Memories: Making Them & Faking Them

19 September 2017
Presented by Chris Smith.

This week, we’re taking a trip down memory lane. How scientists can implant false memories, wipe memory away, and the link between head injuries and Alzheimer’s disease. Plus, in the news, farewell to Cassini, the science of hurricanes, and how scientists are now able to see what’s in the atmospheres of remote planets hundreds of light years away.

In this episode

bacteria

01:08 - Bacteria block cancer chemotherapy

Could bacteria be conspiring with cancer to block the action of chemotherapy drugs?

Bacteria block cancer chemotherapy
with Ravid Straussman, Weizmann Institute

Could bacteria be conspiring with cancer to block the action of chemotherapy drugs? According to scientists in Israel, bacteria can get inside tumours, and even inside cancer cells themselves, and then use their own metabolic machinery to protect the tumour by breaking down anti-cancer treatments, like the drug gemcitabine. Chris Smith spoke to Ravid Straussman…

Ravid - They can either come from the bloodstream, the tumours, or because we were exploring pancreatic cancers, they might come from the gastrointestinal tract. We can see them in different methods, we can characterise them, we know which bacteria they are, and we know it can really affect the sensitivity of these cancer cells to chemotherapy.

Chris - How do you know that it is the bacteria that are doing that and it’s not just that the bacteria are there like a bystander because you’ve got abnormal cancer tissue, the bacteria has settled there, and they’ve got nothing to do with the resistance to the drugs?

Ravid - We know in the laboratory that when we take cancer cells and we put chemotherapy on them it’s really easy to kill them but, when we add specific types of bacteria into this culture of cancer cells, the cancer cells become completely resistant to chemotherapy. We found that bacteria can inactivate the drug by cutting it. We also can show with mice models with a cancer and bacteria, the cancer of the mice becomes completely resistant to chemotherapy. But, if you treat these mice with antibiotics, then you can re-sensitise these tumours to chemotherapy.

We do see the same bacteria in human patients. We know that this bacteria have the genes they need to degrade the drug but it’s hard to know what would be the effect of eradicating these bacteria from human tumours.

Chris - So your hypothesis is that people who don’t respond very well to their chemotherapy or develop drug resistance, at least a subset of those patients may well have tumours in which they’ve got bacteria in the tumour and the bacteria are breaking down the chemotherapy drugs so that they don’t kill the cancer cells?

Ravid - Right. We profiled the 113 pancreatic patients and we found bacteria in the majority of them. Bacteria were found between the cells and even inside the cancerous cells and we know, as we said before, that these bacteria have the right capacity to degrade gemcitabine. From here one can only postulate that if you have bacteria inside the cancerous cell and it can degrade gemcitabine, probably it is going to protect the cancerous cells from chemotherapy, but someone would need to do clinical trials in order to validate how important this mechanism really is.

Chris - What specifically where the bugs that you found?

Ravid - We found many bugs, many types of bacteria; some of these you know like e coli or salmonella. The one thing in common to all these bacteria were that they all have a specific enzyme called CDD, which stands for Cytidine Deaminase, and can come in a short or long isoform. We found that only bacteria with the long isoform of CDD can degrade the drug gemcitabine. When we looked into these patients, in the tumours of these patients, we found that many of them have the bacteria of long CDD isoform.

Chris - So that means that particular flavor is capable of breaking down the drug, it’s in those bacteria, so it puts the weapon, the smoking gun, at the scene of the crime and in the hand of the bacterial criminal, doesn’t it?

Ravid - Yes. We also isolated these bacteria and were able to demonstrate that bacteria isolated from pancreatic cancer patients, from the pancreatic tumours, can degrade gemcitabine that we add in the lab to these cells.

Chris - What about doing the experiment where you take tumours and add bacteria to those tumours that have this drug degrading ability, can you then confer on the cancer resistance to the chemotherapy by adding only the bacteria?

Ravid - We did a few of these experiments. We took mice models of cancer, and if we put inside the bacteria with the long CDD isoform, these mice models of cancer become completely resistant to therapy. Then, if we treat them with antibiotics, together with gemcitabine, then we can make these tumours go away. Another type of experiment that we did, we took mice models of cancer, put bacteria inside of them, but we changed one very small piece in the DNA of these bacteria making CDD positive bacteria into these CDD negative bacteria. Then, all of a sudden, these mice are responding to chemotherapy.

Cassini and Saturn

06:08 - Celebrating Cassini's "Grand Finale"

Cassini's 20-year mission exploring Saturn comes to an end, but what did it find?

Celebrating Cassini's "Grand Finale"
with John Zarnecki, Royal Astronomical Society

Friday the 15th of September marked the end of a 20-year long journey for the spacecraft Cassini because it was purposefully crashed into the atmosphere of Saturn. It took 7 years to reach Saturn from Earth and has been exploring the system of rings and moons for the past 13 years, transmitting data back to scientists at NASA and the Europeans Space Agency. John Zarnecki, who is now the President of the Royal Astronomical Society in the UK, but also helped to build the Huygens probe, which was part of the Cassini spacecraft, was with us to help us celebrate the end of Cassini and reflect a bit what it discovered. Starting off, Chris Smith wanted to know why Cassini needed to end with a crash... 

John - We got to the point where it was literally running out of fuel and it wouldn’t have been possible to control it for any longer to do the fine pointing altitude maneuvers that you need to do detailed scientific measurement. So this was planned destruction if you like, and the safest way to do it from a scientific perspective by burning it up in Saturn’s atmosphere.

Chris - Some commentators have pointed out that by doing this in advance of it running out of fuel and maneuvering it onto this trajectory, which began back in April of this year, it enabled scientists to gain insights into bits of Saturn that would have endangered and imperiled the probe possibly previously?

John - Yes, that’s absolutely right. For the last few months the orbit, which has been changing in such a way that it would eventually end up crashing into the cloud tops of Saturn, but the orbit took it diving between the innermost ring of Saturn and the top of Saturn’s atmosphere. So that’s something pretty risky that you’d never have done during the regular part of the mission but, on this final dive, Cassini came closer in than anybody or any craft had ever been before and so it was able to collect some unique data. Normally the data is stored onboard and then slowly beamed back the Earth but, of course, because of the destruction of the craft that data had to be sent back literally as it was collected.

Chris - Has that data arrived? Do we have it?

John - Yes. Scientists have it and they’re pouring over it at the moment. There was a press conference just a few hours, I think, after the demise of Cassini from the final images taken, which I think were taken the day before the final demise, they were able to work out exactly where Cassini plunged into Saturn.

They’re pouring over the data, and I think what’s going to be particularly interesting is the magnetometer data, so this the magnetic field. It’s one of few ways, maybe the only way, that you can say something directly about what’s going on at the very centre of  Saturn because the magnetic field is generated in the core otherwise, of course, we’ve got really now way of getting to the centre of Saturn.

Chris - One of the other interesting things about Saturn that no-one can explain, perhaps this will shed new light, is the whole question that the top half of Saturn seems to rotate at a slightly different speed than the bottom half, doesn’t it, and we don’t really understand how it can be doing that?

John - That’s right. I think that the rotation is one of the mysteries and, of course, it’s been collecting data ever since Cassini arrived, which was back in 2004. Although there have been something like 4,000 scientific papers published already from Cassini and the Huygens probe, the truth is that this data is going to be analysed for probably the next 20 years.

Chris - It’s also the biggest geyser in the solar system isn’t it? Or at least, not Saturn, but one of its moons, Enceladus, and that was another big Cassini first to discover that enormous plume coming out of this tiny moon.

John - It was and, of course, that was one of the big surprises. Enceladus is a relatively small, 500 kilometre, sized moon. We knew a little bit about it but we didn’t expect anything dramatic to come from it. But, of course, it was found that it is, in fact, spewing out not just water but there seemed to be organic molecules as well so this means that this is a rather active place.

It’s not beyond the bounds of possibility that within Enceladus where there’s almost certainly a subsurface ocean below, or at least large pockets of water below the icy surface. There could even be the simplest form of life living quite happily there.

Chris - I’m going to share with people, John, because our relationship goes back about 20 years. Because you came to Cambridge University when I was a medical student at Cambridge University and you gave a talk because you had helped, as one of the team members, to design this Huygens lander that you said at this talk “I’m going to send this thing aboard Cassini and it’s going to travel through space for 7 years.” I thought that was mind-boggling for a start. “I’m going to send this thing to land on the surface of Titan,” which is Saturn's largest moon. I didn’t touch base with you again until 7 years later and that’s when Cassini arrived in the Saturnian system and then you send me a text message on a phone, which has long since died, but I still have the phone. I still have the message and it says, “pyros blown, probes away!” and that was you deploying the Huygens lander down onto the surface of Titan. What was that like seeing all that 20 years plus of work to get that out there?

John - Gosh. Well yes, you’ve brought back quite some memories for me. We had 7 years of developing the instruments and the probe. Launched in ‘97 and then arrived at the Saturnian system in 2004, and it was Christmas day when Cassini released Huygen. So that was the message that at least told us that Huygens had been let loose and it was on a collision course with Titan.

I’m not a poet, I’m a mere scientist, so I find it hard to find the words to describe the emotions that you feel because, when you work on a space project like this, it really almost totally takes you over. You belong to it, body and soul, and so it’s very emotional.

Heart beat on a digital screen

13:26 - Fuel pumps help heart failure

How have rocket fuel pumps helped those with heart failure?

Fuel pumps help heart failure
with Stuart Higgins

What happens when the science and technology of space comes Down to Earth? This week, Stuart Higgins explores how NASA's fuel pumps have helped to develop more efficient heart pumps back down on Earth.

Stuart - Welcome to Down to Earth from the Naked Scientists. The miniseries that explores the spinoffs from space technology that are being used in life on Earth. I’m Dr Stuart Higgins…

When David Saucier, a NASA engineer, suffered from a heart attack in 1983 little did he know that it would spark a collaboration between the space agency and doctors. After receiving a heart transplant Saucier ended up chatting to his heart surgeon, Dr Michael DeBakey, and realised there was a need for effective heart pumps. The pumps, known as ventricular assist devices, help support a patient with heart failure while they’re waiting for a transplant. However, the existing ones were large, cumbersome and prone to clogging.

Soon, the NASA engineers were meeting the medical team at the Baylor College of Medicine in Houston, Texas to help design a new kind of pump. The engineers were experienced in designing high-performance fuel pumps for the space shuttle. These pumps are used to maintain the fuel injection rates into the rocket engine to ensure consistent levels of thrust.

Together with clinicians they developed a miniature high-performance pump that could be fitted inside patients. The pump helps minimise the strain on the heart while the patient is waiting for a transplant, and the team hopes in the future that the pump itself might ultimately be used as an alternative to transplants.

One of the problems with existing pump designs was that they let regions of slow-moving blood accumulate around the pump. This led to coagulation and clotting causing serious problems in the patient when the clot was suddenly released and got trapped in a blood vessel in another part of the body.

In order to overcome this, the engineers simulated the blood flow through the pump using the same techniques and approaches developed for the space programme. Their computer model allowed them to develop specially shaped inlets and outlets in the pump that reduced dead regions and hence clotting. These changes also minimised the damage to blood cells caused by friction with the pump’s surfaces.

The heart pumps have now been successfully implanted in hundreds of patients worldwide with further trials ongoing. Although there is one side effect to having a pump supporting your heart and that’s a lack of detectable pulse. Although, according to one journal article, after some initial confusion nurses treating patients quickly got used to this.

So that’s how the expertise in modelling fuel pumps for rocket engines has been used to develop a new heart pump for patients suffering with heart failure.

That was Down to Earth from the Naked Scientists and join me again soon to learn about more space technology that’s changing lives back on Earth.

Hurricane Maria

16:21 - Are hurricanes getting stronger?

Late summer is typically hurricane season in the tropics, but what's the science behind these extreme systems?

Are hurricanes getting stronger?
with Nick Klingaman, University of Reading

Late summer is typically hurricane season in the tropics, and in 2017 hurricanes Harvey and Irma have wreaked havoc across the Caribbean and southern USA. Irma is the largest such storm we’ve ever seen. Katie Haylor has been looking at the science behind these extreme weather systems...

[News Items] 

The Governor of Florida has said 20 million people would have to leave their homes…

My house is just gone…

The damage is of unprecedented scale…

The World Health Organisation say 17,00 people across the…

The Royal Fleet auxiliary ships delivered 6 tons of aid to Anguilla which was hit by the full blast earlier in the week…

Hurricane force winds have begun to hammer the US territory of Puerto Rico. The eye of the storm...

Katie - Hurricane Irma is now one of the most powerful storms on record in the Atlantic basin. With winds reaching upwards of 180 miles an hour, the storm has decimated homes and caused chaos across the Caribbean and parts of the USA. Here’s tropical meteorologist Nick Klingaman, from the University of Reading…

Nick - A hurricane is a very large, organised, cluster of thunderstorms essentially, and they can be hundreds, if not thousands, of kilometres across. They tend to form across very warm tropical oceans where there’s lots of heat and moisture available to feed into these thunderstorms. Hurricanes are always associated with an eye in the middle and then these tightly rotating spiral arms of thunderstorms that come out around them.

Hurricanes need a few ingredients to be able to form. First of all, they need very warm ocean surface temperatures so that they can extract a lot of heat and energy from the ocean. They need moisture available in the atmosphere which is why they tend to form in tropical oceans where it’s quite warm and most. They also need a source of rotation because hurricanes are very tightly packed, organised, rotating clusters of thunderstorms, and these sources of rotation often come from waves in the atmosphere…

Florida is now feeling the full force of hurricane Irma. It’s spent many days moving across the Caribbean…

Nick - Forecasts of hurricane intensity tend to be quite reasonable these days. Often we can predict the intensity of a storm several days to a week in advance of it making landfall. Forecasts of the intensity of hurricane Irma, for instance, were highly accurate and we knew days in advance this was going to be a very severe storm for the islands in the Caribbean and for the South East of the United States.

We use very high-resolution weather forecasting models which run on massive supercomputers with tens of thousands of processors to forecast these storms and, indeed, the weather worldwide. Those computer models require observations of the atmosphere all around the globe. And particularly for hurricanes, we get additional observations from reconnaissance aircraft which fly out literally into the storms dropping probes and taking measurements with instruments onboard the aircraft to feed those data into our computer models to help us better predict the track and the intensity of these storms.

Katie - So these are manned aircraft that are literally flying into the storm?

Nick - These are manned aircraft. They’re operated by organisation like the National Oceanic and Atmospheric Administration in the United States, and they do fly right into the storm of all intensities. At the peak of hurricane Irma when the winds were 170/180 miles an hour, you had reconnaissance aircraft flying in there around the clock.

Katie - Rising global temperatures means there’s more energy and more water in the atmosphere. So, considering the devastation Irma has caused for thousands of people, what would the hurricanes of the future be like?

Nick - We do expect that with climate change hurricanes will become more intense. We don’t necessarily expect that they’ll become more frequent but we do expect that they’ll become a little bit stronger. Particularly we might see strong winds, more intense precipitation associated with hurricanes, and stronger storm surges because of sea level rise.

planets

20:43 - Exoplanet atmosphere explored by astronomers

What chemicals can we find on the planets outside our solar system?

Exoplanet atmosphere explored by astronomers
with Ryan MacDonald, University of Cambridge

Next year marks 30 years since scientists detected the first planet outside our own solar system. These are called exoplanets and, since 1988, nearly 4000 more have been confirmed. Now astronomers are going a step further and can even uncover what chemicals are in the atmospheres around these remote worlds and work out what the conditions are like there. Izzie Clarke went to see Cambridge University space scientist Ryan Macdonald who’s been gazing at a planet 800 light years away called WASP-19B. Previously, they knew only that it was a gas giant, Jupiter-sized and sizzlingly hot...

Ryan - We didn’t really know what to expect. We thought there might be hydrogen and helium in the atmosphere but what we were trying to do is tease out the trace molecules, things that we might not even see on any other planets in our own solar system. Firstly we confirmed that there is water in the atmosphere. This had previously been seen in 2013, but what made our measurements unique was that they were of such high resolution and so precise that we were able to go beyond just seeing the water and actually find small traces of sodium in the atmosphere and crucially, for the first time, a definitive detection of a truly alien and strange molecule titanium oxide.

Izzie - Why is that so rare and does this tell us anything about this exoplanet?

Ryan - The reason why this is particularly special is that titanium oxide is a very strong absorber of ultraviolet light, much like ozone in the atmosphere of the Earth. What this means is that the very upper layers of this planet’s atmosphere will start to warm up due to the absorption of ultraviolet light. And, as you might expect on the Earth, whenever a particular area of the atmosphere warms up, it can actually drive strong winds around our own planet. It’s how things like hurricanes work on the Earth. So, the fact that there is a layer of this strange molecule strongly absorbing ultraviolet light will drive strong winds around the planet that could dramatically alter the nature of the planet’s atmosphere.

Izzie - How do you even go about finding this because, obviously, this exoplanet is not in our solar system, it’s very far away so how on earth can you do that?

Ryan - We use a clever technique called transmission spectroscopy. What we do is we stare at the light from the parent star and we wait until the planet passes in front of it; it’s almost like a shadow tracking across the face of the star. Now, when we observe this at a number of different colours of light and, in fact, we looked in blue light, green light, and red light, what you see is that the size of the planet changes depending on the colour you look at. Because, if you look at a colour where the atmosphere is completely opaque, the shadow appears to be slightly larger. Then, if you look in colours where the atmosphere’s transparent, it’s slightly smaller. So, by turning a dial where we change the colour of the light we look at and see how the size of the planet changes, we can use this to extract the chemical composition of the atmosphere.

Izzie - What sort of device are you using? Have you got something out in space that is tracking this?

Ryan - You can absolutely use telescopes in space but for these particular observations we actually use a telescope on the ground - the very large telescopes down in Chile. This is a very exciting observational breakthrough because the fact that telescope’s on the ground are now catching up, and perhaps even going beyond what we can do in space at the moment, is incredibly promising for what we’ll be able to do in the future with an entire new generation of telescopes that are being built right now.

Izzie - Do you think in the future we could actually look into even more greater detail of exoplanets and their atmosphere?

Ryan - Absolutely! At the moment we’re still in very early phases; we’re just doing preliminary investigations of these atmospheres. In the near future, when we have a new generation of telescopes in space such as the James Webb Space Telescope, and new telescopes on the ground such as the Extremely Large Telescope, that’s when we’ll be able to detect brand new molecules like oxygen and ozone for the first time. It’s detecting molecules like that in earth-like atmospheres, that we’ll be able to do perhaps in the next 5 to 10 years, that is what we’ll need to do if we really want to get a handle on whether there is life elsewhere on the universe which is our long term focus in the field.

what is memory?

25:44 - What are memories?

What are memories? And where are they stored?

What are memories?
with Amy Milton, University of Cambridge

What do we actually mean by “memory”? Izzie Clarke has been investigating and began by asking some people she bumped into on the street to recollect their earliest memories...

I remember dancing on my dad’s feet while listening to old 60s music and singing at the top of our voice.

It’s a really hot day and the Sun’s streaming through and I’m checking on stones that we collected from the seaside and we painted images on them and faces.

Amy - Probably the first memory I can remember very distinctly was playing in my parent’s garden.

Izzie - That’s Amy Milton; she’s a psychologist at the University of Cambridge…

Amy - They used to have, I think it must have been a concrete fence post that I used to stand on to look over and chat to the kids in the neighbours garden, and one day I fell of it and fell back onto my foot and then ended up giving me an enormous bruise. I can still remember that quite clearly.

Izzie - Recounting her first memory, Amy not only remembers the pain of the concrete block, but also the event itself. So do we have different types of memory? Well… we have short term, which is really short like the ability to remember a phone number for just a few seconds while you need to dial it and then, poof, it’s gone. But our long term memory is a bit more complicated...

Amy - There are two very broad types of long term memory that we have. There’s declarative memories and these are memories that you can pass on in words, and that would include memories for events. We refer to this as episodic memory because it’s talking about episodes, but it would also include semantic memory which is memory for facts.

Izzie - Episodic memory or event memory is the ability to account things like where you were when you passed your driving test, or the day you graduated…

Amy - We think about episodic memories as having three components: a “what,” a “where”, and a “when.” All three of those in one memory would be considered an episodic memory.

Izzie - How does a semantic memory differ from this?

Amy - A semantic memory is really the memory for “what.” We tend to think of that as being fact based. These memories aren’t necessarily entirely distinct from each other. Memories can move from one type to another.

The kids have started back at school fairly recently so they will be learning, for example, capitals of the world. You may have a small child coming home fairly soon telling you that they know that Paris is the capital of France and they could tell you who told them that information and where they were when the learned it. But, actually, we all learned that at school at some point but we don’t hold on to the where I learnt it and who told me because it’s no longer relevant.

Izzie - If you can describe it in words then it’s a declarative memory…

Amy - Alongside those we also have non-declarative memories which would include things like emotional memory, so memories that give rise to particularly emotional states and skill learning. So things like learning to ride a bike is clearly a memory but, they’re called non-declarative because you can’t pass those things on in words.

Izzie - So, we’ve got different types of memory but do we know where they’re stored?

Amy - We do know that different types of memory depend upon different parts of the brain. Event memory refers on the parts of the brain that sit right at the side by the ears; we call that the temporal lobe and, in particular, it depends on structures in the temporal lobe called the hippocampus. We know skill learning, for example, depends upon areas within your motor system, so the little tiny bit at the back of the brain called the cerebellum. But also, your motor cortex, for example, will show changes as you acquire a new skill.

Izzie - One of the most influential studies into this involved a patient called Henry Molaison who was known as patient HM until he passed away in 2008. Henry suffered from severe epilepsy and no medication seemed to help. So in the 1950’s surgeon, William Scoville, removed the front part of Henry’s hippocampus.

Amy - This was really good from the perspective of the seizures, they reduced markedly but Henry, from that point onwards, couldn’t form any new event memories. So he had this very, very profound amnesia which gave a very, very strong steer to the hippocampus being important for those type of memories.

Izzie - But surprisingly, there was a breakthrough from a psychologist called Brenda Milner…

Amy - What she managed to show was actually a lot of his memory was fine and skill learning was absolutely fine with Henry. So one of the tasks that she used was mirror drawing. He had to trace around within a very small outline, so something like a star, but he could only see his hands in a mirror. He had a screen that stopped him from seeing his hands directly, which is quite tricky but, with practice, you get much better at it. She found that he improved with practice on a single day, and she brought him back in the next day and he was better again, and if she brought him back in the next day he was better again.

Izzie - Even though HM didn’t remember doing this task he was still able to learn a new skill, showing that any skill based memory like drawing wasn’t associated to the hippocampus. But, when it comes down to it, where we actually store memories is an area that still has a few unknowns…

Amy - Looking at HMs case, for example, he had the surgery when he was in his late twenties. Events up to his early twenties he could remember pretty well - his teenage years, his childhood. He could still draw the floorplan of his parent’s house well into his 80s. From the moment of surgery he had no memory, and for a couple of years before that his memories were starting to be much less reliable. So, we know that very old memories don’t require the hippocampus because otherwise HM wouldn’t be able to remember them. We know that those memories go to the cortex so the question then becomes once they’re in the cortex, are they really episodic memories still or are they semantic memories that have become anecdotes about ourselves?

So, maybe I don’t really remember falling off the concrete post and hurting my foot, I’ve just told that story so many times that’s now part of my history and that’s now a fact about me and it’s now a semantic memory.

Deleting Memory

32:43 - ZIP: Drug that wipes memory

Can we delete memories? Scientists have created a drug that seems to do the trick...

ZIP: Drug that wipes memory
with Todd Sacktor, State University of New York

How we store memory is still a hotly debated area. One researcher, in New York, believes that memories are stored in the connections - or synapses - which he likens to leaves touching between adjacent nerve cell “trees”; the strengths of those connections, he thinks, are controlled by a chemical called “PKM zeta”, which is made at each synapse when a memory is first laid down. And what Todd Sacktor and his colleagues have done is to create a drug called ZIP that disperses PKM Zeta and appears to wipe out memories. 

Todd - There are 86 billion nerve cells in the brain and one could picture each nerve cell as a tree that has a thousand leaves, and each is connected to another leaf of another tree - another nerve cell. When two leaves are touching, one leaf releases a chemical, which we call a neurotransmit, and then the adjacent leaf receiving that chemical starts to quiver and we call this connection a synapse. A memory is formed when the leaf that is responding to the release of the chemical responds twice as much as it normally would and that is due to a molecule called PKM Zeta. So when a memory is formed the PKM Zeta molecule gets synthesised as a memory is being formed; the PKM Zeta then resides in that leaf in the synapse.

Chris - Is it fair to summarise then and say I learned something and I make those leaves, which are connecting these trees fire off and because they’re touching they fire off, they form this association, this connection, strengthened by this enzyme PKM Zeta so that the way in which the information is stored is in the strength of those connections, and when I recall a memory it’s basically every tree that connected in my little forest is shaking to recall that memory? It’s created a sort of circuit which is the memory of my holiday in Paris or the apple pie I had for dinner?

Todd - If you recall the sight of an apple then part of that network is starting to fire and then it reverberates throughout the whole network and then the memory of having a particular dessert in Paris comes into your mind’s eye.

Chris - I can almost taste it now. Does that mean that it’s very difficult to unlearn something because once I’ve got those connections between my mental trees, how do I weaken it again if I then discover I was wrong and I shouldn’t have learned that, I should have learned something different?

Todd - Well, what’s thought is that when the group of trees are all firing at the same time that the synaptic connection, the PKM Zeta, breaks down briefly and then gets re-synthesised. So this is an opportunity at that time to change the memory, to add more information that was correct, or to get rid of information that was wrong - to update the memory.  It’s this re-synthesis of the PKM Zeta that we might be able to control with drugs to basically erase specific memories or to alter them.

Chris - Does this mean then that if you were to go into a part of the brain where a memory is stored and wipe away or break down the PKM Zeta which is there stabilising that memory, you could wipe a memory out?

Todd - This has been done in experimental animals. A drug called “zip” has been given to experimental animals and what we find is that all of the memories in that part of the brain are wiped out, even memories that are months old. But the drug doesn’t seem to harm the brain because even though the memories are gone, once the drug is washed out the animal could relearn and the learning is fine, and the storage of the memory is fine.

Chris - But you mentioned that when we do recall a memory or revisit a particular mental process that the PKM Zeta that’s there strengthening that circuit and holding that memory does, temporarily, breakdown and then reform. So might there be a way, rather than just wiping it all out just to prevent it reforming temporarily because that would mean you could discreetly wipe away the memories you were thinking about rather than every memory which could be pretty deleterious, couldn’t it, to wipe away everything?

Todd - That’s right. There’s ways to block specifically the synthesis of PKM Zeta and that should be a powerful way of erasing a specific memory. Basically having someone recall a memory and then give the drug that inhibits the synthesis, and that the PKM will get broken down specifically at the leaves that are connecting up that specific memory. But then, they won’t get re-synthesised again so the memory will be dampened or erased by only in those leaves in which the PKM Zeta had been degraded due to the activation, the quivering of those leaves.

Chris - What about elsewhere in the nervous system because the nervous system isn’t just the brain? We’ve got a spinal cord as well and people say that that does a lot of learning, particularly when you’re little to teach you to do motor things like walk around, but also pain. Is it possible that you could wipe out the pain memory and reprogramme the person’s spinal cord so something doesn’t hurt any more?

Todd - Yes. I think that’s actually where the clinical use of a compound such as zip would be because in experimental animals chronic neuropathic pain is like a memory in the pain pathways of the spinal cord and zip erases that.

Chris - Are there any other applications, not in the spinal cord, but higher up the nervous system where you could see erasing memories as being something clinically very beneficial and useful as a tool?

Todd - We don’t want to erase all of our memories, all associations in our brain or even in parts of the brain. What’s required, I think, is to develop the way to inhibit the action of PKM Zeta for specific memories. So the idea would be to recall the memory that’s painful or extremely debilitating, like in post traumatic stress disorder or depression. And then give a drug that will block the resynthesis of PKM Zeta and that should diminish or erase those specific maladaptive memories and keep the rest of our memories intact.

Prison bars

39:51 - False memories lead to false convictions

How did 70% of people admit to a crime that never actually happened?

False memories lead to false convictions
with Julia Shaw, University College London

How would you feel if you sent an innocent person to prison? What if you confessed to the crime but you didn't actually do it? The way in which therapists or police question individuals can lead to the creation of a what’s called a false memory, which can then result in wrongful convictions. Izzie Clarke spoke to crime Psychologist and author of The Memory Illusion, Julia Shaw from University College London, who’s all too familiar with similar situations…

Julia - False memories are generally fabricated when we confuse something we just imagined with something that we actually experienced. So we think that we went to a party with a friend when really we did go to the party but the friend wasn’t there, so we’ve introduced a person into a setting that they weren’t actually in or, in the stuff that I study, we maybe think we committed a crime that never happened.

It’s a process whereby the brain essentially gets confused and often takes pieces that exist of real memories, so what a real person looks like, what a real situation is like, what a real space is like, and just puts those pieces together in a way that never actually happened.

Izzie - Thinking that your friend was at a party with you when they weren't compared to admitting or thinking that you did a crime are two different types of false memories. It’s quite a big difference between them! Looking into your research, what did your recent study set out to find?

Julia - In my study I set out to show whether we can get people to falsely confess to crimes that never happened and internalise that false confession, so to think that they actually committed this crime. So an assault, an assault with a weapon, or a theft, all with police contact. I didn’t just want to do it for fun, I wanted to show look, this might be really easy to do in a relatively benign interview situation. If you’ve got someone on the stand and the evidence is poor and all you’re relying on is their memory, you have to be careful.

Izzie - Talk me through that interview process. How did you actually have people believing that they committed a crime?

Julia - I contacted their parents ahead of time, so these were university students, and they knew that I’d contacted their parents. I asked the parents about events that happened when the participants were teenagers. Then I asked the participants to come in; they knew it was an emotional memory study so they knew we’d be talking about earlier events and emotional events. Then we started and we sat down and I said, "Okay, so your parents reported this thing happening", and it was a real event so the participant would start saying "okay, I remember that". So we’d go through the cognitive interview, which is currently best practiced for policing, and I’d go through "tell me everything you can remember about the events from start to finish". Then probing questions... "So you mention X tell me more about that." Over twenty minutes they’d build up the sense of "oh, she knows something about my life" and we’re building a rapport - I’m building trust.

Izzie - Is trust an important part of this?

Julia - Trust is a huge part of this. If the person doesn’t trust that you know more about their lives than they do then it’s not going to work.

Izzie - And then what did you do?

Julia - Then I introduced a second memory and this was the false memory. So I said "okay, when you were 14 years old your parents said that you assaulted someone with weapon and the police called your parents", which is allegedly how they found out. "You were with your best friend", and I inserted the name of the best friend, and you were in and then I inserted the name of the home town. So those two bits of reality added a lot of credibility as well.

Izzie - So the pieces about the location and the friend were true?

Julia - True from that age and these are easy things to picture. So, from that point on what I had them do - of course they said "I don’t know what you’re talking about", which is understandable because it didn’t happen. Then I said "would you like to try?" - the illusion of choice - "would you like to try this exercise? Which works for most people if they try hard enough". I said let’s do some imagination exercise. "Close your eyes and picture yourself at the age of 14, you’re with your friend so and so; where are you; where did this happen?" It’s building up what did it feel like to be there; "Why did you engage in this fight; what happened when the police came?" So building up these imaginary pieces but you can see they’re starting to buy into it. After three weeks, the way that I classified the memories, 70% had full false memory. So they confessed to these crimes that never happened and told me why it happened, what happened in multisensory details.

Izzie - Can you give me an example of what crimes we are talking about? The idea of a weapon sounds quite serious.

Julia - A weapon wasn’t a semi-automatic rifle - it was a rock. One girl was saying how she had a rock in her hand and she was attacking a love rival; she’d gone out and thrown this really big rock and every time she was sitting there during these interviews that happened three times, the rock got bigger. So she was really enacting in front of me this crime that never happened. It totally varied, but it had to fit within their life story.

Izzie - This was for research and it was quite controlled by yourself but say in an actual crime, and in a court situation, that can have really big implications.

Julia - In the real world, you can’t undo that process. If you start asking leading or suggestive questions, or you start doing imagination exercises where people confuse reality or experienced events with imagined ones, it’s hard to get rid of those. They can be really compelling and you can sit as a witness on the stand or you can be accused of a crime on the stand, and you can be saying all these memory details of this thing that you think happened that is untrue and you end up sending innocent people to jail.

Izzie - What can we do to prevent that situation?

Julia - What I want people to know is to know these things exist, first and foremost. So know that a false memory is a thing that can happen and in some ways trust your own lack of memory. As far as we know there’s no brain that is resistant to false memories. But also the justice system needs to know about it. I train military and police and I go and educate them on the science of memory and I say you guys really need to watch out with some of these interview tactics especially, for example, in the States, they use fake evidence - "we found your fingerprints at the scene" - that’s incredibly compelling. It’s about making sure that they’re proactively working against the creation of false memories because once they’re there they can be impossible to undo.

American Football

46:30 - Losing memory: Alzheimer's and Impact Sports

Do head injuries from impact sports lead to Alzheimer's disease?

Losing memory: Alzheimer's and Impact Sports
with Steve Gentleman, Imperial College London

According to the 2015 World Alzheimer’s report, 46 million people live with dementia worldwide, and this is predicted to climb to 131.5 million by 2050. The 21st September each year is World Alzheimer’s Day and neuropathologist Steve Gentleman, from Imperial College London, joined Chris Smith to talk about it. If you look inside the brain of someone with Alzheimer’s disease, what do you see...?

Steve - When I’m looking down the microscope, the disease pathology spreads through the brain in a fairly predictable manner. The first place you’ll see the pathology usually is around the hippocampus, in the cortex next to the hippocampus.

Chris - This is in the temporal lobe part of the brain where we think memories originate?

Steve - That’s right. The first symptoms often are people with Alzheimer’s disease will be that loss of short-term memory, so they won’t be able to lay down new memories. They’ll be able to tell you what they were doing 20 years ago but they won’t be able to tell you where their house keys are.

Chris - What are the specific changes that you see in the brain tissue that tells you that’s Alzheimer’s disease?

Steve - We stage the pathology by looking for abnormal proteins. One of the particular abnormal proteins maps very well with the progression of the disease; it’s called tau and it’s a protein found in the nerve cells.

Chris - You can actually see spots of this cropping up in the brain?

Steve - Yes. It shouldn’t be visible when we look down the microscope but when it’s laid down it’s aggregated, it’s causing problems with the nerve cells; we can actually see it.

Chris - That fits with the idea that you’re losing nerve cells and, if you’re losing nerve cells because of the buildup of this tau protein, then that could be consistent with why you’re losing your ability to form new memories because you’re compromising the cells that do that job?

Steve - Yes, exactly. You’re interrupting that circuitry which allows you to lay down new memories.

Chris - You’ve mentioned the protein tau, but there’s another protein called beta amyloid which is very said that’s the culprit or the cause of Alzheimer’s disease. Why have you avoided telling me about that one?

Steve - You’re right. A beta protein is a part of the diagnostic workup of Alzheimer’s disease but, in general, the clinical picture, the symptoms map much better to the tau pathology.

Chris - One of the things that’s made headlines a lot lately is this question of whether or not sportsmen and women are at increased risk of damage to their nervous system when they indulge in sports that have an element of repetitive head injury? American footballers, soccer players who head balls, rugger players, and so on. Is there evidence to support this?

Steve - There’s been a lot of interest over the last few years in this particular potential risk factor for Alzheimer’s disease. As you say, the NFL in the US, the American football players, colleagues in Boston have described this new pathological entity called chronic traumatic encephalopathy. The pathology seen is thought to be related to that repetitive mild head injury. Interestingly, the pathology is the same protein that’s found in Alzheimer’s disease; it’s a tau problem.

What’s different is it’s localised to certain areas of the brain, probably related to the head injury. As you know, the surface of the brain has got lots of convolutions and at the basis of the troughs, that’s where the pathology is found. Our engineer colleagues have been modeling this and, low and behold, this is where the forces are of a head injury are focused. So that’s a good building evidence that this might be cause and effect.

However, there’s also a lot of other things going on in the brains of these people so, at the moment, we can’t be absolutely certain about cause and effect. There are other disease processes going on, other degenerative diseases, so we need a little bit more work to be able to relate what we see down the microscope to the symptoms seen in these patients during their lives.

Chris - So marrying these two entities together, Alzheimer’s disease and then the repetitive head injury, they both produce evidence of damage having occurred to the brain. In one case it’s a sort of physical injury, in the other something else is causing damage to the brain which manifests as a build-up of this tau protein and possibly the beta-amyloid protein we mentioned. In both cases though there is damage to nerve cells and loss of nerve cells which is going to ultimately affect the way your brain works.

Steve - That is correct, yes. Both of them will involve nerve cell loss, shrinkage of the brain called atrophy, which has been put down to that nerve cell loss.

Chris - What about doing something about it because, obviously, there may be people who are quite worried. Professional footballers like Wayne Rooney who’s just finished his professional career in more ways than one, possibly, who are now quite worried because they’ve spent their lifetime heading balls. What can they do?

Steve - It’s difficult to say. To be perfectly honest we don’t know what the risk is. What’s the relative risk of a head trauma in terms of your life risk of getting dementia? There are well-known risk factors, mainly related to your vascular health. So your brain weighs about one and a half kilos; it’s quite a small proportion of your body weight, but the brain takes a fifth of all the blood coming from the heart, so it very demanding so you need to keep your blood vessels healthy.

Chris - So the motto of that then must be a healthy diet, don’t smoke, exercise?

Steve - Exactly.

Dog

How smart is the average pet dog?

This week, Stevie Bain has a ‘ruff answer to this “poochy pondering” from David. We asked Ben Ambridge from the University of Liverpool and author of “Are You Smarter Than a Chimpanzee” what he thought…

Ben - It’s not that difficult to come up with a test that you can give in more or less the same form to a handful of different species. There are plenty of studies comparing humans to chimpanzees, to pigeons, to squirrels, and so on. But it’s impossible to come up with a test that will work across all species, firstly for boring practical reasons, so you can’t get a fish, for example, to swim out of tank and press a lever. But more fundamentally because it’s not clear if intelligence means the same thing across different species.

Stevie - Yes, I cam imagine a game of chess between a squirrel and a sheep may not be very informative…

Ben - So instead, what scientists generally do is to try infer intelligence based on brain size or brain weight. About the best measure we’ve come up with is called the encephalisation quotient which essentially measure whether the brain size is bigger or heavier than you’d expect given the overall size of the species. This doesn’t work perfectly but it gives pretty much the results you’d expect.

So humans come top of the table with a score of 7; dolphins are second with about 5; chimpanzees are just over 2; monkeys and whales are just under 2. And on this measure dogs are actually pretty mid table; they score about 1.2. So, to put that in context they’re just above cats, horses and sheep, for example, who score 1 or just under, but they’re just below foxes and elephants.

Stevie - Hmm. So not a particularly impressive score for man’s best friend. In fact, our domesticated pooches even score lower than their wild relatives - the wolves.

Ben - So dogs in general might not be particularly special, but that’s not to say that dogs in particular can’t do some pretty impressive stuff. For example, in my book I took a border collie, called Chaser, who managed to learn over 1,000 different words, albeit with some pretty extensive training. In particular, those breeds that have been bred specifically for intelligence can be pretty smart.

Stevie - So it turns out you may be able to “teach an old dog new tricks” but if you think that fido has a higher I.Q., you’re “barking up the wrong tree.”

Thanks Ben for putting that one to rest.

Next week; we’re cooking up an answer to this question from Zetty:

When you cook food with wine, brandy, or indeed any alcohol, how much, if any, percentage of alcohol stays behind? Also, what would its effect be on an alcoholic?

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