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

So today I'm going to talk about three topics that aren't normally grouped together. I'm going to talk about

cancer

nano

technology and okay, I'm going to get technical, so now the technology is just about making tiny little devices that are cheap. that is a technical question and the third topic is Diagnosis, so let me start with

cancer

, so cancer right now in the world is one of the leading causes of death of human beings. I don't mean to keep giving you more depressing statistics, but we will. let's move on to the good later, cancer incident rights, you would know as we all get older, come on like this, this is a disease we need to do something about urgently, so if I mean the statistics are such that yes We surveyed The people in this audience, if we talk to you, you probably have encountered it, but everyone here has been affected by the cancer that I have through my friends, my family and let me tell you something that is personal, so my experience is not in biology. in chemistry, physics, and mathematics, yet in recent decades I have had the privilege of observing absolutely strident advances in our understanding of cancer biology.

It is amazing what we now understand about the biology of cancer. The problem is that there is this explosion of information in cancer biology, but if we look at the old Holy Grail that was articulated 50 or 60 years ago about what humans, humanity needs to produce, that Holy Grail was the one that will make a pill will be a pill and that pill will be the magic pill that will be the right cure and will make all that cancer go away, unfortunately and in fact, if you look at our medical system over the many decades that it started, it has aligned in a model that slightly aligns with that type of dream. pill for everyone, so unfortunately, if you look at the advances we've had, he laughs, we've had rapid sequencing, rapid and cheap DNA sequencing, so yes, last decade it took three billion dollars to sequence a human genome, forget that now we do it for a couple of hundred dollars now I can sequence my cat in the time it takes me to make a cup of tea, now that power that is driven by

nano

technology, by the way That power allows us to see cancer in ways that humanity has never seen. before and one of the first things we've seen in the last decade is, simply put, cancer is complicated and it's more complicated than we thought and here are some characteristics that are the first thing you see and a lot of people have argued this Even before sequencing is that every 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 a person, the cells, even the cells inside, They look different. frustrating is that and that really calls a lot of people to say well, what's that pill for everyone to go to work?

It's a bit like asking, we're going to have a song that will excite everyone in the world and some people saying that dream of one pill for everyone will probably never come true, we need a new approach. I'm sweeping things under the rug a little bit, but that's the generic stuff, so in my lab we've been thinking about this topic from different angles. We've been thinking about this issue of complexity and cancer where we're coming from from a raw engineering perspective with chemistry, physics and nanotechnology. What is posible? What could be designed? We believe there is a solution, but it requires realigning that medical aspect. slightly different system, well let me explain how it works.

We think the focus is on really empowering

diagnostics

, which is why it's on my slide, and combining it with nanotechnology to create technologies that humanity has never seen before. I showed you an example. a second ago with how cheaper the genome sequence is and we believe that if diagnoses like this can be enhanced, what will happen is that each of those individual cancers can be read individually in detail to know what to do and it will be profitable and then , if you think and we believe that that is the path to really visit a future where we can engineer the end of cancer

mortality

and, as a physicist working with engineers, I think it is possible, but we need to realign ourselves a little bit and try.

A different approach if you think about it, really from that perspective there are two types of technologies that we need, one is something I call a scanner and the other is somehow called a monitor. Today I will show you examples of both, so what is the scanner? it's basically a device, what it will do: you take the cancer, you open it up and you read all of that and you read the whole gene, the whole epigenome, the whole transcriptome, the whole proteome exercise, etc., and then you do math to look at all of that. mathematical information and find the needles among all that hay and those needles are the treasures those needles are the errors that the cancer has produced and they may represent the software that went wrong that is the scanner now the thing is that once you have done that a time with cancer You don't need to keep doing that, then you can use something I call a monitor.

Once you have the needles, you can simply look up the trace level needles and the cost of the monitor, because you're just looking at the needles. be effectively invisible and that's why we think that through this approach one could, as I mentioned before, make great advances in cancer and therefore what I would like to show you today are examples of those two technologies that we have been developing in our laboratory and testing 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 have created a new Center at UQ that has exactly what I am very proud of: we work with a lot of patients and therefore at the center over the last two years we have interacted with hundreds and hundreds of patients.

I'd like to start by telling you the story of just one of those patients, so this is actually a pretty tragic story: Patient 205, she was patient 250 who participated in a clinical trial and our Center, it's a tragic story. She is a 38-year-old girl who is dead but I hope that part of her legacy and I am going to tell you in her medical history, 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 he was diagnosed with acute myeloid leukemia advanced acute myeloid leukemia is a blood cancer so cancer is complicated blood cancer is complicated many different types of blood cancer but there is one that is really really bad, that is this acute myeloid leukemia (AML) to the doctors in the room and you can see that right away here in this plot, the reason it's so bad is that it just doesn't respond to anything we throw at it in the modern conventional system . medical system and what is plotted here is your advisor, that is, the number of cancer cells in your blood over time and what you can see and this is very characteristic of the late stage of this disease, the cells They are doubling, these are four day increments, so they are doubling every four days, now the body just can't maintain that concentration of blood cells, so what happens to the patient?

These patients usually die very quickly, it's a very aggressive disease and they die from a stroke or something like that. Palliative care is here just to understand that this point is amazing and death is guaranteed around 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 from our clinical trials B. Before this point, what she had endured was immense, so before here she had not one but two bone marrow transplants. Now let's get into the details of that, but this is an arduous process and the chance of surviving not one but two is something like fifty. or sixty percent, so she did very well to get to that point after that, then she endured four lines of extremely aggressive chemotherapy and the doctors did everything they could to try to save her because nothing responds, they have to try and that's . the best they have is a game of breaking the toxicity or it became a game of trying to get a therapeutic effect and unfortunately, as you can see in the plot, there was a brief respite but then it didn't work as happens in many of these cases .

The cancer has returned and at this point all current medical treatments are exhausted and there is nothing you can do, it's pretty exciting stuff. I mean, these are the things that affect me in my lab, so she went into one of our clinical trials. There is a last resort. and what we did was use the scanner that I mentioned at the beginning and it's amazing. We didn't sequence the cat, but what we do is sequence cancer cells and because of these technologies, I don't have time to describe the details of them. but it's quite fascinating the ability to sequence at the speed that we can now sequence not only the entire genome of the cancer cell, but we can also sequence the epigenome and the transcript, although for those of you who are not familiar with Think of it like a machine , what we can do is get a very complete snapshot in hours of the ROM and RAM of the cancer machine.

Is incredible. I never thought I would live to see these technologies come to power. You know, when we do this we can do something called integrated bioinformatics. I mentioned math and this is a bit like a Google bio. What we can do is have all this information that we are looking for. You know, if you like the cells hard drive and what applications the cells run, we can ask you 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 computer science and that is the search for those needles that I mentioned, so in his case what we found was something really surprising.

What we found was that even though she has a blood disease, the needle is the driver's line, if she wants it, and that's the application she drives. the cancer, the conductive pathway really looked like a skin cancer and you could say, well, that's skin cancer, what the heck does a skin cancer do in a very aggressive blood cancer? Well welcome to the future of medicine, cancer doesn't care what part of the body it is in it cares about the code, the code

matt

ers and now we can read the code so we looked into it further and the second part of how I should say with melanoma, some melanoma again, it's very complicated, there are many different types of melanoma, there is one. write a rare type of melanoma that occurs in the back of the eye and it's called retinal melanoma, but you know it's treatable, it's treatable, but the driving mechanism of her cancer looked a lot like retinal melanoma, what the hell, what , what, so the second part of the program what it does is it has a database of all the known human drugs that have ever been approved for use in humans and their connection to the pathways, so it runs a search as a biological search and tries to connect the conductive pathway with the drug.

In his case, all the lights lit up, everything lit up, there is a medicine that sits in a closet that treats retinal melanoma very effectively and with low toxicity. The tablet is located in a closet. so this gap here is the time it took because what we proposed in these days was not me what the oncologists their specialist doctors proposed was something absolutely scandalous in the current system the only medicine fits all those who proposed that a blood cancer being treated with a skin cancer drug, so he sought approval from her, from her family, and from all the appropriate places to, at this point, on his last legs, administer this, it's a tablet, a relatively safe 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 now the transplant did not work the tablet worked immediately and then within three days the cancer went down to almost zero, she technically went into remission and I have to say it. when I saw this result, I mean I still get a little emotional when I talk about it, I just fell off my chair, I couldn't believe it now and the other thing is that I will say it often, but if this was so spectacular it was not at first I believed it, then we checked it and you know, if there is nothing else I do in my career, this is enough, but we have bigger plans, we follow their Bloods immediately.

I should point out that at this point she was so exhausted from the chemotherapy and all those treatments that she needed to recover from all the other treatments that hadn't worked, but she was finally discharged from the hospital to go to her family. she. Now I have photos ofshe riding a horse. some very precious photos we have caught the blood that the cancer actually kept returning to zero. One of the frustrating things here as well is that it is now a genetically confined system and so sometimes these cancers mutate again, but now there is a second and third tier drug, if ever there was one, but four months later she died, what did she die of, she died of a heart attack, so you may wonder why a 38 year old young woman would die of a heart attack, what did she do?

When I came back here, she had a lot of chemotherapy. What happens to 60%? I think it's like 40 to 60% of patients on aggressive chemotherapy for AML. I'm not done with chemotherapy, but in this case, about that fraction died from how the disease arose. These drugs are very cardiotoxic, poisoning the heart, and she died of a chemotherapy-induced heart attack. It's a side effect. The doctors did exactly the right thing. who have no other options, it is the model of a medicine that fits all, it is 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 have a greater impact on cancer?

Let me address those two things, so we need to do early detection first. That is something that stands out for its madness. Imagine if I could have sat down with all of your medical equipment and data. She 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. It was in a closet and it's low toxicity or you can go and we can try it for two weeks and see if it has any effect, if it doesn't, then there's chemotherapy, there's bone marrow transplant and there's no chemotherapy. problem I wonder what choice she would have made, well I know what choice she would have made.

The next thing is we need a 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 it much and it sounds crazy from an engineering perspective, but we just don't get chemotherapy and basically they just go home, do scans and you have a consultation, but we should be monitoring the disease to see if the therapy has worked, if the treatment has not changed, and if the cancers come back, get in early before it can do any further damage.

I mentioned this Anna and the monitor technology, so during the time I have left I will show you examples of the monitor technologies and for the monitor, as I mentioned earlier, we need nanotechnologies to make them if they are going to go into a detection or monitoring program to make them very cheap and very precise, but first let's see how it is done currently in the motorized system, this is how pathology is done today, it is very typical in the way it really seems to me to be a kind of chemical nanotechnologist. which is quite interesting that in our system, although cancer is a DNA disease, we commonly do not look at the DNA of those patients, we do it through histopathology, etc., but it is not exhaustive, that is something that must change, but if DNA is analyzed.

I just have to point out that this is pallava, what happens if someone takes a sample and removes larvae is an Australian Yudish word that means a lot of hassle, so there's a lot of hassle, we could take a sample, go to a lab and then maybe the information comes back. to the doctor and he does something, hopefully, but it's very expensive, a lot of technicians, a lot of dollars, this takes up about 20% of our current healthcare budget and it's increasing so, we need new technologies to greatly reduce the cost of this. So now for the DNA analysis, when it is finished, there are three key steps that I should point out: one is DNA extraction to extract the DNA from the blood or tissue or what follows is the amplification of the DNA and each of these take a bank. things a bench and a technician then the application with PCR something like that and then the third step is what is called detection and for that we need another bench and a person who will be the synthesis by sequencing or an rt-pcr fluorescence reading things like that It's how it's done, so what we've done in our lab is we've miniaturized the three steps.

We've used nanotechnology to miniaturize each of those three steps into a drop of fluid so you can do the testing yourself. We don't need a laboratory that we have technically or effectively miniaturized that entire laboratory in a drop of fluid, so everything is described in this document. This is the extraction step where you get a single strand of DNA, if you like, the megaphone is a schematic. which shows how that molecule was automatically amplified, so the droplet contains all the molecular machinery and that are particles to do this automatically, it is programmed and then the nanoparticles that are here are a program, so if that amplification reaction occurs , they become like velcro, it basically precipitates and you see it with the naked eye, the key features of the test are that what you have is a complete analysis of DNA and RNA in a single drop, as I have mentioned now, unlike in the laboratory, now no lab required, no training, no staff, not even me. you can run this and it takes 45 minutes to run.

You can do it yourself. It's similar to a group test for those of you who have a group. When I do this all the time, they take the sample, do a little bit of this, and then search. a color change, that's all, but now this test looks for pH or chlorine. It has sensitivity to a single DNA molecule. We think it's cool because it's a trail. I can look for those needles I mentioned. We have adapted this for all the pathogens we have shown. that 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 if they do get it, we can test. It's in this document and please keep reading about it, but also another interesting fact is that we can do multiple tests at once inside the drop, so it's like if it's a DNA scanner, you'll basically program it to search the At the moment up to 3 and in the future many more, so we believe it is ideal as a monitor and ideal for points of care. I'll simply contrast this with the $3 billion comment I made in the introduction.

You know, this is obviously of no use. genome sequencing, but it doesn't require the million-dollar equipment we used about a decade ago. That is something that must be preserved. Here is a video of how it works. I'll show you quickly. Do a little of this. Leave it alone. and then with 13 13 seconds, the nanoparticles give you the answer: yes, no, that's it and as I mentioned, they are individually programmable. We have now expanded this to any technician specializing in DNA, RNA and epigenetic signatures. So if you remember in 205 we looked at DNA, RNA, and epigenetics, we can do that here as well, and we think that's pretty powerful now, in whatever time is left.

I want to show you just one last monitor because this is not only applicable. This concept is applicable not only to leukemia, it is applicable to all cancers, so for all cancers, this is our picture of how cancers spread. We think what happens starts with a cell going a little crazy and then forming a primary tumor. Now this guy. It is threatening but it is safe if we can detect it earlier, for example in breast cancer, early detection results in it being almost as good as a cure, it results in almost 98% survival for patients with some surgery, a little therapy, the problem, the really big problem. in cancer it's this blue guy, what happens is they split up and then they travel in very small numbers like criminals in a city through the bloodstream and then they'll form, you know, little gangs.

I had to use this in this analogy that armineh static secondary metastatic sites and they are the really dangerous agents that kill now the problem is that in the hospital systems we do not have any eyes on this system the oncologist does not see it he does not know if it is happening he has to treat the patient as best they can, so one of the holy grails here is to take a look at it and again, it's a needle in the haystack game for a metastatic patient, normally one would have 50 cells in a blood mill that would have 10 million healthy cells, then it is the criminal in the city 50 cells 50 bad for 10 million good, how do you find them?

This is how we do it, we use nanotechnology, no, in the video you will see that this is blood in motion and the reason the blood moves is that we put a C, those are the ones we put little alligator clips that supply a voltage of AC, it's one point of one volt, 100 deaths of 1 kilohertz when you apply the voltage, the AC voltage you 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 is an electrohydrodynamic phenomenon. I don't have time to go into the details, but all you need is a relatively cheap chip and a 1 volt 1 point. kilohertz signal that can be supplied by an iPhone that allows you and that's the kind of thing that there are other technologies that are coming on the market now, but the feature of this one is its precision and its low cost now I don't have time to go through the physics, the physics, I'm biased, I think it's quite exquisite, it drives the flow of fluid inside nanometers of the solution and I'll skip it for the sake of time and just show you a movie, but we published all this if anyone.

You're interested if you take a look at the chip, what there are are thousands of these asymmetrical pixels, there's the AC voltage, the Red guys are the bad guys we're trying to catch and the way it works works like a microscopic airport security station where all the cells kick them, the good guys are lit and the bad guys are lit. 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 it's kind of cool and we published it in all these publications, like this That this begins to give you a vision of that process.

The other wonderful thing about this is that once you catch the thieves, you can interrogate them so we know. They're there, we can free them, open them up, and then we bring in our scanner and look at the epigenome transcriptome of your genome and ask them what's wrong with you and why don't you die when we give you a bunch of drugs. Again, this is just a second example of monitoring technology and how these things are becoming cheap and I think in the future they will be invisible. So what to end where I started? I want to finish with the patient for our five, what are the lessons from the patient? 2:05 and I hope this is one of his legacies.

One of his great legacies is that he teaches us what to do and I think the first is that we must change conventional cancer treatment. It stands out so clearly if you look at his case. We will not choose what is technically called an exceptional responder, but it is the exceptional responders who are the jewels of the clinic. They teach you everything we need to accept the fact that each cancer is different and we must analyze it at a molecular level. Read it at At the molecular level, we need to adopt new technologies for early detection, personalization and monitoring, it is very clear and, most importantly, we need to translate these new and powerful nanotechnologies from the laboratory to the clinic.

We need to change that old medical system a little bit to a new one. Paradigm I have one last slide and I'm going to end there, so in the work that we do it is very unusual that we ever know or even know who the patient is for a sample that we analyze and that's how it should be. is that it protects the privacy of those people, what we obtain are unidentified samples, so through a serendipitous process, not long ago, our laboratory and I had the opportunity to meet the family of patient 205, let me tell you, It was a very humiliating experience. experience and I had the honor of learning a little about her life and about her dreams and I want to finish by sharing with you a little about her and one of her dreams, so this is the patient 205 Alexandra Cox liro, she loved her very much. family and friends and known as Alex, she was, as you might imagine, someone of absolutely tenacious courage, that is what I heard, that tenacious courage was tinged with biting humor and, from what I heard, she had profound wisdom, she was very grateful for the radical approach that was tried. reverse her refractory cancer and reduce it to zero and she had a wish and I think we should remember her wish.

Her vision, if you will, was that the treatment she received would one day be an early line treatment, not a last resort treatment. That's a vision that really motivates me and me.laboratory, and I think it should be all of us who should make this happen and make a difference, thank you.