Beyond Brain Surgery | Peter Dirks | TEDxBranksomeHall

well hello it's great to be here I'm going to tell you a story today that intersects my life in brain surgery neural stem cells and brain cancer and I call it beyond brain surgery and I think beyond brain surgery is science and biology and that's the future in my daily work I get to see the human the live human brain almost every day and every day I'm absolutely marveled at how this tan-colored three-pound organ dictates and is embedded within our feelings our emotions our skills our knowledge how is it that biological pulsating tissue can be the essence of who we are and certainly I love this quote from this physicist this theoretical physicist from the US who says who says the human brain is a hundred billion neurons each neuron connected to 10,000 other neurons and and sitting on your shoulders is the most complicated object in the known universe just the complexity of the human brain is absolutely astounding and 200 years ago we had a simple view of what was going on the brain based on examination of patience and understanding of cos that affected them and affected their functions and then studying their brains after to see which which regions were involved and so we had this map for for movement of different parts of the body and different areas of feeling but now with functional MRI with diffusion tensor imaging we have an exquisite map of we can obtain an exquisite map for every person's brain and it's not that a text book can't tell the story of each person's brain we need to actually write a text book for each individual person's brain and here you can see all the different bundles of nerves that are can interconnecting throughout a human brain and as well Jeffrey Lichtman from Harvard University has devised a method in animals where he can label individual neurons with different colors to study the the cell the cell connectivity of the of the brain and certainly these approaches will come to humans in the future but this is changing the way we think about how these different circuits define the essence of who we are and how we function now as a neurosurgeon we're not we're not quite at the cellular level but certainly these advances in technology are enabling us to do brain surgery safer than we've ever been able to do before and we can take this information not just the anatomy not just the shape of the brain but we can take these maps of the different functions for these four for example we can take language and we can pinpoint where language is in the brain so we know if we have a lesion to remove in the brain we can go around the language area to remove the lesion and keep the person's language functions intact and we can integrate this with computer systems so when we're doing surgery we can point to areas in the head or in the brain that tell us exactly where we are with respect to the imaging and the different functional pathways that we want to protect and preserve and so here's here's us we were pointing at the brain in that patient and this tells us relative to the scan where we are and here just at the bottom left is a tumor deep in this person's brain that we're seeking to remove and so this is incredible technology it's advancing all the time it's allowing us to to devise safe and better access to make brain surgery a safer and safer and and as well we have microscopes that allow us to operate at at a millimeter by millimeter level so I could spend four hours in an area the size of the end of my thumb to remove a tumor for example and and carefully tease it away from from nerves that might be responsible for a person swallowing or their ability to speak for example so all of these tools we have now at our disposal some brain surgery has never been safer and so it allows us to confront a very difficult problem like this with some confidence so here this this was a six year old girl who had headaches she gets a scan and she had this as you can see in the middle that bright areas is a brain tumor within within the very deepest reaches of her brain and so we had a real challenge how do we get to that this needs to be removed she's suffering symptoms and so with those tools with those maps we were able to sneak in in between the two halves of the brain and minimally disrupt the brain so as to remove that person that person's tumor and they woke up beautifully after the operation and everyone was relieved and we were all feeling very good about what we were able to do with our hands with this great technology but the problem with brain tumors is this is that they come back and so unfortunately this person's tumor came back several years later and it came back in a way that surgery no longer had a role and so first as a as a clinician and with this knowledge cancer is a leading cause of non accidental death and Canadian and American children and brain tumors represent many of these because other types of childhood cancers are being cured at a much higher rate for example childhood leukemia and so for myself being a brain surgeon and seeing wanting to always push myself to do better and to go beyond what I'd been taught I I wanted to do much more than that I didn't want surgery to be the last step I wanted to understand more and for this we have to turn to biology what can be done what can be done in science and scientific research and this is really what our main problem is for a lot of cancers that affect many different systems in the human body or problem isn't necessarily with with the for the first the first forays into treatment still surgery is a very important part of treatment of cancer in many different systems so it seems like such a crude act to physically remove but still today it's still one of the most important things that needs to be done in order to treat a person's cancer but the problem is with recurrence so recurrence after first treatment is a main obstacle to cure for many cancers including and especially brain cancer so one of the cancers that were very interested in which is quite common in young young people is a tumor called medulloblastoma and so I turn to thinking about well first what what do these tumors look like under a microscope and so this is a typical picture of a medulla blastoma where here purple is staining the nuclei and pink stains the cytoplasm of the cells and so here there are many cells packed together and essentially all of this looks quite similar all the cells morphologically look similar so I asked a question is that really true are those cells really truly the same and so we started to ask that question by staining tumors for different markers and we had a clue that cancer of the brain might be like an aberrant developmental process based on stem cells and I'll come back to that more detail but so what we wanted to do and this this this was from a model of the same cancer that that can be modeled in an animal and we stained cells within that tumor with different markers and so these these are markers sox2 dcx and new end they represent markers of stem cells progenitor cells and mature cells of the normal brain and so we find these normal markers also in the tumor and this suggests that maybe there's a relationship between those cells maybe this type of cancer represents an abnormal stem cell system and key point here is that the stem cells which expresses gene sox2 are relatively few but we think those are the key cells so we faced with that initial information we want to ask this question our relationships between stem cells and they're more mature daughter cell progeny maintained in a cancer context and I'm going to show you tell you show you a little bit of some experiments that suggest that the answer to that is yes there's a lot of excitement now over the last 20 years that our brain is more dynamic than we ever thought before because there are several regions in the brain where there are new neurons made in the brain that that may play a role in for example in memory formation in a part of the brain called the hippocampus which is on the inner part of the temporal lobe and perhaps making new neurons is essential to being able to generate new memories but so the stem cells reside within they generate other cells that amplify the number of cells because they divide frequently and ultimately they undergo a process called differentiation or maturation into cells that are neurons or glia which are astrocytes are oolagah dentro sites supporting cells for the neurons and so in the normal context during development that process works as a baby's brain grows during development and there's there's more robust activity of that early on in life in humans and there's that diminishes over time but in the normal context to make that beautiful brain that you saw those pictures of that these processes are extremely tightly regulated and are beautifully orchestrated and I like this image from one of my favorite records that that that illustrates the this process but in cancer we think all those there's a resemblance to that those kind of relationships it's now gone haywire but there are some clues within that tell us what we can do so another key point is cancers often represent distortions of our normal selves and to take that one step further in the brain is brain cancers represent a bear and developmental processes and brain cancers we think grow because they contain genetically abnormal stem cells that are our if you will on a misguided mission to grow abnormal brain tissue and so we need to understand that process and so I'm just going to show you one example of one experiment that supports this idea and it's it's a classical experiment that that scientists who are interested in development of tissues does it's something called a lineage trace and it's a definitive measurement of the potency of a cell that's marked in a tissue and it tells us whether how well that tissue can replenish and how how that tissue matures and we wanted to ask this question those five percents those few little green cells I showed you in that picture that expressed this gene key gene called sox2 could those cells be at the roots of growth of this type of childhood tumor and so a graduate student in my lab robert van ER did the experiment it was a very difficult experiment but what he was able to do is he could we used a genetic trick that was embedded into animals that would that would grow up medulloblastoma naturally and this model is very close to the to the sharing the same genetic changes in the same the tumors look the same as the human tumors they express the same abnormal genetic programs as a human tumor so we thought it was it was a terrific model and here was something that you actually can't do in a human being but you can do in a very good animal model so what Robert was able to do is he could mark the Sox to positive cells and show initially that these were few cells in the tumor and then what we did is we followed that tumor over time to trace the progeny of these mark cells and essentially what happens here is that cell becomes acquires a color core this red color when that cell divided and generated two daughter cells both the daughter cells became red and then as they divided both their daughter cells become red and over time we wanted to watch to see if the tumor turn red and essentially and here's the real experiment it shows that the tumor grows based on the division and multiplication of a rare population of cells that reside within strongly supporting that this this type of tumor is driven in a based on an aberrant stem cell system so on the right you can see over several weeks the tumor essentially turns red and it came from few cells so these cells we think are at the root of the growth of this kind of cancer and the key thing here is we then started to test conventional treatments in in in this model to see how do the conventional treatments target these different cell types in these in these tumors and essentially what we found here is that the usual treatments were were fantastic at killing a lot of the cells in the tumor we found good drugs already that also work in patients that are very good at at shrinking these tumors and and improving the symptoms but but what you may not be able to see so well here but on the right is after the treatment we see more red cells in this tumor and what that means is that the we spared a population of cells we're leaving something behind we're leaving a reservoir of cells behind that may show the capacity to regrow the tumor and and so in applying the stem cell biology approach this developmental framework if you will to thinking about how cancer grows we can start to divide up different cell types in the tumor in two distinct compartments I'm not going to go over all of this but essentially there are a few cells that are that have a stem cell property that actually another key point about those cells is that they're very slowly dividing they and our general treatments for cancer are very good at targeting cells that are rapidly dividing we figure that process out but we haven't figured out so well how to deal with cells that are lurking within the cancer that maybe have a very slow dividing potential seems like the drugs that we have don't target these slowly cycling cells those cells in turn generates progeny that divide fast which are cancer progenitors which respond to chemotherapy which we can wipe out and eventually those cells undergo a maturation process not like the normal brain but still resembling the normal brain but these cells that mature actually are short live and are eliminated and although they form a component of the mass of the tumor which can cause symptoms they actually disappear over time they're programmed to disappear and it may be analogous to what also happens in the developing brain we during development we generate way way more neurons than we need and as those neurons start to make connections a lot of the extra neurons are pruned so we there may be this process is also being recapitulated in this cancer context but what this tells us also is that we need different types of treatments for these different types of cells and applying the stem cell thinking means we don't we not we not only have to target the fast awaiting cells we need something that targets the slow dividing cells or maybe what we should do is just force all of these cells to mature into these differentiated cell types and then those cells what cells will have a limited lifespan and will disappear so I think one of the key points I want to get across today and I think it applies generally to cancer is not every cancer is functionally created equal even if they may have the same genetic changes they're not behaving the same way and we need to figure that out so cancer is much more than genetic mutations genetic mutations are essential to get cancer growing are essential to be cancer but but it's how those genetic changes are being used by the cells that also dictates the way that cancer behaves so we think that cancer reflects how genetic changes shape the behavior of normal tissue growth and regenerative processes and in our in our group we've identified a cellular target in medulloblastoma and also in glioblastoma of adults and we're starting to characterize more of the programs that dictate the behavior of those cells and we think that we have the cell in hand that is responsible for the root growth of these tumors but also responsible for the recurrence having these cells at hand gives us the chance to discover new therapies that may more that may better affect long lasting cures so I think there is hope for a better future for for children and adults with brain cancer based on applying this kind of framework to understanding brain cancer and it and really as someone who started off as a clinician as a surgeon I love what I do in looking after a patient's and being able to use my hands and to be able to have a dramatic impact on someone's life with an operation but I recognize that still there's limitations in what we can do with our hands and I think we're not we're not yet to be replaced by robots because still there's aspects of the human motor and sensory systems that still can't be replaced by robots so we need surgeons but we need much more than surgery we need to understand biology and I think the key for for young people is science Canada and the world needs more people engaged in scientific research to ask creative original questions and to think outside the box we think in a way we thought outside of the box and look and looking at brain cancer this way and we're very hopeful what that might mean for the future thank you very much for your attention [Applause]

Channel: TEDx Talks

Views: 19,546

Keywords: TEDxTalks, English, Canada, Science (hard), Brain, Surgery

Id: Elo385hbjBw

Length: 19min 37sec (1177 seconds)

Published: Tue Jun 13 2017