Welcome to the Human Immunome—Conversations with Systems Immunologist John Tsang and Human Immunome Project Chair Jane Metcalfe
John and Jane are key subjects in my new investigative article for MIT Tech Review and Aventine. The column below offers more details and musings on recent dramatic breakthroughs in immunomics
Jane Metcalfe, Shai Shen-Orr, and John Tsang speaking at a recent Human Immunome Project reception during the UN General Assembly in New York City
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FUTURES is a column and a newsletter about possible futures at a pivotable moment in history, where the future could turn out wondrous—or not. I’m asking the most interesting people I can find what they are most excited about and most afraid of for the future, and why.
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In this issue of FUTURES
Theme: The Human Immunome
· Commentary: Is the Immunome the Mother of All Systems? By David Ewing Duncan.
· Excerpt: from my MIT Technology Review article, just out: “How healthy am I? My immunome knows the score” By David Ewing Duncan
· Q&A: John Tsang, Professor of Immunobiology and of Biomedical Engineering, Yale University; Director; Yale Center for Systems and Engineering Immunology
· Q&A: Jane Metcalfe, Executive Chair of the Human Immunome Project, co-founder of Wired Magazine
· Further Reading and Viewing From my Archives:
o Book: Experimental Man: What One Man’s Body Reveals about His Future, Your Health, and Our Toxic World (Wiley, 2009), By David Ewing Duncan
o Article: DNA as Destiny: Here’s what it’s like to take the world’s first top-to-bottom gene scan. By David Ewing Duncan, October 2002
o Video: The Experimental Man Project, TEDx Berkeley, 2010
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Commentary
Illustration from the article in Tech Review and Aventine by Ibrahim Rayintakath.
Is the Immunome the Mother of All Systems?
How important is the human immunome to our health and longevity?
By David Ewing Duncan—October 9, 2025
Like most people, before the pandemic I would have answered this question: “very important.” As a life science writer, I also was aware of breakthroughs in vaccine development and immunotherapies that promised to activate a person’s immune system to help fight cancer and possibly other maladies. But I was not aware of just how crucial and all-encompassing this system really is.
Then the pandemic came and humanity learned an abrupt and bitter lesson in what happens when our immune systems are viciously attacked by a tiny bundle of RNA—a virus—that our immune systems initially did not recognize and were unable to fend off. Most of us just got sick, but millions had terrible and often lingering reactions, and far too many died. We learned new terms like “long haul” and “cytokine storm”—which refers to an important immune system protein that rushes in to attack an invader; sometimes a “storm” happens when they overreact and cause damage and sometimes death.
All this gave us a powerful example of just how critical our immune systems are even as scientists at first seemed helpless to do much about the harm inflicted by the SARS-CoV-2 virus that causes COVID.
If a pandemic wasn’t enough to convince me (and most of humanity) of the importance of the human immune system, my attendance at a summit shortly after the pandemic receded, in the fall of 2022, certainly did. It was held in La Jolla, California by the Human Immunome Project (HIP), a nonprofit that had gathered about 65 top immunologist and experts in AI and computational biology to discuss how to bring together a slew of new technologies, discoveries, hypotheses, theories, models, and ideas that collectively represented a kind of next-gen level of research in immunology.
It was at that meeting that the idea for the story I just published in Technology Review and Aventine was hatched as I listened to a barrage of mind-blowing presentations on the latest in immunology. I heard about how our immune systems are key to how we fend off not just pesky coronaviruses, but every stress, pathogen, injury, allergen, and more that we are exposed to. As I write in the Tech Review story:
Made up of 1.8 trillion cells and trillions more proteins, metabolites, mRNA, and other biomolecules, every person’s immunome is different, and it is constantly changing. It’s shaped by our DNA, past illnesses, the air we have breathed, the food we have eaten, our age, and the traumas and stresses we have experienced—in short, everything we have ever been exposed to physically and emotionally. Right now, your immune system is hard at work identifying and fending off viruses and rogue cells that threaten to turn cancerous—or maybe already have. And it is doing an excellent job of it all, or not, depending on how healthy it happens to be at this particular moment.
One heartening facet of the meeting at La Jolla was a deliberate attempt by the organizers to invite two groups that traditionally have operated in silos and haven’t interacted enough—biologists and computer and AI engineers. I once wrote a story titled “Biologists are from Venus and Engineers are from Mars” about the divide between these two groups who really needed to be working together—a divide that I argued was impeding progress that might be happening if they talked more.
My invitation to the HIP meeting came from a longtime friend and colleague, Jane Metcalfe, a co-founder of Wired magazine, where I used to be a Contributing Editor. We didn’t actually meet at Wired—she was leaving just as I arrived. But we connected and I ended up writing for her wonderful online publication NEO.LIFE (renamed Proto.Life), which offered up a detailed, positive, and realistic take on new technologies, discoveries, and ideas in the life sciences, and the people behind the innovations.
At La Jolla, I also met John Tsang, the chief protagonist in the Tech Review and Aventine article just out. John generously spent countless hours patiently explaining—and explaining again—the intricacies of this very complicated system. He and his team at Yale also spent many hours processing my blood and running me through a complex analysis using cutting-edge technology and AI to determine the health of my immune system—which I am grateful for. I’m also grateful to the other subjects in the article who offered up their time to explain what they were doing—including systems biologist Shai Shen-Orr, Professor in the Faculty of Medicine at the Technion in Israel, and HIP’s co-scientific officer; Rachel Sparks, a clinical immunologist who was a researcher in John Tsang’s lab and now is a translational medicine physician at AstraZeneca; and Mark Davis, professor of microbiology and immunology at Stanford.
Getting my blood drawn in John Tsang’s lab at Yale—blood that was used to pull out almost one million immune cells and biomarkers to assess the health of my immunome.
Two years after La Jolla, I got an email from my longtime friend and colleague at MIT Technology Review, David Rotman, now the magazine’s Editor-at-Large. David told me about a new collaboration between Tech Review and Aventine, a non-profit research foundation that creates and supports content about how technology and science are changing the way we live. The idea, he said, was for Aventine to fund and co-edit and publish long form investigative stories of the sort that I love to write, but that have become an endangered species because the media can seldom afford to expend the resources needed as the industry has contracted in recent years.
David introduced me to Danielle Mattoon, the executive director of Aventine and a former editor at the New York Times. On a Zoom call, they told me about their collaboration and asked me if I had any ideas for a subject to write about that was impactful and wasn’t widely known (editors are asking us writers for this sort of story). I immediately mentioned the human immunome.
Both David and Danielle said: “the what?” I explained that “immunome” was a term that encompasses everything in a person’s immune system, like the term “genome” encompasses all of the DNA in an organism, or the “microbiome” encompasses all of the microbes inside a person or in their gut.
The result of that Zoom is the story being released today by MIT Technology Review and Aventine. Below I have included an excerpt—but please read the whole story on these organization’s websites. Below I also have included interviews with John Tsang and Jane Metcalfe who answer the question I always ask guests to this column called “Futures”—what are you most excited about and more afraid of for the future? Both of them then shared more details and stories about their work and about who they are and why they chose to focus on the human immunome.
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New Article Just Published
How healthy am I? My immunome knows the score.
Groundbreaking new tests reveal patterns in our immune systems that can signal underlying disease and tell us how well we might recover from our next cold. I got my results in a text message.
By David Ewing Duncan
Published in MIT Technology Review and Aventine—October 9, 2025
Link here and here to article →
It’s not often you get a text about the robustness of your immune system, but that’s what popped up on my phone last spring. Sent by John Tsang, an immunologist at Yale, the text came after his lab had put my blood through a mind-boggling array of newfangled tests. The result—think of it as a full-body, high-resolution CT scan of my immune system—would reveal more about the state of my health than any test I had ever taken. And it could potentially tell me far more than I wanted to know.
“David,” the text read, “you are the red dot.”
Tsang was referring to an image he had attached to the text that showed a graph with a scattering of black dots representing other people whose immune systems had been evaluated—and a lone red one. There also was a score: 0.35.
I had no idea what any of this meant.
The red dot was the culmination of an immuno-quest I had begun on an autumn afternoon a few months earlier, when a postdoc in Tsang’s lab drew several vials of my blood…
Go here and here to read the rest of the story.
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Two Q&A’s: John Tsang and Jane Metcalfe
Further comments and thoughts from two principal subjects of the story “How Healthy Am I?” (Scroll down for Jane)
John Tsang, PhD
John Tsang is Professor of Immunobiology and of Biomedical Engineering, Yale University; Director; Yale Center for Systems and Engineering Immunology; Yale Lead, Chan Zuckerberg (CZ) Biohub NY
First, I asked John Tsang the question I ask everyone for this column on possible futures.
What are you most excited about and most afraid of for the future?
In terms of what I’m most excited about, I think we’re on the verge of having a lot of technology and capabilities to start to crack biology across scale. A point where we can design, say, a bioengineered cell, simulate it in a computer and say with a high probability that if you put them in an animal or a person that’s going to work well. What we need and what I expect we’ll achieve is to arrive at a place where we have a predictive and a quantitative understanding of biology, like we do with physics and chemistry, which has produced so many things that we enjoy in modern life. In those fields we can design systems that can operate within very precise regimes, and we do things like putting gazillions of transistors together. We can now engineer products so that they are robust and they perform as expected. We don’t have this yet for biology, but I feel like we are on the verge where there’s a convergence of fields that would accelerate our ability to achieve a level of predictive and quantitative understanding in biology and in my own view about the human immune system.
What about your greatest fear?
I think my greatest fear is fairly classic in that with great power comes great responsibility. With the kind of power I just mentioned, you can do all sorts of good with it, but I can also imagine a world of huge inequity. People who have access to this technology first will set up how we use it and will profit from how we use it. Will everyone have access? Could this sort of inequity lead to conflict?
How do we make sure this inequity doesn’t happen?
If we are wise, we can think about how to do this in a balanced way. I’m not suggesting that immediately everything would be totally balanced. There’s always a curve such that innovators and investors take the risk to break open the barriers, and they expect to be rewarded. What I worry about is that those rewards for new technologies, including AI, have been concentrated in the past few years in a very, very small number of companies and people, and in countries. It’s not my field, but I do fear that this could lead to crazy inequity and maybe gigantic conflicts.
How important is the immune system?
It’s central to health and touches on all the organ systems. It fights against all external and internal stresses. If you look at almost anything, any disease and health condition, you can find signs that the immune system is involved. Evolution has evolved the system to be able to handle all these stresses and perturbations. It’s also a primary system for us to achieve our goal of developing a better predictive and quantitative understanding of human health.
Can you give a brief description of what you’re doing in your lab?
I think the immediate vision is to do for the immune system what happens when we go to the doctor and get tests for organ systems like the heart and the kidney, where they have certain markers that they can test and have a good idea of what’s going on. For the immune system, we’re still not there in terms of having good predictive metrics on how well it’s working right now, and how well it’s going to work moving forward in time. And as certain threats come in—it could be an infection, it could be a vaccine, it could be a potential tumor—how competent is my immune system to deal with these stressors? Right now, we can’t answer these questions, and that’s the vision to move to the point where we can provide tests and make predictions in the clinic so anyone can be able to use this to guide what to do. We also are working to be able to change the outcome, the course of the natural history, by modulating the immune system away from a path to a bad outcome to something more desirable—and to reach more people with this.
Isn’t reaching more people part of the Human Immunome Project, where you are co-chief science officer? HIP is working to offer the advanced immune test that you and others are developing to people around the world.
That’s right, and this also goes back to the sort of equity point I bought up before. A lot of the immunological studies right now use small populations in North America and Europe. HIP’s goal is to capture the diversity and variation across the whole globe. Imagine if we can apply the same approach across the entire world and start to map to capture the true diversity of the human immune system so we can build these predictive models and figure out interventions.
What about the Immunome and the aging of our immune systems as one of the major drivers of longevity—that is, how long we will live and how healthy we will be?
Aging is very complex, there is degradation going on: in our DNA, in our cells. Aging also involves us taking on more and more from the environment because the longer we live, the more exposure we’ve had. The immune system is at the center of all of this for at least two fundamental reasons. First, it’s constantly monitoring these stresses, inside and outside our bodies. It also organizes and deploys responses internally, and the more stresses, the more the immune system has to work.
If you look at longevity science as a whole, if you develop metrics to measure the function and health of the immune system—how well it’s working—this would be critical information to potentially modulate adverse outcomes that make you less healthy and shorten life. We already see this with people we’ve tested who have an immune system that looks to be much, much younger in terms of their function than their actual age—that was the result you got when you took our test. Some people may look much older in terms of their immune system function. So how do we rejuvenate or return their immune system’s function at least back to a healthy and functional level? It’s a key question definitely related to longevity.
How did you become a system immunologist? What is your story?
I didn’t get immunology until I started my own laboratory at the NIH in 2010. Before that I studied systems biology and biophysics, and I was passionate about trying to understand how different pieces come together and work to power of life. Then I learned a little bit more about human genetics and I saw that the immune system was involved in almost everything as I was looking at. But I had no idea at the time what exactly was going on. I became quite curious. That’s when I started to see that, wow, humans are highly variable. And once I got a glimpse of the immune system, I found it so fascinating because not only do you get cells at different levels, they’re all different, and yet they can work together in complex organisms to create humans and individuals who are also very different. Back then, I wasn’t thinking that I could improve human health, I just got really intrigued by the conceptual elegance of these phenomena. So I really followed my passions, and I think it has turned out pretty well.
Jane Metcalfe
Jane is Executive Chair of the Human Immunome Project and the co-founder and former president of Wired. She was the CEO and founder of proto.life (formerly known as NEO.LIFE), a weekly newsletter and website focusing on how digital health tools and an engineering mindset are revolutionizing human biology.
David Ewing Duncan: What are you most excited about and what are you most fearful of for the future?
Jane Metcalfe: I’m most hopeful about the dawn of technologies that would completely transform how we practice medicine that could be built alongside our existing healthcare system, but that ultimately could make obsolete the way we currently practice medicine. And obviously I think that cracking the code of the human immunome is how we get there. Right now, medicine focuses on individual organs to try to get a picture of a person’s health. With the immunome, which is the same basic system throughout the body, you can start with a holistic picture and then drill down into the specific organs or whatever that you can influence.
This going holistic first is a kind of parallel universe that I hope we can build and then just gracefully step into it once it starts to show its worth and proves its efficacy. I think it’s such a big opportunity to really think about precision medicine and preventive medicine instead of sick care. And to understand how your immune system is changing and can be read in real time—this is such a huge opportunity. We have a lot of work to do, but in the next 10 to 15 years, I think this is a realistic aspiration.
It sounds radical, the opposite of how medicine is practiced today, which tends to be organ by organ, and system by system. I want to talk more about this, but first I want to hear what you’re most afraid of for the future.
What I’m afraid of is a society that no longer embraces progress, that no longer trusts science and technology, that does not feel like it has the agency to deploy our knowledge in beneficial ways for humanity. Psychedelics is a an example, a great technology to treat depression and PTSD that was shut down because of fear and politics. I wonder how many people in the sixties and seventies and even today might have grown up in households without alcoholism if we had figured out back then how to use LSD to treat alcoholism. I can’t stop thinking about things like that, because we blew the go-to-market strategy and we set back that research 50 years. I think the same thing has happened with genetically modified foods. Many companies, Monsanto in particular, really blew the go-to market strategy on that technology and scared people and set back our potential for improving farmers’ lives and increasing their wealth by decades.
Your hope and your fear seem like two sides of the same coin. This is the point of this column in many ways—that you have a technology on the one hand that could radically change healthcare and improve how we live and is incredibly exciting, but there are dangers that need to be addressed not with fear and bans but with a smart conversation.
It’s so important to create an environment of awareness of who’s doing what with these tools and having forums and programs where we guide our technologists and our scientists not just with the technical knowledge and skills, but with an ethical framework and mechanisms for testing out ideas, for scenario planning, for incorporating a humanistic component in everything they do in the design phase, in the testing phase, in the feedback loops that they get, so that they’re honored and rewarded for thinking things through.
But I talk to technologists and scientists, and they say, no, it’s our job to invent this stuff. It’s somebody else’s job to regulate it. And I get that, but I also feel like you can’t just turn off that side of yourself. I think we are grappling with the most powerful technologies ever invented with the biggest implications ever imagined. And you can’t not think about it. The nuclear scientists basically said, here’s what we’ve done. Please tell us how you would like us to regulate our work. I feel like that’s kind of been lost and bringing it back into the dialogue is really critical.
Is it regulation that is the key force here, or is it politics? Politics in the broadest sense, not just government, but in the wider society. To me, the biggest impediment right now to a lot of these great new technologies and even creating markets for them is people are afraid, and certain demagogues and podcasters fan these fears. People are preoccupied, they’re distracted by the craziness of what’s going on politically right now. How do we overcome that?
We live in an era where everything and everybody is getting discredited all the time, and it’s very hard to stand up for something because everything’s always being ripped to shreds. And our belief in experts, it was fundamental to moving forward. It’s like I’m an expert at making shoes by hand and you’re an expert at genetic engineering and let’s just agree to have a division of labor, and I’ll respect you for your scientific aptitude and you’ll respect me for my craft. We have this shared humanity, but I feel like we’re losing that when the whole movement of conscious capitalism and multilateralism seems to be taking a back seat to partisanship and disinformation and fear.
This is a nice segue into what you’re doing with the Human Immunome Project, which seems like part of the solution to all the fragmentation and anti-science and loss of hope because HIP is planning to create a huge network of regular people having their immunomes tested to help to better understand this core bodily system that we all have, and is key to keeping us all healthier. Can you tell me a little bit more about that?
Absolutely. 25 years ago, the discussion was maybe we should diversify the group of people whose genomes were going to be sequenced for the first time. Maybe it should be more than a few white males. And here we are 25 years later, and Africa is trying very hard to get representative genomes into the scientific data pool. Israel just announced that they’re doing a 150,000-genome project because there isn’t enough Israeli genetics captured in our databases yet. So that’s 25 years later and it impacts our ability to use that data to use genomic science to its best advantage. We didn’t want to make that same mistake with the immunome. Originally, we hoped that we could just get all the scientists together and look at the data that they had already collected and start to put together some working models of at least the people who’ve been sequenced.
But we immediately uncovered multiple reasons why that wasn’t going to work. The first one is the way the data is collected, which has not been standardized. Data formatting is also a huge problem, how you standardize the organization of the data. What this has meant is that the people who’ve had access to super advanced molecular measuring are a pretty rarefied group of elites, most of whom live in North America.
We realized that the only way to really understand how the immune system works is to get a representative sample from all over the world. This means going into low- and middle-income countries where more than half of the world’s population live and capturing the immunomes of people who look very different and have different stresses with things like climate, race, ethnicity, and gender. Even if we only helped to understand the difference in the immune systems of men and women, that would be a huge leap forward in our understanding.
You just made an announcement about this.
Yes, and we’re so thrilled to have announced last Thursday the 10 partners in our new scientific partner network, which represents the absolute leading edge of systems biology and immunological research on five continents.
Who are some of the partners that you announced?
In the United States, we have Yale, Stanford, and the Allen Institute. There are also two different groups out of the Netherlands that have been working with researchers in Tanzania, Senegal, Uganda. We are partnered with the WEHI in Australia, and the researchers there have access to people in Papua New Guinea and also aboriginal people. We’re also excited to partner with RIKEN in Japan, which is the leading immunological research institute there. And they’ve been doing a lot of work with Supercentenarians. One of the things that happens as we age and why we get sick as we age is that our immune system is aging. Understanding how and why that happens is really a critical part of this. Our latest partner announcement is the Sustainable Sciences Institute in Oakland, which is working in Nicaragua.
It’s an extraordinary lineup of world-class experts in systems immunology who are against all their personal interests coming together as a group to collaborate, which is a rare and beautiful thing because scientists are not incentivized to share their data. This partner network is already the largest systems immunology collaboration in history.
Tell me how you got involved with HIP. You were busy with many projects when you decided to basically drop everything to work with HIP. Why?
One reason is the idea of what HIP wants to accomplish is just so compelling. But I also saw what the scientists needed and what was missing from their organization. I tend to work on things that just need a little bit more to get over a hump or I could just see the kinds of infrastructure and resources that were going to be required to make this happen. I also had spent the last 10 years before I joined HIP publishing stories about how biology was being transformed by digital technology, and looking at the leading edge of longevity medicine, neuroscience, and genetic engineering. I was looking at the future of food and thinking about women’s health. But mostly I was telling stories, which is great and exciting, but at the same time HIP was a chance to actually make something happen that wouldn’t otherwise happen.
So now you have become the story rather than writing about it. In fact, you were literally the story in the story I just wrote for Tech Review.
I suppose so. It’s been a great transition, and we’re just getting started.
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