In this episode, Aaron Carroll talks with Tatiana Foroud, PhD, and Brooke Patz about the Indiana Biobank. Foroud is the biobank director and Patz is the biobank’s program manager. They discuss what a biobank is and how they are using it to help researchers study different diseases, such as COVID-19.
This episode of the Healthcare Triage podcast is sponsored by Indiana University School of Medicine whose mission is to advance health in the state of Indiana and beyond by promoting innovation and excellence in education, research and patient care.
IU School of Medicine is leading Indiana University's first grand challenge, the Precision Health Initiative, with bold goals to cure multiple myeloma, triple negative breast cancer and childhood sarcoma and prevent type 2 diabetes and Alzheimer's disease.
Aaron Carroll: Welcome back to the Healthcare Triage Podcast. This Healthcare Triage Podcast is sponsored by Indiana University School of Medicine, whose mission is to advance health in the state of Indiana and beyond by promoting innovation and excellence in education, research and patient care. IU's School of Medicine is leading Indiana University's first grand challenge, the precision health initiative, with bold goals to cure multiple myeloma, triple negative breast cancer and childhood sarcoma, and prevent type two diabetes and Alzheimer's disease. This episode, we're going to be talking to Tatiana Foroud and Brooke Patz about the biobank. What is it? What does it do? How can we use it for research, including COVID research? Brooke, Tatiana. Welcome. Brooke, can you tell us a little bit about yourself and what do you do?
Brooke Patz: My name is Brooke Patz. I manage the operations of the Indiana biobank and have been doing that for about seven years now. So all of our intake of samples, our recruitment of subjects, that all falls under what I do.
Aaron Carroll: How did you get to this? What training do you have? What did you go to school for? What degree did you get? What do you do to get this job?
Brooke Patz: I have an undergraduate degree from Butler University in Biology, but always liked the ethical issues related to the technology of science. So that landed me in the Master's program at IU. I have a Master's in Bioethics. After I graduated, I took a position with a biobank that was a nonprofit startup biobank associated with IU. Then several years into that role, the company became more associated with IU and I began working for Tatiana.
Aaron Carroll: Tatiana, I know you've been on the program before, but for those who might've missed that episode, and they should definitely go back and hear it anyway. Can you tell us a little bit about yourself, your training and what you're doing?
Tatiana Foroud: Of course. So my name is Tatiana Foroud. I am the Chair of the Department of Medical and Molecular Genetics. I'm also now the Director of the Indiana Biobank. So I got here through, I have an undergraduate degree in Biology and Math. I did that in Connecticut at a small liberal arts college called Fairfield University. Then I got a Master's degree in something called Biomathematics, put those two things together. I did that at UCLA, and then I got my PhD here in Indiana University. Loved it, loved what I did, and just stayed and never left. So I've been on the faculty now for over 25 years.
Aaron Carroll: So let's start with just the basics. What is a biobank?
Tatiana Foroud: So I can start with that. If you take the word apart, bio meaning anything biological, and bank, we all think of a bank as a place you put your money. This is a case where this is a place where you put specimens or biological material. So if it was just a bank of biological material, I mean, it has some value, but it's really valuable when you link it to information about the individual from whom you got that biological sample.
Typically we do this for all kinds of diseases, but we're going to talk today about in particular people who were COVID positive. It lets us ask questions about, for example, why did some people die? Why did some people improve after being in the hospital? Why did some people never end up in the hospital? Why do some people have long-term complications and others not? This marrying of biological samples and clinical information lets you ask those questions. So it's a biobank.
Aaron Carroll: I have so many questions about the logistics about it. So what kind of samples, first of all, do you take in-house?
Tatiana Foroud: One of the things that's really easy to be able to obtain, relatively easy, is a blood sample. So if you think about it, people go to a doctor's office, you get blood drawn for lots of different reasons. So it's a relatively easy thing to be able to collect, but there's lots of different things you can obtain and study from a blood sample. So one of the things that you can obtain from a blood sample is DNA. That's our genetic material, allows us to ask all kinds of things about, people use the word genetic predisposition. Why do some people develop disease? You ask about changes in DNA that might contribute to that. If you take that blood sample now and also do some other things to it, so for example, if you're able to rapidly literally spin a sample, you just spin it in a machine that spins it really fast, you can actually get the blood to separate and it comes into these different parts of the blood. One of the things we study is something called plasma.
Plasma and kind of a partner to it, which is serum, are really valuable because you can measure things called proteins in them. Proteins are things that our body has. A lot of people have been talking about antibodies and things like that. You can measure antibodies, which lots of us have been hearing about, in plasma and serum. So we collect that from individuals that are in the biobank. Something else that we collect is something called RNA. Now RNA simply tells us how much of a protein we make. So we study a thing called expression, how much do we express it? So some of the things that can be important is if we make a lot of something or less of it, and could that be controlled by something, for example, in our DNA. Those are some of the things that we study in our blood.
The other thing that we've been studying particularly about COVID is we can take that blood sample and we can actually sort the different kinds of cells that we have in our blood. It's kind of amazing. We can collect one particular one called a monocyte, and lots of people want to study the different components of our blood, because we can also ask do we have more or less of them, is that affected for example by having certain diseases, what it is that those products are able to make. So we've been studying that. Then the other thing that we've been collecting is not anything related to blood. So we've also been trying to collect urine from individuals who have had COVID to try to understand what we can measure in the urine that might help us understand why some people are having kidney complications and some people are not.
Aaron Carroll: So do you also take samples of solid tissue or is it all liquid?
Tatiana Foroud: So we do all liquid. That's a great way to think about it. So we're not collecting things like skin, we're not collecting any tissues from organs. All of that would be what we call a lot more invasive. Invasive often associates with it might be painful and things like that. So there's not really any reason at this point for us to be collecting that in large numbers of individuals.
Aaron Carroll: How do you store all that? I mean, how many samples do you have?
Tatiana Foroud: Oh, that's a great question. So if you were to ask about the biobanks that we have in Indiana University, it's millions of samples. So let me explain why it would be millions. So the first thing you have is, imagine when you go to the bank and you get this really valuable blood sample that you get from somebody. So the first thing you want to do is you want to make sure, supposing we lose power in a building or supposing something happens, we right away want to split the sample and put it in two places. It's sort of like my main place and my backup place when something goes wrong. So we have lots of samples. We also want to store the sample in a way that we can easily make it available to researchers. So while we might collect something that we always measure in milliliters, so imagine a couple of tablespoons of blood. I don't really want to store it in that tube. I want to store it in a way that I can make it really easy for someone else to be able to request it.
So we typically try to put samples into, imagine in your freezer, a whole bunch of different leftovers all ready for five members of your family to get it. We right away set it up so that it's all set up for leftovers. So someone can just reach in and get that. I don't want to have my big pot of stew, and each time someone comes in I have to go serve it out for each person. So that's one of the things we do, is we right away when get a sample, try to get it ready so that it can go out to other people really quickly. Because when people have a question, they don't want to wait, they want to be able to right away study it.
Aaron Carroll: It seems like it would take up a fairly large amount of physical space. Am I missing something, or does it?
Tatiana Foroud: It totally does. So if you want to imagine, so not just for the Indiana Biobank, but for all the studies that we do, we have samples in about a hundred freezers. So if you imagine your refrigerator at home, we have about a hundred of those with samples. We're very efficient. So if you look in your refrigerator, it's not very organized, I'm guessing. You're not using your space very well. We are really good. We put in extra shelves in our freezer so that we can really jam that thing full with as many samples as we can. So those millions take up a lot of room.
Aaron Carroll: How do you keep all of these organized? How do you know where each thing is?
Brooke Patz: So a couple of things, Tatiana mentioned the numerous samples in a freezer, but we have a really sophisticated what we call racking system. So each sample is put into individual racks, and we have a database that tracks the sample from the point that we draw the sample from the patient, take it to our lab, separate the blood as Tatiana described and stick it in the freezer. We have a database that follows the location of that sample into the freezer. So I can sign onto my computer right now and identify where exactly a certain sample is in that individual freezer.
Aaron Carroll: You clearly must spend hours in the day panicked that a freezer could go down. I mean if my freezer goes down at home, I lose a couple hundred dollars of food maximum. If a freezer with 30,000 samples goes down, that's 30,000 irreplaceable... I mean, there must be backup systems on backup systems on backup systems.
Brooke Patz: Every freezer is on its own power grid. We have them alarmed. We even have a battery based alarm in case the power goes out. It's linked up to several lab folks to their phones. So they get alerts there. We can actually sign on to our phone and look at the temperatures of individual freezers. As Tatiana mentioned previously, we split samples. So even if something would happen, samples are in separate freezers. So we wouldn't lose the entire set of samples. It's a pretty robust system.
Tatiana Foroud: If you can imagine, and this happens pretty regularly, Aaron. If a freezer does go down, it always goes down in the middle of the night.
Aaron Carroll: Of course, on a holiday, I'm sure. Christmas Eve is guaranteed, right?
Tatiana Foroud: So what we have sitting there, and if you can imagine it, you can't do this at home, but we have empty freezers that are plugged in just waiting for this moment. So we will have people, we always have multiple people on that alarm. They get out of their bed, come to work, and we right away move those samples from the freezer that might be having an issue into that empty freezer that's just waiting.
Aaron Carroll: How does this work? Are you mostly collecting from people who have illness, or are you trying to get healthy people sample just for comparison, or both? How do you go out and get the things that you need? Or how do you even decide what you need?
Tatiana Foroud: It's sort of like you want to get ready for everything. We go to places, particularly in the hospital, where people are already going to get their blood drawn. So this is just sort of in general for the biobank. So we're pretty close to large numbers of people who, if you think about it, you go in and you have to get your blood drawn because you're taking some medication or because of just regular labs. We ask individuals who are sitting in those places if they would like to participate in the Indiana Biobank.
Brooke Patz: In addition to asking for an additional blood sample at a point that a patient would be having a clinical draw done, we are now able to ask for a remnant blend sample, which essentially means you're having your blood drawn for a clinical reason that your doctor has specified and there is leftover blood. So we are able to ask patients to allow us to take that leftover blood and put it in the biobank that would otherwise be discarded. So in addition to the face-to-face recruitment that Tatiana was mentioning, we're also doing telephone consenting and consenting using a video, which was largely in response to the COVID pandemic, but can certainly be used in other avenues of recruitment as well.
Tatiana Foroud: One piece I want to stress is one person's healthy person is another person's sick person. All of us have some underlying risks, we're all going to die of something, if I can say that. So the person who's studying, for example, heart disease, they consider the person who has Parkinson's disease to be healthy maybe as far as heart disease. So that's why for us, it's really all comers. Because sometimes we are looking to study things in younger individuals, sometimes older individuals. So it's really important for us to have a really broad swatch of individuals. So we currently have in the Indiana Biobank samples from about 40,000 individuals.
Aaron Carroll: I have my blood drawn every three months at IU, and I don't think anybody's ever asked me if I give blood. If somebody was local and they wanted to, I'm just actually now even just thinking about this, do they have to go and ask for it? Or is it something that automatically happens every time that they give blood? It's not automated?
Brooke Patz: It does not automatically happen. So if you are really feeling altruistic, you can contact the biobank and we will make arrangements to coordinate that. Up to this point it's largely been face-to-face, we'll have a research assistant sit in phlebotomy clinics and approach patients who are waiting to have their blood drawn, consent them at that point, and then we would draw our extra tube with the clinical draw. Like I said, in response to COVID, we're going to be doing a lot more telephone consenting, and then the remnant samples as well.
Aaron Carroll: What kind of research does this get used for?
Tatiana Foroud: A huge variety. So there's a lot of interest in liver disease, for example, and we actually have a very strong liver program here at Indiana University. So we've had one investigator who's done quite a bit of work with the Indiana Biobank, trying to look at individuals who've developed liver disease. Then what they needed were individuals who might've had regular blood tests done, and their what they call liver enzymes were always normal. Not only are they not complaining about any symptoms of liver disease, we actually know from blood tests that they don't have any problems with their liver. So those become kind of the comparison. If you think about liver disease, there's kind of a variety of ways that individuals might develop liver disease. So individuals who consume, for example, a lot of alcohol can sometimes develop alcoholic liver disease. There can also be liver problems that occur from something like fatty liver disease. Then there's also not associated with, for example, obesity. So there's kind of a variety of mechanisms, and each of them potentially could have very different causes.
So some researchers are trying to figure out what things do they have in common, or what things make them different. So that group of comparison people, the ones who had normal liver, well, they're kind of good comparisons in some cases. Sometimes you'd like to have people who maybe consumed a lot of alcohol and didn't have any abnormalities in their liver, or people who were obese and didn't have any problems. So sometimes that's why the Indiana Biobank can be so valuable. Because then a researcher can, and it's all de-identified, and we can talk a little bit about that. They never know who the person is, but they can look for some clinical features that a person might have that lets them find just the right samples from individuals that meet certain criteria.
So that's kind of a great example. We've also had people look at pediatric cancers. We've had people look at certain kinds of heart disease. We've had people look at some neurological disorders. I mean, sort of the sky's the limit. Right now there's a real push in terms of, as we've talked, a little bit about COVID. So that's why the Indiana Biobank jumped in, because we had so many things in place that we could just jump in and start to help with that.
Aaron Carroll: Can you talk a little bit more about other research projects that have been using this, or even to think about the different types I think in general, are they trying to look at risk or how diseases progress, or things like that?
Tatiana Foroud: So the studies related to... Let me start with the liver one, because that has probably the most mature data. So they're looking at genetic risk. So they're looking at your genetic material and asking if there is not a single change, but if there are changes in DNA that makes some individuals, for example, more likely to develop liver disease. So they would look and ask, are those changes more common in those that have liver disease, versus those, remember those controls that we talked about? Those individuals who have normal liver enzymes. Now of course, one of the things that's really important when you're designing a study like this is you can't have all your individuals with liver disease be 80 year olds and all your individuals who are healthy be 20 year olds. So it's really important that you have a well-designed study where you can have individuals who are matched for example on age, it might be important to have similar numbers of men and women. There are certainly racial differences that can occur in some diseases. So it's important to have appropriate balance for that.
So people can use, for example, DNA in lots of different ways to ask different questions, and the breadth of the answer you can ask. But why would it matter that I know what changes might occur in DNA for those individuals who develop liver disease? Well, what you'd like to do, our ultimate goal as geneticists is often to figure out who's at increased risk. I don't want to wait until you have the disease. I would love to intervene much earlier. Intervening might mean I don't put you on certain medications. Intervening might mean I check your liver more frequently. I check your enzymes more frequently. It could be a variety of measures that someone could be suggested to do.
Now you might say you should always have those concerns, but in our health care system often we're trying to prioritize. It's hard to do some things in everybody, so sometimes it's important if I know there's certain people where if I intervene with them, it could have the greatest benefit, then if I could identify those that are at greatest risk for a certain disease, then I could intervene there and really perhaps have a more concerted effort for those individuals.
Aaron Carroll: When you take these samples clearly it's linked to a fairly large amount of health data as well. Where does that come from?
Tatiana Foroud: Some of the health data can come from what we call Indiana University Health. So we're obviously located at IU health, but there's also something called the Indiana Network for Patient Care. Of course, like everything it has an acronym. It's called INPC. That's actually something that involves many more hospital and healthcare systems in the state. Those other healthcare systems agree that it'd be important to have in a common place certain information from patients that they see. You might say, "Well, why would healthcare systems want to do that?" Well, one of the reasons that's important is people get their healthcare in different places within the state and within different healthcare systems. So if we're able to have some information across healthcare systems, it actually helps when that person comes into one hospital that we actually can know, oh gosh, they've been seen previously, maybe not at IU health. Maybe it was somewhere else. They ran certain blood work, or they did a certain scan and identified something wrong in another organ.
That doctor doesn't have to go rediscover that, which could take time, could take money, and could affect the decisions they want to make in terms of the care of this patient. Some of that information then is then available regardless of where that individual is seen, and that can have real benefit.
Aaron Carroll: Do those health data get continually updated, or are they static at the time of putting the sample in the bank?
Tatiana Foroud: One of the great things about certainly the way we consent individuals for the Indiana Biobank is to connect to the healthcare information in the past, current and future. Because what you've said is exactly right. I might've collected this person's sample, for example, in 2015 They decided to participate in the Indiana Biobank, but they develop cancer in 2020. Well, that sample is even more valuable with that added information. So we are able to link that sample to future outcomes that that person's had. And that's what makes those samples so incredibly valuable.
Aaron Carroll: So what are we doing with respect to COVID? I mean, what are some of the ways that people are using the biobank to try to do work using samples involving COVID?
Brooke Patz: The central mission of the biobank has always been to provide researchers with the tools they need to carry on the research. For us tools really mean samples and linked data. With the COVID pandemic we really felt this call to action, and had the pieces in place as Tatiana described to really be able to organize ourselves quickly to bank samples from patients who were diagnosed with COVID, because we knew these samples would be really valuable and needed by researchers who were going to do research to try to find treatments.
Aaron Carroll: How many samples do you have with respect to COVID particularly?
Brooke Patz: Sure. So we began our collection effort in mid April, and we are up to samples from about 150 subjects to date. As we're seeing the rates within our hospitals stay steady or even decline recently, we've seen an uptake in that recovered program. So people that did have active infection are now returning to us to donate a sample as they're considered recovered from COVID-19.
Aaron Carroll: Can we talk a little bit, are there any specific projects going on that we could talk about?
Tatiana Foroud: So I'd say that there's been a variety. So some of the initial requests were about individuals who wanted to set up testing. So if you think about it, if an investigator here at Indiana University who wants to be able to set up tests just literally, because remember, all we have initially is a [inaudible 00:20:47] a long swab in order to do testing. So there was a lot of interest, could some other kinds of testing be developed? Also testing related to antibodies. So a lot of people, if you want to set up a test, need to have what we call a positive sample. How do you know if your test works unless you have some samples from individuals who have COVID?
So we actually got requests for those samples, and we actually also got requests for samples that had been collected pre-COVID, so that those would be for sure negative. So we actually got a rush on some quite old samples that we had, because people wanted to go really far back to make sure that there was no way that individual could have been exposed. We also have individuals who are really interested in understanding this question about complications and outcomes. So we have some researchers who are actually very interested in collecting samples from individuals who recovered from COVID, and unfortunately individuals who passed away from COVID. So they needed to have comparison samples, and they wanted to look at DNA. They wanted to look at plasma, which we talked about earlier, and they also wanted to look in some cases at those different kinds of cell types and ask what was different. In particular, while the person was sick, what was different, what was going on in blood that they could measure, that would help them identify, if you could again identify individuals, for example when they came in the hospital, who's most likely to have a poor outcome?
If you could identify those individuals, you could potentially intervene in different ways. So we now have a lot of interest in looking at people who've recovered. People want to have samples from those individuals because they want to look at what's changed in blood after the person recovered. There's a lot of interest right now about the length of time that you might have immunity, and about antibodies and how long antibodies remain. In terms of the whole question about how long will you remain immune, and people are thinking about how do we come back into society? How do we identify individuals who are unlikely to become reinfected? So we have researchers who want to be able to collect samples from people who recover at regular intervals after they've recovered so that they can look at antibodies and other measures in the blood sequentially over time.
Your ability to participate in research doesn't end just because you've recovered from COVID. There's actually a really important place for research for people who've recovered and to continue to ask what's changing in blood. Then the last thing, and then I'll end, is just linking complications. Some of these people who have longer-term kidney complications, longer-term heart abnormalities that have now developed, being able to identify what are markers that we can measure that might tell us which individuals are more susceptible. Of course, if you think about it, the one group that we have a really hard time collecting are all these people who remain asymptomatic. We're starting to find growing numbers of people who never have any symptoms of COVID, but we know from antibody testing actually must have been exposed. It would be really important to be able to collect those individuals and understand why didn't they develop symptoms? Because that could also give us insights.
Aaron Carroll: That was actually my question, can you? I mean, for instance, I know the state's been doing statewide random surveys, and they find I think 45% of people that they have surveyed have antibodies and were sick, or even are sick and had no symptoms. I think that's anonymized, so I imagine you can't, but how will you go about trying to go get asymptomatic people?
Tatiana Foroud: One of the things is now that testing is becoming so widely available, so as you know in the state now you don't have to be symptomatic in order to get testing. We are going to start to have an increasing number of individuals who were tested and not necessarily as part of anonymized studies, but have been tested and are found to be antibody positive. So there's now a registry being built for these individuals to be invited into a registry so that they can actually be considered and approached and consider participating in additional projects. They are incredibly important to our understanding of COVID. Until testing was widely available, we didn't have a very good way to identify. Most of them might've been found through healthcare workers that were getting some screening just without symptoms. So historically that's where most of these asymptomatic antibody positive people were found.
Aaron Carroll: So everything that you've described is infrastructure. It's the stuff that we set up so that research can occur. But that's hard to fund. So who funds this?
Tatiana Foroud: So we have the Indiana CTSI, that is an NIH funded grant that allows a collaboration between IU, Purdue, Notre Dame, and is sort of a statewide collaboration. It funds a number of research, clinical, translational activities around the state. They identified that having a specific focus on COVID was not only timely but needed. So we have two new directors of our Indiana CTSI. It's doctors Sharon Moe and Sarah Wiehe, and they quickly identified this as a priority. They actually directed specifically funding from the CTSI toward this particular effort so that we could build the infrastructure.
Aaron Carroll: But who funds the biobank, even in general? I imagine keeping the freezers going, the lights on, I imagine it's a significant amount of money. Is that also federally funded?
Tatiana Foroud: A portion of it is. So the Indiana University School of Medicine, the CTSI, and now there's a new collaboration called the Precision Health Consent that has also engaged IU Health. So we're all partnering together, broadly thinking about the Indiana Biobank, and its particular value to how it can help with patient care and developing new approaches to that. So it's getting a broader base of support now, as we expand our initiatives, thinking about translation.
Aaron Carroll: I'm a huge fan of research infrastructure. I've been complaining for decades that it's so hard to fund, because everything usually is an investor initiated project where you're maybe even funded for the couple of years that the project goes, but then it is gone. It's so important to create these longstanding resources that can be used for so much, but they're tricky. They're harder to fund. So it's great to see when it succeeds.
This Healthcare Triage Podcast is sponsored by Indiana University School of Medicine, whose mission is to advance health in the state of Indiana and beyond by promoting innovation and excellence in education, research and patient care. IU's School of Medicine is leading Indiana University's first grand challenge, the Precision Health Initiative, with bold goals to cure multiple myeloma, triple negative breast cancer and childhood sarcoma, and prevent type two diabetes and Alzheimer's disease.