Hans Keirstead, neuroscientist: ‘The immune system is an enigma, we understand almost zero about its diversity’

The researcher is CEO of the Human Immunome Project, which aims to decode the complex biological network that defends the organism from foreign threats

Hans Keirstead
Hans Keirstead, CEO of the Human Genome Project, photographed in the CosmoCaixa Museum in Barcelona after a scientific meeting of immunologists.massimiliano minocri
Jessica Mouzo

Within every human being there is an army of cells, tissues and organs that guard their organism against external threats. Together, these make up the immune system, a complex biological network on which our survival, health and disease depend to a large extent. Science knows about its structure, its modus operandi, and has even learned to train it with targeted pharmaceuticals that recognize the body’s enemies and annihilate them. But despite these advances, our knowledge of the immune system continues to be limited, and there are parts of it that are still not understood, says neuroscientist Hans Keirstead (Halifax, Canada, 56). The researcher is the CEO of the Human Immunome Project (HIP), an international non-profit initiative that has set out to decode this complex biological network.

The project’s first step will be to compile data from millions of people from around the world in order to build a solid and diverse database that will allow it, with the help of artificial intelligence (AI) models, to predict immunological response and accelerate research. Keirstead, who visited Barcelona to take part in a scientific meeting with immunologists organized through the programming of the future CaixaReseach Institute, says that this vast project will allow us to have “safer drugs,” take advantage of “better access” to treatment and even predict the course of diseases and responses to medications.

Question. Is the immune system still an enigma?

Answer. The immune system is an enigma for every immunologist in the world, we know less than 5% of it. We understand a great deal about the immune system, but we understand almost zero about its diversity. We understand it statically, but we do not understand how it changes in response to age, disease, ethnicity, social economic class… It’s the variation that we don’t understand. The Human Immunome Project will code the baseline human immune system in every variation that I just mentioned. The HIP will define the immune system in every population, which will result in more drugs being developed that are personalized to sex or skin color or social economic class, and there will be fewer side effects, which means healthcare costs go down globally and nationally.

Q. Do we have information on what makes a healthy immune system?

A. The world knows what a healthy immune system is, but it doesn’t know how that healthy immune system changes with age. We don’t know how that healthy immune system changes when the patient has a challenge. We don’t know how a healthy immune system in a male versus a female differs. We can define what a healthy immune system is, but the studies have been done on a very small class of humans, all mostly in advanced nations. So, you have a very small representation of the human’s diversity. Therefore, the drugs that are made, that are tested on wealthy Caucasians, when they are applied to Black men in their 50s, who have the highest degree of autoimmunity, those drugs may cause side effects in that population. But we don’t know because we haven’t defined the immune system of that population. I would say that the biggest outcome of the Human Immunome Project is going to be an understanding of the immune system and its diversity. That will have the effect of more drugs, cheaper drugs, healthier lives.

Q. Since so much knowledge is lacking about how the immune system works and all its diversity, do you think that the real power of our immune system is being underutilized right now?

A. I believe that in any state of the human, the immune system is doing its best, but it is challenged by several things that we don’t understand. Perhaps the food that you eat, perhaps the toxins that you are experiencing, maybe it’s the age that you are. They have a very negative effect on your immune system in many cases, but we don’t understand that. So, maybe your immune system is often functioning optimally, but this project is going to establish the correct baseline for you [specifically]. That will then allow your doctor to assess your immune system to see if you’re down here or up here, if you have a relatively good or relatively bad immune system. That is going to allow better functioning of your immune system by detecting the difference from normal. Then we can begin to identify what is it about your lifestyle or your physiology that’s causing a deficit in your immune system, which causes a deficit in your organs.

Q. Is it true that immune response or immune health trajectories can be predicted, as in how a disease will evolve or when I will get sick?

A. The data combined with artificial intelligence will be able to predict degeneration with age or disease because we will have analyzed, as a norm, a healthy person and a diseased person and both those populations at multiple time points with age. Once we have created a Gaussian norm of each of those states — me when I was 20, me when I was 25, me when I was 30 — and we watch in all of those populations how the immune system changes and denigrates with age, then we know how to intervene. So yes, the AI will be able to predict those things. When we get your genes, one patient’s biome, genetic code, we can then compare you to the predictive models and see markers that are correlated with disease that you’re beginning to show. So, we’ll be able to predict disease better. Look at what the Human Genome Project has done by knowing whether a woman expresses BRCA3, it predicts with certainty breast cancer. The distance between the gene and your physiology is very big, but your immune system and your physiology are neighbors. So, if you define and code the immune system, its ability to predict disease is phenomenal, its ability to predict how you will react from a drug. We take your immune system, we don’t give you a drug yet, we compare it to this model when we have the data and we will be able to say, that’s the wrong drug, but this drug is right for this immune system. The power of that, this data set that we are generating worldwide, means safer, more effective drugs for everybody.

Q. Will these numbers open the door to understanding why some patients respond to treatments while others do not?

A. Absolutely correct. This database will allow for predictive modeling of responses to disease and drugs, and in less severe instances, your own daily choices of lifestyle, because knowing how your immune responds to foods allows you to understand allergies. So, you can educate your own lifestyle and behavior, so as to maximize health span.

Q. If the immune system plays a role in how or when we age, can we optimize aging or increase life expectancy?

A. Every manifestation of aging is mediated by the immune system. Muscle atrophy, brain inflammation, arterial stiffness, metabolism, bone density, it all declines with age. It’s a fact. If you can define what the baseline of the immune response is, if we get your immune system fingerprint, we can use it to predict how you are going to age. According to that norm, we’ll also be able to predict how that immune system and your health is going to change and how you can alter your immune system in order to keep yourself healthy. This is certainly going to help with lifespan, but more importantly health span, how healthy you are. Because we know that an old person’s demise is immune mediated. If we understand how and what that is, then we can modulate it.

Q. But to modulate it, to what extent? Will we be able to live longer?

A. I can’t guess right now, but I can tell you with certainty that by understanding the immune changes with age, we can discover therapeutic targets. Right now, we don’t understand, so we can’t target. But if we understand the difference between now and then, we can particularly target what is changing in order to keep you healthier. How long, I can’t say. Theoretically, it should have tremendous benefits for both lifespan and health span. But until we test those drugs, we won’t know.

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