Narrator: Doctor's Kitchen. Recipes, health, lifestyle.
Professor Johnjoe McFadden: There's a huge campaign of course to conserve the climate, quite rightly. We've got to conserve the climate for our children, but we also have to conserve antibiotics for our children. We've seen what happens when we get an infectious agent that we don't have a treatment for with COVID. It's turning us back into 19th century kind of situation where most people could potentially be dying of infectious diseases.
Dr Rupy: Thanks for being on the podcast today. I'd love for you to talk to the listeners a bit about how you got into the field, how you started your academic career and what you're doing today.
Professor Johnjoe McFadden: Yeah, I started my academic career with a degree in biochemistry and then went on to do a PhD looking at viruses, in fact plant viruses at that time, so not human pathogens. I then did a postdoc at St Mary's in London with Bob Williamson then on genetics and looking at genetic disease, human genetic disease. And then, that wasn't a very successful postdoc I must admit and one of the, if any of you are doing a postdoc and having a bad time, and having a bad time, then don't give up. The next postdoc can work much better. So I went on to another postdoc at St George's then, working on Crohn's disease of all things. And then I stumbled into microbiology really at that point by reports coming out that the mycobacterium, mycobacterium paratuberculosis was responsible for causing Crohn's disease. I worked under John Hermon-Taylor, a very brilliant surgeon at St George's, and persuaded him that it was worth going to the US to go and visit this guy, Rod Chiodini, who had the strains. I brought them back, did some of the genetic fingerprinting tools that I'd learned how to use at Bob Williamson's lab and showed that the human strains were the same as cow strains and we published that work. And I did quite a lot of other work on Crohn's disease. But that really wasn't going anywhere to be honest and then I spread further into mycobacterial disease and obviously bumped into TB and started working with TB and I've been working on TB ever since, tuberculosis. So, and then tuberculosis bumped into antimicrobial resistance a few decades ago and it's becoming an increasingly a problem in antimicrobial in that we had drug resistant strains of TB appearing fairly soon after the first drugs such as streptomycin, rifampicin, etc, were introduced. Drug resistance soon followed and that then prompted the use of combination therapy, giving many drugs, and that kept the problem back for many years. But then particularly in the 1970s, 80s and 90s, suddenly these strains were appearing that were first of all drug resistant to a single drug, and then multi-drug resistance to many drugs, extended drug resistance to usually six, seven, eight, nine, 10, 11, 12 kind of drugs. And now we even talk about totally resistant strains. These are strains that are turning tuberculosis in in places where the disease is common from a curable disease to an incurable disease and potentially bringing us back to the 19th century when most people in Europe were dying of tuberculosis because at that time there was no treatment. And with these really ultra-resistant strains of TB that are now prevalent, that nightmare scenario is returning that TB may become untreatable again. So what that is prompting is research and that's what my work is all about here at the University of Surrey on TB and we work on a number of different projects including looking at vaccines and the development of vaccines, but most recently looking at drug resistance and particularly a kind of a kind of pre-drug resistance state that we call persistence. Now what happens in persistence, well actually I'll tell you first of all what happens, what we mean by drug resistance. And that is that if you take a bacterial population, hit them with a drug, say rifampicin if it's TB, then about one in 100 million cells in the population will by chance have a mutation that will make it resistant to rifampicin. And that's what we call genetic resistance. You then take, so if you take hundreds of millions of TB cells, expose them to rifampicin, just rifampicin, one in 100 million will be resistant. And if you grow it up, it will continue to be resistant. And that's what we call genetic resistance. It's heritable resistance and it's caused by a mutation in the genome. And we understand that and that's what's causing the problem in MDR-TB, multi-drug resistant TB, and in other organisms, similar problems of genetic resistance. But there is another state, and that is if you take mycobacterium tuberculosis or any bug and any antibiotic, and you treat it with an antibiotic for say a day or so, and then you remove the antibiotic, you will have killed 99.99% of the bacteria, but some of them will remain. And when you take these and grow them up, they're not resistant. They're just like the parent, they're just as sensitive as the parent to the antibiotic, but somehow they managed to survive exposure to the antibiotic. And these we call persisters and we think they're kind of progenitors of drug resistance because if you get cells surviving the drugs for long enough, then you'll eventually get a mutant turning up. So there are a lot of interest in the field of finding out more about these persisters, these bacteria that are able to survive antibiotic, and no one, we don't really know how or why they are able to survive antibiotic. But we know that it correlates with some factors. For example, growing slowly is a good thing. In order to survive antibiotics, growing slowly. So in the latest paper I call, there are other factors as well that are associated. And what I what we describe it as in this paper that we've just published is what we call a hunkering down hypothesis, that there are many ways by which bacteria will spontaneously and through random fluctuations inside their cells go into a hunkering down. And by hunkering down, I mean kind of just getting under the radar, getting yourself into a bomb shelter, moving slowly, doing everything slowly and protecting yourself, then you might survive the onslaught of antibiotics. And this hunkering down seems to be something that happens randomly. If you for example, look at all of the cells in a population, and we do this by looking down the microscope and looking at how fast it takes for a cell to replicate, you get what's called a normal curve or a Gaussian curve, which has that normal shape like that. One end fast growing cells, the other end slow growing cells. So some of the cells spontaneously grow slowly. Some of them may have other differences, they may make less protein, they may make more protein. And all of these random fluctuations inside cells will end up with some of the cells being in this hunkering down state. And this hunkering down state will allow them to survive antibiotics, but only for a generation or two and then they lose it. So it's not really heritable in the long term, but it's heritable long enough for them to survive a dose of antibiotics. So we're trying to work out more about that and there's all sorts of odd things that we don't really understand. For example, I'll give you one, I'll give you one which is something that's been puzzling us for a long time. It's easy to, easy enough to explain. So I said there are cells that grow fast and cells that grow slow. The fast growing cells get killed by the antibiotic, the slow growing cells don't. So we're interested in what makes a cell grow slowly. So one of the things we decided to look at was how heritable is slow growth rate itself. So if you have a slow growing cell and it divides in two, that's how bacteria replicate, divide in two. So the two daughter cells as we call them, they're actually two halves of the mother cell. So the mother cell just grows long and then divides in two, two daughter cells. So we ask the question, is growth rate itself, the time it takes for a cell to divide, is that heritable? So are the daughter cells at all like the mother cell? So if it's a slow mum, does she make slow daughters? If she's a fast mum, does she make fast daughters? And the answer to that was no, she doesn't, which I can't find enough. But then we found something odd, that that's okay, not heritable. But then if you look at the two sisters, they're almost identical. They have nearly the same growth rate. So it's like if you have twin daughters that look identical, like like themselves, each other, but nothing like you or your wife. How do you do that? Now I just don't know and so it's a puzzle. You take a cell, cut it in two, you make two cells that are totally unlike the mother and they're very much like each other. So and this that phenomenon is is found in all bacteria which we've looked at and actually in other cells and no one really knows why. And it's a fundamental thing about growth that we don't really understand in bacterial cells or indeed any other cell. How come you can take a cell, cut it in two, make the two halves different from the mum and yet identical to each other? So there are all these fascinating stuff and interesting stuff in there, but what we found in the recent study, when we looked at this business of heritability of from one cell, one generation to the next of slow growth rate or fast growth rate, we found there was a gene that influenced that heritability. And that was what the paper was about. And if the cells had this gene, they had a high rate of heritability like I described from the mother, from the between the sisters. The sisters were very similar. But if there was a mutation in this gene, then they lost that similarity. So whatever this mysterious thing is that makes them similar, this gene seems to influence it. So the next step in this study is to try to try to find out what this gene is doing because obviously this is involved with persistence because the slow growers are the persisters. So we can understand what drives them, then hopefully we'll have some clues as to how to knock them on the head and kill them faster because that's the kind of dream of this kind of this field of research. If we can understand persistence and know what it is and what the cells are doing, then we can maybe design drugs that will attack them and completely kill the population, the population of cells. And that's very important particularly in TB, which as I'm sure you know, you have to treat for six months normally. And the reason you have to treat for six months, I'll just finish this and then you can butt in. The reason you have to treat for six months is that you kill 99.99% of the bacteria within a few days. And which ones do you get left? The persisters. So the persisters are why you have to treat TB for six months. If we could kill them more rapidly, then maybe we could have a course of treatment for TB that would only take a few weeks. And that would transform TB treatment and it would lead to less drug resistance because it's that lengthy time that you have to have the cells exposed to the antibiotic that allows them to develop mutations. If we could get rid of them in a few weeks, then we could eliminate the problem of drug resistance. So that's why we need to understand persistence and this gene that we've discovered may be a clue that will give us an an age into killing them faster.
Dr Rupy: I just wanted to ask, the phenomena that you described there where the offspring were genetically identical to each other yet distinct from the former, does that have a name at all?
Professor Johnjoe McFadden: We called it the scary twin phenomenon. The film, the film with Jack Nicholson in the hotel, what's it?
Dr Rupy: The Shining.
Professor Johnjoe McFadden: Shining, you remember in the film, you come up with two twins who look very identical twins. We kind of think of these two twins that have this spooky connection that they're identical to each other. So we call it.
Dr Rupy: Sounds terrifying. So that I mean, I've never come across that phenomenon before. I'm used to sort of the the traditional mechanisms by which bacteria are found to or by which resistance is encouraged. I wonder if we could go through the the typical sort of methods by which we see resistance in bacteria.
Professor Johnjoe McFadden: Yeah, the traditional or the ways in which you develop resistance. Normally in, yeah, I think this is important for a physician's point of view. Normally it's, there are lots of reasons for why a patient who is initially has a strain of bacteria that is sensitive to a drug will develop resistance. One is sheer bad luck. The mutation to a single drug will be anywhere between one in a million, for I know the numbers for TB, I don't know the numbers for others, but they're all a similar range. But for TB, for isoniazid, it's about one in a million cells. For rifampicin, it's one in 100 million. So that's why we use combination therapies because then the the chances of a of a drug being resistant both is the product of those. So that's one in 10 to the six times one in 10 to the eight, one in 10 to the 12. So that's a million billion, I think, something like that. Anyway, it's a lot of cells. So you'll never have that number of cells in your body. Whereas with TB, you normally have around about 10 to the eight cells in your body if you have prevalent TB and that means that if you treat with one drug, you're probably going to get a resistance. The key thing with TB is treating with more than one drug. With other bacterial infections such as E. coli, they normally don't have so many cells in the body, so usually one drug is enough. But sometimes with drug, if you've got possibility of drug resistance strains, you will use combination therapy. So of course, making sure that your therapy is adequate to kill all of the population and not leave any mutants. So that's the most important thing. The kind of things that can happen still if that, if the patient takes the drugs and you and you're doing all of that, is the patient may not continue to take them. In TB, of course, it's it's very common that as you know, a patient may get better within a few weeks. They'll be given the drugs and they'll feel fine. And if they're seeing regularly at a clinic and then you'll keep checking up and okay, you're still taking the drugs. More a problem is in the developing world where patients often will have to pay for therapy, they get well, they feel fine, so they sell the drugs to the guy down the road who's got a cough. And then they haven't cleared the infection in their in their lungs. You've still got some of these persisters hanging on in there. And you take the antibiotic away, then they come back and now there's an increased chance that they're going to have drug resistant strains. So patient compliance is another thing. The quality of the drugs is another thing. This is more of a problem in the developing world where you have drugs coming from all sorts of disreputable sources. Poor absorption is another thing. Not everyone absorbs the drugs. And that's very much a personal thing that patients differ in the amount of absorption. So finding out what the level of the drug is in the serum is usually too expensive, therapeutic drug monitoring. That's a big deal for and you would only do it for very toxic drugs where you're afraid of toxicity and you'd do regular measurements. But those are the kind of factors that will promote drug resistance. And then of course, if a patient has a drug resistant strain, then they should really be isolated because then they can transmit that to another person and then that will be primary resistance where the strain is resistant right at the onset of therapy. And the other extremely important thing in in treatment of course is the the line is goes something like never add just a single drug to an already failing regimen. So if you're giving say three or four drugs for TB and that fails, don't give one more drug. That's the worst thing you could do because the TB will undoubtedly develop resistance to that one drug. You've got to give at least two, preferably three new drugs, new drugs that or three drugs that to which the strain is susceptible to. You've got to do drug susceptibility profiles and make sure that the strain is is susceptible to some other drugs and give preferably at least three more drugs. Because otherwise you're doing the same thing as as developed the resistance, adding one more drug and you had a strain that was was resistant to three drugs. Now it's becoming four drugs and then five drugs and then six drugs. And very quickly you can ramp it up to get a strain that's resistant to practically everything we have in our pharmacopoeia. So that's really a really important point that never add a single drug to a failing regime.
Dr Rupy: Are these observations that you're talking about with TB and particularly multi-drug resistant TB, are those distinct for mycobacteria or is there crossover between different more common infections, should I say? So things like UTIs or upper respiratory tract, lower respiratory tract infections.
Professor Johnjoe McFadden: So persisters are a problem in every infectious disease. You get persisters. Normally say with UTIs, it's not such a problem because you only need to treat for a couple of weeks or so, a week or so. And therefore, and that will kill all of the bacteria, including the persisters. The with say E. coli will replicate optimally about every 20 minutes or so. So you can kill the whole population by having the antibiotics around long enough to get down to the 99.999% until you get rid of the persisters. With TB, the bug only replicates about every day. So that means that that gives you the six-month treatment and that gives you much more of a problem of persisters than with most, so the more acute infections are not normally such a problem with persisters because you normally a fairly short course of treatment is enough to sterilise the patient.
Dr Rupy: What I've witnessed in my relatively short career now as a doctor, I've been a doctor for about 12 years, when I first started, there were some antibiotics I had to literally call up the microbiology registrar or consultant on call to get them prescribed for the patient. And now I've witnessed those same medications being given routinely post-operatively. We've seen a huge shift in the use of stronger, more broad-spectrum antibiotics in response to microbes that are gaining resistance. What is on a global level, I know we've talked about persisters, we've talked about multiple regimes, on a global level, what what are the the main driving factors behind what I see anecdotally and what I hear about in different healthcare systems?
Professor Johnjoe McFadden: Same kind of things as I spoke to before but on a on a more widespread and scary kind of level in that you're absolutely right. The drugs, essentially drug resistance, which is an evolutionary process, we have trillions of bugs in our environment and we're throwing antibiotics at them constantly, not only in in medicine but also in in agriculture. And we are providing them with a huge selective pressure to develop resistance. And that is not going to go away and it is going to increasingly, it's an accelerating thing. You, once you get a resistance, it's going to be in your population for a long, long time. And it makes that antibiotic essentially useless. So what it means is that this has got to be balanced by pharmaceutical companies discovering new drugs all the time. And they haven't been really been able to keep up with that. It's now becoming, now pharmaceutical companies are becoming more willing to invest in antibiotics. But essentially the problem was that from a pharma, a pharmaceutical company perspective, most infectious diseases were quick. We only give them a week or two of drugs. So for pharmaceutical companies are of course much more interested in the long-term drugs for the chronic diseases. They've got more payback on them. So they weren't so interested in developing new antibiotics. But now the world is is being assaulted by drug resistant strains from as well as TB, MRSA is of course in in in hospitals, pseudomonas strains, Klebsiella and all of these pathogens are becoming more and more resistant. And the number of drugs that we have available to them are are getting fewer and fewer. And we've got to really try to do something about prescribing practices. And I think we need to, as well as the kind of microbiological things we can do, finding out more about why physicians overprescribe. And they do. And we know everyone overprescribes. We still know that loads of of antibiotics are given to people with sore throats that they don't, they almost certainly isn't or most usually isn't a an infection that that needs an antibiotic. And so many other things that don't need treatment. And I guess we need to, doctors have to be more more willing to be able to say no to the patient, you're not going to have this antibiotic. It's it may make you feel better just because I'm giving you something, but it's not going to make you better, so I'm not going to give it to you because it's really, I think there's still a huge amount of of overprescribing. And of course, in a developed country like the UK, at least we try to control it, but in countries where patients can just go into a pharmacy and just order an antibiotic over the counter, then that is also a much more serious thing. And that's usually the case in most developing countries that it's possible to buy antibiotics over the counter. And then there's nothing controlling their their usage. So I think it does require a more global approach to trying to conserve antibiotics. I mean, we've been, you know, there's a huge campaign of course to conserve the climate, quite rightly. We've got to conserve the climate for our children, but we also have to conserve antibiotics for our children. We've seen what happens when we get an infectious agent that we don't have a treatment for with COVID. It's turning us back into 19th century kind of situation where most people could potentially be dying of infectious diseases. So antibiotics are a fantastic medical intervention. They are so good, so effective. And they're reckoned to have, them and I think oral rehydration therapy are reckoned to be have the greatest benefit to mankind. But we're losing that benefit by overprescribing. So I think we've got to really try to tackle that problem.
Dr Rupy: Yeah. And another insight I would say from the front line, so I I I often work in A&E. In fact, I mainly work in A&E now. And I had a patient actually with a resistant UTI. She'd been on three different courses. It was an E. coli that was resistant to all the three first-line therapies that we have. The other thing that's very perplexing as a as a frontline practitioner are our the diagnostic tools that we currently have. As of today, in my local A&E where I work, I have to wait a few days for the cultures to come back to find out whether the antibiotic that I prescribed today is still effective, is actually the correct one. And that takes three days, by which time I've started trimethoprim or nitrofurantoin or a cephalosporin. And also mapping where the microbial outbreaks are, particularly resistant ones, so we can be more locally responsive because those guidelines don't change very often at all. So I think there's there's definitely the element of behaviour change and trying to introduce primary care practitioners to more effective ways of educating the wider society, but also we don't have the tools. We're we're really practicing a rudimentary style of medicine in my opinion.
Professor Johnjoe McFadden: Yeah, it's it's it's worse than that really. We do have the tools. It would be possible to to give you and to give physicians tools in which you would be able to get drug resistance profiles within hours. That's possible today. Or it's it's it's just expensive. So it's a matter of investment that how much are we prepared to invest on in developing new tools. We're we're trying to work actually with Chinese partners to try to develop diagnostic tests that you can plug into a mobile phone. Because I think electronics is the way you've got to go. And we have so many plug-in devices that are very expensive that we're prepared to pay for. If you could have a device that we could plug into a mobile phone and give us a drug resistance, which is what we're trying to do with as I said, some Chinese partners for things like Klebsiella in fact, for antibiotic resistance in Klebsiella, which is a big problem in China. That's what and also similarly for therapeutic drug monitoring. We would have better success of therapy if we were able to apply therapeutic drug monitoring routinely, but it's too expensive. Again, if you could get a pinprick test, put a drop of blood onto a little onto a little slide, poke it into a device that you put into your mobile phone, then we should be doing it. And but that may be years away to develop that. But we've already got technology that can identify the genes in all of the bacteria that we currently have problems with, genetic tests for each of those genes, and we can do them in hours already, but it's just that most labs aren't equipped to that. We've discovered how badly equipped our diagnostic labs are in this country. We still, they've had a lack of investment for many years, a lot of it has been privatised, and then they get hit by the COVID pandemic and suddenly we've discovered, hey, we're we're rubbish at doing diagnostics rapidly. You know, people have to go across the country to get a diagnostic test done. It's ridiculous. And this is for a a wealthy developed country like UK that is in this kind of state. And it's as you say, it's even for the routine stuff, waiting three days for something that you can get a a test result for within existing technology in a few hours. It's just not available in your clinic.
Dr Rupy: Yeah, absolutely agree. I can't talk to you without talking about your your sort of, I see it as like a double life, but I'm sure you see it completely intertwined. But how you wrote a book on human consciousness, quantum biology, how you've how you've come to that through your your journey, through your PhD.
Professor Johnjoe McFadden: I kind of consider it that it's this is my paid work, the TB stuff. This is the stuff I get paid for. The other stuff is the wacky stuff. I do get paid for it now. I'm a director of the quantum biology centre here at Surrey, so I do get paid for that now. But yeah, I I got into quantum biology more than 20 years ago now when I was interested in mutation. We talked about mutation and the it's it's importance in TB and in other bacteria for development of resistance. And peculiar mutations seem to be appearing in some experiments that appeared to arise only when they provided an advantage to the cell. And this was highly strange because we think of mutation as being random. Mutations are caused by cosmic rays or radiation or heat or all sorts of things cause mutation. And they're thought to be entirely random. And yet these mutations seem to arise only when they could provide an advantage, which is very strange. Anyway, I came up with a, I'd just been reading a very interesting book by John Gribbin called Schrödinger's Cat, which was I think one of the first popular science books to popularise and tell the general reader how weird quantum mechanics is. I mean, I've read some popular science books before, say about general relativity and stuff like this and you learn about black holes and you think, hey, they're weird. Read about quantum mechanics. Black holes are normal compared to quantum mechanics. It's way, way beyond weird. So and I was staggered by how strange the world is at a quantum level. So essentially, quantum mechanics is the classical physics we see around us, you know, cannonballs, rockets, all that kind of stuff, steam trains, electronics, most electronics just work by all the classical rules that we're familiar with. When we go to the level of fundamental particles, the rules are all different. And they're very strange. Particles can be in two places at the same time. So if a a golf ball behaved like a fundamental particle, it could land in two holes at the same time, which would be very handy for you doctors that are always going on golf courses. I remember my a colleague of mine when doing a PhD with me saying that, oh, I'm going on a course tomorrow. Oh, anything interesting? Yeah, golf course. I'm sure that's definitely not that has all changed. I'm sure that's not happening anymore. Anyway, so anyway, if you if you could quantum golf, you could get two holes at once with one ball. So that's what quantum mechanics can do. Particles can be in two places at once. They can say spin in two different directions at the same time. And they can also be entangled, which is something, I mean, Einstein gave us black holes, backwards in time travel and all sorts of weird stuff like that. And he said, no, this is too, this can't happen. And he called it spooky action at a distance, which is where two particles can be separated, say by the entire length of the galaxy, and if you tweak one, the other one will jump instantaneously. So bang, they'll go like that. And when you tweak one, this one will jump. And they can be a galaxy or they can be the entire universe between them and they'll still jump simultaneously. And that was so weird that Einstein said, no, this is, he called it spooky action at a distance. He called it entanglement, but then experiments in the 1970s showed that the world is that spooky, it does happen. So there's that. Particles can go through walls. So if you're a quantum particle, you could pass through walls that you shouldn't really be able to go through without a battle axe. You can just float through them, ghost-like through a wall. And so all of these funny, weird things happen in quantum mechanics and they weren't thought to be relevant to anything big. But then this adaptive mutations that as it were, as they were described, came up and I thought, that could have a quantum mechanical explanation. And I worked something out on the back of an envelope kind of explanation for it and I thought I can't publish anything about this. So but I talked to some physicists. So I phoned up our physics department and they said, why not come and give us a seminar? And I did and you know, a biologist giving a seminar about quantum mechanics to a physics class and head into the lion's mouth. And I got a fairly skeptical reception, but actually Jim Al-Khalili, who I'm sure you know of, was in the audience. He's also a physicist here at Surrey. And he came up to me afterwards and said, well, it's, you know, there's a lot of problems, but it's interesting. So over the next months or in fact two years or so, we were working on it and trying to make something that worked. And we eventually wrote a paper about it. And and then I I went on and wrote this book, Quantum Evolution back in 2000, making, proposing a more general role for quantum mechanics in biology. And but nothing really happened for a decade or or so, nearly two decades. And then suddenly, over in the US particularly, experiments started popping up which demonstrated that at the molecular level, quantum mechanics was playing a role in biology. And and then myself and Jim got together to write another book, Life on the Edge, which was published in 2013, I think. And explaining all of that stuff. And that showed that quantum mechanics seems to be involved in photosynthesis. The first step in photosynthesis where for example, a particle of light, a photon hits a system, and the energy has to be transferred from here to here. And it was thought to kind of hop around in a random kind of way until it reached here. No, it just goes straight here through a quantum mechanical process where it goes by all routes simultaneously. So remember a particle can be in two places at once, well it can travel by two routes at once and end up at the right place much faster than it would otherwise do. So that seems to be involved in photosynthesis. Enzymes work through quantum mechanics by bringing the substrates to, enzymes say will move a proton say from one molecule to another. And enzymes do it by bringing things together close enough that allows a particle to walk through walls. Remember I said particles can walk through walls, it does this in inside enzymes. And enzymes are are responsible for for making life really and they accelerate chemical reactions by factors of 10 to the 20, one with 20 noughts on the end, which if you could accelerate your walking speed by that, you could walk across the universe in seconds. So that's how much of an acceleration an enzyme provides. And no one really understands how and quantum mechanics seems to at least provide some of the answer. And then even birds, birds fly around the planet navigating, they can detect the earth's magnetic field, you know, so weak that you have to get a really sensitive magnet balanced on a on a little compass to to detect it. And yet birds can detect it and they use their eyes to detect it. And that's involves this spooky action at a distance it seems that the that Einstein didn't like. So quantum mechanics seems to be involved in life. And actually when you think about it, at a molecular level, life is all about enzymes, what they do is move protons and electrons around in biomolecules. And if you ask a physicist, if you want to move protons and electrons around, what science do you need, and that's the science of quantum mechanics. And biology discovered that billions of years ago and it's been working with it and working out clever ways of using quantum mechanics for billions of years and we're now trying to work out how they do it.
Dr Rupy: So what what I'm trying to process through my head is how, I I can understand how quantum biology is related to persistence in in the the multi-drug resistant TB and and how you have this like adaptive pattern that doesn't ascribe to the the principles that we would have thought of random action or random mutation. How does this apply to consciousness in in in humans? How how?
Professor Johnjoe McFadden: Consciousness, well that's that's another story. Another story. And yeah, it actually goes back to the the book I I wrote on quantum quantum biology all those years ago, quantum evolution. Chapter 13 was about consciousness and I put it, I sent it to the publishers and said chapter 13 is on about consciousness. And the reason for that was that actually Roger Penrose who won the who won the Nobel Prize this year, and a American anaesthetist, Stuart Hameroff, came up with an idea about how consciousness works using quantum mechanics. And I thought, okay, well that's cool. I can include that in chapter 13. But then when I started to work on chapter 13 and I looked into their theory, I found I couldn't believe it. It just didn't make any sense at all. And the reason for that is that it required your whole brain to be a quantum mechanical state. And the things I've spoken about already about quantum biology, it involves electrons and protons and very few of them, you know, small numbers of particles. As the number of particles gets bigger and bigger, it's harder and harder to maintain it in a quantum state. And what Hameroff and Penrose were claiming was that somehow you had this quantum mechanical state involving your entire brain. And I didn't, didn't feel I could promote that theory. So I was left with the problem, chapter 13, what do I write? And and what I came up with then, I thought hard, it made me read a lot about consciousness and it made me realise that what was special about the quantum mechanics, why Penrose and Hameroff were interested in it, is it unified all the information because a quantum mechanical body, if you like, is what we would call a field. And a field is is a structure where everything is unified within it. So and how what we know about consciousness, if you just look around you, everything you see seems unified. It isn't that the colour of an object over there, I can see a wall that's painted blue. Blue is actually, that is recorded in your eye, but it's analysed by one part of your brain. The shape of the wall over there is by another part of the brain. The structure of the building is another part of the brain. And all of these things are analysed by different parts of your brain and yet they're all stuck together in our in our conscious mind. And we call this the binding problem. How does our brain stick it all together? Quantum mechanics could have done it, but I didn't think it had, it was possible to unify matter in the brain. The problem with matter is that all the different parts of matter move against each other and that breaks the quantum mechanics. But it occurred to me there is a field in the brain that physicians and neuro, neuro, neurobiologists knows about, and that's the electromagnetic field. It's what when you put electrodes on onto patient's skulls, you to measure EEG or you put them in a in MEG, you measure the magnetic component of the electromagnetic field. And the electromagnetic field in the brain is generated by all the nerves firing. So it has exactly the same information as in the nerves. So that nerve firing that registers the colour blue and that nerve firing that registers the shape of the window over there and the nerve firing for everything else going on in my perception is as well as the information going down the nerve itself like a conventional wire and giving a response, that's a, that's the colour blue, which we can do maybe unconsciously. We do a lot of our, a lot of what happens in our brain is, unconscious is not the right word, it's better to say non-conscious. We're not conscious of what, I'm not conscious of what I do with my hands all the time, but they still do it. I'm not conscious of my lips moving to make the words that I do. And that's an enormously complex calculation that's going on in my, in my, in my brain that makes my lips and mouth and everything generate the right shapes to make words. I'm not conscious of it. So most of what our brain does, we're not conscious of, but some of it we are and it's joined up. It's part of the, it's bound together in our conscious mind. But all of the brains that are driving the outputs of of, you know, our lips and all of this kind of stuff, all of those outputs and our hand movements, they're all making little electrical signals that go into the brain's EM field, electromagnetic field, that are picked up by the EEG and MEG. And it just struck me, well, when we say, when we're looking for consciousness, what what we normally say is, what is the seat of consciousness? And everyone thinks the matter, you've got to look at the matter of the brain for the seat of consciousness because that's the stuff that you can cut up and look at and look, here's a brain and it's the obvious stuff that's there. But there's also an invisible field there. And that is just as real as the matter. If you remember Einstein's very famous equation, E equals MC squared. Matter is on one side, the MC squared. On the other side is energy. The field in our brain, the electromagnetic field is pure energy. That's just as real and just as physical as the matter of the brain and it's just as complex and it's got exactly the same information because every time a nerve fires, it sends a little electromagnetic signal into the into the volume of the brain. So if we could somehow magic away the matter of the brain, we'd be left with this most complex electromagnetic object in the entire in the known universe, which has exactly the same structure as the brain and contains all of its information. And it struck me, that's a better seat for consciousness because everything is joined together. The thing about electromagnetic fields is there's no parts to them. And you can tell that in in in terms of how we deal with electromagnetic fields. Here's a phone. I can pick up a signal. If you call me, I can pick up your signal here. Or if I'm over at the other end of campus, I can also pick up your signal. It's everywhere and it's the same signal. And this is what electromagnetic fields do. They're the same everywhere. The information is overlapping and it's and it can be accessed everywhere. So it just struck me that, wow, this is a much better place to put the seat of consciousness. And it made sense with a lot of data as well. What neuroscientists that looking at consciousness and I wasn't one of them at the time, I'm doing a little bit of work now, but they look for correlates of consciousness to try to understand it better. What's going on in the brain that correlates with consciousness? And one of, the only thing that really worked well as a correlate of consciousness is to do with the synchrony of neural firing. And I think people like Wolf Singer, a German neurophysiologist, they did experiments on monkeys and other people, loads of other people have done these experiments. They look at attention as a as a measure of consciousness. We we know we attend to something. We notice something. When we're looking for, looking for our glasses that for me at least, looking for my glasses, I can be staring at my desk, I don't see them. Oh, wow, there they are and I can see there's my glasses. That moment when we're looking and we don't see, the same information of my glasses is going into my brain, but I'm not registering it. It's non-conscious. What they showed with the monkeys, because they could do these experiments by putting electrodes in the brain and monitoring individual neurons, when the neuro, when the monkeys weren't seeing whatever they were looking at, a banana or something maybe, when they were, when the information was going into the brain and they weren't seeing it, the nerves were firing, but they were firing asynchronously. When the monkeys registered, wow, okay, that's that's the banana, then the neurons fired synchronously. That was the correlate. Now what will happen when neurons fire synchronously when you look at the electromagnetic field? Fields go up and down. So when neurons fire asynchronously, the up part of one neuron will hit the down part of another neuron, and when you add them together, they make zero. When they fire synchronously, the up and downs are all are together. So instead of cancelling each other out, they reinforce each other. So neurons that fire synchronously will project into the electromagnetic field of the brain, into the conscious mind. So that explained, and this was the first paper which I wrote which was making that case that synchrony being the best correlate of consciousness is entirely consistent with the with the electromagnetic field of the brain being a seat of consciousness. And thereby, and I now and I then I wrote various other papers about this over the years, every now and again like in lockdown, I wrote, I thought, what can I do while I'm stuck here in my room all day long? And I wrote a paper, another paper on consciousness which came out a few weeks ago.
Dr Rupy: Yeah, yeah, no, I came across that. And and so just because I know I want to be respectful of your time, what we know about consciousness or what what we believe to think about consciousness being energy rather than the actual physical structure of the brain, differentiates us from computers, which is why computers don't have a consciousness. What what can that, what kind of insights does that give us today, us as humans, us going about our daily lives? What can we glean from this theory that we can put into action today to to live healthier, happier lives? I'd like to leave the listeners with a few tips, I guess.
Professor Johnjoe McFadden: I don't know if you're happy. Yeah, I don't know. It's to me, knowing a little bit more about consciousness does make me feel healthier and happier, but it doesn't make me any healthier and happier. But it can, of course consciousness for neurologists is an extremely important thing to measure. In locked-in patients, are they really locked in? Is there someone in there? How do you tell the difference between life or brain death? And what it gives you is a method of or at least the potential of finding out how you can measure consciousness more accurately than we currently do. And actually how it's measured is actually looking at the EEG and looking at patterns in the EEG and the more complexity of that pattern seems to correlate best with whether a patient is conscious or not. So I think it does have medical significance, understanding what consciousness is and maybe maybe even treating some some forms of of pathologies that may interfere with consciousness. Now I won't dare to to really go into that as I'm not a physician, but we know that consciousness has many different states, some that people interfere with with drugs, etc. But others that people who get depressed and I don't know why, but maybe there are ways in which we can, if by understanding how consciousness works, we can interfere with it. And then lastly, there is the very cool and and rather scary possibility that understanding it more will allow us to engineer it. And this I think I would love to see this in my lifetime, making a robot think. And what a day that would be. I think that would be most, the most remarkable achievements of of humanity if we managed to make an artificial mind that really can think and rather than just calculate and think like us and talk back to us. And that that would be to me would be the most fantastic advancement. So I think, and I think it, I think there are ways, if we understand, if I'm right and consciousness is the electromagnetic field, in order to make a conscious mind, you've got to compute through electromagnetic fields. And there are ways of doing that. But computers aren't made with that architecture in mind. So there is a route towards making an artificial consciousness once we take that on board, but it's a completely different way of making a computer and where we normally computers are made to insulate themselves from the electromagnetic fields that they generate. We call that interference, electrical interference. So computers are made to avoid that. Well, I'm saying is make a computer that uses that, that uses electrical interference as well. If they do, they'll eventually become conscious.
Dr Rupy: Brilliant. Last thought for the day.
Professor Johnjoe McFadden: Yeah.
Dr Rupy: Thank you so much. I really do appreciate the time, Professor. And it's quite a lot. It's a pleasure. It's, yeah, it's definitely a pleasure to chat to you and I'm sure we'd have to do something like this again because I've got a whole load of questions.
