Episode 2 - Genomics Futures: Microbial Life

Show notes

Speakers:

Iruka Okeke, professor of pharmaceutical microbiology at the University of Ibadan in Nigeria;
Olivia Allen, Head of Strategy at Wellcome Sanger Institute;
Charles Agoti, researcher from the KEMRI Research Centre in Kilifi, Kenya;
Nick Thomson, Head of the Parasites and Microbes Programme at the Wellcome Sanger Institute;
Claire Chewapreecha, researcher at the Mahidol Oxford Research Unit in Thailand;
Senjuti Seha, researcher at the Child Health Research Foundation in Bangladesh;
Sophie Belman, researcher from the supercomputing Centre in Barcelona, Spain;
Alejandro Reyes, University of Los Andes in Colombia.

Episode description:

In this second episode, we spoke with organisers of the Our Relationship with Microbial Life workshop, as well as attendees to explore the themes that came out of the gathering. This workshop took place in Bangkok in early 2025. The podcast starts with the main organisers, Professor Nick Thomson and Dr Claire Chewapreecha talking about their aims for the gathering. We then spoke with Dr Senjuti Saha and with Professor Iruka Okeke about the concept of Global Health. The podcast then continues with an interview with Dr Charles Agoti researcher and Dr Sophie Bellman to look at the concept of digital twins and sustainability in the future of genomics research. The podcast then closes by looking at the future of microbiome research with Professor Dr Alejandro Reyes.

Mentioned in the episode:

The Foreign Gaze: Essays on Global Health – A series of essays by Seye Abimbola
Digital twin – a virtual replica of a biological entity or process. It can use real-time data to simulate, predict and optimise outcomes.

Transcript

Iruka Okeke 00:00
What I would hope to see change between today and 2050 is that the benefits that genomics can give will be reaped at a far greater scale and would be accessible to everyone.

Olivia Allen 00:22
What will the future of genomics look like in 2050? Welcome to the second Genomics Futures podcast. I’m Olivia Allen, Head of Strategy at the Wellcome Sanger Institute, co-producer of these podcasts, and your narrator for today’s episode.

Charles Agoti 00:32
I think, in terms of thinking about what genomics will be able to achieve by 2050, I think genomics will be much more enhanced now with the improvement of the analytical methods supported by AI in what actually, how we can learn from the genomes we are generating

Olivia Allen 00:49
In today’s episode, we’ll be talking about the future of microbial life with a long list of guests, from microbiologists to epidemiologists, from computer scientists to science activists. In the first instance, we will hear from Dr Claire Chewapreecha from the Mahidol Oxford Research Unit in Thailand, and Professor Nick Thompson from the Wellcome Sanger Institute in the UK, and we asked them as co-chairs about their hopes for the workshop.

So today, we’re here to talk about the future of our relationship with microbial life. So, how do we view genomics over the next 25 years, specifically the themes and visions that emerged from a group of 30 participants discussing the future during a wonderful two-day workshop in Bangkok.

Nick Thomson 01:28
For me, I think it was an enormous challenge. So it was a request to think about the way you have conceptualised your career, and the career of the people around you over the next 25 years, and to refresh those ideas, to bring other views in, to contribute to their visions of futures, and to really challenge your held beliefs in where we’ll be in 25 years.

Claire Chewapreecha 01:58
Absolutely, I think we’ve observed the enormous power of genomics in predicting disease, for example, how they spread and how it’s going to respond to any perturbation. However, we also see that there are gaps, both in a lack of deep knowledge and understanding. We understand a lot of associations, but not causations. There’s a gap in the data generation as well as the tools, and we try to bridge those gaps for the future.

Olivia Allen 02:31
Great. So a great basis for a workshop. So why did we go with Bangkok Claire?

Claire Chewapreecha 02:37
Oh yes. So I think just to recap on those gaps in data, I think we understand a lot and those understandings are based on the well studied populations, but there’s underrepresented populations elsewhere in the world, and our commitment to have a Bangkok workshop is to decentralise it, and I think that helps promote global equity as well, fostering a partnership all across the world. So it’s an important and strong message to me.

Nick Thomson 03:12
I think the reason that we chose Bangkok was because we are part of a global community. I think if we’re to solve things at the scales that we want to solve, given the data we can generate and our deeper understanding of the mechanisms behind some of the problems involved in both understanding disease and preventing disease, you have to be part of something much bigger, and actually being in a city that’s thriving commercially, with some great health and great research scientists in it, meant that actually, you’re drawing people into a hub where I think there’s already an aspiration and ambition to do great science at a global scale.

Olivia Allen 03:53
So just to refresh our memories, the themes and visions that came out of the workshop, and there was an interesting one that came out on day one, which was advocating for removing global from the concept of ‘global health’.

Claire Chewapreecha 04:06
To me, removing global from ‘global health’ is quite a strong term, but it’s helped open up a lot of conversations on how we could deliver better science that also benefited our local priorities.

Nick Thomson 04:22
The scale of where we work and what we want to achieve means that everyone has a benefit. So that’s equitable, but in reality, it has to encompass all of the observations, all of the data, all of the populations that actually are relevant to that particular question. However, over the years, global has become a negative phrase. It’s become the Western world’s global gaze. So our influence, through funding, through research, through literature, through assumed and perceived wisdoms, our influence on the work that’s done in settings where actually the opportunity to develop those perceived wisdoms, the opportunity to develop strategies to secure local funding, have not had sufficient air time.

Olivia Allen 05:12
Great. So the next theme was around optimising the microbiome for health and the future of microbiome research. So what was discussed here? I’m particularly interested in your views on what this could mean for the individual and for the population.

Claire Chewapreecha 05:27
I think we took both the “person-up” and “population-down” approach. For “person-up”, that’s where we scanned different individuals in depth, so we can look at the microbiome profiling from birth to the end of life very deeply, and see how lifestyle can have an impact on changes in the microbiome population. At a “broader population” scale, I think there’s a clear trend in anthropogenic shift in the microbiome data, and that’s not only human health, but also animal health and the environment. This is likely driven by the heavy use of antibiotics, both due to the poor stewardship of antibiotics over the counter in some countries, intensive use of antibiotics in livestock, and also antifungal and insecticide that pollute the environment. So we’re losing some good microbiomes, and it’s a call to conserve them.

Nick Thomson 06:33
I always come at this from a different angle. I’m an infectious disease biologist, so I want to kill every bacterium I’m interested in. So I think what this speaks to is that our current knowledge of global health actually, notwithstanding the last point, but that means actually the data around that defines the state of health and state of disease around the world. And what’s very clear is that the microbiome has this very strong impact on that. What’s also very clear, and I’ll give you two examples, is that we do our best in our lives to almost get rid of our microbiomes, just as I’ve been working to eradicate diseases, our lifestyle itself actually eradicates aspects of our microbiome that we need. It’s unintentionally, but it’s a really important consequence of a westernised lifestyle, a lifestyle that has a very simplified diet towards simple sugars, and one that uses, as Claire said, antibiotics and antimicrobials to streamline our state of health. So this is actually a precious resource that we are steadily eroding, and I think that’s new. There’s some great observations that actually, Rob Knight was there from working on the International Space Station, and what they saw was that actually your microbiome, over time, depletes. And so actually if you want to spend months, years in space, you’re going to have to top up your microbiome, otherwise, suddenly you cannot, for example, digest the food you’re eating, because the microbiome is a really key component of our digestive tract. It gives us functions that you can’t get anywhere else, and we certainly don’t have ourselves, but also it protects you from disease as well. So suddenly the microbiome, these beautiful little bacteria, often that all of us are doing our best to get rid of, are now a precious and limited resource that we need to preserve.

Olivia Allen 08:22
Absolutely. The last theme that was discussed in the workshop, which is creating a digital twin of everything, essentially, digital twin for infection. So what did you think of this digital twin of everything? What were the challenges or opportunities that came to mind for both of you?

Nick Thomson 08:37
Well, I think it’s really cool. So you know, on a practical level, being able to trial different approaches to understand how interactions, connectivity, interventions potentially, and their impact, not just on the individual cell but across populations, is really exciting. Huge challenges, though, because obviously you can do that in a positive way and you can do that in a negative way, but I think that ultimately the data and the observations and the communities that we have will need to bring them together around single data sets, and so the digital twin is also a metaphor for a single view of all data that allows multiple different disciplines to apply their skills and technology in a setting safely in the theory to understand microbial life. Very exciting.

Olivia Allen 09:33
Removing global from the concept of global health was one of the main outcomes of the workshop, and came out quite early during the meeting to explore this theme further, my colleague Alexandra Canet, co-producer of these podcasts, spoke to Bangladeshi researcher and activist, Dr Senjuti Saha and with Professor Iruka Okeke from the University of Ibadan in Nigeria.

Senjuti Saha 09:54
Genomics, I hope, will become an infrastructure, and it will not remain a luxury. In my ideal world, I think by 2050 I want to genomics to sit kind of where electricity in Bangladesh sits right now, right, a basic infrastructure that communities control and use daily. So let’s say in Bangladesh, that would mean a child comes into the hospital I work with a fever, gets a locally sequenced answer within hours and not weeks. Farmers of Bangladesh can, let’s say, test soil microbes and guide crops. City planners and not scientists only can monitor wastewater to prevent outbreaks. So you know, very, very skilled and accessible to all.

Iruka Okeke 09:54
Yeah, so, I mean, if a patient is ill and the person has an infection, normally, what you would want is to be able to identify what a germ is causing the infection and what available drug can be used to treat the infection. I would hope that by 2050 for each patient, we would know exactly what’s wrong with them. The other thing I would hope would happen is that there would be more options, because we know that genomic data can help us find targets against bacteria, viruses, parasites for which there are no good treatments or not enough good treatments today. So I would like to see a situation where by 2050,
mining for those targets has been done exhaustively, so that we have so many options. We have an option for everyone, for people who are allergic to things, for people who don’t tolerate drugs very well, there would be options to treat their infections.

Alexandra Canet 11:53
Fantastic. Thank you. These are really vivid depictions, and you were both part of the group that was looking in the workshop at removing the word global from the concept of ‘global health’. What was the main reasoning behind this?

Senjuti Saha 12:08
So global in the full term, global health is really a very colonial term. It is simply the latest rebrand after tropical medicine, so global health is derived from tropical medicine, which later on became international health, and then global health. All these three terms describe the same relationship, which is wealthy institutions in resource rich countries, studying funding and directing work in not so resource rich countries. For example, when UK works in or with Bangladesh, it’s called Global Health. But when UK and Canada work together, it is just health or public health. So dropping the word, I think, is a first step to expose that asymmetry and to force us to name who is involved, who decides, and whom the work really serves.

Iruka Okeke 13:14
I’ve always cringed when I hear people say ‘global health’, and it’s unfortunate because there are whole departments, whole institutes, that have that in their name. And you know, global should mean world. But as you said, it really is a way to talk about health where there are a power of differentials that are exploited. Now, one incredible harm from the way global health works today is that certain people have power over others, and this is not good, because that power may be misused, but there are also harms that are done even to the people who experience that. So the people who are disadvantaged, are also themselves harmed because they’re acting out, trying to meet criteria that have very little relevance to their day to day lives. And this is what Seye Abimbola describes as the effect of the foreign gaze. So he’s written a series of essays that he’s now collected into a book that basically say that even if the foreigners leave Nigeria or wherever it is they are working, the fact that we have also accepted that global health is a thing, and in his words, we are so immersed In the field, so educated, socialised to its flaws, that we can’t imagine anything else. That we then start to do our public health work in a way that serves other communities and not us. He has this really nice analogy of taking a photograph. You know, when I look at myself? In a mirror, I’m talking to myself, but when a cameraman is looking at me, then I strike a pose so that I look in a certain way. And so taking away ‘global health’ that terminology is perhaps the first step in asking, Okay, not only do we not want people in Nigeria, other parts of Africa, in Bangladesh and so on, exploited by people who have more resources. But also we would like people in Nigeria, Africa and all these other places, to look at their own societies and decide what kinds of questions around health and research should be asked.

Senjuti Saha 15;39
I also have this fear that, you know, word is only the surface, as you said, and as Seye says, that a lot of our mindset is also embedded in the that, in the colonialism, right? It’s so hard to change that mindset and data, authorship, intellectual property, all these could constantly seem to live faster than the benefits returned.

Iruka Okeke 16:08
I completely agree. And I mean, in response to the question of what we would like to see in 2050, I think a lot of work has to be done. It’s not going to be enough to just change terminologies, as you say, Senjuti, we’re going to have to do a lot of groundwork, not only to stop the exploitation. Some of it is recognised, much of it is not. For example, I mean, I was trained in Nigeria. I currently work in Nigeria. I have spent time, some time outside of the country. But I think even my own thinking is very colonial, because if I want to get my science published, I’m looking to have it published in journals that are dictating how my science should be presented.

Senjuti Saha 16:57
I agree, we even publish in a language that’s not our mother tongue, that most people in my country don’t even understand.

Iruka Okeke 17:05
And when we think of genomics, for example, I mean, it’s a perfect example for this, because genomes are in a language.
People who are very highly educated cannot necessarily read DNA. You need to have a very specialist training to read DNA, and access to that training alone is actually really hard to get. So one of the things I would like to see in 2050 is a domestication of that education so that you wouldn’t have to go to the two Cambridges or somewhere like Sanger to be able to understand how to read a genome, and then you might read it differently, and then be able to glean things from it that the first school that started reading genomes could not even think of. And one of the things that came up in the workshop that we talked about is that when we think of international research, we tend to think of either global health or something similarly colonial. But there are important areas of research, like biodiversity that should be done everywhere, and thinking about how that can be done everywhere by everyone, is one of the things that we have to do.

If it’s a question of, well, people in the places with the most diversity have not yet learned how to read genomes. Reading genomes is something technical that can be taught to anyone. So we can start with making access to that kind of expertise. The second thing I would, I would definitely start with, is is thinking about how hooks are hung, are hung on funding programmes so that only certain people can lead certain things. Some of those are completely rational. Sometimes it’s taxpayers’ money from a particular country, and that country wants to see their money invested in their own country.
But then if the so called taxpayers are also asking for exploration elsewhere, then there have to be equitable ways in which use of that funding is framed so that it’s not just money that comes to the table elsewhere, but people and ideas.

Senjuti Saha 19:38
I agree with you completely Iruka and, you know, sometimes we get confused and we think equity just means access to resources, but that’s not it, right? Equity means agency plus access to resources. Equity means communities should have the agency to define the questions, own the data, build the labs and set the rules for sharing, and I think there are huge gaps there right now. Equity doesn’t mean a charity or just representation on a panel or, let’s say, doing a podcast, but to get there, in about 25 years from now, there are many steps we must take, or at least figure out how to take, and many of them you have already covered Iruka. But I think the first thing that’s kind of what you also said, is move money and infrastructure to where problems are felt. And how we do that, there needs to be very good, I think, equitable guidelines.

We also have to, I think, create very enforceable data governance led by local institutions. Often at times we do not exactly know or understand what is the ethical way of moving data or even sharing data and who finally owns it. We also, I think, think a lot about shifting authorship, IP and credit norms, so contribution equals ownership. We often see that we, a lot of us work on a paper together or on a project together, and a few of us just end up as middle authors, and that is not an equal representation of contribution.

And, at the end of the day, you’re talking about reading the genomes. I think we have to invest in long training pipelines so that a 12 year old girl in rural Bangladesh today can lead a Genomic Centre in Bangladesh in 2040 and we have to do that.

And finally, I’ll end by saying it’s really important that there are more conversations between South,
South network, so more conversation between Iruka and me, so that we learn horizontally and not only vertically, we need to get out, get out of vertical learning, or the idea that learning can only be vertical.

Alexandra Canet 22:28
If, if I asked you to now, imagine what that would look like. So we’re in 2050, we’ve replaced the current model of global health. What does a collaboration, or what does your research look like if you could paint us a picture?

Iruka Okeke 22:45
Yeah. So I’m a basic scientist. I tell my students that, yeah, you know, work on these enterics and bloodstream pathogens, because people die on them, die of them. But what drew me to the field was the fact that E coli looks so cool on a plate. So I love basic science, and I’ve had a number of conversations with people in Nigeria or in America and so on, who think that they don’t have permission to do research across the sorts of borders that global health works with so fluidly because they’re doing something that isn’t going to save a life of somebody in a poor country. So I’d like the questions to lead.

I would like people not to worry that, oh, if I want to collaborate with a Nigerian, I have to first of all start my grant proposal with this number of people die of this disease. I would like people to just come with a curiosity. And by people, I mean people from Nigeria, people from Republic of Benin, which is next door, as well as people from Canada or Switzerland. If genomics has got to the scale and access that I’m hoping will happen by 2050 then everyone will have access to the health benefits from genomics, and then it will be possible to drive science entirely by what are the most interesting questions. And I think when you approach science in that open ended way, the discovery potential is greater.

Senjuti Saha 24:30
I also work primarily on antimicrobial resistance, and we are losing ground on antimicrobial resistance, but we are also losing ground on climate change, which is reshaping microbial ecologies, and our reference databases are really biassed towards a very, very small slice of humanity and environments and that needs, that needs to change. Genomics can definitely help if it becomes faster, cheaper, and most importantly, if it is locally covered, right? So real time resistance tracking, early detection of emerging drug resistant pathogens, perhaps bacteriophage therapies tailored to local strains, microbiome informed public strategies, will all become more accessible and real in 2050.

Sometimes I worry that we act like genomics is going to be the solution to everything. I am culprit of that. I think it’s really important to constantly remember that genomics will only help, first, if knowledge stays where samples are collected, and second, if communities can act on the data.

Genomics is extremely important, but it will not save us from antimicrobial resistance, if basic sanitation and primary care continue to remain unfunded. And finally, I think, remembering that microbes do not need passports. Unfortunately, we live in a world where power still needs a passport. The work until 2050 hopefully will be to make sure that tools to understand microbes can also travel as freely as the microbes themselves.

Olivia Allen 26:38
The second of the themes that appeared during the workshop, looked at technologies and digital twins in the context of microbial life. What were the thoughts and insights behind this vision? To delve into this, we spoke with Dr Charles Agoti from the Kemri Research Centre in Kilifi, Kenya, and Dr. Sophie Belman from the Supercomputing Centre in Barcelona, Spain.

Charles Agoti 26:59
I think in terms of thinking about what genomics will be able to achieve in 2050. I think genomics will be much more enhanced now with the improvement of the analytical method supported by AI in what actually how we can learn from the genomes you’re getting in the next 25 years, thinking about that. So I think a lot will be depending on the analytics, how easy it will be actually to learn about whole genomes and make sense of the genomes. So I think we’ll have much more in the direction of precision medicine, in terms of how fast we get genomes, how fast we interpret them. Definitely we’ll need to have ways of storing the lots and lots of data, and I hope we’d be able to get gadgets much more portable, can easily generate genomes and interpret and give very useful information. That’s what I’m seeing.

Sophie Belman 27:53
I think data storage is a huge issue, that’s something we’re working on, but at the moment, it’s about who owns it and where is it and is it sustainable, which I think we’ll get to a bit later. I would really hope that we’ll have better representation, and then also potentially ability to sort of predict scenarios or understand different scenarios of spillover or outbreaks or transmission. I think we don’t understand a lot of basic biology that has to do with infection, and I think genomics can help us with that.
But I think for that to happen, we really have to have a better representation. So in by 2050 and 25 years, I’d hope we better catalogue the true diversity of sort of microbial life, animal life, microbiomes of different animal and human species?

Charles Agoti 28:45
Yeah, and then it comes actually the question of who decides what’s representative, because what’s a percentage depends on what the interest is actually for the person doing the sequencing. So I think that’s another big question, because in my home continent, I feel like there is a lot more diversity that then appreciated, and a lot of it actually still remains uncharacterised

[Sophie] and unknown, yeah,

and unknown, and internally, the funding isn’t actually there, and those challenges actually go all the way to storage, to analytics, which I think it quickly becomes a problem. Just imagine sequencing a very small genome size pathogens already filling computing clusters in this region. And you can imagine if you went on to now get the full diversity of life.

Sophie Belman 29:41
I don’t think we need to sequence everything. I think maybe focusing our efforts on sort of where we can mitigate disease. And that’s going to vary by different countries; what’s a priority pathogen in one location might not be a priority pathogen at this moment in another, but could easily become one. And so figuring out what is a priority, what kind of diversity do we need to capture to ultimately mitigate mortality? I guess, that’s, it depends on what your goal is. Right? Do we want to predict spillovers? Do we want to understand when there’s going to be an outbreak? Do we just want to characterise what is present there,towards understanding what could cause disease in the future.

Alexandra Canet 30:24
And now with that, we’re on the point of sustainability. There was something I wanted to ask you, is everything we want to achieve in 2050 sustainable?

Charles Agoti 30:32
Actually that for sure, we have a problem of sustainability, and it’s something that requires to be very, very innovative to keep going. But then it comes with energy, the energy needs means, actually, then there is a bit of impact on global warming. I indicated in the initially, actually about the analytics, which are going to require AI, for instance, and AI, I’m told it’s a very high energy demand platform, and thinking about actually some of these become, again, disadvantages, for instance, to my home continent of Africa, where it’s already very hot. So to actually keep the storage facilities cool and the computing facilities cool, you need a lot more to achieve that, and it’s not the same as if somebody is in the Arctic areas, so the energy demands are really high and for sustaining the whole platform. So there is need, actually for us we develop these new technologies, or to actually look at our industry counterparts actually. What are they thinking about sustainability? Are there more innovative ways of storage without needing the current platforms or the current ways like, I know there are people working on, for instance, how sequence data can be stored in far more smaller storage requirements than currently of data structures.

Sophie Belman 32:02
and just to follow on that, I think what you’re going to need in the future, I think a huge effort on sort of reproducibility, and that’s increasing sort of sharing scripts and making sure your scripts are able to be run by someone else and remake the files that you have. But I think really emphasising that is actually crucial for minimising the amount of data we have to store, because maybe it doesn’t matter as much.

Alexandra Canet 32:25
I would like us to delve into one of the visions that came out during the workshop, what was called, at the time, the ‘twinfection’ vision. So is a digital twin of infection actually something viable? From your point of view? What is needed to make this a reality?

Sophie Belman 32:40
No, I don’t think it’s viable without better data storage and better representative data. I think maybe, in one small region, we could… I think digital twins are really sort of sexy term right now. Everyone’s into digital twins, which is, I think, how we kind of landed on it. But what does it mean? And the way we were talking about it was a sort of interconnected scenario, where you could change one thing and then predict what kind of spillover might happen, or whether there’s going to be an outbreak, or how, if you’ve catalogued the serology of a population, how is that going to change the way an infection is going to take hold, or an outbreak is going to take hold. I think on a small scale, maybe we can do that sort of series of models, and people are working on that. But as far as truly having a global digital twin of infection and outbreak and spread, we need to have a better understanding of the microbial animal diversity, both in microbial in animal and vector as well as a better understanding of human population immunity.

Charles Agoti 33:47
I have to firstly, actually, the area of digital twin has not been one of my areas. I heard it more prominently during the workshop. However, I remember speaking to one of my colleagues about that with a senior math model, actually, and said, like Sophie said, actually, it’s a bit still away down the line, but I think the data sets is what we really need, and never undervalue actually investment. So if it’s something that the global community thinks it’s, it’s time that we have it in place and enough resources are invested in it, I think we will get closer. Personally, that’s what I would think. But with the current patchiness of the data sets and the information, it’s unlikely to be possible. So a major component, again, is actually like you saw during the COVID vaccines, vaccine which you are taking 25,
years, 30, 40, years were being made possible. Within a year we had that. And the thing behind it actually is the number of brains which were put behind the concept and the amount of financial resources that were committed. So I think this simply also requires that level of investment. But the question is, is it being met?

Olivia Allen 35:17
The future of microbiome research was a third theme. To look at this more closely, we spoke with Dr Alejandro Reyes from the University of Los Andes in Colombia. What are his views of the future?

Alejandro Reyes 35:30
Yes, I think genomics is a tool, a very powerful tool, and it’s a tool that generates a lot of information, and hopefully in the future decision making will be based on information. So the more information we have, the better decisions we will be able to make. And I think that’s where genomics is going to come in. As we go forward and genomics becomes a more affordable solution and a more affordable tool that we can use it broadly for different needs in different scenarios, not on the human, plant, animal, microbial, et cetera. We’ll see that that amount of information and with the right interpretation, will help to generate information based decision, and hopefully to take better decisions into how to use natural resources, how to approach climate change, how to help better health conditions. And now, not only taking a general approach, but a very specific approach considering the local information and the local genomic settings and the local conditions

Alexandra Canet 36:51
You work in Colombia. How do you see it working in your setting?

Alejandro Reyes 36:57
I think it would be quite related and be more that we stop using other countries reference genomes, microbial genomes, and understand our own. And as we have moved forward and begin to characterising more microbes and more plants globally, we have realised that each one of those are different and many of the aspects that make them unique are small variations that you don’t see very easily with just one central reference genome. So we need to understand the particularities of each plant, of each crop, of each variation, all the difference in human populations and all the microbes, and that many of the ecology and the environmental ecology depend on microbes, so understanding those variations and those difference and how these the microbes here are different and interact differently than the ones in other places that will help making better informed decisions.

Alexandra Canet 38:01
Fantastic. And related to this, I recall you were part of the group during the workshop that was looking at the need for optimising the microbiome for health, and you were also looking at the future of microbiome research. So what are the main challenges that you’ve seen within this field?

Alejandro Reyes 38:17
I think it’s precisely the interpretation of information. So we have a very nice setup in which technology is getting cheaper. Getting access to genomics is more affordable, and we’re beginning to do it at larger scales, and reaching environment, locations, communities that were not reached before. Now, the big challenge is understanding what all that is doing. And if you go back 10-15 years ago, we used to say that almost 70% of bacterial genomes were completely unknown. The genes were just no known function. That percent has reduced significantly, probably to around 30% or something like that. There’s still a lot of that we need to understand. And right now, we are in a process of understanding, for example, carbohydrate degradation and what they eat, or in what environments they grow. And I think in the future, the challenges will be more in terms of regulatory networks and communication, bacterial bacterial communication, bacterial host communication. There have been very good advances in those fields recently, but I think there’s still a lot to be discovered, understanding how in a microbial community, bacteria interact. So I think that that’s a challenge that should be approached in the coming years, and that will help us understand how to build and how to regulate efficient communities to be able to achieve a given setting or an optimised setting for a given environment.

Alexandra Canet 40:14
So we spoke about the challenges, this really good, but now I’d like you to tell me, so in 2050 what your work will look like in terms of the microbiome? So what do you think you’ll be able to find, or do in your in your field?

Alejandro Reyes 40:40
Yeah, I think they are quite different views about that. And even during the workshops, different views arise. And I think hopefully what we all have in common is that we expect by 3050 we will understand, typically, the configuration of a community. We will understand how to manipulate or modify a community in order to achieve a given setting, and a given setting of a community will provide a given phenotype and will be associated with health. The question is, how will you use that information? And I know that, of course, there is some views that will say, okay, so we can make better probiotics. We can make better prebiotics. We can identify the right microbe that I need to provide for people in order to lose weight or something like that. And in a very kind of commercial way, I also have the feeling is like we can, if we understand how the microbiome is modified by food, but by diet, by lifestyle, we can do recommendations for people, in order for with whatever they have on their reach, they should be able to modify their community to get something. And I remember thinking things like, okay, let’s say I have my microbiome characterised, and I know that a given microbe I have is capable of producing a molecule that helps that acts like a hormone and reduces a stress level. So today I have a big presentation, and I’m getting very nervous. So instead of taking a pill for that, or taking the probiotic that will help me with that, I would just know that I need to eat 100 grams of celery, and that will help that microbe induce the production of that hormone that will calm my nerves. So by knowing what what do I have in my gut and how they respond to my settings, to my environment or to my diet, I should be able to control and modify that microbiome that I have to achieve particular means. So I think with a good knowledge of the community and accessibility to characterising everybody’s microbiome, something like that should be possible, hopefully within a 25 year range.

Alexandra Canet 42:52
I love the celery example, that’s great. This brings me really well to my next question, which is AMR was identified as a main risk in 2050 and I think everyone agreed that the role of microbiome could be really crucial in battling this risk. What are your thoughts on this?

Alejandro Reyes 43:34
I completely agree with that and I think microbes are a first line of defence against any external threat, could be a pathogen, could be dietary stress, could be any toxin from the environment. The first thing when any of that gets to us and they get exposed, the first thing to interaction with those are the microbiome, or microbes that we have in our skin, in our gut, or wherever this threat is arriving. So instead of using antibiotics, you can use your microbiome to fight against those pathogens. And those pathogens have evolved very important strategies and to be able to disrupt the community and try to get in into the host, but I think there are possibilities of strengthening your microbiome. And as I was talking before, if we understand bacterial-bacterial communication, we will understand also bacterial-bacterial interaction, including production of antibiotics. So we will know that certain gut microbes usually are good at defending against x pathogen. So if you have that microbe already, and you have the idea that you may get exposed to a given pathogen, you just need to strengthen your microbiome without needing to add any antibiotic into the system, and your microbiome will help you fight against those. So a strong, diverse microbiome will always be a very good line of defence against the entry of potential pathogens. Once they’re in. Yeah, there’s almost not a lot of alternatives rather than using some antibiotics. Another way that we can think of that is reducing the expansion of antibiotic resistance, so starting to have a smart use of antibiotics, or generating ways in which the antibiotic is not being in contact with the rest of your microbiome by degrading it when it gets to the gut, or tailoring it specifically to the region of infection, that will likely reduce the chances of other bacteria to become resistant, and that will be another way of understanding your microbiome and working on your microbiome so it doesn’t promote resistance when you have to use the antibiotic.

Alexandra Canet 45:40
There was also, during the workshop, talks about a global human microbiome. Can you tell us a bit more about this idea, and if it’s even feasible.

Alejandro Reyes 45:50
I think with the time and thinking about 2050 in terms of technology, it will be feasible. Sequencing prices are going down. We have better technologies or more affordable technologies. The challenge will be, if there is the will or the need, I think it’s very important to try to characterise as many environments as we can, as many diverse populations as we can and in a way of not trying to standardise anything like the concept of dysbiosis that is usually used in the gut microbiome, and dysbiosis only means a deviation for normal, but we don’t know what is normal, and normal will be different in every region and every culture and in every community. So understanding that we want to characterise the microbiome globally, not to generate a new normal, but to understand the diversity of the microbiome. And I think that diversity and that uniqueness of each region is what makes it special, and not try to make it converge into a given setting, because that will be impossible and not healthy to try to make everybody with microbiome look the same.

Alexandra Canet 47:09
Fantastic. Yeah, this is a big question, and it’s about equity, which kept coming up during the workshop. But my question to you would be, you know, what does equity actually mean? That will be the first part, and then, what are the steps that we need to take to be able to achieve that equity in 25 years time, if that’s even possible?

Alejandro Reyes 47:31
I think that’s a very challenging topic for many reasons. I think equity can only be achieved unless you approach it in a multi-layered ways. And I think we’re in general, moving forward, probably baby steps, but moving forward, and you can see equity, for example, at the education level, at the access of resources level, but also you want to see equity at the stakeholder or decision makers or grant funding institutions, we need to start understanding what are the regions that we are surfing and and to to have more people from the communities and the regions, to be part of those stakeholders, to be part of those decision makers, to be part of those people deciding in those committees, deciding what are the priorities of funding, and why? Because I think right now, when we talk about equity, we are thinking almost having people from all parts of the world to adapt and to get in line with this way the system has been designed. We have not been thinking of redesigning the system to adapt to all needs, which is a very different and challenging question.

Olivia Allen 49:32
Thank you for listening to the second episode of the Genomics Futures podcast. If you haven’t listened to the first episode yet, an introduction into why we decided to create this podcast. You can find it wherever you get your podcasts under Genomics Futures. The next episode will look at the workshops that had a focus on artificial intelligence and synthetic biology, in which we spoke with different experts in bioethics, generative genomics and automation, about what this could all look like in 2050 and the themes that came out of the workshops, if you want to get in contact, please do, you might agree, disagree, or have your own thoughts about the topics and themes covered in these conversations. We’d love to hear them. You can get in touch with us at genomicsfutures@sanger.ac.uk.