An End to Cancer Mortality with Nano-Diagnostics | Matt Trau | TEDxUQ

so I'm going to talk about three topics today that aren't usually clustered together I'm gonna talk about cancer nanotechnology and okay it's going to give the technical so now the technology is just about making itsy-bitsy little devices that are cheap that's a technical stuff done and the third topic is Diagnostics so let's let me start with cancer so cancer right now on the globe is one of the biggest killers of human beings I don't mean to keep giving you more depressing statistics but we'll get to the good stuff later um cancer incident rights you would know this as we all get older are going like this this is a disease that we need to do something about urgently so if we I mean the statistics are such that if we if we surveyed the people in this audience if we talk to you you've probably found it but just that everybody here has been touched by cancer I have through my friends my family and let me tell you something it's personal so my background isn't in biology it's in it's in chemistry physics and mathematics however over the past few decades I've had the ship privilege of watching absolutely strident advances in our understanding of cancer biology it's amazing what we now understand of cancer biology the trouble is that there's this explosion of information in cancer biology but if you look at the the old Holy Grail that was articulated 50 60 years ago of what humans humankind needs to produce that the Holy Grail was that will make one pill one pill and and that one pill will be the magic pill that will be the cure right and will make all that cancer go away so unfortunately and actually if you look at our medical system over the the many decades it started to what it has aligned itself in a model that aligns ever so slightly towards that type of dream one pill for everybody so unfortunately if you look at the advances that we've had in laughs we've had the rapid sequencing cheap fast DNA sequencing so yeah last decade it took three billion dollars to sequence a human genome forget that now we do it for a couple hundred dollars of a now I can sequence my cat in the time that it takes me to make a cup of tea now that power which is powered by nanotechnology by the way that power allows us to see cancer in ways that mankind has never seen before and one of the first things that we've seen in the past decade is and in a nutshell cancer is complicated and it's more complicated than we thought and here are some features the first thing you see and a lot of people have argued this even before far sequencing is that each cancer is different every person with cancer has a different cancer and what's even more frustrating is that if you take a piece of that cancer out of one person little the cells even the cells inside that look they're different how frustrating is that and that's really calling a lot of people to say well how is that one pill for everyone go to work it's a bit like asking we're gonna have one tune that will be excite all the people in the world and some people are saying that that dream of one pill for everyone probably will never happen we need a new approach I'm sweeping a little bit of stuff under carpet but that's that's the generic and so in my lab we've been thinking about this issue from different angles we've been thinking about this issue of complexity and cancer from where we're from from ant from a raw engineering perspective with chemistry physics and nanotechnology what's possible what could you engineer and we believe that there is a solution but it requires realigning that medical system a little bit differently well let me walk you through it we think that the approach is to really power up Diagnostics that's why it's in my slide and pair it up with nanotechnology to make technologies that mankind has never seen before I showed you an example the second ago with how cheaper is the sequence genomes and we feel that if one can power up Diagnostics like this what'll happen is each of those individual cancers will be able to read individually in detail to know what to do and will be cost effective and so if you think about and we think that's the path to truly and visiting a future where we can engineer an end to cancer mortality and as a physical chemist who works with engineers I believe it is possible but we need to realign a little bit and try a different approach if you think about it there's really from that perspective there's two types of technologies that we need one is something that I call a scanner and the other somehow called a monitor will now show you examples of both today so what's the scanner the scanner is basically a device what it will do you take the cancer and you just bust it open and read all that stuff and you read whole gene whole epigenome whole transcriptome whole proteome exercise etc and then you do mathematics to sift through all that that mathematical information and find the needles amongst all that hay and those needles are the treasures those needles are the errors that the cancer has produced and and may represent the software that's gone wrong that's the scanner now the thing is once you've done that once with the cancer you don't need to keep doing that you can then use something I call a monitor once you have the needles you can then just look for the needles at trace level and the cost of the monitor because it's you're only looking for the needles can be effectively invisible and so we think through this approach one could as I mentioned before engineer big inroads in cancer and so what I'd like to show you today is examples of those two technologies that we've been developing in our lab and trialing on real cancer patients in the clinic and some of these some of the results we think are a little bit interesting to do this what you need is a unique environment you need an environment where you have patients medical oncologists technology developers nanotechnologists mathematicians engineers etc so we've set up a new Center at UQ that has exactly that one thing I'm very proud of is that we engage with a lot of patients and so with the center over the past two years we've engaged with hundreds and hundreds of patients so I'd like to start with telling you the story about just one of those patients so this is a this is actually quite a tragic story it's patient 205 she was the 250 patient that was engaged through a clinical trial and our Center it's a tragic story it's a young 38 year old woman who's dead but I hope that part of her legacy and I'm going to tell you in her clinical story I have the part of her legacy is to teach us what technologies we need to develop and what parts of that system we need to change to eliminate cancer let me tell you the story so she was diagnosed with acute myeloid leukemia advanced acute myeloid leukemia it's a blood cancer so cancer is complicated blood cancer is complicated many different types of blood cancer but there's one that's really really bad that's this one acute myeloid leukemia AML for those medicos in the room and you can see that straight away here in this plot the reason it's so bad is that it just doesn't respond to anything that we throw at it in the modern conventional medical system and so what's plotted here is her counselor that's the number of cancer cells in her blood over time and what you can see and this is very characteristic of the late stage of this disease is the cells are doubling these are four day increments so they're doubling every four days now the body just can't sustain that concentration of blood blood cells so what happens at the patient these patients usually die very rapidly it's a very aggressive disease and they die of a stroke or something like that so for her palliative care is here just to get that this point is amazing and death is guaranteed round about here the body just can't sustain it and the other part of the story this is the important part is before she came into one of our clinical trials B prior to this point what had endured was immense so before here she had not one but two bone-marrow transplants now what go to the details of that but this is an arduous process that the the chance of surviving not one but two is something like fifty or sixty percent so she did extremely well to get that point after that she then endured four lines of extremely aggressive chemotherapy and the the doctors did she's young they did everything they could to try to save her because nothing's responding they have to try and and that's the best that they have it's a game of cracking up the toxicity or became a to try to get therapeutic effect and unfortunately as you can see in the plot there was a short respite but then it didn't work as happens in many of these cases the cancer has come back and at this point all current medical treatment are exhausted and there's nothing you can do it's pretty gripping stuff I mean this is the things that affect myself in my lab so she came into one of our clinical trials there's a last resort and what we did is we used the scanner that I mentioned right at the beginning and it's amazing I don't sequence the cat but what we do is sequence cancer cells and because of these technologies and I don't have time to describe their details but that they're quite fascinating the ability of sequence at the speed now we're able to sequence not just the comprehensive genome of the cancer cell but we can sequence the epigenome and the transcript though for those of you who aren't familiar with this think of it as a machine what we're able to do is get a very comprehensive snapshot in hours of the ROM and RAM memory of the cancer machine it's incredible I never thought I'd live to see these technologies come to power they're here now now you know so when we do this we can then do something called integrated bioinformatics I mentioned mathematics and this is sort of it's a bit like a bio Google what we can do is we've got all this information we're looking at you know the if you like the hard drive of the cells and what apps the cells are running we can ask the question what's wrong with you goddess what programs are you running why are you doing this why are you amplifying like crazy that's the first part of the by informatics and that's the searching for those needles I mentioned so in her case what we found was really something quite stunning what we found was that although she has a blood disease the needle the driver pathway if you like and that's the app that's driving the cancer the driver pathway really looked like it was a skin cancer and you might say well that's skin cancer what the hell is a skin cancer doing in a very aggressive blood cancer well welcome to the future of medicine cancer doesn't care which part of the body it's in it cares about the code code matters and now we can read the code so we looked into it further and the second part of how I should say with the the melanoma some melanoma again it's very complicated many different types of melanoma there's one type a rare type of melanoma that happens at the back of the eye and it's called retinal melanoma but you know it's treatable it's treatable but the driver mechanism of her cancer looked very much like retinal melanoma what the hey what the hey so the second part of the program what it does is it has a database of all known human drugs that have ever been approved for use in humans and their connection to the pathways so it runs to search like a bio search and tries to connect the driver pathway with the drug so in her case all the lights lit up everything lit up there's a drug it sits in a cupboard and it treats retinal melanoma very effectively with low toxicity the tablet sits in a cupboard think of repeated sits in the cupboard enough times yeah it sits in the cupboard so this gap here is the time that it took because what we proposed in these few days it wasn't me what the oncologists her medical specialists proposed was something absolutely outrageous in the current system the one drug fits all he proposed that a blood cancer would be treated by a skin cancer drug so he sought approval of her of her family and all the appropriate places to at this point on her last legs administer this it's a tablet a relatively safe tablet and this is what happened so the tablet was administered here and what you can see is that it took effect immediately nothing else worked he made it work by now transplant didn't work the tablet worked immediately and then within three days the cancer dropped down to almost zero she technically went into remission and I have to tell you when I saw this result I mean I still get a bit emotional when I talk about it I just fell off my chair I couldn't believe it now and the other thing is I'll often say it but but if this was such a spectacular was at first I didn't believe it then we checked it and you know if there's nothing else that I do in my career this is enough but we've got bigger plans we followed her Bloods right along I should point out that at this point she was so depleted from the chemotherapy and all those treatment that she needed to recover from all of the other treatments that hadn't worked but then eventually was released from hospital to her family now I've got pictures of her riding a horse there's some very cherished photos we've trapped the blood that the cancer did actually keep going back to zero one of the frustrating things here too is that this is now it's a genetically confined system and so sometimes these cancers mutate back but there's now a second and third-tier drug if it ever did but then four months later she died what did she die of she died of a heart attack so you can ask yourself the question why would a 38 year old woman young woman died of a heart attack what did she have back here she had a load of chemotherapy what happens to 60% it's like I think it's like 40 to 60% of aggressive chemotherapy patients for AML I'm not through chemotherapy but in this one case round about that fraction died of how did the disease that these drugs are very cardiotoxic they poison the heart and so she died of a heart attack induced by the chemotherapy it's a side effect that the doctors did exactly the right thing it's just that they have no other options it's the one drug fits all model it's a tragic story but then what can we learn from this well I think there are some powerful lessons here one in terms of the technologies we need to develop and two in terms of how do we need to change the system to make a bigger impact in cancer let me hit those two things so first we need to have early screening that's it just stands out by crazy imagine if I could have sat down with her whole medical team and the data it would have been here at this point even before she had the bone marrow transplant we could have had a conversation it's like a scene from The Matrix do you want to take the red pill or the green pill you can try the pill don't mention it was in a cupboard and it's low toxicity or you can go and we can we can try that out for two weeks and see if it has an effect if it doesn't then there's the chemo there's that there's the bone marrow transplant and chemo no problem I wonder which choice she would have taken okay I know which choice she would have taken the next thing is we need person so this is the scanner we need the personalized treatment this is the monitor and the other place where we need the monitor is here and now monitoring in our modern system we don't do that very much and sounds crazy from an engineering perspective but we just don't people get chemotherapy and basically they just kind of go home they kept you know scans and you have a consultation but we should be monitoring the disease to see if the therapy has worked if it hasn't flipped the treatment and if the cancers come back get in there early before it can do some other damage now out loud now focus is very much on I've mentioned this Anna and the monitor technology so for what remaining time I have I'm going to show you examples of the monitor technologies and so for the monitor as I mentioned earlier we need nanotechnologies to make these if you're going to go into a screening or monitoring program to make these very cheap and very accurate but let's first look at how it's currently done in the powered system so this is how pathology is done today it's very typical by the way it really strikes me as a sort of a chemist nanotechnologist that it's quite interesting that in our system although cancer is a disease of the DNA we don't commonly look at the DNA of those patients we do through histopathology etc but but it's not comprehensive that's something that needs to change but if the DNA is analyzed I should just point out this is pallava what happens if somebody takes a sample and zap larvae is an Australia yudish word which means a lot of bother so there's a lot of bother we could get a sample off it goes to a lab and then maybe the information gets back to the doctor and he does something hopefully but it's very expensive lots of technicians lots of dollars this soaks up about 20% of our current healthcare budget and it's increasing like this we need new technologies to drive the cost of this down very much so now for DNA analysis when it's done there are three key steps I need to point these out one is the DNA extraction to pull out the DNA from blood or tissue or whatever next is the DNA amplification and each of these takes a bench one of these things a bench and a technician so the application with PCR something like that and then the third step is what's called the detection and for that we need another bench and a person that will be synthesis by sequencing or a fluorescence readout rt-pcr things like that that's how it's done so what we've done in our lab is we've miniaturized all three of those steps we've used nanotechnology to miniaturize each of those three steps into one droplet of fluid and so that you can do the tests yourself you don't need a laboratory we've technical or effectively miniaturised that whole lab into one drop of fluid so it's it's all described in this paper this is the extraction step where you get a single strand of DNA if you like the megaphone is a schematic which shows how the that molecule was amplified automatically so the drop contains all the molecular machinery and that are particles to do this automatically it's programmed and then the nano particles that are in here a program so if that amplification reaction happens they become like velcro basically they precipitate and you see it by eye the key features of the test are that what you have is is comprehensive DNA and RNA analysis within a single drop as i've mentioned now unlike the lab there's now no lab required there's no training no personnel even I can run this and it takes 45 minutes to run you can do this yourself it's similar to a pool test for those of you have a pool when I do this all the time you take the sample you do a bit of this and then you look for a color change that's it but now this test is looking for pH or chlorine it has single DNA molecule sensitivity we think that's pretty cool because that's trace I can look for those needles that I mentioned we've adapted this for all pathogens we've shown that it works for HIV tuberculosis cancer markers obviously and saliva blood urine all have been published and cattle herpes I don't know why cattle get herpes but when they don't know why they get herpes but but if they get it we can test for it and it's in this paper and please go ahead and read about it but also another interesting fact is we can do multiple tests at once inside the droplet so it's like it's it's a DNA scanner basically it'll you program it to look for at the moment up to 3 and in the future many more so we think it's ideal as a monitor and ideal for point of care I'll just contrast this with the 3 billion dollar comment I made on the introduction you know this obviously doesn't do whole genome sequencing but but it doesn't require the million dollar pieces of equipment that we used about a decade ago that's something to keep in here's a video of how it works I'll just show you quickly you do a bit of this put it down and then with 13 13 seconds the nanoparticles give you the answer that's a yes that's a no that's all there was to it and as I mentioned these are individually programmable we've extended this now for any tech heads out there for DNA RNA and epigenetic signatures so if you remember with 205 we looked at DNA RNA and epigenetics in this we can do this here as well and we think that's rather powerful now in whatever time is left I want to show you just one last monitor because this isn't just applicable this concept is applicable not just to leukemia it's applicable for all cancers so for all cancers this is our picture of how cancers spread we think that what happens it starts with one cell that goes a bit haywire and then it forms a primary tumor now this guy is threatening but he's safe if we can detect that earlier for example in breast cancer early detection gives rise is almost as good as a cure gives rise to almost 98% survival for patients with some surgery a little bit of therapy the problem the really big problem in cancer is this blue guy what happens is they break off and then they travel in very small numbers like criminals in a city through the bloodstream so and they will then form you know little little gangs I had to use this at this analogy which armineh statics secondary metastatic sites and they are the really dangerous agents they kill now the problem is that in the hospital systems we have no eyes at all on this system the oncologist doesn't see it it doesn't know if it's happening he has to treat the patient as well as he or she can so one of the Holy Grails here is to get some eyes on this and again it's a needle in the haystack game for a metastatic patients typically one would have 50 cells in a mill of blood which would have 10 million healthy cells so it's the it's the criminal in the city 50 cells 50 bad guys for 10 million good how do you find them so here's how we do it we use nanotech no so in the video you'll see there's this is blood moving and the reason the blood moves is we attach a C those are we attach little alligator clips that supply an AC voltage it's point one volts 100 kill of 1 kilohertz when the voltage is applied the AC voltage it applied the blood moves when you stop it it stops for the physicists in the audience I'm sure there are some somewhere this is not capillary phoresis it's an electro hydrodynamic phenomena I don't have time to go through the details but all you need is a relatively cheap chip and a point 1 volt 1 kilohertz signal which can be supplied by an iPhone that allows you and that's the sort of in there there are other technologies now that are coming on the market but the feature of this is its accuracy and its cheapness now I don't have time to go through the physics the physics I'm biased I think of it's quite exquisite it drives fluid flow within nanometers of the solution and I'll skip it for the interest of time and just show you a movie but we published all of this stuff if anybody's interested if you have a look at the chip what there are is thousands of these asymmetric pixels there's the AC voltage the red guys are the bad guys that we're trying to catch and the way it works it works like a microscopic airport security station where all the cells Pat it down the good guys are lit through and bad guys I have it on the cool thing is that if we take a cancer patient with 100 cancer cells this chip will find 90% of those cells accurately each and every time and we think that's a little bit cool and we published that in all of these publications the other one so this starts to give you eyes on that process the other wonderful thing about this is that once you catch the robbers you can interrogate the robbers so we know they're there we can release them bust them open and then we bring in our scanner and we look at their genome epigenome transcriptome and ask the question what's wrong with you guys and why aren't you dying when we give you a bunch of drugs so this again is it's just a second example of a monitoring technology and how these things are becoming cheap and I think in the future invisible so what finish where I started I want to finish with patient to our five what are the lessons from patient 2:05 and I hope this will be one of her legacies one of her great legacies is that she teaches us what to do and I think the first one is we need to change conventional cancer treatment it stands out so clearly if you look at her case I can't choose what's technically called an exceptional responder but it's the exceptional responders that are the jewels in the clinic they teach you everything we we need to embrace the fact that each cancer is different and we need to analyze it at a molecular level read it at a molecular level we need to embrace new technologies to detect early personalized and monitor it's so clear and most importantly we need to translate these powerful new nanotechnologies from the lab into the clinic we need the shift that old medical system just that little bit into a new paradigm I've got one last slide and I'm going to finish there so in the work that we do it's very unusual that we would ever meet or even learn who the patient is for a sample that we analyze and that's as it should be it's that it protects the privacy of those individuals what we get is de-identified samples so by a process of serendipity not long ago our lab and I got it had an opportunity to meet the family of patient 205 let me tell you was a very humbling experience and I I had the honour of learning a little bit about her life and about her dreams and I want to finish by sharing with you a little about her than one of her dreams so this is patient 205 Alexandra Cox liro she was loved dearly by her family and friends and known as Alex she was as you would imagine someone of absolutely tenacious courage that is what I hear that tenacious courage was tinged with a biting humor and from what I hear deep wisdom she was very grateful of the radical approach that was trialed to reverse her refractory refractory cancer and knock it down to zero and she had one wish and I think we should remember her wish her vision if you like was that that treatment that she received would one day be a line treatment early not a last resort treatment that's a vision that really motivates me and my lab and I think it should be who've all of us to make that happen and make a difference thank you

Channel: TEDx Talks

Views: 75,999

Keywords: TEDxTalks, English, Australia, Health, Cancer, Data, Science, Technology

Id: ZKv8I0xa7lc

Length: 29min 12sec (1752 seconds)

Published: Fri Sep 02 2016