 Tonight, I'm delighted to introduce Professor Ian McKinnis, who's giving tonight's Graham Medal Lecture to the Society and its members. Ian McKinnis has successfully combined being a practicing clinician with leading a large team in world-renowned research. His focus is on inflammation, a physiological response that can be a powerful friend in helping us fight disease and injury, but also a formidable foe when it directs its firepower to the wrong place. Ian is currently Vice Principal and Head of the College of Medical, Veterinary and Life Sciences and the Muirhead Professor of Medicine at the University of Glasgow. Ian is passionate about understanding the causes of debilitating inflammatory conditions such as rheumatoid arthritis and harnessing this knowledge to treat and cure disease. He's a fellow of the Royal Society of Edinburgh from which he received the Sir James Black Prize Medal, one of the most prestigious awards in medicine. He's also received many other prizes and medals for the quality of his research and was ordered a CBE in 2019 for services to medicine. So tonight's talk, what would Lister do in a post-pandemic world is sure to be a fascinating and insightful view of how the great 19th century surgeon Joseph Lister can inspire us. Now, I don't think this means how he would might cure the next variant of COVID with carbolic acid, something that perhaps Donald Trump might have found very attractive, but more than way in which the way Lister worked can inspire us for the future. So as always, after the talk, there'll be a short break before questions, five minute break, please put any questions at any time in the Q&A box in Zoom versus the chat function, please, which is for general questions. So please use the Q&A for questions to the lecturer. So without further ado, I would very much like to introduce Professor Ian McInnes over to Ian. Well, thank you very much indeed, Phil, and indeed thanks to the Society for the invitation to speak tonight and if you're listening after the event online then thanks too for joining us in whatever time zone you find yourself. I must say I approached this evening with a very significant degree of trepidation. Society more than two centuries old and I made the fatal mistake of looking at previous speakers and they are robust indeed. And this I have to say has generated a certain amount of anxiety in my part. The second disclosure, of course, being that I hope you haven't come to learn about Joseph Lister himself. I'll very briefly introduce him, of course, but really tonight is an opportunity for us to think a little bit about the opportunities that will present themselves for us in the area of clinical medicine and broader healthcare delivery in the next decade or so, all based I think in the key lessons we've learned in the last extraordinary 18 months. So thank you for the invitation. I'm aware it's a very eclectic and diverse and wise audience and I hope that at least some of what I have to say will be of interest to you. So the starting point, of course, was that Lister worked in the east end of Glasgow and Lister is one of my own medical heroes. I was trained in Glasgow Royal Infirmary. I was a junior house officer there many, many, many decades ago. And it has to be said, I still love Glasgow Royal Infirmary. It's an extraordinary place. It's one of the top rated hospitals in Europe at the moment and is performing extraordinary medicine on a daily basis. Of course, Joseph Lister was in the 1860s presented as surgeon. By the way, it's very difficult for me as a physician to have a surgeon, a regis professor of surgery no less as one of my medical heroes, but one has to make allowances for the passage of time. Lister faced an extraordinary challenge and that was Glasgow, of course, was an industrial city at this time. And injuries were common and injuries that nowadays we would simply take for granted as being a matter of wound toilet, a little bit of hygiene, perhaps an antibiotic if necessary, a quick tetanus shot and off you go and you would expect in truth to be going back to work the following day. Sadly, it was not often the case. And many, many young people died of the complications of surgery driven primarily by sexes. This, by the way, is the ward in which Lister practiced. You can see that it's a pretty fine place. I practiced as a junior house also in this very ward. The only thing that's really changed nowadays in the nursing uniforms, pretty much the rest of it looks as it did. And I have to say the first thing that Lister exhibited which I still find extraordinary was a degree of curiosity to drive the need for change. The word curiosity, curiosity is very interesting word that the ancient physicians were driven by curiosity and, of course, most of them are classically trained I'm living proof that that's no longer the case. But curiosity, care and cure all come from the same derivative the concept of curiosity driven care leading to cure for me is a rather elegant and interesting concept and this of course is the plaque in the wall of Glasgow run infirmary. His insight was to travel. Lister's insight was to look at the use of carboxylic acid at that time being pioneered in Paris, he looked to broad he looked overseas he looked to different disciplines. And the chemists who were using and looking at that were not particularly concerned with surgery they were interested in the rapidly emerging area of microbial science but Lister's innovation was to work with the surgeons, Stuart and others as a team, cross disciplines. He actually filled the operating theater now by the way a small lecture theater in the surgical block of the Royal Infirmary. He actually filled the whole operating environment with carboxylic acid. This is the device he used it's in the interior museum if you want to go and look at it. I can say, although we have a record published in the Lancet here it is, of the positive outcome for the patient the very first compound fracture that was treated by this method, we have no knowledge of what happens to the surgeon's assisting Lister, who were presumably inhaling carboxylic acid, and that's probably not a very good thing to do for your lungs by the way. And the other thing just as an aside is that this paper was published before the patient is reputed to have left hospital so fast publication is not quite as new a concept as some of the publishing houses would have as believe, but an extraordinary advance and what do we take from this well of course. The messages I take from this is that first of all, there was the recognition of an unmet clinical need. Not an acceptance of that but curiosity driven drive to resolve that unmet eat. How often do we accept the status quo and not feel able to challenge it, and I have to say particularly in very busy clinical practice at the moment. That's very often the default place. Lister looked for the emerging technologies. He was prepared to look across overseas and to nationally collaboratively at opportunities to intervene. He was prepared to take risks. Well I think clinical risks. And the third thing is that this was a very early evidence of a multi or interdisciplinary approach. Now all of this may seem very self evident, but it has not in fact been the major drivers that I think we will hope to see in the next decade to many of the clinical advances of the last few years. Phil very graciously introduced my interest in inflammatory arthritis, rheumatoid arthritis being the disease that I suspect many or most of you will have heard of although they're actually a range of different inflammation within the joints. This is, I think one of the most dramatic ways of depicting the impact of rheumatoid arthritis. This is Renoir, of course, and if you're interested, this is a beautiful article in the British Medical Journal from 20 years or so ago, when Paul Renoir, Renoir's grandson, presented to the rheumatology community the impact of rheumatoid arthritis on Renoir's painting over a period of 30 or 40 years. What's extraordinary is that in the end Renoir was only able to paint by tying the paintbrush to wooden splints around his hand and wrist and then adapting the canvas so that the canvas could be moved to allow the limited movement in his shoulder to accommodate the extraordinary creative imagination that he had and wished to put into the visual arts. And his was an optimistic approach out of doom and misery, the most beautiful song may rise coming from Dutch proverb. So what is rheumatoid arthritis in 2020? Well it's a complex disease. Of course, the title gives it away. It's a disease of the joints, what may be less well known to you is that it's a disease of the cardiovascular system. It is a disease of systemic bone. It is a disease of the metabolic system. It is a disease of the brain. 40% of people with rheumatoid arthritis at some point will exhibit suicidal ideation. People with rheumatoid arthritis are 50% more likely than the general population to die of heart attack and stroke. And this is a disease that costs, it costs individuals, their autonomy and independence. It costs families. The contribution that family members can make and it costs society an enormous amount of money, both in the direct health care costs and indirect loss to societal benefit. And these are the pictures of rheumatoid arthritis and the picture on the right hand side is what you probably have in mind certainly it's the image I've conjured up in your mind when I showed you Renoir and his extraordinary functional deficit. But actually the really remarkable advances of the last number of years are shown on the left hand side. This is early rheumatoid arthritis and this from left to right takes something in the order of 10 to 15 years. But most of the patients we see nowadays look like this and very, very, very few look as the right hand panel depicts and why is that. Well, let me just reflect a little bit on some of the advances that took place. We were driven by the observation 30 years that rheumatoid was a miserable business. This is an article from David Scott and Debbie Simmons both now retired, but now in Detroit, which they had followed up the outcomes for people with rheumatoid arthritis. And they showed that the graph in the right is not particularly relevant. It's the amount of damage to joints and you can see that there was a lot of damage to start with and even more 20 years later. Because of remission inducing drugs as fallacious early treatment might be useful. And what did that treatment entail. Well, this is, I hope you will be persuaded a dramatic impact and insult to function for a human being and their family. So what did we do we gave him an aspirin. This is what we did for many, many decades, they were given an aspirin from the early 1950s they received steroids that earned pension colleagues and Nobel Prize steroids are very, very toxic. And so we then came over a number of later years to the use of broader spectrum immune modifying medicines and the triangle on the right hand side was so called primitive care. And this is taught as a medical student and before you ask it's not that long ago, we would give people aspirin like drugs the so called non steroidal anti inflammatory so you, you've seen them in roots the chemist it's proofing neurofine that kind of medicine. If that didn't work we gave them totally non evidence based medicines injected them with gold would give them penicillin, a metal collator, we potentially give them steroids and then eventually we would give them to people like me as experimental physicians, all the time as therapeutic surgeons to operate. And molecular immunology came to the rescue in, or around the year 2000 the turn of the millennium. What is a biologic drug a biologic drug is a drug that is mainly antibody based antibodies of course are very much in the news at the moment those are the, the the body makes to kill off viruses, but we can now make antibodies in the laboratory and we can direct them at anything we like. In this case inflammatory proteins. The idea of this so called magic bullet comes from Paul early whose photograph in Berlin I'm depicting here, and you can think of these as molecular scalpels, they tease out a very specific point in the very complex network that comprises our immune system. That is a network of cells and molecules that communicate freely with each other, allowing an immune system to evolve in the left of the finger, and then mediate defense in the right big toe and anywhere in between. These are cartoon depictions of what these proteins look like their antibodies often depicted as why shape molecules, they're actually just like a big scrambled up ball of paper in the real world of structural biology but these are quite useful ways of thinking about them. This was the ultimate immunologic reductions approach as immunologists, we looked at rheumatoid arthritis and we said, is there a single point in the disease that we can intervene blocks stop the disease that if you like, the notion was that the disease was driven by a single pathway. And when you stop and think about it that was a somewhat optimistic approach and it wasn't correct because the, the best outcome from even these very exquisite and by the way quite effective medicines. Was there about one quarter of patients would achieve a high or no response. And that it took more than half a century if you look at the timeline here, these broad spectrum immune modifiers gold and others that I mentioned to you were in broad widespread use in the 60s and 70s. Thereafter we introduced and borrowed from the cancer literature a drug called methotrexate, and then please worry not too much about the details of the medicines but more the timeline. When about half a century went by before the immunology resolution pathogenesis understanding disease led intervention, finally delivered the so called TNF blockers, and TNF blockers are the biggest selling medicines of all time. You can get the biggest selling medicine of all time. When only half of your patients have made it to remission enormous unmet need and in 2022, we now still face a large number millions of people in the world who have this debilitating destructive disease of joints, which is not yet being resolved by this very reduction single one molecule drives all approach. So hold that thought. Many of you may remember where you are on or around the seventh or ninth of January 2020. I was in Glasgow at the time. I've actually heard from a friend in China that there was something slightly odd going on with an emerging virus. And I don't think any of us had any idea that the Wuhan pneumonia outbreak was going to change the world and the way that it did a short number of weeks later, while UK folk were still heading off for skiing holidays, our friends in Northern Italy were starting to experience. The word is here tsunami of mainly respiratory presentations and the whole health care system and the Italian health care systems are very interesting place it's actually a very well provided for system you can in the lots and lots of hospitals. I had to play it against our Italian medical friends because when people felt and where they were admitted into hospitals they had enough beds and of course that was a great place for virus to spread. And I'm very struck by this quote from a not terribly famous but very committed physician. Everyone became part of a single team. The disciplines disappeared. The minority became the norm as we sought to face the tsunami. And we had no evidence base. It was as if we had gone back two centuries of medicine and Osler of courses, perhaps the master of that early medical observation you will draw from your errors the very lessons which may enable you to avoid the repetition. It's a beautiful depiction of what happened next, we made many errors but we learned very very quickly. And I think I'm showing you here airplanes converted into intensive care transfer units, and the SEC is the Louisa Jor. And this is the beginning of the next part of what I want to tell you about tonight because they, of course this has been a truly dreadful two years at every level. But from every adversity there has to come the spring of hope and I want to just share with you some of what I think are going to be the first shoots of hope coming through. But let's let's just, just out of interest share a few thoughts about the villain of the piece, SARS-CoV-2. It's so named it's a coronavirus it came from from bats almost certainly into the human population. SARS-CoV-1 was the cause of the SARS outbreak 20 years ago in Southeast Asia. This is a picture of the virus itself in the left hand side but David Bella who leads the cryo em facility University of Glasgow, you can see the picture of these molecules around the side and the idea is that this is a crown. And the spike proteins that you hear all about that's what your vaccines are detecting they identify and neutralize the spike protein and the spike is a bit like the hand that grabs the handle that lets you get in through the door into the office. The spike grabs the human cell and allows the virus to enter into human cells particularly in the upper airways that leads to destruction of the upper airway and the virus can migrate down in about 10% of people into the lower airway and bad things happen. All over and this is the range and extent of the symptoms and in some senses, a complex illness. Yes, of course, an illness of the respiratory upper and lower respiratory system, but also patients who came in with other groups and we didn't know this at first. So we had people coming in with diarrhea and we didn't think of testing them for SARS CoV2 and so the hospital was very quickly full of people with with swollen glands with with diarrhea with rashes, and we weren't immediately putting them together of course this was a retrospective analysis that was put together by investigators right up and down the country. And, but the Glaswegian component here coming from Tony Ho in the Center for Virus Research and University, and you can see that this is a broad ranging systemic disease involving yes the lungs, but also the brain the kidneys that deliver and this widespread destruction of normal immunology is rapid but only occurs in a small proportion of patients. Therein lies and very obvious question, how can such complexity be resolved. And there should just be the beginnings of a minute. These immune diseases that the McKinnis was telling me about rheumatoid arthritis and other immune media disease. They're also complex they also involve the heart, the brain, the joints other tissues. These are parallel emerging. Well, this is pre vaccination data but I wanted just to remind ourselves of pre vaccination data. The, the truth is that a proportion of people who did badly did very badly indeed. And these are the data from people who went into hospital. So that was around about 5 to 10% of patients, and sadly very many of them died, particularly people over the age of 70. This was a medical catastrophe make no mistake. The catastrophe was caused by what has been termed the cytokine storm. And what is, I must be honest, I would very rarely talk about cytokines in general company but they've become quite commonly discussed in August scientific websites like the BBC and Sky News. The cytokines are the proteins that allow the immune system cells to talk to each other they circulate in your blood they go into your, your lymph system they're going to tissues, they are, they're about 100 of them known in the human immune system. And they allow cells to talk to each other but normally in a very regulated way. And they're a fabulous system I spent 25 years of my life studying the cytokine networks they're an exclusively beautiful biological system. But the, the storm or simple chaos is what we see in people who have risk factors. And so what most of us will manage in our throat with the virus managed here restricted here yeah we'll feel a bit grubby for a few days. There's a small number of individuals around 10% of patients, perhaps those who were smoking or a little overweight people with high blood pressure, and people who diabetes, or people who are particularly over the age of 68, especially over 70 the curve really starts to go up. The immune system is not well behaved over the age of 70 we have something called in flammaging that is we actually just generally get a bit of inflammation going as we get older. But the immune system becomes less well regulated so called immune senescence, we forget to regulate immune function and so in this subset of patients immunologic chaos ensued. What was it. Well I'm going to show you actually only two experiments all night but here's the first one I want to show you. It actually this experiment comes from Yale, and they took the fluid blood and bronchi alveolar lavage fluid taking fluid out the lungs of people. And there were 33 severe patients 18 moderately involved and 100 or so health care workers who had not been infected. And they looked at all of those site kinds these immunologic proteins that were present in the circulation of the patients. And when they put them all into a single map. This is what they showed if you are reeling in horror at the complexity, then you're very wise you should be. Now, why am I showing you a heat map. The answer is not because I want you to commit the detail to memory. Each of these colors, black or dark color is an up regulation, yellow is a down regulation, pink, red, roughly neutral, these are the up and down of the individual, different proteins in lots of different patients and it turned out that your age and your likelihood of survival were directly related to the largest number of chaotic site kinds that were present. In other words, the immune system was doing the killing, not the virus. So in an extraordinary coalition of medicine rheumatology infectious diseases and immunology came together. And I think most of you will have heard of the recovery trial. Back to steroids remember Hensh in the 1950s the very first treatment for rheumatoid arthritis became the very first proven treatment in the management of patients with severe covert 19. And you'll see here that dexamethasone is steroid. This is the original New England journal paper from the recovery trialists who comprised investigators all across the country. And here in Glasgow, we put many, many hundred patients into the study but so too did colleagues in other parts of Scotland all the way through the country we take no pride or pleasure in that it was part of a national emergency effort. Coalition cooperation coming together. And you'll see the red line is the steroid treated group did better than the black line which wasn't know if that gap doesn't look very much to you remember that at that time we had nothing. And that step change is actually rather significant in the clinic. And so the idea that immunologic dysfunction that we had identified over two decades as being the causative and treatable problem in people with rheumatoid arthritis beg the obvious question could we use similar drugs that had been effectively developed for the management of rheumatoid to the severe end of the covert spectrum. And the answer is beginning to look to be yes. This is a drug. It's called tocalizumab. For those of you who really into this area of biology it blocks a particular site kind called into looking six. And by the way rheumatologists have speech therapy regularly to allow us to pronounce the names of our drugs there. They're not easy. Try tocalizumab when you've had a cup of tea. So, and the line graph in the left here depicts the red treated group receiving this anti rheumatoid arthritis drug were less likely to die than those who were given standard of care and this was a Dutch hospital where they give very good care indeed. So there was early evidence that really understanding was the beginning to therapeutic resolution. And then finally the last part of the molecular immunology revolution was the very obvious one of course this is Jenner. And the idea that we could specifically immunize against that spike protein. Again, exquisite molecular specificity using these really extraordinary RNA vaccines, which I'd be very happy to discuss later on if time and your level of interest allows, because they have general interest in going forward, a great lesson for us post COVID. But this was the idea that we could prevent the severe end spectrum that we're not it turns out preventing transmission, particularly well, but we are definitely preventing severe end spectrum disease, and that is going to be transformative in society. So what do we learn from Lister post pandemic. We, the pandemic has been a dreadful thing but the transferable skills that came from recognizing immunological dysregulation. And applying that even to an extraordinarily complex state. The, if you like the site kind of storm in intensive care in what was very, very challenging medical environment. What do we learn from that where can we take that going forward well, I think the first thing to say is that the medical models change forever. The idea of sitting next to your, your favorite physician and discussing how you're feeling. Well that's possibly been gone for some time but we're almost certainly going to end up with virtual clinical practice. And I'd certainly at best I think it's going to be a hybrid model and that has real implications for the way we understand diseases. And as I'll show you at the end how we might think about treating them. The second obvious lesson is that partnership post pandemic to understand disease and resolve disease must be without borders. COVID has been a global response. And the remarkable progress that I would argue molecular medicine has made would only have been possible if the international cooperation collaboration that has taken place did indeed take place. And this is just because we live in a beautiful city in Glasgow, but it is a city that has a most unfortunate and sinister underpinning of health and equality. The inequality of outcome for people suffering COVID-19, those in the lowest socioeconomic classes doing quite considerably worse has brought to the fore the inequity of health care outcomes. And this is by the way not a new problem. Here's a paper that my, my colleagues in the Glasgow run infirmary rheumatology department published many, many years ago demonstrating that social deprivation has always been an adverse modifier of outcomes for chronic immune disease, but only recently has that been properly recognized and post COVID. I hope it will be recognized ever more so. The idea where the post pandemic revolution and I think this is where listed would have gone is to really unleash the power of the molecular revolution. The idea that instead of us using really very crude measures, putting a hand on the patient, a microscope, an MRI machine, an X-ray machine, a blood test, what an unbelievably crude way to look after people in the era of the molecular revolution. So let me just describe a little bit of what this is about. Here is a photograph of the Scotland and England supporters at a football or a rugby match, I care not which. It's pretty obvious who comes to sport England and who comes to sport Scotland. But that doesn't really tell you about all of the face of personalities, the different parts of Scotland or England from whence they come. And what you'd really like instead of just judging someone by whether they have an English flag or Scottish flag above their head, you'd like to judge them, knowing much more about them. In those appearance, you'd like to pick out the people in this crowd who have a Scottish flag, blue socks, black shoes made by Nike, if that's your preferred option, and maybe a white t-shirt and a very unfortunate CME Tami on their head. And that would start to pick out a subset of people who had common characteristics. The medicine is that we make all of our treatment decisions on the basis of the whole population and not on the basis of that subpopulation that would properly identify people most likely to benefit from the medicines that are about to receive. So how do we get to that if you're like holy grail of medicine where I only give a medicine to someone who A needs it, B will respond to it and C is unlikely to have a toxic event. It's not all precision medicine, but actually it's really just the, the ultimate rational use of pathogenesis understanding why somebody is ill. I want to just share a little bit. Well, first of all, Lister would have loved the fact that surgical techniques have evolved considerably and we can now get bits of people out with microbiopsies that allow us all manner of approaches to understand the distinct tissue environment. What is skin look like when it's inflamed? What is a joint look like? What is the brain look like when it's inflamed? And we can start to think about these different tissues and their different physiologic functions, and then start to think about how different tissues and organs communicate with each other. This, by the way, I think most of you will know the inaccessible pinnacle extraordinary. I believe this is not a photoshopped. It is a very real photograph. I do not recommend you try this at home, nor do I understand why you would ever want to try it, but it does make for a beautiful depiction that even formerly inaccessible places can be reached for modern medicine purposes. Those tissues, be they blood or be they direct small microbiopsies are now subject to the consequences of human genome project. The original race to sequence the human genome has spawned an extraordinary range of technologies that allow us to look at the single cell level now. We can understand which different genes are switched on in any one individual cell, and that allows us to move from the top of the slide from a very organ based model of disease. And that's what I was taught at medical school. We were also taught about cells and I'd love to say I stayed awake during those labs I did some of the time to a very different molecular network based approach to medicine. So where would that leave us? Nowhere unless there were parallel evolution of computing science. And I hardly need to tell you that artificial intelligence is driving our world already, and in medicine is going to drive our world ever more so this is a little hypothesis article we stuck into the couple of years ago. And AI is already used in the recognition of diabetic retinopathy, eye disease in the depiction of skin cancers. AI is far better than a dermatologist at recognizing skin cancer. It's also by the way far better at recognizing pneumonia and a chest x-ray than a radiologist and so AI methodologies in the black box is rapidly clearing and is now part of everything in medicine. So molecular technologies used to be complex and difficult to understand. The biomedical philosophers amongst you will recognize the output of something called mass spectrometry. This is a way of depicting the different compounds that are in any biological sample. This is an experiment that we ran with our colleagues in the Glasgow Polyomics Center. If you're interested in the different chemical makeup, each spike depicts the presence of a different chemical in a in different samples and you'll see with these different samples. You may be wondering what kind of disease these come from. And actually these different samples are all clearly separated by their molecular fingerprint. They're all different kinds of whiskey as it happens and we can in fact choose the different individual malt whiskeys even to the origins of the distillery using this kind of exquisite sequence based approach. This is the discipline of whiskey omics, which is what I'm particularly fond of. But why do I seek such levity well of course, the whole idea is that we can now move from organ based medicine to a molecular and cellular atlas of the human being and then look at the atlas to depict that which is normal and that which is not normal. And so the technologies that have accelerated beyond belief during the COVID pandemic are now already they were being applied in medicine, but they're now being applied rapidly at force with funding and with cooperation across the world that is seeing advances at real and exciting pace. This allows molecular medicine to ensue. And I'm going to show you this is the second experiment that I'm going to show you tonight before I stop. This is the second experiment we did in Glasgow working with our, our long term collaborators in Rome, Stefano Oliver Nini was one of my clinical fellows can work with me in Glasgow for three years and for reasons I still can't understand went back to Rome something to do the weather he mentioned I can't imagine why, but we take microbiopsies out of the joints of people rheumatoid arthritis and, and then we, we submit that biopsy to an in depth sequencing analysis in other words we ask, what cells are in the biopsy. And in each of those cells, what genes are switched on. And when you start to look at that, we actually prepare a map and this is a single cell map, each of these individual colored dots represents a cell. And what we've done is we've organized the cells now into subsets that look most like each other. In a way what I've asked the soccer crowd to do is I've asked everyone wearing black shoes to go to the top end of the stand, everyone wearing quite sharp to go to the top left hand end of the stand and eventually the probability of one cell looking really very like another allows us to pot this probability map. This is a, this is a computationally generated map. Who cares, well we care because when we found patients who had lots of these turquoise cells on biopsy, we then stopped the treatment. And what happened. Those patients that please don't worry about the molecular detail they happen to be marked by proteins called Merty K and CD 206. We called friend and gene it doesn't matter. The point was that we identified the proteins and cells that depicted unique functional properties. And those functional properties when they were present in the biopsy meant that when a patient had this biosignature, I could stop their medicines and identify at an odds ratio of 16 which is colossal in the world of biomarkers. And I think that's a clear and those who would not. In other words, we can now choose patients in whom we can stop treatment with a high level of expectation that they will not need to start again. That's getting awfully close to clinically useful cure and I never thought I'd be saying that my career. And just a couple of final remarks that COVID pandemic, we've all gone online, everything has gone online. We can now take all of these numerical digital databases, the molecular signal the clinical data can all be interrogated in silico and so clinical trials will be done in silico that many of the antiviral drugs being developed and currently being used Malapiravir and others were actually developed in silico. In terms of the known sequence and by the way, helpfully for us, the known sequence of variants of concern of of SARS-CoV-2 is as life goes on as it inevitably will. And that then allows us to look at the genes of the host immune system, we then go into bio banks of large numbers of molecules we can use those to think and then finally, we will go into a clinical trial. And that means that the future ladies and gentlemen will lead in my view to the loss of organ level diseases, we will not be talking about rheumatoid arthritis or Crohn's disease or ulcerative colitis that's the panel on the top. It's organ based diagnostics. It's so last century. I put it to you ladies and gentlemen that we will actually be defining patients by the molecules that are driving their disease. Again, worry not about interleukins are another name for sightings. These are the sites kind pathways that separate these clinical syndromes. This will allow a molecular definition disease that will allow a molecular selection of therapy. And so as we study disease and future will be using cellular therapies will be deconstructing the complexity, and we're actually going to create extraordinary complex data sets as a result of that by creating increased complexity of data and applying AI driven solution of that, we will actually be able to finally reduce the disease back down into plausible and logical candidates for therapeutic targeting. We'll do that using electronic health care records advanced informatics will do that by in silico trialing. Eventually we may even do a clinical trial, and we will be anticipating diseases before they happen. We are now doing pre rheumatoid arthritis clinical trials, we're actually doing trials to prevent the onset of rheumatoid arthritis which is, I still find an extraordinary concept. I have to say the field is a little divided don't we all love the Kelpies, and the field does contain many Kelpies who look a little bit like that in the right hand side, still looking away and giggling and smiling quietly but I think the field of those who believe that we can mark disease at molecular level is growing quietly attentive Kelpie in the left that's the one I much prefer. And where that takes us is a is a just for the purposes of reality check. This is not happening quite yet. But could you imagine a day when the person's journey with arthritis takes them online for a self e consult with fully I capability. They're worried well filter so that we don't all self diagnose incorrectly. There will be the clinical in flammology service will then confirm the diagnosis that doesn't exist yet but it will very soon. And then we'll look at what else is going on in that patient to the heart problems lung problems diabetic problems. This by the way will be done in your local waitrose. You'll have your biomarker driven precision drug selection because the computer that has your record on the chip that will be essentially connected to your to your consultation online will also allow you to say well hang on this this individual is already taking the medicine to the diabetes I better be it will then bring all of that together in your multi morbidity risk score that will then adjust the various additional inputs that are needed to control the complexity of your progressive rheumatoid arthritis which of course will not now progress. Actually I said this wasn't happening now but e consultations post COVID are the norm. The worried well filters already exists. clinical in flammology is the field of I'm at immune media and plant diseases, which we are already very much at the center of and biomarker driven precision drug selection is coming in the next five years and multi morbidity risk score that the researchers were actually devised in the University of Glasgow working with collaborators in Dundee and are actively used clinically already. This vision of the future is very very close to tomorrow and has been accelerated in its arrival by the response that we've made as a community to COVID. Thank you very much for being here. Ladies and gentlemen, Chairman Phil with a thought from Eric Huffer the products of the human mind simplicity marks the end of a process of refining, while complexity marks a primitive stage, I'm unashamedly still as an physician and clinician at the primitive stage of my understanding, our diseases remain extraordinarily complex at the molecular level, but using the technologies that have been accelerated by the pandemic, and that would have enticed list around quite sure. We are now able to refine to a level of simplicity to allow interventions that are effective. Of course, Huffer was not referring as far as I know to COVID-19 I think his ideas were focused more around the, the Sistine Chapel and Michelangelo's exquisite depictions they're in, and anyone who's been in there will know how one's eyes always drawn to the very center of the ceiling. And with that, I shall conclude. I hope there will be some questions. Thank you so much for your attention, when there are so many other distractions midst these Omicron written times. Thank you very much indeed. Well, thank you very much indeed Professor McKinnis I think just to follow on from some one of your analogies I think for me listening to this talk was like a bit like watching a tremendous spy film where there's a lot of things going on and you're not quite sure what's happening and they seem to suddenly bang it all comes together in the in the in the last 10 minutes and you suddenly kind of get it in this, you know, in this inspiring moment and I think that has very much inspired myself and hopefully all of our listeners. That was absolutely terrific. Thank you very much. So, if you don't mind waiting around there's plenty of questions coming in we'll just take a quick break for five minutes, keep the questions coming everybody and we will join Professor in McKinnis back in a couple of minutes just to answer some of them. Thank you. Hello, and welcome back again. Thanks Ian. Thanks once again for a fantastic talk. The questions are coming in thick and fast and lots of really positive comments. Thank you very much. So let's just start with a pick out a couple of them relating to as a few questions on personalized medicine. I think you maybe are you on mute just to check. Hopefully I'm off mute now. Yes, good. So, in terms of personalized medicine, personalized medicine sounds amazing. But isn't it going to be a lot more expensive than giving everyone an aspirin. Can the NHS afford it. And also, and also this personalized medicine will require the public to be willing to hand over a lot of very personal information do you think people will be willing to do that. Do we need to get less paranoid about how our own data will be used so a question relating to cost and to privacy. Two excellent points. So most of the modeling and the health economic predictions of a biomarker which is a could be a blood test, the skin test, the saliva test, it could be whatever you make it into. Most of the modeling suggests that they will substantially reduce the cost of delivering health care and actually looking through the questions of the very student remarks about the value of prevention. And really prevention is far better than having to treat a disease per se and the use of precision medicine to anticipate that which is going to go wrong. And then prevent it will in fact in the long term be much cheaper for the NHS than allowing people to develop disease states and then have to use often very complex interventions to try and resolve the matter. So almost all of the modeling that's been done in the United States and here and even here in Scotland would strongly suggest that in fact appropriately used precision medicine will reduce health care costs. And the amount of data is is much more complex. At the moment we do actually give a fair number of our personal secrets to the medical health care professionals to look after is and we do that in the understanding they won't disclose that any further than is necessary. I guess at one level, we are simply giving up more information to those health care professionals we're giving them a medical map that is at the digital level now rather than at the organ level. And so you can argue at one level that that's just simply a degree of molecular detail that the health care professionals would already be receiving. So we move though to how data are used outside that doctor or health professional patient relationship, and when you start to think about how those decisions may be made in silicone one of the other questions has asked me to define in silicone I'll do that momentarily but if you do that in the virtual world and there isn't actually ever a human being involved. Well of course the concern then is that those data end up somewhere else and someone uses them for another. I mean purpose perhaps that's been the debate about the use of NHS data for research purposes, or potentially for more nefarious means and I'm not villainous enough to think what those could be but I'm sure there are others who could. And so, I think appropriately contained the data necessary to sustain and support a precision medicine approach will simply be a development of the ethics that already cover the way in which we use data in the clinical world. And it becomes more complex and I'll freely concede I don't think we've got all the answers is when we're using wider population level data to permit and furnish further general medical advances, anonymization techniques certainly help. But inevitably you begin to lose some of the power of the analysis when you've become either fully or pseudo anonymized so an imperfect answer to your second but the first piece I'm pretty confident that actually appropriately use precision medicine will be cheaper. Okay, thank you very much. And questions on vaccines, not surprisingly given the current state of affairs. Should vaccines to cover be targeted to members of the population based on individual risk I guess you could use some of these molecular techniques to find out, you know in general things to find out how at risk people were, or does the communal interest take precedence over precision. Medicine and and and secondly watching this would have made two vaccine deniers as a second one. Now I'll come to the second one a moment. Well, so to that isn't that is a very astute question. So first of all, vaccines are sometimes used in very distinctive subpopulations. Think of the shingles vaccine for example, we use shingles only in the older age groups, and that's because the likelihood of you requiring to have that extra protection only really becomes worth the risk of having a vaccine over the age of 50 or 60 and it varies in different parts of the world 50 or 60 being the general cutoff. But in the context of a pandemic, the, the role the vaccine plays in protecting the public health and also the individual's health as a consequence falls much more at the population wide level and that's why the vaccine has been rolled out in over 18 population, and in different societies also now in 12 to 17 year olds and indeed, even in children younger than that, that is all to do with creating a level of herd immunity that is that the population is collectively protected. Now, you will have heard some people say well the virus is still transmitting itself so the vaccines haven't worked well I think the evidence is strongly suggesting that the vaccines have worked beautifully because what they has dramatically reduced is that proportion of patients to that very severe end spectrum disease that I described to you, and that's because the immune system, I hope I convey to you, is actually normally beautifully regulated. But in that subgroup of folk in whom it isn't chaos ensues, the vaccine allows the virus to be destroyed and neutralized, even if it's the second or third time you've seen it before that degree of immunological chaos can develop and so the likelihood to progress to bad things is reduced I think pretty much why the vaccines are working so well. Now what would Lister have said well I wish I'd been in the operating theater with them. Most surgeons I know use a very interesting set of adjectives. I suspect Lister would have said, I respect your right to make individual decisions about your own well being and those medical interventions that will be given to you. But I would also respectfully ask you to think very carefully about the consequences for those near and dear to you, and your wider community on you not being part of that breaking of the transmission chain. The argument is weaker because the transmission chain it has been reduced considerably, but it hasn't been broken completely and that's one of the arguments that the vaccine deniers are putting out there. By the way, I separate those who have genuine concerns about medical risk from vaccination from those who think that it's the government trying to implant them. I'm afraid that sits somewhere out in the definitely need of psychological health department. That's a different argument and I can imagine Lister might have been quite blunt with those. I would hope that Lister would have been a little magnanimous and recognize that there are genuine concerns that people have. But eventually explanation of the relative risk of being vaccinated against the relative risk of something really terrible happening to one strongly favors going for vaccine. And I would hope that an appropriate understanding of those relative risks would lead a vast majority of people at Lister's integration or even others to actually go ahead and accept the vaccine. There are a small number of tragedies after vaccine, but there are a very much larger number of tragedies after incidental contraction of the virus. And some of the saddest stories that we in the healthcare profession are talking to each other about are those who denied or did not accept the offer of vaccination and who then either die themselves or even worse have transmission within their family and see loved ones dying. And I'm afraid there's certainly no told you so there. That is simply a tragedy. Yeah, yeah, absolutely. I would concur with that. I'm sure many, I'm sure many people would absolutely. One of the subject one of the topics you just touched on was was public health and public medicine and not surprisingly there's quite a few points to do with that. So, one question. Thank you for a very interesting talk science is captivating but is it a sustainable model when the prevalence of lifestyle based disease is so rapidly increasing how can we. It's almost like we can do all this but it's going to be overwhelmed. How can we utilize this type of technology and novel approach in preventative medicine. There's also a question saying of course, will the will people who are in deprived areas have access to internet and so on realistically to be able to to to take to take part in that as well. You mentioned the inequalities in health care in Glasgow UK. These are even more obvious internationally do you think there's any real appetite including funding to use potential mobile phone access in many countries, leapfrog the organ based focus of medicine to the molecular medicine you describe. So a lot of questions on on on the wider, you know, public health issues. Would that I didn't know the answer to those questions I'd be a very wealthy young man or old chap as it probably is more truthful to declare. So yeah, let me start with the issue of lifestyle modification and how that sits alongside the provision of high technology medicine. The two can happily coexist. I'd like to well they do at the moment and I'd like to hope that in the future that will be will be sustained. There's a different argument and I don't have the right answer to it as to whether lifestyle choices that we make should have some influence in our ability to access the high technology medicine that's a very different discussion. I'm at the moment for the record I still treat patients who release and I still treat patients who smoke and I do so without any sense that they are more or less worthy of treatment and I think that's where most physicians sit in the argument. But the issue is the whether we can just afford to continue to throw technology at lifestyle driven diseases. I'm not quite sure where the sentiment lies in the question but if the sentiment is, should we not be getting going with the social science that needs to be implemented to stop lifestyle behaviors that lead to disease. Well actually, for me the continuum of science and this is something that I'm, I'm working on very hard with my friends and colleagues in the College of medical science is in the university in Glasgow. We're playing together experts from the, from one end of the social sciences, all the way through to the molecular biologists to start to think about how we do combat for example beast. And so, I think lifestyle modification has got to be part of the answer. Actually, there may also be some molecular solutions that could diminish or minimize the impact of lifestyle behaviors on the emergence of subsequent diseases. But that's not as fanciful as it sounds. We're starting to understand why obesity causes heart attacks, understand why obesity causes diabetes. These ultimately have molecular chains. And yes, of course we'd like people to lose weight and in a perfect world they all would. I'd actually like my two daughters to behave themselves and stop spending money online every week as possible but it's highly unlikely to happen anytime soon. And so some kind of mitigation in there, limitation of online access might be a starting point, but some kind of mitigation that allows us to diminish or mitigate the impact of social behaviors would certainly help. And in that sense, high quality science and, and lifestyle modification could potentially work in tandem to reduce the burden of disease. I hope that's the beginning of an answer. I accept it's not definitive, but it's the way in which certainly I would try to rationalize the relatively, the relative value of the high technology science that we're talking about. Yeah. Yes, I mean clearly the use of technology within the different groups I think that's something you emphasised. It's not just between the patient and the doctor which is, which is clearly going to change but also allowing different groups to work together a question for myself really. I mean, is, is has has was this is just this an acceleration of the trend that was already happening fun ability of groups together funding individuals funding changing the way people get money. Not it's not this team in Liverpool in Glasgow in London doing the work it's much, it's much more global now. Yes to all of the above and the pandemic has accelerated the tangible benefits that can accrue on that kind of collegiate. Team based approach. Now not everyone agrees with with this idea and I respect the argument that says there should be still this single iconic scientist driving the pioneering vision of the future and by the way actually think there's a huge place for blue sky science and all of this I don't for one minute argue that the only science that should be done should be solutions focused on quite the contrary I've been a free user of blue sky science for my whole career and I've been very grateful to some extraordinary minds have allowed their science to enter into our translational space. But ultimately, ultimately, I think the meeting place is is going to be team science when we bring our collective knowledge and expertise together. I have to say if you wander out in another part of my life I spent quite a lot of time talking to patient groups I don't actually like what patient very much people with arthritis groups. If you say to someone with arthritis, different disciplines are starting to talk to each other to think about curing your disease they'll just look at you a scans and say what you mean you weren't doing that before. You know, it's a bit like I get an airplane, hoping fully expecting the air traffic control, the fuel department, the food department, the pilot and the man that actually puts the lights on in the runway are all talking to each other. So the idea in biomedical research that we don't have basic can scientists clinicians that we don't have the social scientists that we don't have informatics that we don't have it all joined up is actually pretty preposterous when you put it into that context so for me the future is team science, and I think one of the one of the enormous benefits of the pandemic is that the tangible benefits of team science have been made much more obvious to the community, as we've achieved extraordinary developments, and to consider that the pandemic has delivered vaccines, mRNA technology delivered vaccines, an application of therapeutics in about 18 months, it took us half a century to get from the identification of what cells in the rheumatoid joint we're doing to biologic and really quite a sophisticated immune modifying half a century to 18 months it's extraordinary, really extraordinary. And that's because team science technology all came in the same place. So I think we're going to go back to being slow once this is over or do you think it will things will be done as quickly as this in the future now. Really hope so. I really hope we will inevitably will slip back. But if you look at the way the MHA are looking at regulatory approval speed off. When you look at the way the pharma sector is looking at developing drugs and the kind of, you know, rapid. I'm not going to use this phrase in silicone. I'm, I'm, I'm seeing several questions saying what is in silicone, but I talk about in silicone so that is the concept that we actually never go near a patient, not even a cell in vitro and a culture dish. We actually do the whole experiment using the data sets that have been brought together on to a hyper computer, and we actually the computer will create virtual patients and we will give virtual drugs intervening in in the patient will be defined at a virtual particular level. Now don't worry, you're not going to be given a medicine that has never actually been near a human being as a licensed approved product there's still going to be the classic phase one through phase four design for a good number of years to come. But what we hope is that that in silicone or computer based modeling that allows us to choose the compounds earlier and more astute play will lead to fewer failures. Remember that nine phase two positive phase two trials out of 10 fail at phase three, and hundreds of positive phase one trials fail at phase two that costs billions of dollars and euros and yen and pounds, but even more offensively, that's lots of people who entered a clinical trial and committed themselves to this, the scientific discovery process, who were actually given a medicine that ultimately was doomed to fail. So, and that so I hope that helped that that's the concept of the in silico science that sits under pinnings. And of course in silico science, the first COVID trials were all done in computer. So hydroxychloroquine, for example, was shown not to work very well and come by a computer paste, and then some some pretty clever clinical informatics much to Mr. Trump's disappointment. And the, you know, we discovered, for example, in the computer, that an arthritis drug called barisitinib, which what it doesn't really matter but it helps people through arthritis that does matter to me and many patients. But it was also it was shown by computing science to also inhibit the virus. And so there were clinical trials of the use of barisitinib because you can think of that's quite a useful juxtaposition isn't it, antiviral and anti inflammatory. So you take the virus and you potentially down modulate the way the inflammatory response occurs leading to fewer complications, kind of cool and that came from the computer that would never happen with conventional medical strategic approaches to drug design so I hope that begins to help how the, how the in silico world that I'm talking about. And if I may feel I didn't answer the other part of your earlier question around inequalities. I was inspired by, by, by Hilary capel and other mentors to me and Glasgow around firmly many years ago to respect the impact that health inequality has, and it stayed with me through my whole clinical career. I believe that health inequalities drive molecular abnormalities. I've got one of the other questions that's sitting in the Q&A, one of our questioners has said well look, what is the impact of age and will we understand that and in fact, that is the field of epigenetics. And for those of you who are not interested or into epigenetics, you may have been told that you get your genome you get your genes at birth and they don't change very much and then you die. Right. We get our given genes at birth and yes that basic sequence stays the same throughout life. But what we do in life will lead to molecular subtle, but real molecular alterations to those genes. And if you're overweight, the genes will be influenced in one way if you smoke in another. There's an extraordinary story if I feel I don't know how much time we've got but if this is remotely interesting the Dutch hunger winter is an amazing example of this. The nutritional deprivation just towards the end of the Second World War in the Netherlands, led to a cohort of babies who were born whose mothers during pregnancy had less than 500 calories of intake per day. Of course the Dutch investigators amongst the best in the world and 50, 60 years later they've looked at what happened to the, to those babies when they grew up into middle and later years, compared them to the babies whose had a normal diet and the, the Allied forces relieved the Netherlands and to those who were in a modest diet in the years just prior to that and of course those impoverished babies in utero had profoundly greater rates of diabetes of osteoarthritis and other, and that's because their genes were altered from birth. And we actually now have evidence that the deprived areas of Glasgow, there is this epigenetic molecular effect. Why is that important? Well, if you can find the molecular change, actually, you can intervene and alter that molecular change. And so the molecular deficit, people in deprived areas are often accused of being the authors of their own downfall. I profoundly disagree with that. I think they have conferred upon the molecular disadvantage from an early stage. That's true in Glasgow it's also true by the way overseas and other areas of deprivation. And for that reason we have a lot of work going on in partnership, for example in Malawi between the University of Glasgow and the Blanta Blanta, I said in Malawi, which takes a whole more hour to talk about it so I won't take you in that direction but the globality, if you like the global impact of understanding how health and equality influences outcomes has universal applicability if we can get it right, which is, I think, an exciting derivative of this line of thinking. Okay, that's pretty tough message but quite clear actually and to hear about that work on deficiency in nutrition in early stages, that's not great to hear. Right, so, sorry, I have one question. So there was a question about siloing of, we're able now to join teams together working perhaps the same disciplines across the globe now using technology but because medicine so complicated there's so many specialties, you know in Lister's day you would have been able to go and have a chat with the surgeons and the, you know, those small teams in relative, has it become too siloed really in terms of, has medicine become too siloed in terms of specialty or can different teams give each other ideas, especially as now we're working at home I guess a lot and bump into each other in the cafe quite as much. Honestly, I think it has. I, I'm a strong proponent of the immune disease is no longer being treated in different clinical disciplines. Now, not everyone agrees with that view I accept that it's a little controversial. But in truth I think anyone with an inflammatory disease whether it involves the gut that would normally go to gastroenterology, the joints to rheumatology the lungs to pulmonology, even the brain to neurology seems to be there are fundamental commonalities and why these people are getting ill and the kinds of therapies that can be used to reverse that illness. And of course, an additional benefit of bringing those disciplines out of the clinical silos and into common space would be that the conversations would start again the corridor conversations would occur more commonly. I think though that just to be a little more optimistic, the, the advent of in silico zoom teams and conversations has allowed us to talk to people much more easily. And that also has some very interesting consequences so last night I spoke to a colleague in California about a patient. And we did so for 10 minutes and zoom together and I dare say we might have picked the phone up before, but now you just kind of click a button, there you have a quick chat, quick conversation and off we go. I chair the UK governments independent advisory group now on the advent and use of antivirals and covered as a rheumatologist, but we meet every week with experts with a broad diverse and inclusive approach from all across the United Kingdom. Now that wouldn't have been possible in the pre computer communication age. And so I actually hope that the technologies will begin to bring the conversation to the forum will make it easier. I also think that nothing brings people to the conversation, more than success of others. And as we have seen the success of computing scientists and biological scientists coming together. So to the disciplines will see the merit in talking to each other. And actually my experience, particularly of academicians is that we are drawn to successful models. We're intrinsically a curiosity driven bunch. And if we see something working in one discipline, very often we'll go and look and start to think well I wonder if it would work in my place. And that's of course what Lister was doing when I went to Paris. I don't want to overplay the Lister analogy, just for purposes of everyone's sanity tonight, but this, I think mutual curiosity will also help to bring disciplines together. And I would also say that contrived bringing together of minds very rarely works in my experience. This has to be a curiosity driven coming together the multi disciplinarity. If you like the multi disciplinarity that is the common coming together a curiosity driven individuals is actually now I was trained in a discipline where multi disciplinarity was drilled into me from the beginning. So for me it's not a foreign concept, but for many disciplines it is we've, you know, we've been trained in talking silos but I hope that those relatively random thoughts eventually come together as an optimistic message that yes, the silos are breaking down and in my view should continue to fall. Brilliant. Okay, thank you. Let's keep going. So there's this question there's a couple of questions on the, on the applicability of, of the molecular approach for different, different types of diseases and how far can it go really. There's, there's autoimmune disease with dementia osteoarthritis, I guess that would be the closest how, how, what are what are the limits really perhaps of the molecular approach. Yeah, well of course it depends whether you get me before or after a glass of wine I can sometimes get carried away with these things filled with Tim. I speak lightly and forgive me for that. So there will be limits that's the first thing to say you sometimes hear folks saying well there's no limit to the power of molecular medicine actually there are limits to the power of molecular medicine. I talked about some of them already the fact that there are other external factors that drive the outcome for individuals their lifestyle choices their health economic circumstances, the wider economic circumstances of a society. However, I don't think we are anywhere near the end of the beginning of the molecular discovery revolution. What do I mean by that well, we are as I emphasize this ability to get access to difficult to get to places the inaccessible pinnacle. We're not easily able to get into the brain, but we can get into pretty much every other tissue in the body now even difficult to get at places like 10 and we can now get into that. And the, the principle and forgive me I stuck to rheumatoid tonight in the interest of trying to retain some coherence to the argument because I was aware that there were two or three different strands and feel you're very gracious in saying they did come together at the end. I was quite relieved to hear that because I was aware there were several strands in the argument and rheumatoid was kept for simplicity but the same principles can be and are currently being applied to diabetes to to heart disease to and yes to dementia, the proviso that getting the brain out is a bit more difficult, especially getting the brain before the dementia has become clinically obvious, the molecular changes that imaging shows us in the brain are evident long before necessarily the behaviors have become either clinically debilitating, although they could potentially be clinically meaningful at earlier stages and that's why psychology based methodologies using artificial intelligence are actually picking up. They have personal specialist expertise, although I read the literature and voraciously because it's fascinating, but actually psychologists using a methodologies can pick up dementia long before anyone actually knows it's coming. That in turn, because I am ultimately a molecular pathologist at heart must have some molecular underpinnings, those in turn, and here with the clever bit one of the next innovations I think that's coming that's going to be rather exciting is that we'll be able to use imaging methodologies so that's an x-ray, an MRI, the current molecular void is called PET positron emission scans where we actually look at coming close to molecular level and as that technology advances we'll be seeing how individual molecules behave and difficult to get at places, the brain I think will be the final frontier for that, but if you follow the logic we can currently do that in tissues that I can get at. We can then use your new imaging method in those tissues that you can get at, we can do the correlates and then go to the brain and you can start to make that leap of faith into molecular understanding. And so yeah, I actually am fairly optimistic that even some of dementia's secrets will be given up. I'm not going to give you a timeframe on that because I think there's still some pretty significant hurdles to get over and I wouldn't wish people to leave this lecture and conversation thinking that we can Thursday the Daily Mail report a cure, although we actually do know that the Daily Mail reports a cure for cancer every week or so and I would be very judicious in believing everything that I read there. Okay, thank you. New diseases, I guess is part of the same thing, what kind of type new diseases think will arise from the implement, I suppose that's like reading the future. I mean, I mean we don't know what new disease perhaps it's hard. Do you think well there's been a lot of talk that this is going to happen again and new diseases going to come more quickly. You know, this is just the first of a number of pandemics, you know, and I because of population movement, you know, you know, and so on that this may may happen again quickly what what's your thoughts on that. The truth is that we will have another pandemic. I don't know when it'll happen. I suspect we probably got a bit lucky that it's taken this long for a truly economically threatening and sadly health threatening global pandemic. We probably got lucky with SARS-CoV-1 20 years ago in Asia. I think they're there for they're all undoubtedly be more pandemics and that comes from overpopulation, it comes from people living longer. It comes from that means we as a natural host, just an interesting thing to think about if you're ever bored. We as a human host have changed incredibly in the last 100 years. Remember for about 10,000 years we got up in the morning had an interesting life chase and will be mammoths and quietly died in our early 30s. And then about 10,000 years or so years ago we somebody worked out that you could grow wheat if you stayed near the water long enough to stop wandering and so an agrarian revolution took place. And then suddenly in about the 1800s life expectancy rose precipitously. One of the things that we as a human host look very, very different to the viral world than we did even 100 years ago. We've got these interesting things 80 year old people, what are they? Well they're very interesting and they've been genetically altered and their immune systems behave differently. Oh and their lifestyle means that they've got different tissue propensity for a virus to come in and alter so I actually think the likelihood of pandemic is increased. Do I lie away worrying about that at night. I'm really worrying about the quality of my golf. I worry a lot about my friends and family just because that's what we do is sent in humans. I don't think I'm going to lie away worrying about the next pandemic. I actually think we've learned huge lessons in 2020 2021. I think we are far better prepared to move quickly and I guess post pandemic where we are far more ready to work together to combat the next pandemic. I also suspect that particularly zoonotic that when when animal human interactions are involved in the propensity for an infection to emerge. We have to become much more aware of the potential for zoonotic emerging disease and and with that a sense of social responsibility. We hear these interesting conversations about the pandemic is only over when everyone's vaccinated and by that we mean the world not our country. But the argument could be developed beyond that to a sense of social responsibility to bring equitable quality of life and dissemination of modern medical promise. If we were to do that the risk of global pandemic would begin to reduce. And so the idea of social and collective responsibility on a global basis is something I feel again pretty strongly about. I appreciate and understand there are valid arguments against what I've just said, but certainly from where I'm sitting, the global responsibility, it's the global village and make no mistake. COVID-19 has reminded us of that big style. Yeah. Okay, thank you. First, let's just do five more minutes. Okay, if that's if that's good with you. I'm sorry I'm not going to be able to get through everybody's questions. There's so many positive comments in the chat about about the talk and I think we could carry along. Is there anything you any of the questions that you particularly wanted to pick up on in the Q&A. Well, actually, if I may, I'm hoping that's my my dear friend David Stott who was asking can we prevent immune diseases. Well, that's what we're trying to do. And David we're, we're right in there with immune modifying medicines and people who have antibodies in their blood but don't yet have swollen joints, and we are we call that pre rheumatoid arthritis. And even here in Glasgow we're part of European groups who are doing collaborative clinical trials to try and prevent the onset of full blown clinical rheumatoid. We're not there yet of course we can't prevent them but there are some extraordinary immune therapeutics that actually theoretically could be preventative. Another question which I think it may have disappeared but it was an interesting question it's a follow on to the use of vaccines and selective vaccines. A follow on to that is selective use of antiviral drugs. You know, should we be sub selecting who gets antiviral drugs. That's very topical because we don't have an unlimited supply of anti COVID antibody neutralizing antibody. So we have, for example, we don't have unlimited supply of malnipere via the oral and the oral anti COVID and packs slides coming along packs of it or others coming along shortly in February. And in one of my other lives I'm actually sharing a group who are focused at UK level and trying to understand who really are those most that need. The answer is that I think we probably can identify people now on the basis of their likelihood of bad things happening if they're infected, and the likelihood of them benefiting what is the clinical capacity to benefit from antivirus medicines. So although I don't think the vaccines will be sub selected. I think the use of antivirals could be very, very uselessly sub selected in society, and hopefully we'll be able to identify those people most likely to benefit. So those are relatively scarce resource to be most impactful in society. So those were the couple of thoughts Phil that leapt out of me from the question list but actually the question is fabulous thank you you've given me lots to think about plenty of homework. Okay. I have a question but it's gone about whether you've been inspired to paint or sing by your Michelangelo reference is that, is that correct for your painter those paintings behind you yours. I noticed a couple of comments, I think my, my hidden secrets as a closet singer has been, has been disclosed by one or two. Genius individuals in the audience, there was a time in my life when I was known to embarrass myself in public and sing, and I can barely do a stick man so I'm afraid I have no claims to the visual arts at all. But I'm an appreciator of fine music and have occasionally been known to, to dabble in a little bit of the same myself but, but I would say that actually medicine, medicine is an art isn't it. It's, it's, it's, or it's somewhere between science and an art and I think it's that that creativity that goes with the art of medicine that there is I think it's well known that many medics are, are musical and many musicians are medical so perhaps there's a little bit there but I think people are being a bit naughty out there and I, I know who they are and they'll, they'll soon hear all about it. Well, at that point I think it'd be a perfect time to wrap up really sorry that I haven't managed to get to everybody's questions but thank you all for those who have submitted them and I hope we've done our best to, to answer them. So once again from society. I'd really like to, to thank you, Professor McKinnis for for your time this evening it's been a terrific, terrific talk and thank you for so enthusiastically answering the questions and thank you to all the members and non members who attended tonight's lecture I just want to hand over to our President Pat Monaghan, just to say a few words at this point over to you. Okay, thank you very much. So, as Phil said I'm the president of the society and I have the nice job of donning the society presidential chain and handing over to Ian, the Graham medal. Okay, we haven't yet got to the stage where I can actually hand it to you, but I have a picture of the medal behind me here it has Ian's name engraved upon it this is the society's Graham medal, which is in memory of Thomas Graham a brilliant scientist who was born in Glasgow in 1805 and spent half his career in Glasgow. He did pioneering work on gas diffusion, and also laid some of the foundations for dialysis kidney dialysis, at least a precursor of that. Thomas Graham was a key figure in the history of the society and that played a big role in its development. We have a medal to commemorate him. Ian I'd like to congratulate you on giving us a great lecture you simplified some very complex topics very well you did it with a sense of humor. You did it with enthusiasm, and you gave us celebration of science and medicine and brought together past and present and made us optimistic about the future so thank you very much indeed for that. I just want to follow to being able to give you the actual medal in person but there it is that's what it was not quite that big, but it's a very nice medal. And I just like to end by just reminding society members about the next lecture, which is also a named lecture it's our Adam Smith lecture and associated with the new Adam Smith medal. It's going to be given actually by Ian's boss, if you like, also my boss. I'm Tom Muscatelli, the principal of Glasgow University who is an economist, and the title of his talk is the health and wealth of nations. And he's going to talk about the pitfalls and opportunities in economic recovery after the pandemic pandemic so we look forward to everybody joining us again in two weeks. Time and as Phil said, we're hoping that we can go back to at least hybrid lectures by then but that remains to be seen so thanks very much Ian. And thanks everybody. Good night. Thank you very much indeed.