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The first digital twin of the human immune system highlights the vast societal opportunities in physical-digital fusion. This project in the making could make us safer, healthier and better prepared for the next health crisis. Discover the exponential potential of true immunity modeling.
Liam Helikar is a bright eight-year-old with light hair and a cheeky grin. He loves skiing. To the outside world, he looks like any other little boy. The difference is he needed a lung transplant at nine weeks and is now on a regimen of drugs that suppress his immune system.
The recent health crisis brought immunity into everyone’s consciousness. Suddenly nobody knew their risk. For people like Liam, where immunosuppression means additional risk every day, the fear went into overdrive. And when Liam did become ill in December 2021, he did need hospitalization and he did require aggressive treatment.
His dad, Tomáš Helikar, was beside himself. And like for any parent in this situation, it was made far worse because there was nothing he could do. But unlike other parents, Helikar had a plan to change things. Since 2016 he’d been racing against the clock to build a digital twin of the human immune system – a virtual replica of biology to first help people like his son but then help anyone, anywhere, whatever their immunity status.
Virtual replicas of ‘real life’ give humanity exponential insights
We tend to think of the real world – ‘real life’ – as tangible and solid and quite distinct from things experienced through a virtual box. But this isn’t entirely true. Much of the real world – like the seabed, the innards of cars, or the workings of our bodies – is hidden.
Digital-physical fusion creates dynamic representations of real-world objects, systems, and processes in the digital world and can make these things become clearer. And the human immune system is, in many ways, the ultimate example.
Immunity is very complicated. At the start of 2020, the NHS in the UK created a 3.7 million-strong official ‘shielding’ list of anyone it considered high risk. “It was terrifying, and I had no idea how bad my immunity really was,” says Sarah [name changed], a fit and healthy lymphoma survivor then in her late 30s who appeared on the list.
“My nurse wasn’t even sure either. My immunity could have been weakened by the initial [blood] cancer, the chemotherapy treatment I previously received, or the ongoing maintenance injections,” explains Sarah.
Most cancer evades the immune system in one way or another. And many blood cancers – like lymphoma – change how immune system blood cells work. But even this is only a tiny fragment of the big picture because not all people who appeared high risk back then really were. When Sarah caught the virus, she was fine, while others, who sounded better on paper, were not so lucky.
Helikar explains: “We don’t even know what a healthy immune system is.” This is because each immune system is completely individual and based on numerous variables. Your unique immunity will factor in your age and general health, the illnesses you’ve had, any vaccines you’ve been given and any medications you’re on. Drugs could suppress one part of the immune system but also have a complex knock-on effect elsewhere.
This makes modeling the immune system a vital first step to really understanding it and critical to opening the door to a raft of insights. “My [ultimate] goal is to be able to program the immune system to do what you want it to do,” says Helikar.
Why do we need a digital twin of the human immune system?
Digital twins provide a raft of advantages in all walks of society and business. The immune system project could mean:
- A clear model of something very complicated
- The chance to see – and understand – connections that were previously opaque
- Immediate support for tackling immune-dependent conditions like organ transplants, cancer, and autoimmune diseases
- Quicker and cheaper drug discovery
- A doorway to drugs with less harmful side effects
- The route to personalized medicine
The first 25 cells lay the foundations for personalized medicine
In August 2022, the project won a $5 million slice of the University of Nebraska–Lincoln’s first Grand Challenge to build a working model in five years through its expanded Digital Twin Innovation Hub.
The secret to the task is to be “iterative,” says Helikar. So, first, the team worked with a host of respected immunologists to identify the first 20 – 25 cells necessary for the immune system to function. The next ongoing challenge is to build out every cell and every physiology into a virtual model.
The initial question was how to “connect the cells mathematically,” explains Helikar. To achieve this, they began to model CD4 and T-Cells, which are the innate and adaptive immune system. “We got one of the hard parts,” says Helikar. “Now we need to scale.”
Like any technology project, scaling is often the toughest part as it must move quickly and efficiently while incorporating diverse elements. For example, this needs to be accessible to non-computational biologists.
Helikar stresses, “if this is just an academic exercise, it’s not a complete success”. It needs to be able to tackle all the complexity of real situations, real diseases, and flex to real working practices.
“We always want to show the utility of the models as we’re building them,” he says, and as a result, the team is testing its iterative model in different settings along the way. In the first instance, this is on different immunity-related diseases.
There’s work in progress with the University of Nebraska’s Medical Center to look at how building computational models can identify the most effective and least toxic immunosuppressants for liver transplant patients. A previous study looked at the validity of certain drugs for a set of autoimmune conditions, like rheumatoid arthritis.
How else can digital twins be used?
Digital twins have a raft of uses – from simple virtual replicas to models with exponential benefits:
- Complex machines, like car engines – to aid production and efficiency
- Industrial assets, like factory machinery – to track equipment health and maximize productivity
- The network – to monitor operations and improve available services
- Smart cities, from town planning to streetlamps – to facilitate safer, greener spaces for people to live
- Biological processes, like the immune system – to see deeper into the human body and enable the next frontier of medicine
For people with conditions like this – where existing treatments can cause headaches, reduce fertility and heighten the likelihood of other infections – the hope is better drugs will be developed faster and cheaper. Because the sobering statistic is that it can take ten years to develop a single drug and a present 90% fail clinical trials.
“Doctors tend to look at one or two cell types and fail to take into account the others,” says Helikar. It’s like playing a game of Whac-A-Mole. You don’t know the other systematic effects.”
The ultimate aim – which is still some considerable way out – is to build a blueprint that can be fully personalized. So, in the future, you visit your doctor and they have your up-to-date digital twin on file, which includes any information from your health provider, like vaccine statuses and blood tests, but perhaps also incorporate a regular flow of information from any relevant personal tracking devices.
For those like Liam Helikar with conditions that directly impact immunity – it could be life-changing as it could show heightened or reduced risk. Maybe Liam’s fine to go skiing on Tuesday. Maybe he isn’t. Perhaps this new drug will suit him. Perhaps it won’t.
Complex solutions are only possible through a brilliant collective
At the start of 2020, a small group of talented scientists from various academic institutions – including Reinhard Laubenbacher from the University of Florida and James A Glazier from Indiana Bloomington – got together to model viral pandemics. Since then, this group of scientists has snowballed, coming together on the digital twin of the human immune system project, and publishing a “roadmap” in Nature Digital Medicine.
“To deliver an immune digital twin is a billion-dollar project and cannot be done by a single investigator,” Glazier told an Indiana University press release. “This group and this roadmap are paving the way to make it happen. Now it seems much more tangible.”
In an interview with our Real Conversations podcast, he made an analogy to the Human Genome Project, which was a huge endeavor but for a long time, “looked like it was never going to happen. Once it happened, it didn't happen primarily through classic science. There were big projects and there were commercial projects that did it.”
This full collective of individuals involved has now swelled to over 30 professionals, including undergraduate researchers and respected scientists from across universities. While the wider social benefits – and challenges – are also becoming apparent, Helikar is increasingly focused on working with federal agencies, the private sector, and other stakeholders to open the door to new opportunities.
The last three years have shown us what a secretive superpower immunity really is – both for us as individuals and society as a whole. If a digital replica of this hidden reality can bring this out into the open, then who can argue? Helikar’s hopes for the project are numerous and varied. He’d like to speed up drug discovery, open the door to personalized medicine, and maybe – just maybe – be better equipped to help little Liam through his next health crisis.