Chronic Inflammation & Cancer - Spiritual Bohemian

Dr Angus Dalgleish explains what causes chronic inflammation, the impact it has on our immune system and the subsequent reasons for cancer development.

Audio

Summary

Chronic inflammation is a key driver of many cancers, leading to immune suppression and an imbalance between T-cells and other immune cells1.
Mycobacterium vaccines like BCG and M. vaccae can help restore the balance of the immune system, boosting T-cells and reducing harmful inflammation1.
Long-term studies have shown that BCG vaccination in childhood is associated with lower rates of cancer and heart disease decades later, likely by setting the immune system to a healthier equilibrium1.
Anti-inflammatory agents like aspirin have also been shown to reduce the risk of certain cancers, further demonstrating the link between chronic inflammation and cancer development1.
Vitamin D is a crucial anti-inflammatory that plays a key role in immune function and cancer prevention. Low vitamin D levels are associated with increased cancer risk1.
Other nutrients like iodine may also be important, as deficiencies are linked to higher cancer rates, though this area requires more research.
Moderation is key – both excessive inflammation from factors like high alcohol intake, as well as overly restrictive diets, can be detrimental. Maintaining a healthy balance is crucial.

Full Transcript

Dr Campbell: You are most welcome to this talk and particularly a warm welcome to Professor Angus Dalgleish.
Professor Dalgleish is a fellow of the Royal College of physicians in the United Kingdom and Australia, fellow of the Royal College of Pathologists, fellow of the Academy of Medical sciences and currently professor of oncology at St George’s Medical School in London and of course a consultant oncologist and long-term cancer doctor so what we want to talk about this morning Professor if it’s okay with you is the causes of cancer. First of all very briefly, what is cancer?

Dr Dalgleish: Well cancer is a disorder of growth and differentiation of cells basically they just escape from their programming you know they no longer read the script as it were, and decide like escaped prisoners, hey this is interesting I can do what I want and so they start growing or spreading etc. That’s it in a nutshell.

The important bit though is that this is a procedure that is expected and heavily regulated (in the body) so there are a lot of genes to try and prevent this which is one of the reasons why cancers take decades in order to manifest. So it takes a long long time and things can accelerate or switch this process off so that’s the first thing I think is really important, to be aware.

Dr Campbell: I was just smiling there because I’ve never heard the Escape prisoner analogy before and it really just rang true with everything I know about cancer. We want to get on to the idea shortly, is it basically true to say that cancers can be described as mutations?

Dr Dalgleish: Well cancers arise as a result of a series of mutations so you’ll get a mutation in a cell and nothing much will happen to that except that it is less likely to die when ordered to do so. This cell life-cycle are the same, I mean they’re born to do their job whatever it is, then they die, and it is having a mutation that delays that dying that allows them to continue for a bit longer and this increases just by pure random chance the chances of a second mutation occurring and that cancer is often a result of several mutations, at least six. In some cancers over 60. So we know a lot of the detail and I’m not so sure that it enables us to do as much as we’d like to prevent it. However that’s been in a way, my sort of life’s job to understand this with all the various tools at our disposal, and the the one that really got me was viruses. I mean the the fact that viruses can cause cancer particularly in mice, and that’s what really got me very interested in what are the real causes of cancer and the mice were the ones where they discovered the first mutations. Like the Ras Oncogene . If you have this mutation then the cells are much more likely to survive to get a second hit and then become cancerous. So that is where we got a lot of our information from and interestingly a lot of these viruses in mice, where we studied cancer, are retroviruses and so I got very interested in this. This is what I did my MD thesis on and unlike most people I did my MD thesis after I’d finished all my clinical training. Normally you were meant to do some registar work and then take two three years off and do the thesis. Well I was offered many but I never found any of the projects remotely interesting and so I just carried on doing the clinical until I discovered that viruses were probably causing human cancer as well. It was just much more subtle and that’s how that’s how I got very interested in it. I focused on retroviruses initially because that’s what you did in the laboratory. The only retrovirus at that time that was recognized was the human T-cell Leukemia Lymphoma virus – HTLV1 which had been found to cause leukemia in Japan and the Caribbean particularly.

So that was what was already known at the time when I went in. Then this is where it gets more interesting in that we were able to work with this virus and see how it causes cancer as it were. But at the time I moved in, AIDS had become really big and it was rumored that a retrovirus might cause AIDS and there was massive research in this.

As we now know both Montagnier in France and Gallo in America both isolated their own viruses which turned out to be the same. They were called – HIV – in that time now the interesting thing for me as an oncologist at that time, was that AIDS was associated with presentations of lymphomas and Kaposi sarcomas which were both malignancies, so I felt Justified my time delving into what was going on with this retrovirus. The conclusion is it’s indirect it’s not a direct transformation turning on Oncogene. It was indirect by removing the immune surveillance, these lymphomas and Kaposi sarcomas, popped out they’ had their policemen removed as it were, so that they felt that able to multiply they didn’t have any of the restraints. The interesting thing here is, and what really got me, is both the lyphomas and the Kaposi sarcomas, (it took us decades later before we understood the Kaposi sarcomas), but both of them were driven by viruses which is sitting there very well controlled by the immune system.

So you can see where I’m coming from with regards how I got interested in how viruses cause cancer and looking around there’s viruses other than retroviruses. So that’s how I got involved very much and this is how I came across the concept of what cancers arise best in chronic inflammatory States. The viruses are absolutely a great example of chronic inflammatory states. The first big example on the ward that I came across when I was working in Sydney as a senior registrar doing medical oncology. After two years I had the qualifications to be a consultant which I then became but I had some very interesting cases. I was particularly interested in the hepatoma. There was a lot of hepatoma in Sydney and hepatoma means the primary cancer of the liver. So it was a cancer of the liver and it would kill people and there was no good treatment. They’re just starting to get some reasonable treatments now, but then it was essentially a death sentence. I was told particularly in my training as an internal medicine registrar in general medicine, when we had these cases I was told that they were due to alcoholism they’re all due to alcohol.

I thought that was a bit odd because we knew people who had lots to drink as it were and never got hepatomas and then I found when I was looking at some of the patients they claimed not to be interested in alcohol or have given it up years ago. I thought something was not quite true here. It has been reported that by that time a herpes virus, a hepatitis virus, Hepatitis B it was called is fascinating because it had a link with Australia. It had an Australian antigen in it because it was found in some indigenous populations but it was common in Asia as was the hepatoma. I got rather irritated that everybody were being told this “fellow’s got hepatoma and it is due to drinking alcohol” and some of these people who have Chinese extract weren’t drinking alcohol at all. So at the time I basically got hold of a very very early tests for this virus in fact it was a a pathology collaborator in the Sydney University who was developing a reliable test so they could identify this virus. I thought well what I’ll do do is I’ll get everybody who died of hepatoma cancer of the liver in Sydney in the last two or three years, and we were able to identify them in their own Hospital. There were over 40 and so fortunately because of the interest in this there was serum from them. So I was able to get stored serum and all I did was take the serum to the Pathologists who developed this test, and some serum from other patients as controls. I asked them to run through them blind and lo and behold all the hepatomas were Hepatitis B positive, I mean it was really quite remarkable. All the controls were negative, I wrote that up as one of my first what I call epidemiology papers. So I started looking at what Hepatitis B does and basically it causes an acute hepatitis often which is an acute inflammation of the liver and it settles down but then it goes on to cause chronic hepatitis and then as it goes on to a more consolidating phase, it’s called cirrhosis, and it’s only when you get that stage,that the cancer kind of breaks out. So it’s taken all this being fed by or protected by this environment of chronic inflammation and this goes on to the point where it escapes immunity. It’s interesting in the serotic phase there’s a lot of angiogenesis there which gives any cell that’s had one or two mutations more growth factor. It’s like watering the rose garden.

Dr Campbell: So the serotic phase is when there’s fibrous tissue in the liver and the angiogenesis means there’s something there in this very fibrous scarred liver that’s stimulating the production of brand new blood vessels.

Dr Dalgleish: This angiogenesis, I don’t fully understand the exact mechanisms but it’s just that’s the association that you see from the pathology papers but only then do you get this liver cancer. Now the other interesting thing was they were occasionally getting liver cancers that were Hepatitis B negative, but they were all from people who’d had a history of chronic hepatitis, but they hadn’t got Hepatitis B. What they had had (and at this time) this was called hepatitis Non A and Non B, you remember that very well I remember it well. There’s now a few viruses in that group, but the dominant one was Hepatitis C and it did exactly the same, it gave you acute hepatitis chronic hepatitis after years and then it too could lead to a primary liver cancer. Now what I was very excited about is these viruses couldn’t be more different . Your Hepatitis B is a big complex herpes virus like with DNA multiple DNA and the hepatitis C is a little RNA virus completely different. Yet they induce the same thing.

So I got very interested in pathogenesis, this it was the principle in the story that was required for cancers to evolve, so this was the first Insight. It’s not confined to a specific virus like Hepatitis B, any virus that induces this inflammation can cause it, so that’s when I got really really interested in the virus that cause cancer. I think it’s worthwhile pointing out at this moment that I realized that there were a lot of other viruses that can cause cancer. I mean the next high-profile one is human papillomavirus which I remember reading the papers in nature saying it was caused by herpes simplex virus. Big complex papers saying absolute proof, and also rejection of people who said it’s due to another virus which turned out to be the human papillomavirus which is the cause. However, it wouldn’t grow in the culture so that’s why it was thought not to be a real virus. It was identified with molecular biology and everything in the end and so that was another example and that virus actually is very important because it causes chronic inflammation in the mucosa and that’s what leads you to have it for quite a long time before you get the cancer develop. The same principle same story, we now know It’s associated with mouth cancers over 50% of mouth cancers are are driven by he human papilomavirus, esophageal cancers and throat cancers. Some cancers have this human papilomavirus driving the cancer, so at a stroke you’ve got the enormous number of cancers that we are common that we recognize caused by viruses.

So just to recap uh recapitulate I’ve done the hepatitis ones, Hepatitis B, Hepatitis C and I’ve mentioned the ones associated with HIV the lymphomas which we now know is EBV driven – Epstein bar virus and the Kaposi sarcomas which is driven by a herpes virus which again is only discovered relatively recently – HHV6 – and they’re driving it because they’ve been released by from the immune system. Now then you have the papilomavirus which is clearly a mucosal transmission one. So I basically was asked to give a lecture in Leicester when colleague called Kenno Burn was there as a consultant. He’s now a professor of oncology in Brisbane, so we kind of switched over. I’d done a lot of training in Brisbane and here in the UK in Ireland, and I gave this talk up there and saying that after all my HIV work that I thought that cancers arose in immuno-suppressed environments. Well we knew that from transplants Etc, but that unlike HIV, the immune suppression of the big common cancers, lung, breast, colo rectal, prostate and what have you, that the immune suppression is much more subtle. I said I think from the model of the viruses, it’s due to chronic suppression by the cancer and the environment they arise in leads to a chronic immune suppression. Afterwards I’d given this talk and we went for a few beers afterwards, and Kenno burn says “Well I agree with everything you say, but I don’t think it’s the immune system’s got anything to do with it’s obviously angiogenesis”. He said “this is a process where angiogenesis gets to thrive and becomes more and more enabled. It makes sense because a cancer is a living tissue so you would need a blood supply otherwise it would simply go black and the necrosis.

So this is where so we were basically two scientists examining an elephant and he reckoned it was say the Tusk and I reckon the important part was say the ear. After a couple of pints, or perhaps more, we suddenly realized I said “Ken we’re describing the same process but from slightly different angle. The only thing that causes a chronic immune suppression and stimulates chronic angiogenesis is chronic inflammation and that is what these viruses are doing in it and if this is true then we can look at all the other viruses to see if that fits their pathophysiology. So then that would be it, and you don’t need a virus. Well I cut straight to the point, we suddenly realized you know, you got lung cancer that occurs after at least a couple of Decades of chronic bronchitis stimulation so it has the perfect chronic inflammation and angiogenisis etc. The other big solid one is colorectal cancer. Colorectal cancer we already knew was much more common 50 times more common in patients with Ulceritive colitis which by definition is a chronic inflammatory state but there are patients who don’t have Ulceritive Colitis who get colon cancer. Then we know there’s another predisposition polyps. So
I said polyps you can have familial polyps or just random polyps, but these olyps if left to grow, and grow enough mutations, then they become cancer. I asked the pathologist what he would classify polyps as. Do they have certain things hereditary genetic inflammatory Etc. He said oh without a doubt they’re inflammatory lesions inflammatory adenomas but benign, but left to their own devices for 2 or three years they will become malignant which is why if you have a propensity for these they screen you and cut them out. If you’ve got a familial polyposis or even if they suddenly found you’ve got a problem and they find you got polyps and they go well we better keep an eye out in case more pop up and that’s obviously the right thing to do.

So we suddenly realize this in fact is what is the big precursor of the majority of cancers. I mean there’s not one theory for everything but this is not far off. I think this is over 90% of cancers fit into this and then Ken given his due, he started to research what how chronic inflammation affects the oncogene cycle and the suppressor cell cycle. At this time we had the NIH – National Institute of Health in America, National Cancer institute, they released this progression of cancer cartoo, which basically had you know one cell mutates a bit then next one lives long enough for another mutation. This is the classic you needed about six to become a Cancer and start metastasizing and we suddenly realized that this this was a lovely model just to sync into our chronic inflammation thing. It was like planting roses into a flower bed you know this inflammation was the food and the growth factor. More importantly, from my point of view
of the immune system, chronic inflammation causes immune suppression and prevents an active immune response from doing its surveillance and we know T- cells can pick up an oncogene that mutates and kill it. But iff it’s in a chronic inflammatory State, T- cell can’t get to it so then this random mutation survives in this chronic inflammatory State, the T cells are suppressed, they’re pushed away and that allows them to go on and get the second mutation. So this explains how you have a scenario where cancers take two three four decades in some cases before they manifest. So then the good thing about this is that you’ve got a long time, you got a lot of warning time and from my point of view it really does say what things can you do to reduce chronic inflammation because that will reduce your chances of getting cancer dramatically.

Dr Campbell: Just a geeky Point Professor, if something’s inflamed I would associate that with uh an influx of white blood cells like cytotoxic tea cells.

Dr Dalgleish: Very that’s very good and very true except you’ve highlighted that the immune system is quite complex and full of different different soldiers. It leads to a big influx of white cells like neutrophils for instance and macrophages what have you but the T-cells can’t get there because this is becomes a very inflammatory environment. So we now know that if you do have a lot of nutrifil in your blood with a cancer patient and very few lymphocytes that’s a very bad prognosis. If you can convert that so you have a healthy T-cell and you reduce the number of white cells then you have a much better prognosis. There are several papers that have been reported over the last two to three years just pointing out this fact. Saying you know I wonder why that is how does that occur because like you were say implying that lots of white cells means a good immune system means it will control it. No this is a very good thing, it highlights that the immune system is a delicate balance between T-cells the Frontline Warriors, your front line of the army as it were, and when they encounter a foreign invader like, covid for instance, they charge up and they beat it up and they send signals to the B cells, which take a while to kick in. This is especially so for a new one and then they make antibodies and then your program memory cells so when you meet it next time you should make the antibodies very quickly as they have the program. So what we find is if this Natural Balance is disturbed and when we wrote these papers we’ve done many papers and books and chapters on this. When you have the chronic inflammation, this balance is completely disturbed so the T-cells are completely suppressed and we found out it was no different in patients with TB, HIV and cancer. A remarkable similarity and therefore a potential can you use something to restore those T-Cells and would it work and help in HIV TB and cancer. Well of course that is where we realize that there was something that did that and that was these Myco bacteria.

These were being used for TB they were then shown in HIV patients to reduce their chances of getting T. Big papers published in what then was a useful reliable journal the Lancet, which I don’t believe in anything published there now because it seems to be a purely political Journal. It used to be the absolute gold standard in the old days, and it’s been totally perturbated I think it is tragic and a disgrace. So basically that’s what put them together and then out of that you know I must give credit Graham Rook and John Stanford (John Stanford sadly has passed away). They realized that BCG made a difference. There was a problem with it and they wanted to make it better it’s a story in its own right but they discovered myobacterium vaki was the core to getting a good reliable immune response in TB patients exposed to TB and patients with HIV to stop them getting TB. When I looked at what they were doing, I took a great interest in this concept and I realized this funny heat killed organism, was able to reverse the seesaw. It was able to boost the T-cells and more, importantly, suppress the over-enthusiastic and actually dangerous chronic inflammatory responses of nutrifil and microphases and that’s exactly what it does. Then I said well this is exactly what’s going on in cancer, courtesy of my big interaction with Kenno Burn. Anything that boosts the T-Cell response and dampens down the inflammation, can only be a good thing so that’s how I ended up getting hold of the Mycobacilli. In the days before the European Union clinical trial directive, which is a mechanism to stop Innovative creative and useful Studies by academics such as mysel. A time when you were allowed to be a doctor, I basically said I want to do a trial on this to my patients. At that time we had nothing and they would go for anything and I was very happy to try anything, providing it wasn’t toxic of course. At the time we were allowed to give them interferon, I was only in the clinic for a few months and I said this Drug’s ridiculous and remember it had been approved. I said I not impressed by any benefit but I am impressed by the side effects, they’re just unacceptable, particularly for patients with low volume disease. So I switched to the studies and with Mycobacilli and in no time at all you could see that there was great benefits. Much better than interferon, using this and that trial I was able to write you know, dear sir I’ve got this stuff I’d like to try it in the cancer patients. It’s been given to thousands of people with HIV and TB so there’s no problem there, this that and the other and then at the end of the month the chairman of the Ethics Committee said we don’t see any problems with it off you go. I say that because anybody will laugh t this knowing if you want to do a trial now, you’re looking six months to a year to get started. You got big pharma behind you who suddenly decide that they want to get this out as soon as possible then all these obstacles seem to disappear as we found with covid vaccines.

Dr Campbell: Things like that absolutely yeah and if this micro bacterium VY vaccine was available I would have it because I think if it boosts my T-Cell response it’s going to reduce the probability of cancers developing.

Dr Dalgleish: It will exactly and as I said at the time and I offered it to Witty that we did actually have enough of the vaccine to do every Frontline Hospital staff in the covid crisis and they turned it down. “There’s not enough evidence”, can you believe it that means not enough understanding or common sense, on the grounds of the people who should know better.

Dr Campbell: So it’s a pity because not only would have these people have been protected from viral and bacterial infections by the regulation of the T-Cell response, we’d also potentially have a massive reduction in cancers in all Health Service employees, over the next 10-20-30 years.

Dr Dalgleish: Well I mean that’s a ludicrous thing, solution to jump to if I may say so, but it’s one that should be tested but I suspect you are right do you know why I suspect you are right? Because I’ve tried to keep busy as you know and I’ve been to all sorts of Immunology meetings virus meetings and cancer treatment things. So one of the little groups I was in which is basically is a sort of clinical immunology and diseases in humans that are difficult. One of the things that staggered me, as I became a great fan of BCG which is why I got it, but you can’t use BCG more than a couple of times, otherwise you get a negative response.

Dr Campbell: This is the standard vaccine against tuberculosis

Dr Dalgleish: Exactly, so I got very interested in that and I realized you needed a stimulation given repeatedly, and that BCG doesn’t do that. So that’s why we got into these heat killed ones which do, so just explaining that bit. But the reason I suspect you’re completely right was that at one of these meetings I think it was one we had in Cambridge, it used to be as a nice place we could chat and go to the local pub as usual that sort of thing, and chat over it. One of the things that they had found in long-term followup for BCG was in Africa. The guy presented because they were able to do long-term followup which you can’t do with most grants these days cuz they’re 5 years or something. So what they found and what they presented, they said we’ve got some data here and it’s real and we really didn’t believe it. We can’t understand it, they said, but in our cohorts of children given BCG in Africa we’ve compared them to children in
those countries where they wouldn’t let us give BCG, I mean there are such things and it’s amazing, he said the people who got BCG as children 50 years later they have lower incidence of heart attacks and cancer so that means at that early stage their immune systems were set. Like this seesaw with the T-Cells was a bit damped down but it had corrected it and that equilibrium was enough for them to come across all sorts of things, for the rest of their life. They have a lower instance of heart disease and cancer so that’s why I said your your statement was ludicrous because that’s what I’d say to myself. Because I make those things I said but here to my amazement I must say it is the one paper at that conference I remember I don’t even remember my own paper!

Dr Campbell: I can make plenty of ludicrous statements but it’s nice to to have it been discussed by someone who with your experience

Dr Dalgleish: But I think you’re absolutely right, but we can’t make claims for products you have an invested interest in. They won’t allow you. Because I’ve always you know played with the idea you have a new drug thing you could call it like Cura or wonder you’re not allowed to do that because it implies untested efficacy. So that’s why I’m saying.

Dr Campbell: I think I’ve started to understand that cellular imbalance now because if you’ve got chronic inflammation presumably that’s going to alter the the cytokine profile of the local area of tissue and cyto kindes are actually specific to particular immune cell types. So you know I think it’s important actually to to to relate these things back because this does make sense in terms of basic science. It does so what you’re discussing has got complete scientific credibility as well as provisional pretty convincing empirical evidence and it just seems tragic that this isn’t being followed up. Especially when the risk benefit analysis is so positive. Because what the heck is the risk of giving a few heat attenuated MCO bacteria vaki into my armor? I can see pretty well no risk from that and yet the upsides are potentially immense.

Dr Dalgleish: No as you say there are no risks and there haven’t been any risks in all these studies because it is heat inactivated.

Dr Campbell: Yeah you’re giving a precise known dose it’s not like one of these RNA viruses where you could produce six viral particles or Six Trillion trillion viral particles.

Dr Dalgleish: No it means it’s totally safe because it’s heat killed it can never be resurrected to life, like RNA or BCG. You see BCG is attenuated and this is life and I have dealt with uh two patients over my time who were on BCG trials in collaboration with Donald Morton, the John Wayne Institute. A lot of the vaccines had BCG as the adjuvant. Occasionally they can cause lymph nodes and you find that these patients have got a very low level of TB. Fortunately it’s very easy to kill because it’s attenuated you can just do it with a short course of ? you know it’s very easy. But less than 1% , but it’s still there so the fact we don’t have to worry about that whatsoever it gives us you know confidence that we’re not going to do any harm with this one.

Dr Campbell: One of my early memories about working with cancer patients as a young staff nurse is so many women coming in with advanced cancers pathological fractures, horrible horrible things after after cervical cancer. That’s another human papillomavirus. The term retrovirus can you just unpack that a little bit, what’s the difference between a virus and a retrovirus?

Dr Dalgleish: Well a retrovirus is a virus first of all. So it’s a sub classification a sub classification. Most viruses that we have associated with cancer in humans have been herpes virus, like the Hepatitis B virus, like the epin bar virus for instance. I mean they’re they’re the big ones.

Dr Campbell: These are the big DNA viruses?

Dr Dalgleish: Now DNA makes RNA which makes protein which makes money, as one of the people in the Cambridge molecular biology laboratory said in Cambridge. I can’t remember which one that was.

Dr Campbell: Sad but true

Dr Dalgleish: I think it was Sanger or Perute one of these big guys who were there. I always remember them saying that, because they were predicting the biotech Revolution. So your DNA a makes RNA makes protein, but a retrovirus is an RNA virus that codes the other way. So it goes into DNA and recodes that to produce whatever it does and make make its proteins to replicate etc. In that little definition that I’ve just told you, I think I’ve just told you why I believe messenger RNA viruses are so so dangerous. So completely utterly dangerous and why I’ve been campaigning for them to be banned. You know I’ve I’m used to all sorts of insults and I know that I was told I just a cancer doctor what do I know about viruses Etc. I have been on many many scientific Boards of companies is developing vaccines and you know gone into it great depth and I have been on the board of a company that purely focused on making messenger RNA vaccines. So I mean I was on the board for 5 years and I did my cycle. I got to know that there was a big problem and that big problem. So I left that board 7 years ago and I now know that problem’s still not been sorted. This pandemic was used as an excuse to get round all the problems that the regulatory people wouldn’t let them go through before and that’s a terrible thing. But that explains what a retrovirus is. It is actually an RNA virus that can reprogram go into the DNA and reprogram it. In mice and we know for the they’ve only got one human virus that does that – HTLV1 – they reprogrammed it and you get cancer. So it’s a big risk.

Dr Campbell: Well congratulations on leaving that when you did. Now this DNA makes RNA makes protein is what we call the central dogma isn’t it of genetics you know every student learns that DNA makes RNA makes protein. But we clearly know that these retroviruses RNA makes DNA it goes the other way around and of course that DNA can make more RNA which makes more makes more protein. Now in order to get RNA to go to DNA we need an enzyme called reverse transcriptase. So transcription is the DNA to the RNA. Then everse transcription is the RNA to the DNA. Now that reverse transcriptase enzyme which is essential, is that produced as an endogenous product of human cells or is that always coded for by RNA that comes in with the virus.

Dr Dalgleish: Where the virus is involved, it encodes it itself, it has its own reverse transcriptase thing.

Dr Campbell: So the virus the RNA and the virus itself codes for its own reverse transcriptase.

Dr Dalgleish: That is what provided the first target for treating HIV. They used reverse transcriptase Inhibitors so it wouldn’t be able to integrate and have the life cycle.

Dr Campbell: So it’s a bit of an unfair question really but is there endogenous reverse transcripts do human cells produce reverse transcripts or do we know that.

Dr Dalgleish: I will be very honest here I’m not sure, and so I’m speculating but we do have endogenous retroviruses. There ar a large number of them in the genome accumulated over millions of years of evolution. They can they can escape as it were and we think that other viruses help these Escape. Because this is the pathogenesis of multiple sclerosis. There’s a lot of work out there to suggest that these sleeping dormant retroviruses which should just part of our genetic baggage that we come with about 90% of our genome is so called baggage. That’s another fascinating thing is why do we carry it around. Just for the viewers, the simplest solution is, I think it is if you imagine you pass all your genes on all the time and they’re just a big baggage of genes, how are you going to make maximum use of it?Whereas I think that 90% of baggage is the equivalent of a library’s shelving and retrieval. So it allows you to put the useful genes in an order an assembly you can retrieve them when you need them. I mean it’s not been proven but that is speculation which I feel most comfortable when discussing these. So what happens with the so-called multiple sclerosis is that another virus comes in and helps provide a reverse transcriptase that that virus does not have and enables it to wake up. Multiple sclerosis, we still don’t know exactly what’s going on but I think that’s the that’s the closest model to it. There’s other complications in that it’s very genetically restricted and it’s clearly got an autoimmune component to it. So I just wanted to answer your question but I don’t want to get into multiple sclerosis.

Dr Campbell: No I would love to because it’s we we’ll try and stick to the topic. So I think basically what we’re saying is we have this idea that we’re in a mix of viruses, Epstein bar virus for example, I assume we’ve all been exposed to that. So we live with all these viruses most of the time they’re kept down by an active immune system. Chronic inflammation comes along and messes up with this cellular differential we get more of these neutrophils. Of course they are brilliant if yo’ve got a bacterial infection is exactly what you want. But it’s what you want if you’ve got chronic inflammation. So suppresses the T-Cells and it’s this chronic inflammation that leads to to the development of cancers and that kind of combines the initiator and promoter model of cancer really doesn’t it.

Dr Dalgleish: It does and can I just add an extra piece of information I forgot to show that the chronic inflammation causing cancer is a reality and that interfering with this is a reality. The experiment has already been done, rather like the BCG and TB looking beyond that how it actually reduced cancer and uh heart attacks 50 years later. Remember they did Big studies looking at the effect of aspirin. Now aspirin is a is an anti-inflammatory agent which blocks Cox-2 pathways, and it also blocks prostaglandins. Therefore propensity to clotting. In other words it reduces the production of inflammatory mediators so we know that it made a difference for heart, but once again those big studies also gave the signal that the people on the aspirin had a lower instance of colon cancer. So that’s a perfect example of serendipity. You set the study out to do one thing but if you broaden it and look and ask other questions and it showed that anti-inflammatories would reduce the instance of the of colon cancer. Unfortunately aspirin is very cheap but easy to to get. To take it has the problem that if you take it as a tablet wihtout meals, it can give you gastric problems and bleeding and occasionally very occasionally the bleeding can be fatal. The problem is that GP only needs have a one or two of these in his life, he gets very wary about advising aspirin at all. But that is to forget that aspirin you can have it in a low dose for the clotting at 75 but you need higher than that for its anti-inflammatory. But I’ve uh always advised that if you take the anti-inflammatory soluble with a meal it greatly reduces this problem. I do that myself I mean that’s the way I would not have an aspirin in the middle of the day for a headache, cuz that’ be guaranteed problems. If I need something for a headache and sometimes sinusitis, it is the best treatment for a chronic sinusitis, I just pop the soluble in and I take it. If it’s urgent in the middle of the day then I’ll take a yogurt with it. It’s something to protect the stomach so all these you know sensible logical things to do can be worked through. But at the end of the day I mean I’m a great believer in Daily anti-inflammatory tablets for everybody over 40 to reduce these Pathways, I mean you might be targeting the one for colar rectal it’s probably preventing others. It looks like it has a benefit on lung cancer as well. But there’s plenty of other anti-inflammatories which uh can be looked at for prevention. Now the other causes of chronic inflammation. I mean smoking is obvious so I’m not going to waste any time on that. I mean most people who present with lung cancer have a history of chronic inflammatory upper respiratory diseases every winter, chronic bronchitis etc. They get admitted and eventually they’re found to have the cancer that’s a fairly logical one.

Dr Campbell: It’s obvious smoking is going to contribute to the chronic inflammation isn’t it. Is the tie with direct carcinogen as well is it kind of a double whammy?

Dr Dalgleish. it’s double whammy absolutely sure it’s it’s a double whammy. In fact there’s so many carcinogens in Smoke we don’t know which one is doing it. It justs increases your risk it’s as simple as that. But what I wanted to get on to there is another cause of chronic inflammation which is driving up cancer of all Sorts. Initially the signal was for renal cancer people wonder what on Earth causes renal cancer. Then it was womb cancer uterine cancer endometrial cancer, what causes these. This is I think the most fascinating link ever. The link is with obesity. Now obesity if you have to describe it put it in a pathologist pot as it were they only have a few pots but everything has to squeeze into one of them. Obesity squeezes into chronic, inflammatory State. If you are obese you have far more cells than the thin person next to you. Therefore they need feeding and they need turning over and they produce their own inflammatory growth factors etc. So obesity is a chronic inflammatory state, so probably the very best way we could reduce cancers in this country would be to prevent obesity and do everything that’s required for it to be reduced. Because it is associated where you’re much more likely to have all the cancers, all the common ones. So that and to me that’s this is really like reaching the peak of the Mountain of this because it is so overwhelmingly explains why these people have more cancers. Couple of very simple things, first of all, because they’re really obese and big they’ve got a lot more cells. Then when you’ve got a lot more cells you’ve got a lot more opportunity that one of those might go malignant. Just on a random alone let alone the fact that the more there are, like you know people in a room they huddle up the warmer they get. That sort of Warmness is an inflammatory State producing more Warmness more growth factors, more immune suppression.

Dr Campbell: I wasn’t aware of that. I assumed that in obesity the adiposite number was this fat cell number was fairly constant and they just kind of swelled up and got bigger and bigger. But there’s actually an increase in the number of the cells present.

Dr Dalgleish: That’s a very very good technical Point. I’m not qualified to answer that, in I’d actually want to research that but, let’s move to a paradigm. It is certainly true that bigger people genetically without being obese, are more likely to get cancer because they got more cells, they’ve got more cells for the random mutation, and we know that that’s the case in dogs too. Bigger dogs much more likely to get cancer than the smaller dogs.

Dr Campbell: So my thinking here then would be that the amount of fat whether it’s more fat cells or whether it’s full fat cells, that’s going to cause the abnormality in the function of the cell that causes these cells to release inflammatory mediators systemically. Is that kind of what’s going on?

Dr Dalgleish: Well it must be a way because why if you eat too much do you get fat? As you say these cells go into adipose tissue and they are there to deal with excess fuel to store it in times of when there is non. That’s one of the reasons why people in the Pacific Indonesian Islands are so big and the Maoris. They adapted in good times, they got big because they’d have to sail the oceans for several days without any food at all and that extra capacity allowed them to do that. The problem is with obesity there’s no downside so it keeps going on, storing, storing, storing, and that interferes with all the metabolic pathways diabetes is one of the obvious very common on and vascular disease and everything like that.

Dr Campbell: So this is so interesting. So all of the common cancers, lung, bowel, prostate, breast, pancreas, esophagus, liver, bladder, obesity is a potential factor maybe to varying degrees of biology but a potential factor in all of these really common cancers.

Dr Dalgleish: Yes and of course in two of those breast and prostate you have a hormonal aspect as well. But then the hormonal aspect can be affected you know by chronic inflammation and immune status. So that that’s very comp complex I mean I think the breast and prostate are more complex because of the hormonal aspect but to me prostate is more understandable than breast. I think breast is much more complex with regards to the the real cause of inflammation. Obviously hormone has a lot to do with it, but males get breast cancer too obviously, not nearly as common, but shows that the hormonal aspect just makes it much more likely. But the other aspects can also be affecting these tumors as well.

Dr Campbell: I tend to think of the male breast as being like a prepubescent female breast in a way that there’s still like a basic ductal system there that can be stimulated. Of course men do get breast cancer. Physical activity is that, I mean it’s good obviously, but in terms of cancer, is it protective do you think?

Dr Dalgleish: I don’t think I know. They very detailed results in mice where they all identical they’re all given the same stimulating factors to develop cancer they’re known to get cancer eventually so you know so it’s a very good model for what you can do to reduce the cancers. So they’ve done, this has been repeated many times, you’d have mice which should just walk around the cage and then there’s mice that have the opportunity to run in a wheel for you know a certain amount of time a day. This is all monitored, so the ones that have a lot of exercise develop tumors far slower than those that don’t do a lot of exercise. I’m sure unlike quite a few things where the mice doesn’t quite translate the human condition, I’m sure this is very relevant.

Dr Campbell: I mean it’s good to be physically fit anyway so it’s generally. If you don’t mind just a few minute to run through some of the common causes that I used to teach my students about certainly. Sun and ultraviolet radiation? Just skin cancers or anything else could be involved in that?

Dr Dalgleish: Well that’s inducing a chronic inflammatory state in the skin. When I was trying to work out you know what was going on with melanoma I said you know what’s causing this and I actually at a conference actually said there’s a great irony that all the cancers seem to be involved with chronic inflammation except the one that I’ve been given to treat melanoma. Actually the pathologist came to me afterwards and said “it’s no different” he said “I can tell melanoma patients just looking at their normal skin because they don’t have normal skin they have a sort of chronic inflammatory fibrous skin”. He also said “that is one of the reasons for your other big Quest is why do so many melanoma patients have such low vitamin D levels”. He said “It’s the skin has become inflammatory and no longer does that vital conversion for the sunshine vitamin”. As we know from the title of one of David Grimes books and so that is why, so even the melanoma has a chronic inflammatory state which leads to the perpensity of developing melanoma.

Dr Campbell: Wow that really fits in well and vitamin D of course which we know well I think I’m safe in saying that we know low vitamin D levels are involved aetiology of many cancers. That is vitamin D activates many genes and controls genetic expression but it’s also anti-inflammatory isn’t it?

Dr Dalgleish: Yes it is very anti-inflammatory I mean it’s absolutely vital for the immune system and it’s actually vital for the inflammation. I remember when I was doing really hard research on this and I found that a very good paper of Immunology. If you do not have an adequate level of vitamin D then your activated CD8 cell will latch on to an antigen on a tumor cell and it will just sort of kiss it and go away.

CD4 – Helper Cells
CD8 – Cytotoxic killer cells

CD8 The cytotoxic killer cell and the CD4 is the helper cell that gives it all the signals. So the cd8 won’t kill that tumor cell
unless there’s a healthy level of vitamin D. So vitamin D is actually required for the T-Cells to do their job. Then I found another paper that says that there’s over excessive antigen production in low levels of vitamin D. Well this appears to be a paradox initially, but no when you look at it very carefully it’s dendritic cells presenting the primary antigens to the immune system to program it. If it there is low vitamin D it’s not very good at presenting just the necessary ones, it gets sloppy and this leads to autoimmune disease. So this is why autoimmune disease is associated with low vitamin D and most people working autoimmune diseases now one of the first things they do is pick up on low vitamin D and treat it. One of the first where this was recognized was multiple sclerosis multiple sclerosis. I mean the first thing you do is correct their low vitamin D levels and that’s the start and the path to treatment. Being able to help with them because it is basically an autoimmune disease. You are attacking your own mylin.

Dr Campbell: Different radiations as a cause of cancer. I mean x-rays for example, x-ray exposure or I mean what would be the mechanism there? Can the radiation physically damage the genetic material that’s what I always thought?

Dr Dalgleish: Yeah and it’s right and it’s a matter of dose and time. I mean that’s why we can safely use X-rays because we know the dose is very low and also why we get worried about people who need x-rays frequently for long periods of time. We go out of our way like people who have a lot need a lot of CT scans for instance they’re now much lower radiation. So we’d switch to the MRI which doesn’t do that so we’ve got an alternative or Echo I mean a lot of tumors and things can be detected with very very sophisticated Echoes.

Dr Campbell: That gives another cause of cancer which is iatrogenesis caused by medical treatment.

Dr Dalgleish: It’s fortunately quite rare now so yeah I think it is very rare in fact the things that come to mind more radiotherapy causing other diseases later in life like uh heart problems and people who had their chest irradiated for Hodgkins when they were very young. Once again we are we no longer give too higher dose and two we’re much better at focusing it and avoiding structures that might be damaged by it.

Dr Campbell: Of course in the iatrogenic category you already mentioned there people that have had transplants and need chronic drugs to suppress the the natural body’s natural repression. Is it true that they are more prone to certain cancers after years of immuno supression.

Dr Dalgleish: Absolutely, especially skin cancers very interesting of all sorts.

Dr Campbell: Shall we recommend people to have a good diet and avoid junk food.

Dr Dalgleish: Well obviously and this this links in with obesity. Obesity is associated mainly with junk food, I mean I’ve done my own observations that what do fat people eat and they have a terrible diet.

Dr Campbell: I mean and this is a common observation we see this repeatedly don’t we.

Dr Dalgleish: The other thing they seem to be eating all the time, even while driving. I mean I’m quite now so a good healthy diet is important not only to avoid go being overweight but you need a high fiber diet in order to have a good microbiome in the gut. Which basically means you have a good healthy immune system. So the diet even helps program your immune response and your immune system and of course in the absence of the right amount of sun and everything a major part of that is Vitamin D. Vitamin D in that it’s a fat soluble vitamin. Well actually as David Grimes have pointed out, the tragedy of vitamin D, was it was found after vitamin c, and it’s not a vitamin it’s far more important than a vitamin.

Dr Campbell: I agree with that and we’ve just done an excellent recording with Dr Grimes which will be available. Friendly chit chat.

Various minerals I mean I’m you know I’m thinking about Japan, South Korea where they eat lots of seaweed high amounts of iodine I’m thinking about the UK much higher rates of breast cancer where basically we don’t eat seafood. Do you think there could be anything in things like iodine being replete in iodine and other minerals.

Dr Dalgleish: Yes I do it’s not an area I’ve researched in depth but I have engaged with others who are are convinced in the the same way that I’m absolutely for vitamin D in cancer. The next thing that you get these people who’ve done a lot of research in is funnily enough iodine. They talk about lugol’s iodine being most important because of its deficient. So yes and there’ll be many others that we we don’t know about.

Dr Campbell: I take a drop of iodine a couple of times a week now just I think it’s a milligram or two right, you get used to the taste. I mean I was working out you know if you eat kelp for example you’re getting huge amounts of iodine and we get nothing like that amount of course it’s homeostatically regulated. So within reason you know if you take more than the body needs it will simply be excreted in the urine.

Dr Dalgleish: You remind me that you live closer to Derbyshire than I do.

Dr Campbell: I do yeah of course the reason you’re saying that is Derbyshire neck or Switzerland neck or Nepal neck where the thyroid swelled up through simple lack of iodine. But of course the other thing that’s fascinating is this idea of the the amount the levels of things like vitamin D and iodine were set to prevent. The amount of vitamin D was calculated on the amount to prevent rickets which of course is an extreme form of Bendy bone disease the amount of iodine was set to prevent Goiter, which is a sign of really quite extreme iodine deficiency. So there’s a difference between the amount of substance needed to prevent a particular deficiency syndrome and an Optimum level and I think that’s what a lot of these blood levels and dietary recommendations haven’t quite come up to date with yet.

Dr Dalgleish: Well neither have so-called experts I mean there’s a special advisory committee like said Sub one of sage which is one of the most inappropriate acronyms ever invented. Anything but Sage they should call it, but the other one is the special advisory committee on nutrition who are full of such dimwits that they feel that 400 international units is the maximum that should be given to the British population. I’ve challenged them and Whitty he agrees with them. I mean tiny amounts of vitamin D that’s a good thing that you that is probably what you need for rickets because it’s the extreme yeah but for good health, you need far more than that. You need at least two three times as much of that. I mean the minimum supplementation should be a thousand international units and in the winter in the north the minimum is 2,000.

Dr Campbell: I mean if you think about it so we’ve got the government recommending 400 units but if you go out on a sunny afternoon without with just your shorts on you’re going to make 20,000 the difference is just incredible. Can I keep drinking some lager on Friday nights?

Dr Dalgleish: Well I think it’s terribly important to have some alcohol if you’re used to it and I think uh that uh suddenly becoming righteous and stopping it in my observations isn’t doesn’t seem to be a very good thing to do. I don’t know why, but I mean a moderate amount of alcohol is is full of things. I mean beer stimulates your Peyer’s patches. The yeast in in real ale particularly, so that’s the justification for my beer.

Dr Campbell: If you’re watching this video and you don’t drink please do not start based on this conversation. I mean it’s true huge amounts of alcohol though cause chronic inflammation.

Dr Dalgleish: That’s right huge huge amounts of chronic inflammation but the other thing about red wine, the active ingredient in that apart from alcohol is reservatol, which is a very powerful anti-inflammatory. So you know things in moderation are fine everything in excess I mean the moderation is the thing isn’t it. Take food if you don’t eat food you starve if you eat too much you’re overweight, you need something in between.

Dr Campbell: Very often in physiology we don’t have a linear relationship between two variables like alcohol and cancer it’s very often an s-shaped curve isn’t it so it’s low at the bottom essentially no risk, then it goes up sharply when you get to a particular critical dose. Physiology often follows this sigmoid curve. Workplace cancers, I mean asbestos for example I mean that’s a clear risk isn’t it.

Dr Dalgleish: Yes and it’s very interesting asbestos, because I worked at the time I was involved with the MRC, that they came out not this has nothing to do with me I was working independently, they did these big surveys, because they did you know the one on lung Richard Doll and Pito did the big survey showing that smoking clearly caused lung cancer. The industry fought against for years and years and years so it was super obvious to everybody. Well there was asbestos and Mesothelioma and that link was there for a long time. They monitored it for about 20 years and I remember they came out and said there was no link.

Dr Campbell: I think Richard doll knew about this in in about 1960 I think.

Dr Dalgleish: I’m sure he would there’s no link and so that became an official report. But thereafter the link became stronger and stronger and stronger.

Dr Campbell: It was only when became absolutely totally obviousthat the link was admitted it’s just ridiculous.

Dr Dalgleish: It was and the interesting thing about asbestosis and Mesothelioma it is it average is at least 40 Years of exposure and what is the exposure it is bits of the asbestos that get ingested they can’t get rid of it. They’re indigestable quite literally and that gives rise to a very low chronic level of inflammation. So Mesothelioma rises out of a Mesotheliatus basically due to the macrophages and fibrocytes having real problems trying to dispose of these particles.

Dr Campbell: Mesothemioma is a totally hideous disease isn’t it. Plural membranes swell up occupies virtually the whole Space squashes the lung terrible.

Dr Dalgleish: It is terrible disease and I must say applied those principles to treatment and I have treated patients with Mesothelioma with the IMM when I could get it anywhere. I can’t the moment because it’s going for registration trials but I was able to do that.

Dr Campbell: So the IMM is one of these micob bacteria vaccines.

Dr Dagleish: It’s the one that we’re focusing on now and maximizing anti-inflammatories which in these cases it me included vitamin D because vitamin D is a very strong anti-inflammatory. I’ve had amazing stabilizations with that in patients who refuse chemotherapy they they look at the chemotherapy and the surgery and the radiotherapy and it’s been staggering. So once again it proves an anti-inflamatory and people will say you can’t possibly say that on a few patients but I can say that on a few patients because that is what years of being a doctor dealing with all these things, you’re very good at sniffing out what’s effective and what’s not. They only say you can say it when it’s been shown in a randomized trial. Well I have no longer got any big faith in randomized trials and I’ve got people who agree with me ever since we published The Book The Death of Science. I’ve had people contact me saying that they basically want to look at writing papers and doing a thing that should be the death of the Rand, is the death of the randomized trial. Because now we know that the randomized trials for covid were completely perverted they weren’t randomized at all.

Dr Campbell: I mean there’s nothing wrong with the principle of a randomized control trial that’s a great scientific principle you know that that go that go goes way back to the discovery of streptomycin for tuberculosis that’s great. But it’s the way it’s now applied in practice and he who he who pays the Fiddler calls the results of the clinical trial.

Dr Campbell: Briefly we we’re nearly finished Air pollution microparticulates are they a risk ?

Dr Dalgleish: Yes clearly

Dr Campbell: So things from smoke incineration diesel fumes.

Dr Dalgleish: you here I have a little cough there but from time to time it’s not covid it’s none of these things I call it diesel lung. That’s you know after years of been exposed to lorries spewing out these particles it does make a tiny particles and it does make you cough. I mean it’s it’s possibly worse than smoke but I mean the we go over the top now we want all these things to be electric but actually the new diesel engines are really very clean as long as long as the filters are working as long as the filters working rightly yes.

Dr Campbell: Yeah but you’re right we’ve been exposed fortunately unfortunately in our generation to yeah many decades of uh abuse. Is radon gas a problem globally or is that just a UK thing in very small pockets of the UK?

Dr Dalgleish: I’m I haven’t looked at this in detail I’m not an expert in it but my understanding is exactly your last bit that it’s a problem in small pockets in the UK where there’s very high levels and it’s been linked with uh lung cancer.

Dr Campbell: I think Ulcester near me was known you have to test the cellers to see if it accumulates there and and cancer of course gets more common with age. One thing I’ve never understood why are occasional cancers more common in young people so for example you think of testicular cancer more common in young men whereas the vast majority of cancers are are more common with with age. “Yes they are”. Why is there a difference there?

Dr Dalgleish: Again testicular cancer I don’t think associated there’s exceptions to a general broad hypothesis of everything this of course so I think that testicular definitely does fall outside. The good thing about testicular cancer in young men is it’s completely curable if you catch it very early it’s just incredibly curable. But thank you for giving me that lead because it reminds me to make it very very clear to everybody, that the your major risk of cancer that you can’t control are your genes you inherit from your parents. So genetic so just because you get a cancer and this is true you get lung cancer in people who’ve never smoked. You get early cancer in all sorts of things but they’ve never been subject to chronic inflammation but we’ve known much more about that it’s more in the textbooks. You get these these genetic conditions which make you much more likely to develop cancers and they you’ve inherited those and uh I mean the one that springs to mind is the “BRCA” mutations for breast and ovarian.

Dr Campbell: “BRCA” breast cancer exactly and of course if we understand these causes we can take steps to prevent it which is the entire point of this study. You know I think that stuff is absolute gold dust I was just fascinated that’s an hour and 50 minutes I was just riveted all the way through really it’s and it’s really good to get confirmation of some of the things I’ve taught over the last 30 years. That they are actually correct because you know talking to a specialist is really reassuring in that respect. Professor Dalgleish as always, thank you so much, for your time and giving us the benefit of your entire medical career all canned down into one video. Absolutely amazing not that we’ve done it any kind of justice of course.

Dr Dalgleish: Some of the things I’ve just touched over 30 seconds when in fact I could go on for hours and hours and hours in depth of many of those things. So I’m just giving you the broad brush.