Naren: Hello everyone, welcome to another episode of the Let It Flow podcast show. This is Naren your co-host and I’m excited to be joined today and I have for you my dear friend Doctor Kwan the author of the book let it flow.

Dr. Kwan: thank you very much there and I’m excited to be here today talking about cancer

Naren: yes and the topic today exactly is is some is cancer simply an evolutionary process? I know it’s a question that typically people don’t hear is cancer simply an evolutionary process. So I would love to get into this, and as the author of the book let it flow for our listeners who are listening to us for the very first time, your fundamental argument is, it’s blood flow and the cells that, that, you know that transport nutrients and oxygen that are critical for us living healthy and I’m assuming you’re going to tell us more about what causes cancer and is it really an evolutionary response.

Dr. Kwan: Yes, briefly just to talk about cancer, the history of cancer in America cancer has been around as you know as long as mankind has been on Earth. It’s it was declared President Nixon declared war on cancer in 1971 and his Hope was that it would be eradicated by 1976 at five years time, but as you know that this this war on cancer is still being fought, today. Right, and cancer killed 600 000 people a year in America. Six hundred thousand people in United States alone. So that’s sixteen hundred deaths every day from cancer alone. So this is a huge problem in America and it’s something that’s on the rise so I think it’s important to talk about this and I think in order to really find a cure for cancer, I think we need to First learn and, and, find out what initiates and what causes cancer. So today I think if you open up or you Google generally about cancer everyone I think in the medical community and in the research Arena, I think have a consensus that cancer is a genetic disease, right, are you are you you’re familiar with this Naren, right?

Naren: yes

Dr. Kwan: That the cancer is

Naren: We think that you know my my parent had cancer or my uncle had cancer. So I’m gonna have cancer.

Dr. Kwan: yeah so it’s well it’s a genetic disease also meaning that yes it’s a it it can run in the family and also that the the cancer is caused by a mutation in in our genes, right, and that’s called a genetic mutation theory of cancer basically and that’s the most commonly accepted model for cancer, that we have this incredibly complex and and long DNA, part of our chromosome, right, this DNA we call it genes this DNA basically contains, is a it contains all the things that allow us to live and it makes all the proteins in our body and all the all the cells, however when there’s a mutation in this DNA, the scientific community at large feel, that’s what causes cancer and I’m I’m going to be a little bit contrarian to this. I don’t yes mutation is involved at some point but I don’t think this is what causes cancer. I don’t think it’s a mutation in the genes that causes cancer, or initiates cancer. So what I believe is basically for cancer I believe it’s what I call hypoxic, hypoxic, theory of cancer meaning that I believe that the cells Felder we have 37 trillion cells in our body and the cells need oxygen and nutrients to live. So the blood has to flow to our cells through our massive complex intricate circulatory system, oxygen and nutrients that deliver to every cell in our body, and when these cells don’t get enough oxygen, there’s bad things can happen and I talked about previously about the diseases, diseases, occur when cells don’t receive enough oxygen.. However other things can happen to cells, when they don’t receive enough oxygen. So disease means that the cells are still still living it’s a it’s sort of struggling to survive but it’s still living because there’s enough oxygen and nutrients to support it. However when you cut off a certain amount of oxygen to the cells, cells, start changing to to basically adjust to this environment. So this is sort of what what I call sort of evolution evolutionary sort of take on cancer development, and just to talk about evolution in general, our our our cells are trying to adapt to this this new environment of lower oxygen and I believe that this is what really triggers, triggers cancer formation. So before I go on further I I think we have to talk about basically Evolution, because I believe we have to get Evolution right if we want to get cancer right, because I think they’re very close I think what happens in evolution I think occurs in in cancer as well. So again current sort of thought on evolution is, is, is, sort of what we call Neo Darwinian theory of evolution that you’ve heard of this natural selection, right?

Naren: yeah the the idea that the strongest survives the strongest survive

Dr. Kwan: right that’s that is called survival of the fittest but that’s not what really Darwin said but yes you could infer that from what Darwin said but so today’s Theory basically on on on evolution is that the that the, the, basically species, species, and give in a given environment sort of behave based on what the environment is and, and, the species basically that survive that has the best survivability or that that are able to survive in that given environment is the one that’s going to go on to sort of reproduce and, and, produce offspring’s. So, this is sort of the natural selection process. So the, the, species in that environment that is the strongest and that is most adapt to living in the environment is going to live on and so that’s sort of what Darwin said this is called natural selection and then if you combine that with, with, genetics because Dolan’s time Darwin never knew that genes existed but if you this is called a Neo Darwinian so because you combine both Dawn’s Theory with with mendelian genetics and you come up with this thing called neo-Darwinian, that’s the most I think the popular Evolution theory that most people accept. So based on this Theory basically from the gene you, you, you, produce this specie. So the genes basically dictate what the species is going to be and that species living in the, The, creatures living in this environment and the environment selects out who the winners and losers are going to be right

Naren: so that’s that’s that’s what we consider to be a Neo-Darwinian Theory however. So any any creature that’s not able to adapt to that environment ends up dying. That’s what they said and then the other thing that came out of all this is of this theory is that every once in a while a mutation could occur in the in the in the species and the mutation that occurs that is favourable, that creature now is able to better able to adapt to that environment and live and reproduce. So the if if there’s a good mutation, that’s going to give that specie a survival advantage. That specie is going to go on and reproduce and and and pass down its genes. That’s basically in a nutshell of what Darwin’s theory is but I don’t see I I don’t quite agree with that theory. I think what happens really is that the thought that yes you have this Gene that gives this specie. This Gene, Gene, giving rise to this what we call phenotype, this the species. The genotype is the gene, phenotype is the species. So genotype gives rise to the phenotype to specie, and this creature that’s living in that environment now it’s not just one creature, it’s a whole sort of tribe of this creature, right, that’s living in that environment they’re all under the same environmental pressure. So the I believe what happens and this has been absolutely shown, this is not a theory this has been shown that the environment interacts with all the species and the species now all the species who are living in that environment in order to adapt to live it live in that environment must have the ability to have their genes sort of adapt in order for them to adapt. To this environment they have to have their genes changed. So this is what I believe occurs is that these species given this environment whether it changes or not if it changes let’s say the the environment became suddenly very cold, the species now has to go back to their DNA and the DNA not have to change their expression. Expression, so the species can live better adapt to that environment. So it’s not one one specie that has a mutation that’s going to survive it’s all of the species in that environment are going to have that same Advantage they’re going to be able to tell talk to their DNA and have them basically, basically, give them a different DNA expression and give it a rise to different sort of looking or different sort of adaptability, capability, to live in that environment so all of them are going to be able to better adapt to live do you follow that?

Naren: yes so you’re saying, like I mean I’m just using an example. So let’s say if if some person moves to a colder place 5 000 years ago, a thousand years ago, the genes start changing to be able to better adapt to that environment.

Dr. Kwan: that’s right it’s not that it’s not usually one person let’s say a whole whole whole whole tribe movement is called them or the Earth suddenly became much colder right?

Naren: right

Dr. Kwan: then yes then they have to either they’re going to die they’re going to become extinct and die or they must be able to adapt and change to that that environment right. So basically environment is dictating what the species, the way the species behaves, right.

Naren: yeah so what are you saying is

Dr. Kwan: because if you don’t adapt if you don’t adapt to that changing environment, you’re going to die.

Naren: right like just like on the outer world, we learn language like if I go to France, I need to learn French

Dr. Kwan: yeah yes

Naren: so yeah the body itself, the genes itself, do the same thing. They start

Dr. Kwan: well what’s amazing that we find is we have this ourselves. So this has to occur in order for these changes to occur, it has to occur at a cellular level. I don’t know if you understand what that means. It has to occur at the level of the cells. Basically cells themselves have to change in order for the whole species to sort of adapt to that environment, right.

Naren: Yeah

Dr. Kwan: when the when these when I when I say that these changes are occurring they that the that it’s talking to the DNA and DNA is changing expression, it’s basically at the level of the cells. So each cell is is changing, because of this environment. So it’s it’s changing so in order for the cells to change at that level it has to change the way the DNA expresses. So now with this, if the cells change cells change into something else that that change is called we call that we and we’ve seen this and we’ve seen the laboratory and we see this in real life, that change is called metaplasia, or it’s called trans differentiation. It’s called metaplasia, the cells themselves are literally changing, okay, to to adapt to this new environment. We know that this occurs, this is not a theory this absolutely occurs

Naren: and does it happen

Dr. Kwan: we know

Naren: within like the same lifetime you know like in other words

Dr. Kwan: yes, it’s happening real time it happens quickly and and I’ll give you an example of where. So I believe that the the way the evolution occurs is through this way. It literally occurs because the environment is telling them to change and it can really change fairly quickly. It’s not doesn’t occur this this this Evolution doesn’t have to take thousands and ten thousands of years. It literally can occur fairly quickly. It’s not changing exactly what the species look like, it’s not going to give the species three noses and four eyes and things like that it doesn’t occur that quickly but what it does is at this level of the cell those cells are changing, and it literally occurs really quite quickly and I’ll give you examples of this. If for instance when there’s a there’s a disease called Barrett’s esophagus. I don’t know if you know what that is Barrett’s esophagus. Are you familiar with this disease?

Naren: No I am not, I am not Doctor.

Dr. Kwan: you’re familiar with reflux right?

Naren: yes

Dr. Kwan: reflux esophagitis, it’s called reflux when you reflux when your stomach content refluxes into your esophagus, okay.

Naren: right this is called the reflux and many people have this condition called reflux where stomach content actually goes up back up into the into the esophagus. That’s the esophagus is basically the tube that goes down from the mouth all the way to the stomach, okay. That’s called the esophagus and this esophagus basically the distal part of it the portion that’s near the stomach has a lining has this lining called the squamous epithelium lining. It’s got turn lining that deals with what the content the environment of the esophagus is. However, in people who have reflux disease, the stomach content that’s high in acid and you’ve heard of this that stomach has high acid content, right?

Naren: yeah

Dr. Kwan: it’s much much it’s acidic much more acidic than the esophagus. So they don’t usually intermingle. The content stays in the stomach basically, but with this disease, this reflux disease this stomach content with high, high acid content with bile containing high amounts of bile can actually reflux back up into the esophagus. So when it does that the esophagus sustains damage, right?

Naren: Right

Dr. Kwan: to sustained damage because the the acid is going to cause damage and so as I said before with damage what happens inflammation right?

Naren: right

Dr. Kwan: so damage occurs then our body has to unleash immune system and to heal it so it it mobilizes its immune system. With the immune system basically immune system there’s a chronic and we call this chronic inflammation occurs. With chronic inflammation of that the distal portion of the esophagus now with the chronic inflammation as I said one of the things that the very thing that happens is that the very small blood vessels get shut off and basically hypoxia occurs, right, lack of oxygen. So the distal esophagus now is getting less oxygen, because of this reflux. That’s the ultimate result. Less oxygen. When it gets less oxygen it must change because if it gets less oxygen, the cells are not going to be viable, right.

Naren: Right

Dr. Kwan: So it must change and so we know that we know it it tries to adapt to this new environment with this acid and this low oxygen, so this change occurs actually really quickly, quite quickly, and the lining of that distal esophagus changes to a whole different kinds of cell called the columnar cell from from a squamous type of epithelium to pseudo columnar cell, and this columnar cell is a completely different kind of cell than the squamous cell and there and and when it does that it’s much better able to survive that kind of acidic environment. So we know that this happens and it’s happening in our all it happens all over our body, in real time, really, it occurs that quickly to adapt to the changing environment and we know that evolution, in evolution, Evolution, works this is exactly a similar way when there’s a changing environment for that creature living specie whether it be human being or any kind of animal living in that environment and if the environment changes, then the species must change and it it doesn’t suddenly grow a new head and, and, and, do that I’m not suggesting that that. That can occur in a longer period of time. However, at the level of the cells many of these changes are happening fairly quickly to adapt to that environment, and we, we, have proven that this happens. So that’s what I but so these these small changes that are occurring, I call this incremental Evolution. So I think Evolution occurs on an incremental level. It occurs very slowly on the outside but at the level of the cell, it’s occurring in real time. It literally occurs at that moment to deal with changing environment, and so how does this all tie into cancer. Well what happens is, in cancer as I said I believe cancer is a disease where the cells are not getting enough oxygen. So let’s go back to that Barrett’s esophagus again, that distal part of the esophagus, is now injured and so the cells change to accommodate for the injury and one of the things that happens with this injury is that, when when there’s lack of oxygen, when there’s lack of oxygen, at the level of the cell, we call that hypoxia, right? Hypoxia

Naren: right

Dr. Kwan: that’s lack of oxygen. When there’s hypoxia one of the things that the cells cannot make if there’s low levels of oxygen, it cannot make up energy. The cells need energy to do everything. You’ve heard of it. So it’s called respiration, I don’t know if you heard of respiration, it’s an it’s basically the cells receive sugar glucose into the part of the cell called mitochondria. I don’t know if you’re familiar with mitochondria. Mitochondria is a is a small organelle in the cell that actually is the power plant of the cell. So it takes in oxygen and glucose and produces energy. However, when there is low oxygen or hypoxia, it cannot do this it cannot do this. So what does it do. It switches off it switches off and it triggers, it triggers a factor in our body to change all this, because it’s saying warning, warning, there’s not enough oxygen we can’t make energy we’re going to die what do we need to do. So our our body signals uses the, signaling, protein complex called hypoxia inducible Factor, hypoxia inducible Factor. So when there’s low oxygen our body activates this Factor called hypoxia-inducible Factor, and what hypoxia inducible Factor does is, it mobilizes all the necessary proteins required to live with low oxygen which means, one of the things it does is it shuts off this process of making energy using oxygen and turns on a process called, glycolysis. It’s making energy without oxygen, it makes energy without oxygen, and our body has ability to do that our cells have ability to do that and this is a more primitive way of making energy. However, this process called glycolysis only produces two units of energy from one given sugar molecule, whereas if you use the regular way in the mitochondria using oxygen you can make 32 to 36 units of energy. So it makes roughly 116 to 118 amount of energy using this process but it has to because there’s very low oxygen and it has to conserve it and has to use this process. Do you follow that?

Naren: yes, so let me understand

Dr. Kwan: so this transcription Factor called hypoxia inducible factor is triggered and next thing you know, our body is beginning to mobilize all these factors and proteins that allow us to live and adapt with low oxygen including using this energy making mechanism called glycolysis, and glycolysis is not done in the mitochondria. It’s done outside in the cytoplasm of the cell. I mean this is technical term but it’s not in the mitochondria. Mitochondria is where the majority of the energy is made on a normal cell but if there’s low oxygen or very little oxygen or no oxygen, it has to be made anyway because without energy, the cells will die. Okay do you understand?

Naren: yeah, let me ask you a question doctor. So

Dr. Kwan: Yes

Naren: what you’re saying is a typical cell that has as much oxygen it needs will make energy we’ll convert that into energy using the hypochondria correct?

Dr. Kwan: in the mitochondria

Naren: mitochondria,

Dr. Kwan: mitochondria, it’s called oxidative phosphorylation oxidative phosphorylation

Naren: right and when there’s not enough oxygen then

Dr. Kwan: but

Naren: its, its, choices are either to die or to become this other form where it can still make energy but less energy, with less oxygen

Dr. Kwan: Yes, it still makes energy but it it makes energy through a process called glycolysis instead of oxidative phosphorylation and so it’s still producing energy without oxygen and it’s still it’s still surviving, right.

Naren: Right

Dr. Kwan: that’s a survival mode so this hypoxia inducible Factor does that hypo so hypoxia inducible Factor does that it also does other things including it also mobilizes a protein called VEGF, VEGF it’s called vascular endothelial growth factor and what this V, VEGF, does is it ends up inducing angiogenesis, which means making new blood vessels. So when our body does not have enough oxygen, it switches its energy making mechanism, it also in order to bring in more blood flow and more oxygen it lays down more blood vessels because that’s what it thinks it needs, more blood vessel more oxygen and nutrients, right.

Naren: Right

Dr. Kwan: so we we end up with this thing called angiogenesis and you see this everywhere in the body, you see this in the body. You see this in multiple areas in the body and this is commonality. So this angiogenesis, so hypoxia inducible Factor, switches us into this new way of making energy but we all have this, in fact all the cells have this and cells make uses this mechanism every once in a while, it prefer not to use this because it’s much less efficient. So given that there is enough oxygen they will not use this but our body uses this on a regular day. When you’re running for instance 100 yard dash quickly you that energy that comes is through this this system called glycolysis. We do we do this because there’s not enough, this one of the advantages glycolysis it can make energy very quickly and and and when there’s low oxygen around. So our body naturally uses this process as well however in in the cells that that have issues that have damage and that that have low oxygen levels, our body triggers this process and and and and mobilize this and then going back to I want to go back to our case of Barrett’s esophagus. So I already talked to you about this. It’s a this the reflux disease that occur with with the gastrica this acid and the and bile that’s going into the to the distal part of our our esophagus, and causes changes, right. We talked about that

Naren: Yes

Dr. Kwan: and it causes injury and then the lining changes to a different kind of cells and it switches into glycolysis and when you study it those cells not only change the type of type of a type of a cell that’s going to more be adapt to that environment, but it also switches and it does this through HIF, hypoxia inducible Factor, and it by doing this it changes its cells. So literally evolution is occurring there right? Naren

Naren: Right

Dr. Kwan: there that’s Evolution literally it’s changing itself to adapt to the new environment right?

Naren: exactly

Dr. Kwan: That’s Evolution

Naren: Right

Naren: that’s Evolution occurring right there. So evolution is occurring and and literally it changes its cell type it literally switches the type of energy making mechanism it it makes energy through a process called glycolysis now, and then guess what Barrett’s esophagus does if it continues on with this process. It goes on to a process called dysplasia where it becomes more I don’t know if you heard of what this pleasure is that’s pre-cancerous lesion. It’s called pre-cancerous condition called dysplasia. So if left alone, if you allow the gastric acid to continue to reflux up into that area, first the the lining changes, it changes to this this glycolysis, it changes its lining, it by inducing this hypoxia inducible Factor. It even and then it the next step, I want to I want you to guess what the next step it would be if you left it alone, it becomes cancer

Naren: right

Dr. Kwan: so that’s the next step so it goes through this change initially to adjust to the new environment if we still don’t fix that environment then it it goes on to further because now you’re robbing more oxygen now it changes even further it becomes closer to cancer called dysplasia. You leave it alone long enough now it’s not producing, you’re still under very low oxygen. After a while what happens is now I think the cells believe that this is the condition that they’re going to live in and finally they switch and so they go back to the to the DNA and literally cause a mutation in the DNA and the DNA actually mutates to accommodate this condition and that’s called cancer. So you end up cancer, cancerous transformation starting with basically initial adaptation. So I believe initially the cells try to adapt to the new environment, but, but, if you leave it alone if you leave that condition where it’s getting less than less oxygen, given a prolonged period of time, it cannot stay in that and thrive in the situation. However, once it becomes cancer though, once it becomes what we call adenocarcinoma of the esophagus, esophageal adenocarcissoma, that’s a cancer the esophagus, if it becomes that the cancer cells thrive in the setting even in a low oxygen setting because the cancer cells guess how cancer cells make its, its, energy guess how it makes its energy the cancer cells it makes its energy primarily from glycolysis using no oxygen. So that’s the mechanism. So it makes all the all its energy essentially from however one of the things that cancers need it doesn’t need oxygen to make energy, but it needs one other thing to make energy, in order to make energy you need lots of sugar. You need lots of it. Cancer cells consume tons of sugar because you could as I told you one sugar molecule only gets you two units of energy versus 32 units. So you’re going to need 16 times more sugar in order to make the same amount of energy. So the, the, cancer cells are incredibly sugar hungry sugar hungry. So it goes after and there’s a study that’s done often in patients with cancer called a PET scan. It’s called positive emission thermography and basically it’s labelling sugar molecule radioactively tagging sugar molecule injecting into a patient with cancer and guess where it lights up, it lights up where the cancer is, because that’s where the cancer is consuming all of this.

Naren: Right

Dr. Kwan: so again, so again I believe that cancer is an evolutionary, cancer the development of cancer is an evolutionary process once cancer becomes cancer by the way there itself cancer itself there’s an evolutionary process that goes on. So within the cancer now, once it becomes cancer now you have this cancer cell within the cancer, within the cancers all these cancers cancer is not made up of one one cells it’s made up of millions and millions of cells, right, and among this cell because it’s rapidly dividing and not dying, that’s what cancer is basically. It’s, it’s, an it’s a proliferative cell it’s just it’s just growing and multiplying out of control and within all that cancer, there’s different DNA basically a DNA mutations that occur, and basically within the cancer, cancer, colony, it selects out which of the cancer is is the strongest, and that’s it becomes even more dangerous, it becomes more aggressive cancer. So even with the cancer cell more, aggressive cancers are selected out. the ones that are more resistant to our immune system because once so once our normal cells become cancer it no longer is part of our it is it it now is recognizes something foreign. So our immune system will try to get at it our immune system will try to get rid of the cancer cells because it recognizes foreign. However cancer cells put up a defence, and it does this in many ways. It puts up barriers through blood vessels and by the way cancer cells have a market amount of angiogenesis. I talked to you about that, again cancer cells depend on a factor called hypoxia inducible factor, HIF, which as I said triggers glycolysis. It also triggers angiogenesis, and cancer cells need, I believe cancer cells need angiogenesis to bring its nutrients lots of nutrients to it. It doesn’t necessarily need oxygen it needs lots of nutrients though so it needs lots of nutrients to make energy.

Naren: So you mean

Dr. Kwan: so as the cancer cells grow it needs more and more nutrients and you know as the cancer cells grow parts of it die because it it lacks the nutrients and then it loses its blood supply to that area however more aggressive cancers grow in other parts of that within that cancer.

Naren: right I mean you mean not nutrients sugar, right?

Dr. Kwan: sugar, nutrient I’m talking about yeah for the cancer nutrient could be sugar or it could be glucose or glutamine. That’s an amino acid. So cancers could feed on both glucose and glutamine, glutamine.

Naren: Okay

Dr. Kwan: it’s an amino acid. So it could so you can’t necessarily I mean I know that we can try to starve the cancer by not giving sugar, but cancer cells also they’re smart. They could also feed on glutamine as well so you can’t completely starve a cancer by cutting off sugar molecule besides, sugar is you know abundant in our body and it’s, it’s, going to steal it from our body so it’s not like you can starve ourselves. I mean there’s a diet called ketogenic, ketogenic, diet which is a essentially high, high, fat essentially. No sugar or very low sugar diet. In Hope of starving cancer, cancer cells and it does work at times that diet works at times. However it’s not foolproof and in many cases it does not respond to that diet as well. What’s the of the interest note is that this year 2019 the winner of Nobel Prize went to in medicine and Physiology went to a group that discovered hypoxia-inducible Factor.

Naren: yeah I was reading about that and the first person I thought of is you that’s kind of interesting can you tell me more about this particular Doctor Who won the Nobel Prize?

Dr. Kwan: well this doctor is his name is Doctor Craig Samanza he’s from Johns Hopkins University along with a couple other doctors from Europe, Doctor Craig Samenza, he was the he was the major, a major sort of the author in this and he discovered that this this complex it’s a hypoxia inducible it’s called hypoxia inducible transcription factor HIF and there’s it’s this heterodimeric complex the protein complex that gets activated in part in in our body all over our body when there is lack of oxygen. It’s an it’s basically an adaptation a tool that our body has to survive hypoxia or low oxygen state. So any part of our body that is that suffers from low oxygen you have hypoxia inducible factor that is that is activated and and I see these examples everywhere, everywhere, in our body. For instance when you have a condition called AMD, age-related macular degeneration. It’s one of the most common causes of blindness in adults and then this diabetic retinopathy which diabetics get. It it affects the retina the eye and they end up losing vision. So this these two conditions basically if you look at it in the retina, because retina needs a lot of a lot of blood supply and needs lots of oxygen. It needs lots of oxygen because it’s highly vascular for because retina is highly metabolic. It is what we basically use for vision and in basically patients who have AMD and these occur in elderly population their their blood vessels are damaged in the retina, and when they have a damaged blood vessels they have lack of oxygen they suffer from low oxygen to the retina, and because there’s low oxygen to retina, guess what gets mobilized, hypoxia-inducible transcription Factor. HIF, so hypoxia inducible Factor basically gets mobilized and it does all its things and along is it, it, it, it, it, it, it, it, produces a and it initiates angiogenesis in the retina. So it’s our body’s trying to basically say there’s low oxygen, we want to bring more oxygen. So we want to make new blood vessels. However problem with, the with, the with these new blood vessels that are made especially in a low oxygen setting if there’s a low oxygen setting angiogenesis that occurs, those blood vessels that are made are highly fragile and highly leaky, leakage very leaking blood vessels that are unstable and dysfunctional. So those blood vessels don’t necessarily bring end up bringing more oxygen. They end up actually rupturing a lot of them and they end up actually into causing blindness. So a protective adaptive mechanism that that we use, actually can actually cause of a problem. It’s trying to protect us by trying to bring more blood vessels to bring more oxygen, but it doesn’t succeed, in AMD, and that’s the similar thing happens in, in, cancer the cancer this angiogenesis that occur is in cancer, these blood vessels are highly fragile dysfunctional many of them are clotted off already and they’re dilated the tortuous. They’re not good blood vessels. So then they’re highly dysfunctional and they don’t bring uniform blood flow to the cancer. So there, this is being studied and there’s a treatment the to try to knock off angiogenesis. I believe androgenesis in our body is actually a good thing, and, and, it occurs in our body for the for the most part it’s a good thing in our body and really trying to do a good thing it’s an Adaptive response that our body has, has, developed during Evolution and like for instance when you work out when you exercise your body produces engine induces angiogenesis and this is incredibly good for us and by producing angiogenesis, it’s highly beneficial for us we get new blood vessels that are growing in our muscles, it, it, ends up you know it ends up bringing much more blood flow and oxygen to all over the body, right. So that’s a good thing. In a menstruating woman there’s every month with menstruation there’s angiogenesis that occurs in the in the in the endometrial cells. So this is this is a really good thing, getting ready for basically implantation and and and it does this every month and women. Angiogenesis we need it after we get injured for instance if we suffer a big injury and we get a huge wound problem and there’s a big chunk missing from our part of our body, there’s a big wound, that healing process occurs through angiogenesis and we need angiogenesis to bring new blood vessels. this hypoxia inducible Factor will lay down noble vessels and new blood vessels will bring more oxygen and it’ll heal that area. So angiogenesis I believe is a good thing and some have demonized angiogenesis, but the reason that cancer cells Harbor angiogenesis, but again it’s it’s just a way it’s an it’s an evolutionary adaptation, adaptable, adaptation mechanism developed by our body to deal with low oxygen state. When there’s low oxygen the cells are going to suffer, they’re going to become they’re going to die in in to prevent dying you our body tries to do everything it can including switching to glycolysis, including trying to make new blood vessels, it mobilizes all this complex. So it’s it’s a good thing for our body and we need to just for me the solution to really cancer. One of the solution for cancer is just to bring more oxygen to the cancer site by bringing more oxygen to the cancer site you actually stabilize the angiogenesis and actually contrary to what the many of the researchers believe, really if you stabilize the blood vessels around the cancer, it’s actually better for cancer treatment and actually we can knock off cancer by stabilizing one of the reasons why we have a hard time treating cancer patients is that they have this blood vessels through angiogenesis that are highly unstable. When we try to inject chemotherapy, into them this chemo agent goes everywhere in our body except to the cancer because those blood vessels just don’t deliver proper amounts of chemotherapy to the cancer site. So it ends up causing harm to our body, but doesn’t necessarily knock off the cancer, because there’s this unstable Body. By improving and making those blood vessels stronger, actually we’ve actually been more successful with chemotherapy and what are the things that can make those blood vessels and androgenesis better, like exercise when you exercise the cancer site blood vessels around the cancer sites are stabilized. We bring more oxygen and the blood more oxygen means better blood vessels. Better blood vessels means we could deliver more oxygen and study out of Duke University showed that, in mice that were injected and injected and basically induced with breast cancer and they divided the mice into four groups. First group of mice they, they left them in the cage. They all have breast cancer now so they they left them in the cage just sitting around second group they actually put a little a wheel, exercise wheel so the mice can exercise. Third group they give chemotherapy for that breast cancer and fourth group they gave chemo plus exercise. Guess what happened to the first group. First group the cancer grew out of control. Second group with, with the chemotherapy. I’m sorry I have in reverse. The second group had the chemo the chemotherapy group when you gave him chemo to breast cancer obviously the cancer slowed, its growth. What was surprising in the study is the third group where they just put the exercise wheel, the cancer grew just as cancer slowed growth slowed just as much as the chemo group, which was surprising, and the fourth group where they gave them both exercise and chemo the cancer really slowed its growth and this is because the blood vessels are stabilized. You’re bringing more oxygen to the cancer site. So the really the answer to this to cancer treatment really is to get more oxygen to the cancer site, because the cells need when you provide more oxygen to the cells the whole site our normal cells are stabilized. The cancer cells now are going to be more vulnerable because if we bring chemotherapy, the, the, chemo will enter the cancer much read more readily. Once the just just to point out once cancer once our cells turned into cancer, it’s, it’s, it’s, it’s, virtually impossible to flip it back to normal cells, okay, just by itself. So you can’t in other words you can’t just necessarily because you have cancer you can’t just exercise alone or just provide more oxygen, that can grow more blood vessels and stabilize the cancer site, but it’s not going to necessarily kill the cancer cells. That’s some people have this misunderstanding, you provide oxygen oxygen will kill it no. It will stabilize it but you do need a an agent like chemotherapy or immunotherapy or some agent that that will get to that area. So we need to be able to deliver these things to the cancers because can’t once cancer means what cancer means is that these cells have transformed into another kind, basically flipped into this differentiated into this kind of cell, and it’s not going to flip back on its own. So we have to get rid of it. We have to kill it

Naren: right

Dr. Kwan: does that do you understand that?

Naren: yeah, absolutely I totally understand

Dr. Kwan: so what he’s saying is yeah so I’m saying what I’m saying is oxygen is key what lack of oxygen I believe cause cancer and I’m not the only one that believes in this I believe lack of oxygen through Evolution through Evolution to try to adapt to live in this low oxygen, so in synopsis basically, low oxygen setting in these different cells in our body causes this environment that’s hypoxic and to survive this hypoxia, our cells have to adapt to live with less oxygen. In trying to live with less oxygen it changes and that change we call this change metaplasia, metaplasia, or we call this trans differentiation even. Initially we we do we mobilize this adaptable response and change and we deal with it. However, with continued hypoxia, with continued low oxygen, it eventually converts to cancer and once it converts to cancer, then that’s it it’s cancer. That means that mutation has occurred. So what I’m saying is literally the mutation that occurs that we find in cancer is secondary to hypoxia. So hypoxia is what caused the cancer initiated cancer and cause cancer. However that can’t because of this hypoxia, the cells, cells, have to mutate DNA had to mutate and became cancer. So hypoxia is the initiating event. Not the genetic mutation current, current, understanding is that genetic mutation is the one that triggers cancer what triggers cancer in my opinion and what what some believe is that what triggers cancer is low oxygen, because when our cells have to adapt to live with that low oxygen and that adaptation process leads to cancer

Naren: makes a lot of sense so this is why you know the title of the of the of the podcast today. It’s, it’s, really asking you know is cancer simply an evolutionary process makes total sense now doctor

Dr. Kwan: yes yes that’s an it’s a fascinating subject I think it’s something it’s an issue that it’s not going to be resolved today, but however I think it’s interesting to think about and I think we have to get this right if we get this right, if we get really if we find and truly identify what initiates cancer then I think our treatment is going to be different,

Naren: Right

Dr. Kwan: our treatment is going to be different then we’re going to be able to better Target cancer as of today we do not have a real uniform treatment and cancer as you know once you have cancer many Die, many die, in in certain cancers especially there are virtually no survivors and we we’re still nowhere close to curing cancer and I believe it’s because we’re looking at the wrong place. I think we’re looking at the wrong place and we’re looking at this wrong. If we really identify what truly initiates cancer, then I think that cancer treatment is going to follow, and it’s going to be easier and it’s going to be much more effective way of treating cancer

Naren: right makes total sense, thank you so much doctor any final thoughts now this particular researcher who won the Nobel Prize is he doing anything on this topic right now I mean is he still working on it

Dr. Kwan: I’m sure, I’m sure he is I mean I personally have not contacted him however he is a he’s a he’s a paediatric oncologist at the Johns Hopkins University and yes I’m sure he’s doing more work on it but the but you know I think it was an incredible discovery that that this this really hypoxia inducible and we call it HIF, hypoxia inducible Factor, but it’s we call it really hypoxia inducible transcription Factor, because transcription means that it’s transcription I don’t know if you know from your biochemistry, transcription is when DNA makes a copy of MRNA and MRNA makes protein called translation through a process called translation. So transcription is actually making a template, so we can make the protein ultimate protein. So this hypoxia inducible factor is actually changing the way the DNA behaves. It literally changes the way the DNA behaves based on what the environment is that’s evolution

Naren: right

Dr. Kwan: thank you

Naren: thank you so much doctor I really appreciate this conversation and if you’re listening to this please you know get a copy of the book it’s amazing. Also share this episode with your friends who might be thinking about this topic and thank you so much for listening

Dr. Kwan: thank you