Mickey Kertesz - Kids & Art Fireside Chat
/At our 2019 Networking Fundraiser, Mickey Kertesz, Co-Founder & CEO of Karius shares how he was thrown into the world of infectious diseases and cancer. He describes how the Karius test generates genomic insights for infectious diseases in a non-invasive manner
We provided this lightly edited transcript to share his presentation to a wider audience.
Thank Purvi for what you and the team are doing for the kids and my personal connection to how I was thrown into this world of infections and cancer in a minute. But before I do that, I'd like to link the first couple of slides that I prepared here to that amazing moment where corporate pulls out that beads chain and thinking about each and every bead and and the pain and the confusion and anxiety that each and every one of those taps and biopsies and chemo sessions. I'll share one story and through that to learn a little bit about what Karius does with the company that we founded about five years ago to research here at Stanford.
But I'll share first this one case. So an ALL patient, that is admitted with with a fever. Initial cultures are positive for CL and pneuomonia. And so they put them on [pain medication] and [pain medication] seems to do the trick. She improves. I think she is discharged, actually goes back home, but comes back a few days later with, again fevers. They think us through the various standards work up that is done for fevers. Think of all those beads now, and those are non-invasive for the most part, but more cultures and more draws and PCR panels for some infections because they suspected infection, obviously, an additional PCRs and additional bio-markers for fungal infections and so on and so forth. And all of that comes back negative. Eventually, they they take her for some imaging, showing that indeed, something is horribly wrong, but they can't biopsy her she's too weak to survive a biopsy at this stage. This is the top center here in the US just a year and a half ago I think this case. Those cases don't end well especially the immunocompromised patients with with ALS. Lucky for her it was Rob that time that this institution started using the Karius best. And so they sent the test and a day later they receive the result. HHV 6 is not a big surprise, but [test result] that is somewhat common in the immunocompromised, very hard to diagnose otherwise, certainly not non invasively directly from blood. Based on that they can put her on the right therapy and continue with the treatment. So when I think of all those I see those beads and when I think of the mission that we have Karius have is to replace those beads with a single bead. If those patients could go home with a single bead, done, go on with their lives and we've accomplished our mission.
“Actually about 40% of leukemia patients are lost to an infection not to cancer”
Before I tell you a bit about what I think is on the edge of science fiction in terms of technology and the science that is underlying, I'll share my quick story of how I got into that. I moved here about 10 years ago from Israel for my postdoc at Stanford.
A couple of years into that postdoc in bioengineering started my first company, which was a long read DNA sequencing company. Eventually sold it to Illumina, which is a DNA sequencing company. But then after spending about a year in the big corporate decided to go back to Stanford, and that's where the story of Karius starts.
In the spring of 2014, so a bit more than five and a half years ago, I'm back happy at Stanford's biking to work, biking to to the lab doing some interesting research, specifically on bone marrow transplant patients and looking at DNA sequencing as a tool to predict or to identify early rejection of the transplants, of failed bone marrow transplant. The way we did that was by by using next generation sequencing, so generating tons of data. At that stage it was when others NIH identified that there is a weak signal coming from microbes. So one in a million of those sequences AG Cs & T's that the sequences spits out. Somebody is not a human it is of equal light. And then the million reads later, you get lactobacillus read another billion rates, you get the toxoplasma. So started looking at that and digging deeper and working with the team at Stanford's the bone marrow transplant center. We shared that observation and started devising some tools that will allow us to answer the question is this signal that we're seeing from microbes real? Is it really coming from the microbes that may be affecting those patients?
And it was, those things always happen on the weekend on the Saturday morning that one of those clinicians calls me and says Mickey, we need you to test patient zero on your system.
Then wait, what the patient we're talking about? This little system is just an initial observation that we think maybe this signal from DNA from microbes is linked to infections, but it's far from being ready for primetime.
Turns out, four year old child that is treated, post bone marrow transplant is not doing well and they can localize the infection to the lung, but they cannot get to it and imaging CT shows huge nodules, and they tried everything. And that patient again is too weak to survive the biopsy. And they want us to try to use what is then the research used only on that patient.
So quickly decided to do that, to put together the emergency IRB so that we can use this completely non validated test as a last resort for maybe helping the patient. Got that approval on Sunday, drew the blood to get through the chemistry. Put it on the DNA sequencer. Monday I believe. And all of that time few others in the lab and myself just working day and night because the system was not ready. The software was all in the patches and the databases were.not ready for prime time.
But we knew that a few days later the sequencing run will be done and will have access to the data. It's a battle against time. So on day four of that marathon, on Wednesday around noon, where we were sitting in the lab really expecting the sequences to be available any moment. One of those clinicians with whom we worked on came into the lab and broke the sad news that that child didn't make it.
I can still remember that it didn't register. We were so busy just fixing another bug in this algorithm, that it took another half hour before the news sank. I shut down my laptop, went for a walk on campus and realize the 3 days if we had that technology ready, we could have potentially helped this patient and others. So after recovering for a couple of days of sleep and reassembling the team in debriefing. We eventually diagnosed the patient, that diagnosis was confirmed by an autopsy, which gave us some confidence that what we see is real. Certainly not when you how you want to confirm in an autopsy, but at least give us some confidence.
That was basically the initiation of saying, Okay, this is great science. And I'll tell you two minutes about that in a second. But it needs to go to the clinic, it can help. And we ran a few more, I think, 4 patients to test on that, on that system. And I spent the next few months still at Stanford, talking to clinicians really understanding this link between infection in cancer, infection in general, and learning that actually about 40% of leukemia patients are lost to an infection not to cancer, and learning of the impact that diagnosing the infection quickly could have on those patients.
So towards the end of that year of 2014, I left Stanford, started the company, licensed the technology and spent the next two years basically redeveloping it. So we spent two years developing, a year running clinical studies and getting the regulatory approvals. And for the past couple of years, we've been providing the service nationwide, working with about 200 hospitals and healthcare systems now. We've helped thousands of patients and every morning when the results are out of the pipeline, and I scan those, and I know that this is very meaningful. Those things that we see the things that we can report back to patients within a day are life changing. So that's the high level story of the initiation that Purvi, asked that I share with you.
“Best of information you can think of the blood is that it’s the information highway of the body, everything is there. It’s encoded in DNA.”
Let me tell you a little bit just about the science because I think it's it's exciting and the impact that can make and then just end with maybe a link to how diagnostics can actually help. Also with the psychology and the anxiety that I've learned, this is part of, of the journey of a patient that goes through so many stages of treatment.
So that's a little bit of a science lecture here, but I'll try to keep it really short.
Think of, maybe I'll skip this one. And I'll just skip directly to this one, one slide that I want to share, because this is something that surprised me and others. The fact that even those microbes that grow deep in your lungs, and deeper in your brain, extremely deep in your spleen, and deep in your bones, we have now shown those microbes. There are zero live microbe in your blood, which means that all your blood cultures will be negative. Those microbes shed their DNA into the bloodstream. So a bacteria or virus, they have their own genome and as they replicate and die, they miss this genome, this DNA sequence, this DNA molecule is shed into the bloodstream. And that's where we pick it up from from the bloodstream. So think of it is those fingerprints that they leave, and those are unique and e-choli because they have a unique genome 5 megabases. Toxoplasma is different. That's where we pick it up, in the plasma, this huge amount of information, actually 30 billion molecules per mil of plasma.
So think of it as this best of information you can think of the blood is that information highway of the body, everything is there. It's encoded in DNA. A lot of that is human, but one in the million or one in 100,000 is actually microbiome. And if you're able to look at this microbial signal, you can turn that into a diagnosis. So what what we do with Karius we take that plasma, we remove actually the human signal, so that we do not spend money on sequencing boring human parts of our sample and only look at the non human. Within map those fingerprints, those short DNA sequences to a huge database of microbes, analyze that, and return the result. We're doing that as I mentioned all within one day. So time is of the essence from receiving the tubes of blood from across the country. FedEx does great job and bring it at 8am to our lab in Redwood City, running it through our sample processing, the chemistry on big liquid handlers, running it on those machines that turn DNA into bits into data sequencers, running the analysis and reporting back. Doing that currently 1400 microbes so when you think of the breath of test again, and why there are so many beads on many of those patients strings is because the clinician needs to guess or do an educated guesse. Is this infection?, sending one PCR Is it that infection okay once serology so and so forth. So one of the main advantages of using genomics is actually they could do all of that within one test.
“So if you can diagnose a child that is sick within the day, instead of a week, that’s great. If you could do it within half an hour, that’s even better. But I think we’re at the edge of going negative in time. And so basically being able to diagnose infections before you even have any symptoms.”
Share, just one other. Another think I have any slides on that tier No. One other exciting results just recently when when we think of where, where is all this going? It's certainly going to earlier and faster and better diagnosis. So if you can diagnose a child that is sick within the day, instead of a week, that's great. If you could do it within half an hour, that's even better. But I think we're at the edge of going negative in time. And so basically being able to diagnose infections before you even have any symptoms. And in the study that we are about to publish the next few weeks, hopefully to finally come out with St. Jude's Children's Hospital, in which we rolled,again leukemia patients infected by an unknown microbe. We have shown that using genomics with with Karius, you can actually diagnose the patient before the patient even knows, the clinician even notices any the problem. Those patients seem to be healthy, but the signal from the microbe is present in the blood, 3, 5, sometimes 7, 10 days before any symptoms arise. And this especially for this immunocompromised weak population can be life saving, because by the time you have symptoms, and by the time autopsy be there to diagnose that fungal infection, for example, can be already disseminated in ways that are really hard to treat.
But if you can tell that that patient is sick, except that they don't have symptoms yet, but they have the infection a day, 3 day,s a week before and start treating them. That's a game changer. And so I think this is where we're going into not only being able to quickly diagnose once it's apparent that something is wrong, but also to monitor especially in high risk populations. Obviously, I wouldn't monitor us now here, but especially in high risk population, monitor so that you can treat before there's any symptom. So I think this is a very exciting development that we see coming into infectious disease diagnostics in the next few years.
Just the quick links to the psychological aspects which honestly I never thought about until I heard Purvi's story and in the focus of using arts to remove the anxiety and the unknown. And when I think about it a diagnosis, or diagnostic test, it can detect over 1000 passages is useful not only to detect that one pathogen, but it's very useful to rule out the other 999 pathogens. So that's also a shift in the mindset, in the paradigm, from even when a clinician hits the right hypothesis and there's one microbe that shows as a an active microbe the PCR test or the serology comes back positive. You can never know that there's not something in addition to that. And by using something that covers so many microbes, you put the clinician and maybe by extension in some way, the patient, peace of mind to make sure that they do not worry about anything else. If there is a fever, it is because of a relapse now, and that can be treated differently.
And all because it could be a weird fungal infection that they just didn't test for. So this is just the first time I'm thinking about diagnostic and how that helps not only to diagnose and treat but also to put the patient information at ease and then there's nothing else on top of what they already know. All right. It's great.
Kids & Art Foundation is thankful to have a vast community of artists who create with us. Our artists share their passion for art and their commitment to make the world a better place. Without them we cannot heal pediatric cancer through art.
If you believe in the healing power of artists then please support our artist stipends with your donations and corporate matching. All donations are 100% tax deductible and our EIN is 27-1415727