Just to give you a preamble. This slide shows leading causes of death in one year alone, worldwide.
So in 2023 alone, 61 million people died due to just top 10 diseases. We're not talking about a whole range of diseases. We're only talking about just the top 10 diseases and these include non-communicable diseases like cancer, cardiovascular, and so on as well as communicable diseases like bacterial infection, parasitic infection, and so on.
Seven out of 10 people died due to infectious diseases. Looking at these numbers, the most distressing aspect to me personally is that these numbers have remained significant despite our advances in antimicrobial chemotherapy and supportive care and to make it worse, the number of new drugs are on the decline. In addition to drug resistance that we are observing against many of the drugs.
So, from 1983 to 1987. Only 16 new drugs were approved by the FDA. And the next five years, the number got down to 14, then 10, 7, 5, and two. So the fact that the number of people who are dying every single year is 60 to 65 million, the number of new drugs are on the decline and even these are not really new drugs. These are existing drugs, which are slightly modified. So you see in a pharmacy, second generation antibiotic, third generation antibiotic, 4th generation antibiotic, and so on. So we really need to understand the biology of these diseases. We need to understand the mechanism by which we can prevent these diseases.
We need to understand the mechanism and come up with new drugs against these diseases. And that's precisely what we are doing at the University of Derby now.
I don't know why I show this slide. I think but probably zoonotic diseases, that's another burden. So in addition to 60 to 65 million people who are dying due to top 10 diseases, we also have to worry about animals spreading disease as well. So the threat is real. We have to investin these areas. Really important.
You're not going to like this, but I believe that humans are not a good species. We came on this planet maybe a few thousand years ago. And there's already talk of extinction. There's talk of bringing this planet on its knees and of the world and so on. And we forget that we are not the only species. There are millions of other species that are living on this planet for millions of years. And just to give you one example of cockroaches, only because I wanted to spoil your dinner later, that cockroaches have been here for more than 350 million years. And they're thriving. They live in the most polluted environment, the most unhygienic condition. If you see them, you want to step on them. Please don't. And yet, they're able to survive for a very long time. So, we ought to be learning from these species. We need to understand what are the mechanisms.
When COVID happens, we have to wear masks. They don't. They must have some mechanism, they must have some protective molecule that can prevent them from getting COVID or superbugs or bacterial infection or anything else. We ought to take out those molecules and bring them to human use for clinical use for us. And that's precisely what we're doing in our lab, so we wanted to explore that how they're able to thrive and survive in these environments without being extinct, without being threatened by the very superbugs who are able to cause major infections and outbreaks to humans.
But just to give you a little bit of background, we all know cockroaches are one of the most hated species on this planet. If you see them, you want to step on them. Please don't bring them to me. We can get some use out of them.
We have an excellent insectary here as well. They are one of the most hardiest insects on this planet. They can survive without food for more than a month. They can survive without air for more than 45 minutes. They can be submerged underwater for more than 30 minutes. They can tolerate radiation level 50. Fifteen times more than what can kill me and you, very high tolerance to radiation, 15 times more, one of the only few species that have survived nuclear testing. And they have been here for many, many years, for more than 350 million years. They have seen everything. We have to learn from these species. We should not consider them as inferior. We should learn from them and use those mechanisms for ourselves. And it doesn't matter what kind of insecticide you get from the supermarket, you just can't get rid of them. They're everywhere. They're very difficult to eradicate.
So what we are proposing and what we are suggesting to our students and our research is to learn to coexist. Do not try to eradicate one species for the benefit of another species, especially Homo sapiens. We should learn to coexist with these species.
So there's talk of who's going to inherit this planet from us. And you will often hear that maybe it's viruses that will inherit this planet from us when we're long gone. Maybe it's a superbug, but I believe that cockroaches are also one of those species that have the potential to inherit this planet from us.
So we wanted to find out that how do they survive these challenging environment, how they are able to cope with these unhygienic conditions, this pollution, and still able to thrive.
So we got cockroaches. The species that we worked with is Periplanita americana. I know it sounds like coffee, but it's not. And they're very easy to culture, they're very easy to grow in the lab. You give them anything and they'll feed, as you can imagine. Actually, when we are growing them, somebody complained about me to the Dean saying that, you know, Naveed is not looking after cockroaches very well because, you know, there's animal welfare on those rights as well. So just to keep everybody happy and satisfied, I brought some cookies, wrapped in the newspaper, and gave it to cockroaches. The following day I came, cookies were still there, but the newspaper was gone. The point I'm trying to make is that they will feed on anything, and they are very, very easy to grow in culture. So what we do in our lab, this is how it started. We collected their various tissue, their oral cavity, their gut, their brain, muscles, fat bodies, all the tissues basically. And then we tested them against one of the superbugs which is really affecting UK population, UK hospitals, MRSA, which is known as methicillin-resistant staphylococcus aureus, which is a huge problem, causing approximately 5,000 deaths per year in the UK, which is a very, very large number.
So we took those organs from the cockroaches and we added them to these bacteria. So these are bacterial plates and you can, these colonies, what you see are the bacteria. When we put these cockroach lysates, what you see is those 1 million bacteria were completely gone. There was 100% kill rate. Due to the life set of these cockroaches.
Suggesting that they must have something very powerful in them, which is killing, which is eradicating 100% of these MRSA, these superbugs which are very, very resistant to the antibiotics that we have at our disposal.
And this work was highlighted in the Science News and also the BBC that came to our lab as well. And many other agencies that made documentaries.
So what we are hoping for is that finally the cockroaches will find their way into the affection of the human race. So you will probably not like them, but at least don't kill them. And bring them to us.
So somebody asked me, okay, what are you suggesting really? Are you suggesting that we take these cockroach and have these cockroach farms so when somebody gets diseased or sick, that we mash them up and then give it to them or feed them? No, that's not what I'm suggesting. What we are suggesting is that we need to identify those molecules from those cockroaches and then synthesise them in our lab at the university and then bring those molecules to a pharmacy. That's what we are suggesting. That's what we plan to do. So we need to understand where do those molecules come from. But there are two possible mechanisms. One, the immune system. So perhaps it's the immune system that's producing those very powerful molecules to help cockroaches defend them against those bacterial infections. So that's one possibility.
Secondly, maybe it's the gut bacteria that are producing molecules to prevent those infections.
Now, that's not a very unusual concept because 70% of antibiotics that you see in a pharmacy today are being derived from soil bacteria. So the question that whether gut bacteria living inside the cockroach gut producing those molecules is not unusual. It's acceptable. It makes sense. So instead of going after the soil bacteria, what we propose is that we should be looking at bacteria which are exposed to the organic waste, which are exposed to the pollution, which are exposed to the type of superbugs that we are being exposed to as well.
So that's what we are trying to do in our lab. So we basically, I don't want to drag too much on this, but basically we collect their bacteria, culture them in our lab, and then we use analytical tools to be able to identify those specific molecules in our lab.
Now, this is a huge task. You can imagine that each cockroach has hundreds of bacteria in their gut, and each bacteria is producing hundreds of molecules, and then each molecule has to be tested against many, many bacterial pathogens and viral pathogens and parasitic pathogens.
So it's a very long-term project. We need to identify that each molecule has those properties, and that's what we're doing. So just to give you an example, so one of those bacteria we isolated, and then we produced, try to identify that how many molecules there are, we found out more than 200 molecules from a single bacteria. So you can imagine that there are hundreds of bacteria in the cockroach gut, in their oral cavity as well, and then trying to identify each molecule as well as the structure of those molecules, which is critical because if you are going to synthesise them in the lab, we need to understand the structure of those molecules, and that's what we are doing.
So we thought, okay, that's interesting. So we are finding that this work was funded by the Ministry of Defence in the UK. We thought, okay, that's interesting, but why limit ourselves to cockroaches? There could be other animals which are being exposed to the pollution and maybe we can use them as well. To ask the same research question. And that's what we're doing in the lab.
So what kind of animal that we can look at? So one of the animal that I'm really fascinated about is crocodile. Hence this lecture about crocodile. So we decided that we want to understand the oral microbiome, oral bacteria and the gut bacteria of crocodile, and try to find out whether they also produce these anti-infective, antibacterial, antibiotic-like molecules that can help us, and we can bring that to the pharmacy.
So the main problem that we had was that UK doesn't have Crocodile. We do have cockroaches, but so we decided to then fly to Malaysia. That's where one of the reason you're driven by the research question that you're asking. Crocodiles are one of a fascinating species. Why? Because they are very hardy. They live in very stressful conditions. They feed on rotten meat. And I tell you, I don't know how many of you have visited crocodile farms or sanctuaries. If you go there during their feeding time, it's very smelly. So when I went there for the first time, so I asked the manager that, why are you feeding them this rotten meat? Why can't you give them clean meat? And he said, sir, you know, it doesn't matter if we give them clean meat or rotten meat, they'll make it rot anyway. Because that smell of rot or yellowish and gooey, that's like biryani to them. So, you know, we may not like that smell and that taste, but to them, that's the taste they prefer. So even if you give them clean meat, they'll make it rot before they'll feed on that. So the question is that how can they, they can withstand that bacterial contaminated meat without getting infected while we have to cook it to death, right?
So put all the curry masalas and everything. And they endure a very high level of radiation, so some of you may not be aware. Crocodiles don't get cancer. One in two people in the UK will die of cancer. But crocodiles do not get cancer. We have been working with crocodile farms. We have been working with crocodile sanctuaries. We have been working with the vets who have been working with crocodile for the last 80 years. We have not come across a single case of cancer in crocodile, in those farms, in those sanctuary, that's amazing.
My wife goes out in the sun and she puts all the sun cream to prevent her from getting these problems. But crocodiles, they are always sunbathing. They're always living with heavy metals. They're always feeding on rotten meat. How can they survive? So the answer that we believe is in their gut microbiome. That's the one that's being exposed to that organic waste. That's the one that's being exposed to that pollution, those heavy metals. It somehow translate or transfer or degrade those heavy metals, contaminants to ensure that crocodile is protected, and that's what we're looking at.
So as I mentioned, this is a kind of water that crocodiles live in, and we tested this water is full of heavy metals. So it is bizarre that they can live for 100 years longer than humans, and yet they do not get the problems that we are getting as humans. And they've been here for more than 350 million years, so again, one of the amazing species that have survived and thriving in those environments.
This is the kind of meat that I was talking about that they're feeding to crocodile. This is a close-up just to ensure that you spoil your dinner. And these are the crocodile that we're working with. So one of the key questions was that how are we going to collect the oral microbiome from a live crocodile? Well, this is how. This is my son. He's very brave. So I'll show you that, yeah, they may look threatening species, but they are able to, there are people who can really tame them, who can play with them without getting threatened by this species. I just have a small movie on that if I can play. So this is our collaborator. This is 1, 14 feet long crocodile. So when we visit them, we all, I take my kids as well, but I make sure they stay away. So, you know, we don't trust. And so this is a guy who's who helps us correct collect the oral microbiome. It's just amazing the way that he was, you know, when you see them live, it's really puzzling how they're able to just play with them and then he wants to give the crocodile a kiss, I think. He was very proud, so. So I did ask him, why would you do that? I think they were just trying to impress us. They can handle them easily.
So, that's how they collect the oral microbiome of the crocodile, and the next thing what he did was that he put his head in the in. in his mouth and I just couldn't bear making that video anymore. So I just gave up. So we bring this crocodile into the lab. So in the beginning, we were also looking at the immune system of this crocodile. So for that, we had to again test their organs as well. So we bring them to the lab. This is Team Crocodile Dundee. I don't know how many of you have seen that movie. So they're really brave. We're also building capacity as well, you know, and training our younger scientists as well, who would be enrolling at the University of Derby.
No. Very brave. So again, whatever research you do, you have to do ethical research. You need to get the right licence to operate on all these species. Because UK doesn't have crocodiles, so we had to work with the government of Pakistan, government of Malaysia. It took me two years to get the licence to operate or to work with crocodiles for medical research and it is quite painful. It just takes time. So we are collecting their oral microbiome and what we do, I don't want to bore you with this, so what we do is we identify what kind of bacteria they have, how many. Again, you can imagine crocodile gut. They have thousands and thousands of bacteria in them. And then each bacteria is producing thousands of molecules, and each molecule has to be tested against many, many pathogens. So it's a very tedious task to work with these animals. So that's what we do at the University of Derby. Again, I don't want to go into detail. I've shared this with you already, but basically we test their bacterial products, those molecules, against the superbugs that we are seeing in the public, and then we identify how they're able to eradicate those pathogens, and then we try to identify their molecular structures. With hope that we can bring to a pharmacy that could be the first antibiotic from cockroach or from crocodile in the near future.
Again, my apologies. It's just a very busy slide. One question that came up was that when we isolate these species, bacterial species from crocodile, some of them are named similar to human bacterial species. So like the Pseudomonas is a pathogen. We see them in humans causing infection but we see the same pathogen in crocodile as well. But when we tested them for the molecule they produce, it's entirely different. So it's the same organism producing entirely different thing under different environment. So suggesting that we cannot just assume that they are the same bacteria. They're very, very different because of probably the environment. So we have to look at every single bacteria which is being isolated from crocodile or from cockroach or from other species and then determine their properties. And then we do molecular work to determine their molecular structure so we can synthesise them in our lab. with our chemistry colleagues.
So now we can expand that to other species as well. So one of the species that always caught my attention is a cobra or snake. You know, snakes, they eat rodents, germ-infested rodents, live, live rats, basically, so the same question that how can they eat live rats which are full of germs and thrive on that?
You know, my mother cooks chicken curry and she cooks it to death, but they are able to thrive on live rats. So how do they do that? So we wanted to test that. So for that, we had to go to Pakistan. They have lots of cobras in there, different species of them.
So we got one of these cobra there. And then we did a similar thing with cobra. There as a myth that maybe there is something in the venom of these snakes, which are antibacterial or antimicrobial, we tested that zero effect. It actually promoted the growth of bacteria and the viruses, rather than inhibiting the growth of bacteria and viruses, so venom has nothing.
And we identified again that is the products which are derived from the gut microbiome, which are being circulated in the snake, and then allowing the snake to prevent those infections that we contract from these pathogen.
So I don't want to go any further on this. So basically, we're working with crocodile. We're also working with the python from Malaysia.
That's another species. Water monitor lizard, another species, which is very interesting. And we found very interesting molecules on that. Tortoise is another one that we were interested in. And ultimately, what we believe is the gut microbiome plays a critical role in the human health. And if we can identify that what kind of gut microbiome these species have that allow them to live a very healthy, long life.
So whale can live up to 200 years. A shark can live up to 400 years and they don't get cancer. That's a very long time. So if we can identify that what kind of oral and gut microbiome they have, then that we can bring that and identify those molecules. So we are hoping... We have one of our colleagues, Professor Michael Sweet. So he promised that he's going to bring us a shark. So that will be the next research here. And many of the other species which are very interesting.
I just wanted to kind of in a nutshell describe, my apologies for this very busy slide, that hardy animals, overall what we believe is hardy animals are a potential source of anti-stress and anti-cancer molecule. And we have done, I didn't want to today show those molecular analysis and molecular mechanistic work. But those mechanistic work and the molecular work have been well published. I'll be more than happy to share those findings with you who are interested to showcase that how come these kind of animals are able to survive and thrive under those pressures, under those conditions, that we are finding it very difficult to survive. So those extreme resilience of some of these species and what kind of bioactive molecules are being produced from the gut microbiome and oral microbiome and how they are anti-stress or anti-cancer properties they have at their molecular level in a mechanistic way. And that's what we are looking at, at the University.
I want to just switch briefly to a different topic. Again, you know, you're driven sometimes by the priority areas of the funding agency. So the recent funding that we have gotten in the last six years is on the physical activity or physical inactivity.
People who do not exercise, we know that they get cardiovascular problem, stroke, cancer, kidney, other diseases as well. So when I go to my GP or my physician, they will say that you have to exercise or you will get these problems. But crocodiles, they don't exercise. They just sit there, as well as several other species. Same thing, people who are bedridden. You know, due to hip replacement, due to ageing, old age, due to, you know, some trauma, some surgery, and then so on and so forth. If they are bedridden, they become physically inactive, so their blood flow changes. Same thing we see in microgravity as well. In microgravity, blood is not pulled down, it becomes more horizontal, so it's the blood flow changes, so our heart has to work really hard to pump the water so it can reach our extremities. This is a challenge. And what changes? So the question that we were asking was that when people are physically inactive or they are bedridden because of a problem or ageing or so on, or they are in the space they will, their gut microbiota changes. So from good bacteria, we will end up having more bad bacteria. And that creates a problem. Because when you have too many bad bacteria, you again have similar kind of conditions of cardiac effects, angiogenesis, neurodegeneration, neurovascular syndrome, and cardiac atrophy and so on.
So what changes is that normally microbiota, it synthesises these molecules which are being circulated in our bloodstream and reaches the organs that we have for our normal human physiology of each organ. So that happens normally. But when we have these changes in the blood flow, due to physical inactivity or due to microgravity, that those molecules or those bad bacteria will end up producing those metabolites or those molecules which are unable to produce the same effect, which can create the same normal physiology that we need for our functioning.
So what we are doing... and this is the work which has been funded by the US Air Force, is to identify that what kind of molecules are being released when we have such stressful condition due to physical inactivity, due to microgravity and so on, and then supplementing those molecules in advance. So if somebody is going on space mission, for example, if we give them those products, those molecules, those metabolites in advance as a food supplement, then they can prevent those problems. As you know, in the recent Artemis, astronauts came back. So normally when astronauts come back from the space mission, they are kept in isolation because they often show symptoms such as vision problems, dementia, so they're kept under observation for a few months because of the metabolites, because of the bacteria that changes from good bacteria to bad bacteria, and that allows the production of metabolites which are not healthy, which cannot have a normal. physiology of our organ system. So what we are doing is creating those molecules in the lab so we can give them as supplements before somebody goes into for a space mission or before if somebody is aged or somebody has a surgery or a hip replacement and so on. If you can identify those molecules which are critical, for the normal human physiology, then we can give them a supplement. So even though they are not exercising, they will still have the same normal physiology. So they will not get, hopefully, dementia, they will not get vision problem, they will not get hallucinations, which is a very common problem we see in ageing population as well as people who go on space mission and that's the connexion with the US Air Force or that's how we sold it to them anyway and they bought it.
So our hope is that development of those novel therapeutics in the form of prebiotics, probiotics, postbiotics, we want to take it one step further. If you go to Tesco or Sainsbury or any of the supermarkets or booths, you will find these food supplements. But they are derived from human bacteria or human good bacteria. What we are saying is that if we can come up with these bacteria which have been isolated from these hardy animals and then give them as a food supplement, then that will have remarkable effects for our ageing population, for people who are suffering from these communicable and non-communicable diseases, or people who are suffering because of physical inactivity for whatever reason, because they've been having a surgery or ageing or whatever. And that's what we are hoping to develop.
So we have identified these products and we are hoping that that will be the first product. We know the mixture and we have shown and published that those products work in our models. And we just need to show that they are working in humans as well to bring to a market. And that will be a remarkable achievement because UK population is ageing and we have to focus on the problem that we have within the community.
So the research opportunities don't end there. They're remarkable opportunities. Again, they come back to the same point. There are millions of species we can learn from. We're focusing on cockroaches and rodents. So cockroaches are the one we're using. They're being grown in the lab. You know, they're clean cockroaches. Can you imagine those cockroaches which are in the gutter? They are super cockroaches. They must have those bacteria which must be very powerful because they are constantly being exposed to that sewage and those pollution. And if we can isolate them, we may end up with a remarkable new molecule and new species of bacteria. That can help us improve human health.
Marine vertebrates, invertebrates, a remarkable resource. We are an island. And yet, we are not looking at the marine environment. So, so far we're only focusing on land animals or land species, but going into the marine environment, there's the huge potential.
When I go to Karachi or Mumbai, the water which is being thrown into the ocean, sometimes it's not treated effectively, as though that sewage water is gone straight into the ocean. So the question is that those species which are living in that ocean, they must be remarkable. They must have very resilient properties to be able to withstand those pressures of pollution and superbugs and so on. So we should be looking at that as well.
Birds captured from garbage dumping areas. You know, I was really interested in vultures. That's one species I wanted to look at. And again, I came to the hurdle that UK has no vultures as well. So we have to know, that's one of the reason that we had to go to Turkey, because they have their vultures there, because they again feed on that contaminated meat. So if you can find out what kind of oral microbiome or gut microbiome they have, we can identify those molecules, and then hopefully we can make that into a product for human use.
And other species, lizards, snakes, frog, feeding on pest, insects, rotten meat. So again, these are potential species that we should be looking at. And also the microbial organism which are living in that environment. We should be, instead of isolating bacteria from the soil, we should be isolating bacteria from this pollution, from polluted environment. because those microbes must have the ability to withstand a lot of pressure as well. If you can identify those molecules, we should be able to come up with new ways or new molecules that will have antimicrobial or anti-cancer or anti-stress properties for our use.
So our plan is the gut microbiome is the key, and what we are hoping to do is that using these animals as a resource in addition to the animals living in the marine environment, identify those gut microbiome, test their antibacterial, antiviral, antifungal, anticancer properties. And you can imagine that to do that, we need to bring different disciplines together. And that's one of the ethos of the university, that we cannot work in silo. We cannot be discipline specific. We have to work together in teams for chemistry colleagues who can identify the structure of those molecules.
Drug delivery is another challenge. So even if you identify a compound or a molecule, you need to be able to deliver that to the patient who is affected by that condition. So to do drug delivery at a concentration, which is not going to have any side effect. That's another challenge. And translational science and biosciences and zoologists, so we need to bring these teams together to be able to do meaningful, impactful work, and that's precisely what we are doing at the university.
Finally, I just want to thank everybody who has been part of this research and of course the funding agency. But of course, I'm very thankful to these animals who have contributed sometime their life to this work. And thank you very much for your attention.
Professor Naveed Khan's Inaugural Lecture: War on Terror Cells: Exploring how species such as crocodiles and cockroaches could help improve human health and performance video
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