Podcast Episode Transcript

Elaine Quinn

In celebration of science week Ireland, we are delighted to welcome a very distinguished guest today. Dr. Howard Jacob is VP and head of genomic research and data convergence at AbbVie. AbbVie is a global research-driven bio-pharmaceutical company that is using 1 million human genomes to build precision medicine.

Howard spent many years in academia before turning to rare diseases. And then, a few years ago moved into the pharmaceutical industry to focus on genomic research for drug development and the opportunity to make an impact on even more patients. Perhaps, most notably Howard led the team that sequenced the genome of four-year-old, Nicholas Volker, who had an undiagnosed disease. This resulted in a diagnosis for Nic and was the first use of genomic sequencing in the clinical setting for an individual patient.

Howard, you’re very welcome to In Sequence.

Howard Jacob

Thank you very much, Elaine. It’s a pleasure to be here.

Elaine Quinn

Well, before we hear the inspiring story about Nic Volker, perhaps he can put into context for us, the significance of our DNA and the information we hold about ourselves.

Howard Jacob

Thank you for that question around what’s DNA and give you a little bit of background around that. Every cell in your body has the exact same DNA but clearly, the cells that make up your eye, the cells that make up your heart, the cells that make up your big toe are completely different from each other in terms of their function and how they work and how all that happens – but it’s still the same DNA. So, your DNA is the instruction book that tells the cell what it is and how it works, and I like to think of that altogether as being the blueprint.

And when we think about that, you know, the scale of that information, that knowledge is extraordinary – at least I think is extraordinary. I mean, it’s, it’s really big data. And, and what do I mean by that? So if you were to take all the DNA in your cell and glue it together, so you unwind it, it’s inside the DNA and the chromosomes and you unwind it and you glue it together, your DNA in every single cell is two meters long which is pretty amazing to think that that much information is packed into a little tiny cell that you can’t even see. And then if you were to take your trillions of cells and glue all of that DNA together, it would be 666 times, actually 666.5 times, to be accurate, roundtrips to the sun. I mean, that is an amazing scale and that size of data or that volume of big data is what makes us, unique.

Elaine Quinn

That certainly does put it into context for us – now we hear the term precision medicine a lot these days which is the idea of us using a more targeted approach to our healthcare than is traditionally used. How can we take this huge amount of information we hold in our DNA and use it in a meaningful way to drive precision medicine?

Howard Jacob

So, even with that much information, we’re all 99.9% identical to each other. So, it doesn’t take a lot of variation to make a big difference in us, right? Whether we look at, you know, our genders, or we look at our skin colour, we look at the things that we always look at, but it’s also true for medicine. Yet, having said that, we all have different healthcare trajectories that we’re on. We’re all going to have different diseases. Now our family history gives us some insight into that, but it’s really much more complicated than that. And so, the goal, at least one of my major drivers is how do we use that information? How do we take that information and understand what makes each patient individual so that we can make sure they get the right drug at the right dose at the right time?

And even more importantly than it is for you, what about your physician? I mean, you may have never stopped to think about this, but your physician has a person that comes in – they know who you are assuming this isn’t your first time that you’ve seen them. They know something about your family history because you’ve told them that. But we’re not very good at, we’re not very accurate at knowing what we have or what we didn’t have in our family. And then they measure you and they do stuff. But wouldn’t it be cool, wouldn’t it be amazing in fact, if they were able then to pull up and say, ‘Oh, this is Howard’s blueprint’, ‘Oh, I see that Howard is at risk for type two diabetes’, ‘and let’s now focus on what do we need to do for Howard’, instead of coming in like we do now with our physical and have me get the same test as everybody else.

So, that’s that whole idea of individualized or precision medicine and being able to move in that directionality, and that’s something that I’m really excited about. And so that’s a place where I think we can look at it and then you start saying, okay, if you can get to the individual level, can you treat people at the individual level? Can you now really, really know what that person has and I think we can, and there’s some evidence around that in rare disease. So, I think we’re in incredibly exciting times.

Elaine Quinn

Absolutely, it really is amazing to think that our health management can be customized to suit our individual needs and what that might mean for people who maybe do not respond to what is considered to be a standard treatment for a particular condition

Howard Jacob

So, the other part that I think is worth mentioning here is that although, as we look at each other or people around you, you know, there’s a lot of differences between us – but we’re 99.9% identical at the level of the DNA and that’s independent of which part of the world you’re from, what your ethnic background is, where your heritage is. None of that matters. I mean, to your DNA, your 99.9% of the time. And so really medicine, if you will, and drug companies in particular have leveraged our sameness to create all these medications, to try to give medications to millions and millions of people. But rare disease shows us, that a few small changes in your genome makes big differences. For some people, they’re catastrophic differences. But it also means that the medicine may not work as well for you. So, we’re in this interesting time, I think, where we’re at the point where we can start reading people’s DNA, take out their blood, a small amount of blood, about a tablespoon of blood, a few millilitres, extract the DNA from that and then read it. So, how do we leverage how we’re practicing medicine now with this massive amount of information, and I think we’re at the Dawn of a new era.

Elaine Quinn

And as we begin to see how genomics can potentially revolutionise how we practice medicine, what do you think are the challenges with traditional approaches to medicine that we can potentially resolve for both clinicians and for patients?

Howard Jacob

You know, I think our challenges are a couple of things. So, from the patient’s side, right? One of the things that we know to be true, and in fact, we are all doing genetics all the time. Every time you go in and see your physician and you fill out a family history form, that is really, how we’re trying to do genetics right now, right? We’re using that information to help your physician know what’s the family history that you have, and while we all do this, we also largely don’t know anything about our family history. People don’t talk about this. We don’t share our medical information. We don’t share what we’re going through with our family members. We don’t talk about the medications that we’re using.

And so, I would encourage families to have these conversations. Make sure, you know, the family members know what are the diseases that are in your family? What are the medications that they’re taking? If a medication hasn’t worked, I mean, this is all really, really important information that we can start right now. It’s simply having conversations when you’re together with your family and sharing this information. So, that’s something we can all do.

You know, on the physician side, you know, they’re under a tremendous amount of pressure to see more and more patients and make it more and more efficient and make the right decision every time. I mean, it’s a pretty darn hard business if you think about it. I mean, you know, you walk in the door with, with symptoms that could be, you know, hundreds of different diseases and they have to narrow it down to the right disease. So, our physicians are really trying to, to navigate this, right! They don’t have the tools and we haven’t been able to give them the tools yet that allows them to create that blueprint for you.

So, your physician is using different types of measurements for you. You know, they may measure your blood pressure, or they may measure your reflexes, or you take lab tests. But really, to me, the fascinating part is what this big data is, can you turn this into something that is even more meaningful that we can give the physicians much more information to be able to go forward to and, and layer all that information in place.

So, you know, I think we have to continue to get better tools to the physician so they can practice medicine. And the reality that we all face, which is we don’t have enough doctors, we don’t have enough money to pay for everything. So, how do we do this better? And so, again, I think it’s in partnership with the, with the physicians that, that we need to change this. I mean, we’re all part of the same team; the pharma companies, the patient, the healthcare providers, the healthcare systems. I mean, I think we need to continue to drive and have more dialogue about how do we help people live and do a better job.

And we really need to start moving towards, you know, a health care system. And, and I think if we really back up and take a look at it, we don’t actually have a healthcare system. We have a disease care system. How do we move it to a healthcare system? How do we change the disease? And I will tell you that, at AbbVie, I mean, we are now approaching, how do we cure? And so, you know, we’re starting to ask those questions. How do you create a cure? And so again, I think these are all places, we couldn’t possibly have imagined asking some of those questions 10 years ago. And so I’m just excited about the fact that, you know, by talking with our family members, by engaging more with the physicians, by working together across this continuum of health care or disease care, as I just said, we can really change how we, what the future looks like. I mean, we should be able to leave a medical system in much better places for, for our kids and for our grandkids, if we continue to work together.

Elaine Quinn

Well you have already led some truly ground-breaking work when you led the team that carried out the first genome sequencing for use in the clinical setting. And that was of Nic Volker who was only four years old at the time. And he had really been in and out of hospital multiple times at that stage, but no diagnosis or treatment could be found. Maybe you can tell us about Nic and why his story had such an impact.

Howard Jacob: Yeah, it was, this was 10 years ago. I’m happy to say Nic is 14 now and his gut disease for which he had, has been cured to the extent that I know. And he had basically a hole, or a couple of holes that went from the outside of his, of his stomach all the way down into his intestines. And there was some kind of, you know, really aggressive form of inflammatory bowel disease and no one knew what was causing it. So, they tried all different kinds of medications and what was wrong and so, his physician at Children’s Hospital, Wisconsin, Alan Mayer approached me and said, ‘Hey, Howard, could you read his genome and see if we can figure out what it was’. And so, a team, Liz Worthey, Mike Tschannen, and Joe Lazar and a host of other people, David Dimmock, all worked on this to figure out that Nic actually had one single change in his DNA. And so, if we go back to, you know, what we were just talking about, how big of the DNA is, is that, so you have 6 billion data points; 3 billion from mom and 3 billion from dad and Nic had one single change in one gene called XIAP that he got from his mom, that gave him this disease. And so, with that information, we were then able to say, okay, how can we potentially cure Nic? And the answer was to do what’s called a cord, like as a placental cord blood transplant, which is like a bone marrow transplant.

So, we would basically irradiate his body and give him core blood from a matching donor and then reconstitute his immune system. And so that was done by Dave Margolis for a transplant. The part of the story that is, well there’s several amazing parts. So first of all, his mom, Amylynne, you know, was really a huge advocate that we’re going to find a solution for this. There’s gotta’ be something here. The medical team that went after this and to figure it out and the DNA hunters, if you will, who tried to figure out what, what the point was. And the challenge with this whole story was, Nic is the only person that is carrying this mutation. And why does Nic have this and not as mom? Well, it’s because it’s on his X chromosome and boys only have one X chromosome and girls have two X chromosomes. So, he had one bad gene. One bad change that ended up causing this disease. And so, here’s one person that’s got this and so there’s no ability to do clinical trials. So, there was no evidence in the literature that this was actually going to work. And so, so the team had to make some hard decisions and the family had to make some hard decisions about, are we going to try this core blood transplant, which could potentially have killed Nic, to see if we can cure him from the gut disease.

So, the whole story was this series of activities around, you know, a really, really sick little boy and trying to figure out what was wrong with him. And then what do you do after, after you figure it out? And then we were very fortunate that this, we could find a cure and, and help Nic and his family.

Elaine Quinn: Well, it must have been a pivotal point for you in your career and it certainly was for genomic research. So Nic’s condition was obviously very rare. How can genomic research help other people affected by rare diseases?

Howard Jacob: Yeah. You know, what most people don’t appreciate is that rare disease means there’s less than 200,000 people in the United States. So, there’ll be a little bit of a different number in Ireland, but basically, if you do the math, the difference is in our population. So less than 200,000 people have that disease. That’s what rare means. But because there are so many genes, and a change in a gene can cause a rare disease, about 10% of the human population has a rare disease.

So, each gene disease is rare but collectively, it’s common. And I use the analogy of cancer. Most of cancers are rare also, but because we call them the same thing, it looks like, you know, there’s a lot of cancer. And so, what this opened the door to was ending what are called diagnostic odysseys. And this is where the physician doesn’t know what’s wrong with the patient. Not that the physician is doing anything wrong, but they’ve never seen it before. If you’ve never seen it before, how do you know what it is? So, these poor people and their families go from doctor to doctor, to doctor and the doctors then, of course try to bring in their colleagues and say, ‘Hey, do you know what this is?’, and since they haven’t seen it before either it turns into this, you know, this, this diagnostic odyssey that’s, that’s expensive, it’s hard on the patients, people die. It’s one of the major killers of children under the age of five.

And so now what you have is a new tool where you can actually go in and read the DNA and start to assemble this blueprint, and align it against what’s a normal genome or what we call a reference genome and then look to see where there are differences. And that’s completely changed. The last I, the last I checked, there’s been over 500,000 people that have had this test now, done, and which is great, and we have a lot more people that need to do it, but yeah, that’s really changed the landscape. And there’s groups of people out there that are still pushing to make this happen in rare diseases, which is fantastic.

Elaine Quinn

And incredible for families, too. Now I know you spent much of your career focusing on rare diseases but then you changed direction and decided to move into the pharmaceutical industry. What was it that made you want to work for AbbVie?

Howard Jacob

That’s a great question. I have to back up a couple of steps, before I answer that. So, so my passion since Nic Volker has been, how do we get genomic sequencing into healthcare and not just for rare diseases, but, but I truly believe everybody should have their DNA read on the day they’re born. so all the physicians and all the care teams that are going to manage your life have this information. I just think it’s that vital.

And so, I’d hoped that we could take the rare disease platform and drive this into medicine and to get this to become more and more accepted. The challenge is, at least in the United States’ healthcare system and true around the world even though we have very different healthcare systems, is healthcare is expensive. And so, adding a really expensive test, into the, into the toolbox sounds great, but it makes everybody nervous, right? Are we just wasting money? And so, inside the United States, we have some very unique characteristics of – basically all 50 States have different rules about insurance. And so, it became for me a very difficult activity to try to drive the adoption of reading people’s DNA and building blueprints for them, into care just didn’t seem like it was going to be possible, in the short term. I mean, in the long-term it’s going to happen. I just don’t know how long it’s going to be.

So, AbbVie approached me with a position and said ‘we’re going to have a million genomes. Would you like to come in and work with a million genomes?’ and I thought, geez, maybe that’s another way that I could help is that if we can use a million genomes and demonstrate its value, maybe that’s another way to help get this information into clinical care. So, we’ve got people out there already doing rare diseases. It’s happening little by little. So, what if I came from the other side? What if I came from common diseases and from a bio-pharmaceutical perspective, you know, could we make better drugs? Could we make the medications faster? You know, it’s a long road – it’s up to 10 years and you know, a couple of billion dollars to make a drug and those, those are huge costs, right? And it’s not just cost in terms of dollars, although that’s meaningful, but 10 years, you know, people die in that 10 years. So, so this is a meaningful time window.

So, coming to AbbVie just seemed like a great opportunity. I’ve been here almost three years and it’s been wonderful to, to really have resources in place and to work with companies like, you know, Genuity that are out there working with, with the, with the local people and with the local physicians and the patients and, and working together to now try to figure out how do we get this information and make better drugs and change healthcare? So, so it’s, again, like something I wasn’t planning on doing, but it just seemed like a logical other way that I could help drive towards a solution that I really believe in, which is getting genomes for everybody.

Elaine Quinn:

You mentioned the huge cost and lengthy time associated with developing a drug today but there is also the rate of success of these drugs. Will the integration of genomic research into drug discovery and development improve the success rate of drugs developed by companies like AbbVie?

Howard Jacob

We’re still early, in the game because it’s such a long game, right, you know. But we are, at AbbVie, looking to double our productivity using genomics and in our early target development, we are seeing that we basically are bringing about double the number of targets into the next round of research. Remember, there’s multiple steps that go through, you know, making of a drug and finding the target is just the very beginning.

But, we basically are using genomics to help double that number right now and we’re trying to take this information from these different populations and work with that information then to try to enrich the probability. It’s something that we call on the pharmaceutical industry ‘de-risking’ right.  What we want to do is be investing our research dollars into targets that are going to work. Then we can get the chemistry on board and then we can get, you know, the clinical trials on board and we can, we can get that drug to a point where it has a higher probability of success. And so, so the jury is still out on you know, how fast are we going to be able to change that. So, it’s going to take us, you know, probably five years before we’re going to know for sure, how fast is all this moving?

I think the good news is that there’s a lot of other companies that are doing this. So, it might surprise your audience to know that the pharmaceutical companies – we’re involved with several different pharmaceutical companies together that are working together to help identify what the genes are that cause the disease. And so, this is something that’s called ‘pre compete’, so, we’re not competing with each other. I mean, the companies are obviously competing with each other commercially, but we’re basically getting together and saying, hey, let’s try to work together and figure out what’s causing the diseases. And then the chemists and the commercial organizations and the clinical trials organizations, you know, then they can all compete. But this is a place where we can all work together to, to, to help improve the research knowledge, which is fantastic. I wasn’t expecting that coming into pharma. But I think that’s another illustration of, of the companies being realistic and saying, you know, if we’re going to get drugs to people faster and better, we got to work together.

Elaine Quinn

Now in thinking about how the genome can help with drug discovery and development at AbbVie, you’re not just looking at the genome alone are you, there are also a lot of other factors you’re considering.

Howard Jacob: Yeah. So, so we do a whole bunch of things, so we can read your DNA. We can also read what comes out of your DNA, which was called RNA. And then RNA is used to make protein. So, you can read your RNA, not from all cell types, obviously for cells inside your brain, that’s impossible to get to, but we can you know, do a lot of that. We can also read proteins and try to figure all those different pieces out. And then we have amazing things that are happening that people might not even be stopping to think about. Many of your audience are wearing Fitbits or wearing smartwatches that are able to start measuring their healthcare information, right. Your heart rate, how well are you sleeping? Our buying habits, right, how we go and we buy things. What kinds of food are we buying. What kinds of medicines are we buying. And if we really start to think about that, we’re all creating this digital fingerprint that could be incredibly important to our healthcare system.

So, instead of just me walking in and seeing my physician for a physical. So, I go see my physician once a year for a physical, we now have this ability to start pulling in all of this information and start using it. So, this big data, you know; what’s your heart rate every day? What’s your blood pressure look like? Are you really exercising like you say you’re exercising? Are you buying good food? This now, although we’re not using that yet, we’re starting to really think about, you know, how do we leverage that type of information, and use that as surrogates. And it’s quite interesting, you know, we’re all quite aware of the COVID-19 events happening around the world but there are some leading indicators when there’s going to be an outbreak. And some of those indicators are that people are now feeling sick and this is, you know, people now start going to their drug store and they’re buying more cold medicines and more over the counter things because people are now starting to not feel well. I mean these are types of information that we never thought we’d think about as being part of our medicine. And then you’ve got your standard care, right? You’re going in and you’re seeing your physician. We have a better ability to do lab tests and to measure different things. So, it’s taking all of that information.

So, my other job besides genomics is data integration. How do we take this information and look at it in a in a different construct? And so now what we have the ability to do is to layer this information together and have, I’ll call it, a foggy crystal ball of what causes disease. Over time as we have our genomes done, and we can share this information that people are comfortable sharing with – I mean, let’s be honest, people have to be comfortable with sharing with this information – it really is going to change.

So, it’s not just your, your DNA is kind of the beginning of where we actually know how everything works, we’ve got to get these other pieces of information together. And so, I think we’re in fascinating times and we’re collecting data on ourselves in so many different ways that’s telling us about ourselves. It’s telling us about, you know, are we really practicing our healthcare the way we should? And I’m hoping that we’ll get better and better as humans. We’re not very good at this. You know, most people check their stocks, or they check, you know, their bank accounts or they check their other things, but they don’t check their health care, you know. So, how could we change that? How do we get this to a point where we’re paying attention to it as much as we are to our money? You know, if we say your health is your wealth, we really do a bad job of paying attention to our health. And so, I’m hoping these types of information pieces that we’re pulling together is really going to change that dynamic.

Elaine Quinn

And looking at the combination of all of those different data pools and the detail you can get from that really is incredible. Can you give me an example of how AbbVie is using genomic research for drug discovery?

Howard Jacob

One of the places that I’m really excited about having come into AbbVie is, you know, looking over the horizon for, for where we’re going. So, we’re looking, we’re working in three major areas at AbbVie, which is neuroscience – you know, what causes Alzheimer’s disease? What causes Parkinson’s disease? What causes neurodegenerative disease? You know, inside cancer, we have a host of cancers, blood cancers, and solid tumour cancers. And inside immunology, you know, what causes inflammatory bowel disease like what Nic had, although Nic was a big extreme on that. What causes psoriasis? Atopic dermatitis? And so, if you take all those diseases together, what is really interesting from a scientist’s point-of-view is with all this information that we’re having is that we’re starting to see that some of these diseases that we think are completely independent actually have relationships to these other diseases.

So, you know, medicine is practiced very specifically around specific diseases, right? You go to see your dermatologist for a skin disease. You go to see a nephrologist for a kidney disease. You go to see a neurologist for, for a neurological disease. But guess what? Some of these diseases actually have these intersection points in their genome, that tell us, that some of the ways we can treat is going to be different. We can really look at different ways of different therapies and look at, you know, developing drugs that can benefit more than one type of disease and that comes back to, you know, that’s a benefit for everybody, right? As we’re going through this process of developing the drugs and making sure they’re safe and making sure they work – Wow! What if that drug works for multiple diseases at the same time? Think how amazing that is. And I can tell you that we’re seeing some really, really cool data that’s showing us that some of the definitions that we make medically with this molecular fingerprint as we call them, is giving us insights that we didn’t know existed. And I just think that that’s a wonderful opportunity for my colleagues here at AbbVie and other pharmaceutical companies then to hopefully develop, you know, better drugs, faster.

Elaine Quinn

Now you have had your own genome sequenced – what kind of information did that reveal that was useful for you?

Howard Jacob

Yeah, it’s a good question. You know, and my sister married an Irishman, so she may be listening to this somewhere in Dublin! You know, one of the things that is fascinating is, is that so, you know, where, you know, where do I come from? And so, reading my DNA, first of all, where I thought my heritage is, is not what it is. Geographically, it might be true but it turns out that, you know, I have, 18% Spanish in me. We have no idea where that came from. Well, I can tell you where that came from. Somewhere in the family, somebody who was dad, is not dad. And so, inside you know, us being humans as we are, about, one in 20 people, dad is not dad. So, we have that issue that you have to face. So, those are some things that we need to be thinking about. But it also then opens the door to us, you know, asking some other questions, and for myself is that, so there’s also – and oh, by the way, it looks like my dad is my dad, but somewhere in the family, clearly something happened here.

But then for my own healthcare, there’s something that’s called pharmacogenomics, which is a fancy scientist way of saying, your genes also determine what medications you can take. So, I have this information, so there’s about 50 different medications that I can’t take the same way as, as somebody else would be able to take and I’ll use one example of this – is that I get kidney stones, and the number one way of treating pain when you get kidney stones is to give morphine. But morphine doesn’t work for me because I chew up the drug three times faster than the normal person. So, when I’m having a kidney stone, I say to the physician in the ER – don’t give me morphine! The look on their face is usually quite extraordinary and I can remember it even though I’m in pain because that’s how they’re used to treating it. So, there’s just one silly example.

And then for looking at my own healthcare. My father, is a lean type two diabetic. I’m a lean prediabetic and even though I exercise a lot. And so I started asking myself where the heck is that coming from? So, as I go in and look at my genome, I discovered that I am carrying multiple genes from my Spanish side, Spanish side of the world that gives me a predisposition for type two diabetes, and inside, some segments of the Spanish population, that’s enriched for. So, by having that information, I now know that I’m carrying these genes and I really have to pay attention to this. I am likely going to end up being a type two diabetic someday, but I’m really working hard to avoid that. So, so there’s just three examples of, of, in me. And so, when people say, ah, it’s not going to give me any information, I’m going to say, I think it’s going to be beneficial for everybody based on my own experience of being able to go in and use it.

And you don’t have to be a physician to know all this stuff. I think it helps obviously that I have a science background, but there’s more and more tools that are being developed and if we look at things like ancestry.com and 23andme, you know, there’s creating that kind of a knowledge base that patients in the future will be able to come in and use this information and ask some of these questions and to work with their physicians to help their healthcare. I mean, imagine that, if you really know what genes you’re at risk for. In my particular case, it’s completely changed how I eat. It’s completely changed how I exercise. It completely changed how I get healthcare when I have kidney stones. And I think that’s, that’s pretty impressive.

Elaine Quinn

Yeah. It must be a very different experience for you when you go to see your physician, being equipped with all of that information already

Howard Jacob

Yeah. It makes for an interesting finding a new physician. When I walk in with my iPad and we have a conversation about that I have my entire genome on my iPad. And it’s an interesting conversation. I will say there have been some instances where it takes me a couple of tries to find a physician that thinks this is a good plan.

Elaine Quinn

Well, hopefully we’ll be all moving in that direction. Well we’re just coming to the end now so just one final question. Where do you see medicine going in the next five years?

Howard Jacob

Oh, the next five years. I think we’re going to start to see the payoff of some of these big datasets that are coming in. And what we’re going to discover is that we really need more data. We need more information. We need more of these relationships that I was talking about, which is – the patients aren’t separate from the physicians, from the providers, from the healthcare system. We really need to figure that out is how do we share that data in a way that’s appropriately to protect the patients, to enable them to have privacy and to use those type of information though, to help us benefit each other, right. So, I think we’re going to see some big changes coming in that space as people start to realize that, that we can all help each other in our own healthcare journey and how do we do that in a responsible way that keeps my privacy, the way it is, but the learnings of me can benefit others.

And I think we’re going to see a lot of this. There’s something that’s called Identification Tokenization. So, what you’re able to do is you can basically create a digital fingerprint that you could now use to track my health care system, if you will, all about me. You can have my genome and all of that, but you won’t know who I am. You don’t know who I am. So, you can protect me from that, but you could share my information about what’s in my healthcare system. You know, what do I do? And then use that type of information to help each other out. And I think we’re going to see some interesting changes in that. Again, it’s going to be this, this assemblage of data that we’re all accumulating as individuals into these blocks of large data pools, as you mentioned, that’s going to be the game. And then you layer on top of that, that baseline. Oh, that’s my genome. How does that data fit with my genome? And I think we’re going to start to see that really start to explode in the next five years.

Elaine Quinn

Yes indeed, some exciting times ahead. Well it certainly is a fascinating field to be working in and it has been fantastic to hear your insights, Howard. Thank you so much for joining us today, it’s been a pleasure talking to you.

Howard Jacob: Thank you so much, Elaine. I very much appreciate the opportunity to share with your audience.

Part 2 – A personal story by Terri Brannigan

So many of us have been impacted by illness – we wanted to take some time at the end of each episode to share a personal story that helps exemplify the need for precision health. This episode we hear from Terri Brannigan who has been living with Crohn’s Disease since her diagnosis at the age of 15.

I was diagnosed with Crohn’s disease at 15. It actually took about five months for me to be diagnosed. So initially, they thought I had food poisoning and it just didn’t settle at all. So, it took months to settle. I lost maybe I think it was about four stone within the space of those five months when I first got diagnosed. So, I was diagnosed on the third of January. I was 15 years of age. I’m 34 now next week. So obviously at 15, it’s a big thing to be diagnosed with something especially something that causes constant diarrhoea and pain. It can be quite embarrassing.

So, basically they put me on medication, and it worked okay but I was kind of still in and out of remission for a long time until I was 17 and they did a bowel resection. So, they took out half my colon and a foot of my small bowel. So that was at 17. Then because at the time when they’d done the bowel resection, they didn’t want me to have to have an ileostomy or a colostomy. They decided that to leave a small portion of diseased bowel there. So, this of course, within the space of a couple of months, I had flared again and was put on more medication which I found out very quickly that I was allergic to. So, with that, ended up within a couple of days, I think, is vomiting, diarrhoea, fainting. As soon as I took the tablets really, so obviously taken off that, put onto another drug.

Tried on and off for years, tried loads of different drugs until they found infliximab which was the miracle drug for me for a long time until something happened that I developed antibodies to it and had a delayed allergic reaction where exactly to the day, to the hour, to the minute, that I was given that infusion all my muscles ceased and I was in terrible pain. I couldn’t move. I was pretty much being carried into the hospital because I was in that much pain.

So, with that, steroids were the main thing for me. They helped me as much as I hate steroids, they helped me a lot and they did have to put me on steroids quite a bit and quite high doses of steroids as well, which of course caused side effects and weight gain, I suppose mood swings as well, my family would probably say! So, steroids were a huge part of probably my teen years I suppose you would say, along with hospital appointments.

It effected essentially my teen years – not a lot of social life – I was in a lot of pain for a lot of the time, I kind of settled with a lot of things when it came to like school and college and I was telling my very close friends. So, they would have known what was going on to an extent. I probably wasn’t as open as I am now about it because no 15 or 17-year-old wants to talk about diarrhoea. So, my friends knew to an extent and they were all great. Like when I had surgeries they were always up to visit me, but I found it quite difficult that I didn’t have a social life. Especially like I’d kind of go through phases of being not able to go at all because I was so sick and then I’d get high doses of steroids so, I’d be out constantly with my friends, and then I’d drop straight back down again and be sick again and end up in hospital.

I ended up having to trial everything; having really bad side effects to everything. And I did find for a long time that with a lot of these drugs, I was being prescribed the drug but then I was being maybe prescribed two or three other drugs on top of that to combat the side effects. So even though one was helping my Crohn’s, I always needed probably one for a migraine one for nausea, and one for anything else that might have been going on. So, there was always bag-fulls of medication floating around my house.

I ended up losing a lot of my hair at one point as well, which I think that was just before my sister’s wedding. So there was a moment here in this house, I think it was maybe six months before my sister’s wedding, where I was traumatized about the fact that I might be bald for my sister’s wedding and my sister told me, well, if you’re going to be bald, I’ll be bald. And I kind of said, well, no we’ll get wigs, it will be fine. But, yeah, there was a few moments like that where things happened, but I think I think over the years I have dealt with quite well and I have a great family around me and great friends that have always kind of understood where I am and how I’m feeling, and they can kind of tell by me on a day to day basis, especially when I when I am sick, they can kind of tell that if I’m quiet on probably in pain.

So, yeah, I actually went on a trial drug probably about six or seven years ago. And we were hoping that this was going to be my cure, my Saviour. The team in the hospital – they had great hopes for this drug and for me, because they had seen me go through everything else – all the biologics, all the immunosuppressants, I had gone through them all. So, everybody was really hoping that this would be it and that this would be the drug that would save me. Unfortunately, obviously, it wasn’t the case. I went into false remission, I suppose, a couple of weeks after starting the trial and I actually felt the best that I had ever felt in years. And I was able to go out walking, which was a huge thing because I normally couldn’t have even walked from like upstairs to downstairs in my house without needing the bathroom.

So, yeah the trial initially was great and then I started to feel sick again and by the time I was due to get the third dose of the medication, I had been rushed into hospital. I was vomiting maybe 30 times a day. I think, at one point, I was going to the bathroom 70 times a day and I was in horrendous pain. I hadn’t eaten for weeks. My potassium was low, which was affecting my heart rate and my heart in general. My body was just under so much stress.

I think, that was the one time where I genuinely – I have a memory of waking up in the hospital and my sister being sat at the bed beside me. And I remember waking up and she’d been there for a while – she was just watching TV or something like that. And I just remember saying to her oh I’m so sorry I didn’t know you were here and she went no, you’re fine, go back asleep. And I just remember thinking, I’m just so tired, I can’t even speak to my sister. And I think that was the one time that I genuinely kind of felt, this is probably it. And thankfully, it wasn’t. It was very upsetting when it didn’t work. And I think it was upsetting for my whole family, not just for me because obviously they could see how well I got on with the initial doses and then how quickly I went straight back down and to literally being picked up off the floor, I was that weak.

I was put on very high doses of steroids and within the space of a couple of weeks I was I was back home again. I pretty much had to learn how to re-walk because my muscles had deteriorated that much because my potassium level from all the levels in my body had just depleted so much. I struggled walking up and down the stairs, so my mom was a great help with all of that kind of stuff. She really to kind of took on the role of my carer from the age of 15 up until probably even now to be honest. I do spend a lot of time with my mom and over the years, she literally has been the one that’s kind of dragged me to appointments, even when I didn’t want to go.

So yeah, learned how to re-walk, I joined the gym, and even though the steroids had kind of picked me up again I suppose and reduced the inflammation from the Crohn’s, once I started reducing the steroids, the Crohn’s flared up again and with that I also had Crohn’s related arthritis, so that obviously affected my joints and I couldn’t walk again and all that kind of stuff.

Yeah, they put me on another drug and it was a slow acting one and they told me it was going to take six months to kick in and I kind of knew myself at that point, I was like, I don’t have six months for this to kick in. And at this point I had started doing my research. And I was 28 at this point. And I started doing my research and kind of decided that at my next hospital appointment I was going to go in with my stack of research and say to them, you need to operate. You need to give me a stoma bag now, because if you don’t, I’m not going to be here in the next couple of years.

My parents thought I was too young, which I probably was and the doctor, initially thought we could try more things but eventually I was allowed to have a conversation with the surgeon and the surgeon was great. He was totally on my side with it and he kind of looked over my chart and he just said no, you’ve had enough now. So I turned 29 on the 13th of November and on the 17th of November, I had my colon removed and fitted with an ileostomy.

It is genuinely the best decision I have ever made. It’s a big one. It’s a very, very big decision. But it’s definitely the best decision I have ever made. I have my life back and I’m able to go out and see my friends and I’m able to go to the gym. I’m very, very active at the minute. I still do struggle with side effects of having Crohn’s disease and like I still suffer from fatigue a lot of the time and joint pain and stiffness and occasionally pains in my stomach but, I can safely say that having an ileostomy fitted was 100% the best thing I’ve ever done in my life.

There’s no family history of it. A cousin on my mom’s side has colitis. We do have some autoimmune diseases in the family. My uncle has rheumatoid arthritis and I think there’s lupus there somewhere. So, there are a lot of autoimmune diseases associated with the family, but nobody has Crohn’s disease. So yeah flying the flag for that one solo within the family, thankfully.

Yeah well in terms of genomic science and research, it is something that I’ve kind of been curious about, especially for the last maybe five years, probably since I got my ileostomy, I’ve been really interested in it. A friend of mine works for Genuity Science so she made me aware of studies that were going on and it turns out I’d actually signed up to a study for Genuity Science. I know that genomic science probably isn’t going to be able to help me too much because I already have a stoma bag now at this point, which I’m perfectly happy with but I feel like if it had been available to me in the past maybe when I was 15 or 20 that it could have saved a lot of pain in my life. I might not  have a bag for starters, but I think it would have been a lot easier than having to trial all the medications, whereas I’d know by my genomic makeup what medications were more likely to work and what weren’t. So, it would have been a lot easier. But if it can help my niece and nephew, or if I have kids in the future – I would at least like to know that they’ll be able to see what their genomic makeup is, to see if they might possibly get Crohn’s disease in the future or any other illnesses and know that if it does happen that it will be a lot easier for them to figure out what medications – there won’t be as much trial and error and a lot of hospital stays. So, I hope that genomic science will be available for younger people in the future so that they won’t have to go through what I went through in the past.

Thank you for listening to this episode of In Sequence, a podcast by Genuity Science. While we know a lot about the human genome, there is still a lot we don’t understand so keep tuning in to learn about what we do know and be inspired to be part of the discovery of what we don’t. Be sure to subscribe on Spotify, Apple Podcasts and Google Podcasts and turn on your notifications so that you get alerts when there’s a new episode!