of interest to us are the ‘cannabinoids’. There are 100 or so in the plant...
Chris - ...But the two we know the most about are cannabidiol and tetrahydrocannabinol - CBD and THC. These are also the cannabinoids which are also present in the largest quantities, with THC is the responsible for the ‘high’ that recreational users of the drug are looking for.
Izzie - These molecules are very similar in shape to chemicals used in our own bodies when some groups of nerve cells communicate... And it’s by mimicking the action of the brain’s own chemical signals that cannabinoids have their effect...
Chris - But what’s the history of cannabis, where did its use originate, and when did it become illegal? Gary Potter is a Senior Lecturer in Criminology at Lancaster University:
Gary - The medicinal properties of cannabis have been recognised for at least 5,000 years. They’re referred to in ancient Indian medical texts going back to at least 900 BC. Referred to in ancient Chinese medical texts going back to at least the first century AD. It came to the UK around the mid-19th century. It was brought to Britain from Calcutta and then widely prescribed for a number of medical complaints, particularly migraines and chronic pain. It was banned for recreational use in 1928 following international agreements to outlaw cannabis.
Izzie - So why was it banned?
Gary - Initially, cannabis was banned in recognition of international agreements to try and control certain narcotics. International discussions were mostly focussed on heroin, opium, and to an extent cocaine and coca. Cannabis was brought into those discussions just by a minority of countries that were concerned with some of the moral implications of cannabis use amongst their populations.
Izzie - That’s interesting. How have things progressed since then?
Gary - After 1928, the initial ban for recreational use, cannabis remained clinically available in the UK until it was reclassified and prohibited under the Misuse of Drugs Act in 1971. The Misuse of Drugs Act was again a follow-on from international law, from the UN Single Convention of 1961, and again, the placing of cannabis in the tightest of restrictions internationally was particularly led by America and a couple of other countries and not really considered by the rest of the world.
Izzie - Is there some sort of scale of legalisation?
Gary - Within the Misuse of Drugs Act, in the UK law, drugs are placed under different schedules. Cannabis is currently a schedule 1 drug. A schedule 1 is reserved for the drugs that are perceived to have absolutely no medical benefit. The placing of cannabis as schedule 1 was contrary to the available scientific evidence even at the time, but was ultimately a political decision. Since then, there’s been an increase in scientific and medical evidence and the current discussions are about moving some cannabis products into schedule 2. Schedule 2 drugs are still very tightly controlled but are recognised to have some medical benefits and, therefore, may be available for prescription by doctors for certain conditions.
Izzie - Is it this discussion of progressing medical cannabis onto schedule 2, what we’re hearing so much about?
Gary - Yes. The current proposal by the government is to move some cannabis medical preparations into schedule 2. Not to move cannabis as a whole into schedule 2, but just some preparations of cannabis. But, at the moment, it’s very narrowly focussed on epilepsy and maybe a couple of other conditions.
Izzie - Who actually uses medical cannabis?
Gary - It’s hard to be sure because, as a controlled substance, people don’t necessarily admit to their use. But research would suggest that thousands, and possibly tens of thousands of people in the UK are using cannabis for some kind of medical benefit. This particularly include conditions such as chronic pain, multiple sclerosis, nausea reduction, eating disorders, sleeping disorders, anxiety disorders, epilepsy, various neurodegenerative disorders, migraines, schizophrenia, even cancer amongst other things.
Izzie - We’ve seen it in the news quite a lot recently so what are the varying attitudes towards medical cannabis?
Gary - Well I think that we would recognise that there are some people that deny any medical benefits at all. They point to the current legal system; they say it’s scheduled as a schedule 1 drug, which implies that there is no medical benefit and the take the law as based, if you like, on the evidence. Other people, based on anecdotal and historical evidence and personal experience, would suggest that cannabis is useful for a huge range of medical conditions. But perhaps the sort of middle ground there is that increasingly there is good scientific evidence as well as anecdotal and historical evidence that for certain conditions, for certain people, certain preparations of cannabis are objectively beneficial.
Izzie - I’m glad you mentioned that because it’s been approved in the US, but what’s the legal situation in the UK like? Are attitudes changing in the current climate?
Gary - Attitudes are changing. We have seen a number of countries around the world and a number of states in America, although not America as a country, that are recognising the medical benefits and are making provision for legal supply of cannabis for medical purposes. People in the UK are seeing this happening elsewhere and it’s happening in some highly industrialised, democratic countries such as America and Canada, and people are saying it’s clearly not a black and white issue. These other places are recognising the medical benefits, why not here. Then of course we’ve had a couple of very high profile media cases recently, particularly around epilepsy. The two young boys with a serious form of epilepsy and that, of course, has attracted media attention. So you’ve got the focus on those high profile issues and the background of change around the world.
Izzie - Given your expertise, do you think it will be legalised?
Gary - We’ve seen suggestions of a movement already to legalise very limited preparations of cannabis for very limited conditions. At the moment, most of the conversation has been around epilepsy. I think that is a first step. If nothing else, it acknowledges that there are at least some medical benefits of cannabis, and moving even some preparations to schedule 2 will open up research into other uses of cannabis for medical reasons. So, I think we maybe will see an increase in the availability of cannabis or cannabis derivatives for an increasing number of medical conditions. But I think we’ll still be a long way off from any discussion about legalising for recreational purposes and the government have made it clear that’s not on the agenda at the moment...
36:27 - What are the effects of medicinal cannabis?
What are the effects of medicinal cannabis?
with Harry Sumnall, Liverpool John Moores University
There is such a mismatch between the law and the scientific evidence. But what does the science say about the effects of cannabis? To find out, Chris Smith was joined by Harry Sumnall, Professor of substance use at Liverpool John Moores University...
Harry - Well, as you mentioned in your intro to this piece, cannabis itself is a very complex plant and it contains hundreds of different chemicals, mostly notably the cannabinoids. You’ve already spoken and CBD and THC which are the cannabinoids that most people are familiar with if they know anything about cannabis. But cannabis also contains lots of other chemicals as well, so other cannabinoids, CBG, THCA, CBN. the list is almost endless. But there are also aromatic chemicals as well called terpenes and this gives cannabis its distinctive smell. But when we think about whether it’s the recreational use of cannabis or the therapeutic effects, most of the focus has been on CBD and THC.
Interestly, the body has its own cannabinoid system. And actually, one of the first endogenous cannabinoids, the body’s own cannabinoids was a drug called anandamide, which is derived from the Sanskrit word for joy and bliss which is rather appropriate.
But the body has two main sets of receptors and these are these chemical locks which cannabinoids and other chemicals act upon. There’s the CB1 receptors and these are located in the central nervous system, and these control functions such as pain, memory, appetite, and even muscle tone as well. There’s another set of cannabinoid receptors - the CB2 receptors - and these are in the periphery, and even in some cells associated with the immune system.
So going back to those two chemicals, THC and CBD, THC acts in the central nervous system and therefore has profound effects on neuronal function, and perception, and all those other functions that I mentioned. CBD doesn’t have a psychoactive effect because it’s acting at CB2 receptors. And, interestingly, this is why CBD is not controlled under the Misuse of Drugs Act which Gary was just talking about.
Chris - And that’s why you can buy it in health food stores, for example. So, basically, what you’re saying is you have in your body a system of communication between cells, including brain cells, which have on their surfaces these receptors or docking stations that these chemicals bind to, and cannabis subverts the system we have naturally in place? It triggers it artificially which is why it then produces these effects?
Harry - That’s right. And we know a bit about THC pharmacology so it has direct pharmacological effects. We know less about CBD. It doesn’t seem to have this direct affect on those receptors, but it may seek to modulate the function of other hormones and neurotransmitters as well. We’re finding a lot more about it.
Chris - Does it matter how you take the drug into your body? Because, obviously, there are a range of different routes in. You could eat this for example. You could swallow the oil that people are talking about. Some people also smoke these drugs. So does it matter how you take it?
Harry - Yeah. Route of administration is very important. So lots of routes of administration, so if you smoke it, it’s inhaled, it’s absorbed through the lungs, you feel the effects within a few minutes. If you eat a cannabis product it needs to be absorbed through the gut and then get into the bloodstream to the brain, and that can take half an hour or an hour.
Anecdotally, some patients also report people who are using it for medicinal purposes, the different routes of administration also have subtly different medicinal effects as well, but that is largely anecdotal.
Chris - When we’re talking about things like relief of pain and so on, do we know which of these different systems, the central nervous system or the peripheral effects are most important in achieving those benefits?
Harry - We think for pain relief, then the CB1 system is primarily important there because they are receptor sites, these locks, which are directly located in the central nervous system. There’s lots of interest in the use of cannabinoids and cannabis derived medicines for treatment of epilepsy for example. Now some of the effective drugs that we have there are working on the CB2 system which are outside of the central nervous system and, therefore, they’re having some novel and unusual effects which you wouldn’t usually associate with anticonvulsants that are usually prescribed.
Chris - We’ve dwelled very much on the medical side of this, Harry, but what about the psychological and emotional consequences of people using things like cannabis?
Harry - We know a lot about the potential negative effects of so-called recreational cannabis use. If we’re thinking about what the potential negative effects of medicinal use are, then there is already a body of knowledge there. I think it’s quite important to separate some of those harmful effects with recreational use from medically supervised use.
A lot has been discussed popularly about mental health impact of cannabis, and I think sometimes there’s a tendency to completely discount the mental health effects. But there is some good evidence to show that the particularly high risk individuals, maybe individuals who've had a greater susceptibility to psychosis, for example, that are regularly using cannabis in whatever form, whether that’s oral, whether that’s smoking, is not a good idea. And regularly using cannabis, particularly at early ages, can increase the risks of experiencing psychotic symptomatology.
Chris - But some people argue, Harry - sorry to interrupt - that people who are at risk of developing those conditions are just self-medicating, and they’re taking the cannabis because they’re beginning to experience mental ill health and it makes them feel better, rather than the cannabis comes first and causes the mental ill health downstream?
Harry - I think there’s probably a lot of truth in that perception. We do know that from some of the surveys and studies that have been done that when particularly young people in their early teens, when they begin to experience some of these symptoms, unusual symptoms, they do report that smoking cannabis can actually make them feel “normal.”
There’s also some interesting research which also suggests that even the tobacco that people mix cannabis with in this country in joints might also increase the risk of psychotic symptomatology. So I think the exact mechanisms are unclear, but I think there’s a very simple public health message, particularly for young people, is to delay use of cannabis and also to reduce frequency of use as well. Regularly using cannabis is not good for your mental health.
Chris - So far we’ve talked about side effects in one particular tissue - brain tissue. If you’ve got this wide distribution of receptors all round the body, are there side effects in other organs and tissues and, therefore, would a person experience things other than just maybe mental ill health if they abused cannabis?
Harry - I think the honest answer to that is we don’t quite know. If we look at the some of the clinical studies which have been undertaken with some of the pharmaceutical preparations then patients do report side effects. These can be side effects related to some of the psychoactive effects, so confusion, many memory problems, or excess sleepiness. But then also some patients are reporting physiological side effects as well, gastric disturbances for example. So the potential is there, but I think we don’t know a lot about this and how counter this because we know so little about how cannabis related products are actually working, so we don’t know a huge amount about the pharmacology.
44:26 - Drug development: from pot to pill
Drug development: from pot to pill
with Stephen Wright, GW Pharmaceuticals
How do we go from a plant - containing hundreds of different active molecules - to a safe drug where the doses can be easily and reproducibly measured out? One company who grow cannabis and turn it into medicines, including a preparation for epilepsy called Epidiolex, is GW Pharmaceuticals. Isabelle Cochrane went to see them...
Stephen - I’m Stephen Wright. I’m Senior Medical Advisor to GW pharmaceuticals having been Chief Medical Officer for the last 14 years.
In 1998, the House of Lords Science and Technology Committee produced a report which started from the observation that people were using cannabis allegedly as a medicine. And they felt that rather than simply clamp down on people who were using cannabis for medicinal purposes, it would be better to see if there is a genuinely medicinal use for cannabis or for components of the cannabis plant. GW was setup at that time specifically to try and meet the requests to determine whether there is genuine medicinal value in the cannabis plant or its components.
Isabelle - It’s not unusual for a medication to originate from a plant. For example, the active component of aspirin is also found in willow trees. But taking a tablet for a headache is clearly quite different from chewing on a piece of willow bark. Similarly, taking a cannabis derived medicine for a complex medical condition is a million miles away from smoking a joint. So how do we get from pot to pill?
Stephen - There are three main pillars of drug development: quality, safety, and efficacy.
The first of them - quality - means can you guarantee that the process you use for producing your medicine produces exactly the same medicine one week as it does another week. When you’re developing medicine based on a plant that is a particular challenge because have many many components, each of which has to be present in the same proportion with every batch that you produce. And it’s a challenge that has to be satisfied not only in the finished product that you produce but also at every stage of it’s production, so the plants we produce have an essentially identical chemical composition from batch to batch, week to week, growth to growth. Of course, within that you have to recognise that in the UK, which is where we grow our plants, cannabis is a schedule 1 drug so everything that we’ve done has been under licence and under inspection by the Home Office.
Isabelle - Once the quality of your drug is assured, meaning you are able to extract it from your plants and manufacture it reliably, the other two pillars Stephen mentioned - safety and efficacy - are determined as with any other pharmaceutical drug in pre-clinical and clinical trials. The end product of this process, in the case of Epidiolex, is pure CBD as a syrup, so you can just pop it on a spoon and swallow it. On the surface of it, sounds like cannabis oil, so is this much different to the various medicinal cannabis preparations you can get on the street?
Stephen - The material that has been seized by police forces around the world are quite demonstrably is more and more and more rich in THC, which is what sought by recreational users. So I think it’s become more difficult to determine what people mean by medicinal marijuana or medicinal cannabis since the plant has been manipulated by growers with a particular aim in mind.
When people have gone through a systematic analysis of cannabis oils and other products sold sort of on the street, what they found is that around half of them contained no cannabinoids at all, let alone the cannabinoids that the claim to contain. I think this emphasises you have to ensure the quality of the medicine that you’re giving to patients otherwise it’s tinkering. You don’t know what you’re doing.
Isabelle - So, perhaps as you might imagine the key difference between a pharmaceutical grown cannabis preparation and the stuff you get on the street is that, in the case of the medicine, you know exactly what’s in it. You’re guaranteed to have the active ingredient in there, but you should also be safe from getting high from your medicine since the levels of THC and CBD, even in the plants themselves are tightly controlled.
But, in the eyes of the regulatory bodies, this does not change the fact that the medication is derived from a plant which is use mainly as a recreational drug…
Stephen - There are certain preconceptions about some medicines that mean the body of evidence you have to produce in order to demonstrate safety and efficacy may be a bit bigger than you might have to produce in other circumstances. And I personally think that medicines based on cannabis do fall into that category.
We are also obliged during development to show whether a drug has a liability for abuse, so are people likely to abuse it? And part of that is does it get diverted away from the patient into the general population? Now it’s very clear, and the Home Office is very comfortable through their advisory body, which is called the Advisory Committee on the Misuse of Drugs, that that has not happened with our cannabis containing medicines, and that’s in marked contrast to some other medicines.
Isabelle - But what does the public think?
Stephen - I think the general public probably has the same preconception that a medicine based on cannabis may get you high. And I think that there has been a duty on us to produce a very substantial body of evidence that it doesn’t. Fortunately, we do have the tools, the measurement techniques, which have enabled us to overcome that particular hurdle.
Isabelle - So what can we expect in the future?
Stephen - There are a lot of cannabinoids, and we believe that a number of them may have therapeutic potential. So what we’ve done, and continue to do is to take out individual components of the plant, or combinations of them, and to explore the therapeutic potential of those individual components or combinations in our preclinical models
50:39 - Can medical marijuana treat epilepsy?
Can medical marijuana treat epilepsy?
with Hannah Cock, St George's Hospital - London
How do drugs like Epidiolex work, and who might they help? Hannah Cock, Professor of Epilepsy at St George’s in London, joined Chris Smith in the studio.
Hannah - Epilepsy is not one disorder, it’s hundreds and hundreds of different types of disorder but, essentially, it’s a disorder of the brain characterised by recurrent unprovoked seizures and by a range of associated biological, sociological, and psychological consequences. So things like memory problems, difficulty functioning, anxiety, and so on. There’s an enormous spectrum from people who are, essentially, 100 percent normal other than for the few minutes when they have their seizures to people with much more complex and very frequent events.
Chris - What about the mechanism of their epilepsy that means it might be amenable to being managed with cannabis?
Hannah - I don’t think we know the answer to that question yet. With respect to Epidiolex or indeed any other drug, the drugs are being tried in particular rare syndromes at the moment but that doesn’t mean that the drug won’t prove to be effective in other types of epilepsy in the future.
Chris - Do we have any idea as to what it might be doing to the nervous system in order to make the seizures less serious? Do we understand actually how it influences epilepsy when people use these agents?
Hannah - With respect to cannabidiol which is the CBD, which is the one that’s been best studied rather than THC, we don’t know how it works in epilepsy. It doesn't seem to be by the CB1 and CB2 receptors that were mentioned earlier. It might be affecting some of the brain’s own mechanisms that stop seizures being there all of the time. Most people with epilepsy aren’t fitting 100 percent of the time. We have our own internal switch that stops seizures so there’s a lot of interest that it might be influencing that, but we don’t really know.
Chris - I wondered if because people are swallowing this whether rather than it going into the brain and having an effect, it might be influencing perhaps the bacteria in the intestine - the microbiome, the nervous system that supplies the intestine - therefore other parts of how the body is working and that in turn is having a knock-on effect which is having benefits of how the brain responds?
Hannah - There’s absolutely no evidence to support that. Epilepsy is a disorder of the brain and actually these drugs they’re very very fat soluble and so they do penetrate the brain very readily even when you swallow them.
Chris - What might be the long term consequences for someone who uses one of these cannabis-like agents if they treat their epilepsy with it, because they’re going to be doing that chronically for a long period of time aren’t they?
Hannah - Yeah. And I think with respect to the agents that contain THC we do know that long term use is associated with problems. With damage to memory and thinking, to mental health and brain structure, particularly in children who seem to be very vulnerable to this. With cannabidiol, that’s why doctors and scientists have focused so much on cannabidiol rather than the THC components. And we don’t yet know what the long term consequences might be because these are relatively new trials and that people have been taking them, some people for up to a few years. But we don’t know what the long term consequences might be yet.
Chris - It’s rather worrying to me that we’re considering changing the law and perhaps allowing people to try these agents, admittedly in people with severe disabling epilepsy, when we don’t actually know how they work.
Hannah - Any new drug, any advance in medicine, there’s always a degree of uncertainty when it’s first licenced and first available because, by definition, there won’t have been decades of evidence. And that’s why it’s so important that if people do take these drugs it’s part of a well regulated controlled study, and with the knowledge of the health professionals so that we can monitor in the long term what the side effects might be.
We do also know that even in the short term there’s a bit of an urban myth that these drugs don’t have side effects - they do. One in three people in the studies who took cannabidiol did have side effects like diarrhea, reduced appetite and vomiting, and in about 1 in 23 people, there were quite serious side effects. So it’s not that these are blanket safe, much better than existing drugs. We don’t know that yet.
Chris - So not to be taken lightly. Thank you Hannah Cock, St George’s, University of London.
Izzie - So the take home message is, yes, there is truth in the idea that cannabis-based products have medicinal value in some cases for some medical conditions. But on the flip side, there is still a whole lot we don’t know about it.
55:09 - What makes a non-stick pan non-stick?
What makes a non-stick pan non-stick?
We had this question from Martin. To help out with this sticky situation, Adam Murphy spoke to Jess Wade, a materials scientist at Imperial College London, to get her take...
Adam - It’s a question that leaves people ‘stuck.’ Why does a single layer of black stuff on a pan turn it from an after dinner, eldritch cleaning nightmare to well, still a chore, but a much easier one?
On the forum, Tomassci says one word - Teflon. And they might be onto something.
To get the answer, we put the question to someone who wouldn’t ‘slip up,’ material scientist Jess Wade of Imperial College, London to see what she had to say.
Jess - In the 1930s, Roy Plunkett, a chemist at DuPont was trying to find a new refrigerant material. At the time, sulphur dioxide and ammonia were used in fridges but they were killing people in their homes.
One day Plunkett was making an alternative, a safer gas called tetrafluoroethylene and he stored it in super cold cylinders at -80 celsius. When he went to chlorinate it, he found out the gas wasn’t a gas anymore but had turned into a white powder which was resistant to heat, chemically inert, and super slippery. Although he had to saw the gas canister in half to find that out.
Adam - So, Plunkett had made a mistake, but like any good inventor he was about to turn it into something revolutionary.
Jess - Plunkett had created polytetrafluoroethylene, which we know today as Teflon. Metals that we make pans from like stainless steel aren't actually perfectly smooth. If we look at them with a microscope you actually see lots of cracks and holes. When the heat up, the metal expands, food seeps into the cracks, dries up and makes them tricky to clean.
Adam - As anyone who’s spent and evening scrubbing an old metal pot can attest to. But coating in in Teflon changes the game…
Jess - But if your pan is coated with Teflon the metal surface becomes much smoother. So smooth in fact, that geckos can’t stick to it, and geckos can even stick to glass. That’s because PTFE is made of long chains of fluorine and carbon really strongly bonded together. That means that they don’t want to interact with anything - even water.
Adam - Things that repel water like this are called hydrophobic. And it’s Teflon’s hydrophobic nature and really low friction that make it so non-stick.
Jess - Teflon’s not entirely perfect. If the temperature goes above 260 celsius, it starts to break apart, releasing fluorocarbons into the air. And if you cook mega-hot regularly, falkes of it can sneak off stopping your pan from being non-stick. Me and my dad love our non-stick pan.
Adam - And how does the Teflon stick onto the pan in the first place? Well, that bit’s easy. You just need to really really rough up the pan first.
Thank you to Jess for giving us something to ponder while we fry our breakfast.
And while we’re pondering, next week we’ll be answering this question from Geoff:
It’s often stated that there are more stars in the universe than there are grains of sand on all the beaches on Earth. My question is - who counted?