9 Million Samples: A New Era of Medicine... Dr. Lincoln Nadauld, President & CEO, Culmination Bio
As excited as we are at being able to read our DNA and measure the status of all things biological, data is only valuable when we understand what it means. Today, we visit the frontier of figuring it all out. Doctor Lincoln Nadauld is the president and CEO of Culmination Bio in Salt Lake City. Doctor Nadauld, welcome to the program.
Dr. Lincoln Nadauld:Thank you for having me. It's my pleasure.
Dr. Moira Gunn:We're talking about Culmination Bio today, but I wanna start by talking about a different organization, Intermountain Health. And that's because Culmination Bio is an outgrowth of Intermountain Health, which itself is a big story to my mind. So tell us about the geographic extent, the services Intermountain Health provides, and how that is a basis for Culmination Bio to come about.
Dr. Lincoln Nadauld:Well, Intermountain Health is a large not for profit health delivery network headquartered in Salt Lake City, and it operates 33 hospitals and approximately 400 physician clinics. And is spread across seven primary states and cares for approximately 9,000,000 lives. Beginning in 1983, it implemented one of the very first electronic medical record systems in The United States and in the world. What that allowed then is the subsequent capturing of health outcomes, the the results and the journey of patients over the subsequent forty years. So that was the first unusual thing about Intermountain Health.
Dr. Lincoln Nadauld:And the second unusual thing regarding culmination is Intermountain has not discarded or thrown away any of the tissues or specimens collected from patients in its existence. And what that means is any tissue biopsy, any kind of surgical resection, anything collected from a patient, for the most part, has been saved, stored, and preserved, which represents a remarkable and unique data asset.
Dr. Moira Gunn:Now let me ask you this. How many biospecimens do you have?
Dr. Lincoln Nadauld:Well, you can probably appreciate that if you never threw anything away, you would collect quite a store. And now Intermountain has over 9,000,000 unique individual biospecimens and over 20,000,000 histopathology slide images. So it's a very extraordinary and deep dataset.
Dr. Moira Gunn:Listeners might say, well, so what? Well, the so what is now today with today's technology, we can take those specimens and we can convert that into data. We can analyze what's there and compare it to the treatment outcomes. Isn't that right?
Dr. Lincoln Nadauld:You've got it. And what's amazing is when the health system began storing and saving all of these samples and collecting this data, they did not know what their ultimate purpose was. They weren't collecting these saying, oh, we wanna do this big study in forty years. They just had an intuition that these would be valuable down the line. And now here we are forty plus years later and technologies are available that we can liberate DNA, RNA, and these other molecules from these stored samples and analyze them in very high throughput, very sophisticated ways.
Dr. Lincoln Nadauld:And when you combine that kind of biological data with health outcomes data, you can now make very powerful statistical conclusions and inferences. For example, you can say, here are the set of biological factors or, you know, biomarkers is one of the words we love to use that would have predicted or been prognostic for this patient's subsequent outcome. And that's exactly how we're using this dataset.
Dr. Moira Gunn:I just wanna get sort of a comparison for people to understand what's out there and just how big this is. I mean, if we consider twenty three and Me, to date, it has sold some 12,000,000 kits. Okay. That's more than your 9,000,000. And they've done partial DNA analysis, but they have very little treatment history or outcome data.
Dr. Moira Gunn:Now this breadth and depth of source data is on a much smaller scale than what's the potential here with the Intermountain Health biospecimens?
Dr. Lincoln Nadauld:Yeah. I think there are two different scales that are useful for comparing datasets. One is just the raw number of available biospecimens, blood or tissue that can yield, biological information. And so here we are with 9,000,000. There are others out there that have less.
Dr. Lincoln Nadauld:There aren't very many that have more, but the other spectrum that can be used for comparison is the depth of clinical data or outcomes data, and that's where this is really extraordinary. On average, across our 9,000,000 biospecimens, we have twenty two years of clinical history, and it's continuous, unfragmented, and comprehensive across laboratory, imaging, medications, other diagnoses. I mean, it's a little bit overwhelming, honestly.
Dr. Moira Gunn:When you go back in anyone's life and they've had some tissue removed for something, you know, whatever the problem may be, they also had other treatments with it. In the case of cancer, they might have had radiation, one chemotherapy or another. How did it work? Did it work well? Didn't it?
Dr. Moira Gunn:We know a lot more about that today. So we can analyze that to see what worked and didn't work in a way that we we couldn't predict whenever that happened years ago.
Dr. Lincoln Nadauld:That's exactly right. So we can do that in cancer, like the example you used, where we find patients with breast cancer, colon cancer, and lung cancer, and say, here are the therapies they received, and now let's analyze the biological data from their samples and say, could we pick out the one or two or three markers that would have successfully predicted their their outcome? Now that's just cancer. And this is what's so fascinating about this data is it spans the whole spectrum of human diseases. So there are entire companies that are very successfully built and have become very big just in the cancer space.
Dr. Lincoln Nadauld:Well, we have hundreds of thousands of cancer cases and cancer journeys, but we also have hundreds of thousands of cardiovascular disease cases and hundreds of thousands of neurosciences and hundreds of thousands of autoimmune disorder cases and on and on the list goes across the whole spectrum of human diseases with hundreds of thousands or more patients in each one of those. So you could envision conducting these analyses, performing these studies, doing these investigations with any disease that you can that that interests you.
Dr. Moira Gunn:In general, you probably have an example of that disease somewhere in these biospecimens. Whatever disease you're talking about, ninety nine percent chance you're gonna get there.
Dr. Lincoln Nadauld:Well, of everybody that I've talked to so far that has had an inquiry, I have not yet returned an answer of zero. We've always had some number of cases in their disease of interest.
Dr. Moira Gunn:Now I'm also reminded of the UK Biobank, a tremendous effort ongoing effort headed by sir Rory Collins who's been on the program. It has health records and outcomes because there is a national health service.
Dr. Lincoln Nadauld:I have a lot of respect for the UK Biobank and what they've accomplished. It's an extraordinary dataset. And, you know, I think they have acknowledged that they have about 500,000 participants. What they've done a very nice job of is analyzing the genomes of all of those. So they know the health histories and they also know the genomes, and that's very powerful.
Dr. Lincoln Nadauld:You know, in by way of comparison, at Culmination Bio, we have 9,000,000, you know, contributing disease journeys and biospecimens. We haven't analyzed all of those. In fact, we've only analyzed about the first two hundred and fifty thousand. So we have made progress, but, you know, 250,000 out of 9,000,000, and and by the way, there are more pouring in every year, you know, we we have plenty of runway ahead of us.
Dr. Moira Gunn:So now let's get to culmination bio, and you're relatively new. Where do you start? You didn't just say, well, we'll just take the first one in order. I mean, did you have a a plan here?
Dr. Lincoln Nadauld:Well, I I just have to acknowledge there are two individuals that are worth commenting on here. The first is a person named Homer Warner, and he had this, you know, crazy idea that computers should be used in health care. He was right, of course, as we all now know. But in 1983, he's the one who developed this first EMR, this electronic medical record, and that is what generated all of these electronic outcomes for us to now use. You know?
Dr. Lincoln Nadauld:And I'm glad he did it in 1983 because now forty years later, we get all of that data. The second person worth commenting on is doctor Elizabeth Hammond, a a very well respected and now retired pathologist. And she's the one who fought like crazy to not just, quote, unquote, throw away all of these biospecimens. She made sure that they were preserved and cataloged. And to answer your question, how do you approach this?
Dr. Lincoln Nadauld:Well, we have fought the temptation to just start at the beginning, so to speak, and and plow through it as a brute force effort. Instead, we've been thoughtful or we we're trying to be thoughtful in our own estimation and work in two ways. The first is we have curated all of this data according to human diseases. So we look, we we think about it and catalog it in terms of oncology and autoimmunity and so forth. And then the second thing we do is ask interesting clinical questions.
Dr. Lincoln Nadauld:Could we predict or diagnose disease earlier than it's currently being diagnosed by taking advantage of this data. And because we know we don't have a corner on all of the great questions in the world, we work very closely with partners and make this data available to them knowing that we may accelerate some of their discovery efforts, which we're fine with because there's so much data here. We need as many bright minds as possible to work with us on it.
Dr. Moira Gunn:Let's put a pin in the fact that Homer Werner wanted to have electronic medical records. And when he got everybody to say yes, I guess, he couldn't go down and say, well, let's let's put a a request for proposal out, and all of the people with electronic medical record system will give us their best. No. They didn't exist. Forty years later, you've got the same problem Homer did.
Dr. Lincoln Nadauld:You've got it. And our big challenge is how do we analyze all of it? Well, we have now also had to go and build some of our own technology to query this data. We, first of all, have pulled it off of, you know, hard drives and landed it in a cloud based data lake. And this data lake is exactly as it sounds.
Dr. Lincoln Nadauld:It is a vast pool, an enormous reservoir of data, but that's not enough just to have a big reservoir of data. You have to have a way to sift through it and survey and query it and interrogate it. It. So we've had to do this second thing, which is build technology capable of diving into that data lake, organizing the data, querying it in real time, and delivering information back that is usable to anybody that that needs access. So the technology that we have built that allows us to query the data lake is Apex.
Dr. Lincoln Nadauld:And Apex is the name of our data platform, and it's what we use, and it's what we allow our partners and customers to use to query this vast data lake.
Dr. Moira Gunn:So the hundred million dollar question, and I don't know why I said hundred million, I just picked a number out of the air, is how do you put all this data together to get some new answer? What can you do with this data that couldn't be done before?
Dr. Lincoln Nadauld:Well, the big trick is to take all of the data and and not just analyze it wholesale, but to analyze it with a rational question behind it. And so you, you know, there's so much data that if you just take millions of patient journeys and all of their biological data, you end up with trillions of data points. And the key we believe is to ask questions of the data. And so these can be clinical questions and these are questions that we haven't historically been able to ask. Things like patients with condition X, you know, use inflammatory bowel disease as an example.
Dr. Lincoln Nadauld:Patients with Crohn's or ulcerative colitis. What are the biological factors or markers that would predict for people who are going to respond to the first available treatment compared to patients who won't respond to anything and will end up having to have, you know, significant surgeries throughout their life. That would be helpful to know. So when we ask questions of the data that are informed by clinical scenarios, that's when this data becomes so powerful. And we know that we don't have all of the best questions in mind, and that's why we have worked on it with partners.
Dr. Lincoln Nadauld:We have other customers and partners who come with very specific questions of their own, and they're looking similarly as we are for markers or underlying data that would be associated with certain outcomes. We have other partners who wanna use it to validate new technologies and still others who wanna use this data to train some of their own models.
Dr. Moira Gunn:I know you've already gotten some results. I know there was at least one publication in Nature Genetics.
Dr. Lincoln Nadauld:Yeah. We have found working with one of our partners, Amgen. In fact, they were one of our very earliest partners. And together with Amgen, we launched a study where we were looking at hundreds of thousands of participants and analyzing their genomes and using that genome information combined with their health outcomes information to make discoveries, and we've published many of those together. And, really, it's through the, arm of Amgen called DecoGenetics in Reykjavik, Iceland who are so good at this.
Dr. Lincoln Nadauld:They're they're, I believe, one of the best in the world at taking large scale, population scale, genome, and clinical data information and making discoveries. And together with them, we've have found and published, for example, the 17 genetic variants that contribute to fatty liver disease. That's something that scientists have looked for for for decades. So to now understand the genetic underpinnings for a common and rapidly growing disease like fatty liver disease is very helpful. And and now now companies and and scientists can begin to look for medicines that will help those patients or develop new tests that can diagnose these patients earlier when their disease can be treated more easily.
Dr. Lincoln Nadauld:That's exactly what we hope to accomplish.
Dr. Moira Gunn:So I know you're working not just with Amgen, but with Merck and others. But what is Culmination Bio doing on its own?
Dr. Lincoln Nadauld:Well, we certainly work in those specific disease areas with our partners, but something that we're frankly getting quite good at is the ability to diagnose disease just off of digital information. Meaning, we can develop new diagnostics that don't require a new blood test. So wouldn't it be nice to know that your health care provider is using some of your previously captured information to look for diseases that historically we didn't have a diagnosis we didn't have diagnostic tests for. And that so that's what we're doing. We're enabling that, and it's very powerful.
Dr. Moira Gunn:And I'm assuming that you're open to working with others.
Dr. Lincoln Nadauld:We're very open to working with others. In fact, in developing some of these tests that work off of digital data, We've worked closely and are continuing to work closely with partners who have their own experience here. And by putting our minds together and even by testing our algorithms against each other's datasets, we can refine our approach, and and we can be faster.
Dr. Moira Gunn:Well, talking about faster, you started here with 9,000,000 biospecimens and their health records. How many of the 9,000,000 biospecimens have you analyzed, and how long will it take to analyze them all?
Dr. Lincoln Nadauld:I'm kind of chuckling because, you know, we have analyzed, as I referenced before, a a few hundred thousand, but we have 9,000,000. And what's kind of startling is we have 450,000 new, fresh, unique biospecimens that come into our repository each year, which means I am not utilizing or analyzing each year more than are coming I'm not exhausting faster than it's coming in. So, we're we're getting behind.
Dr. Moira Gunn:This reminds me when when, astrophysicist talk about the the the universe and how it's getting bigger and bigger. It's going further away all the time. It's like, to ask you when it's gonna be done is, like, never at the rate we're going now. So, we're gonna hope for more partners, better technology, and better ideas, you know, about how we how we're gonna ask these questions and get the answers. Well, doctor Nadauld, thank you so much for for seeing us, and, I hope you come and talk to us again.
Dr. Lincoln Nadauld:I would love to. It's been a thrill. I really, really appreciate the time.
Dr. Moira Gunn:Doctor Lincoln Nadauld is the president and CEO of Culmination Bio in Salt Lake City. More information is available on the web at culmination.com.
