Digital twins are simulatable replicas of real-world systems and have been employed by many industries that work with complex data, such as manufacturing, but never for any of the intricate systems of the human body.

Thomas Helikar, associate professor of biochemistry, aims to change that, and has earned a Grand Challenges Catalyst award for his ongoing work to build out a digital twin of the human immune system.

Like all digital twins, which are computational models that can identify and prevent issues prior to implementing significant changes to an existing real-world operation, Helikar’s digital twin of the human immune system aims to predict responses to pathogens and treatments to immune-related diseases, and will be instrumental in understanding disease processes and for developing life-saving drugs and preventative medicine. The project is deeply personal, too, as Helikar’s son is immune-compromised due to a lung transplant he underwent as an infant.

“In many ways, we’re playing a game of whack-a-mole (with his treatment) because when you start looking at the relationships and connections between these different cells in the immune system, there are feedback mechanisms that affect other parts of the system,” Helikar said. “I’m hoping that we’ll be able to control the immune system in a safer and more predictable fashion.”

It is a lofty goal, but Helikar has made crucial strides in the last few years, including attaining ongoing funding from the National Institutes of Health in February, and in May, publishing a “roadmap” for building out the digital twin immune system in Nature Digital Medicine.

The five-year, $5,039,652 Grand Challenges Catalyst Award will establish the Digital Twin Innovation Hub, which will broaden the team and disciplinary expertise working on the project. Helikar is the principal investigator, and is joined by co-investigators Lindsey Crawford, assistant professor of biochemistry; Bhanwar Lal Puniya, research assistant professor in biochemistry; and Hongfen Yu, associate professor and director of the Holland Computing Center. Sara Aghamiri, computational modeling engineer in biochemistry, will serve as manager of strategic partnerships.

Helikar sat down with Nebraska Today to talk about the project, how the Catalyst Award will shape its future, and the future of medicine with digital twins.

You’ve had a lot of success with this project in the last year. How will the Catalyst award propel this project forward even more?

We are now finishing up a model, or roadmap, of the immune system at the cellular level, which will be a blueprint for “the house” we’ll be building. Right now, in our lab, we have about 15 people. A result of the Catalyst, we will be hiring another 10 to 15 people, plus about 60 undergraduate students over the five-year period.

The NIH grant enabled us to build the tools and methods that we will put to use here at scale and will enable us to develop, in a much faster way, this infrastructure for the virtual immune system. Our five-year objective with the Catalyst award is to have a first draft of the digital twin of the immune system that will be hopefully usable for the scientistfic and clinical communitiess, and researchers. We are already part of large international communities interested in the development and use of an immune system digital twin, and this award will provide infrastructure and enable collaborative work much beyond our team.

The Catalyst award also allowed us to establish a partnership with the Johnny Carson Center for Emerging Media Arts (Megan Elliott and Robert Tercek), to help us design our digital twin for different users. We’ll be hiring a designer who will work with our team, as well as our external partner, David Bolinsky, who is a renowned medical artist, to help us design the user interfaces. Dr. Pam Boyers of iEXCEL, specializing in medical simulations for training, will also advise us on the implementation.

The immune system is so important, but I think most of us take it for granted, or don’t fully grasp how complex it is. When you think of overall health, what role does the immune system have?

It literally impacts everything and it changes with our age, and changes in response to our environment. It really impacts us in every single possible way, even our brain.

Cancers develop when the immune response or the immune system is unable to clear cancerous cells. If you’re immunosuppressed, in particular, because you had a transplant or are an HIV patient, the risk increases for cancer because you now don’t have the full immune surveillance that would normally eliminate cells that could develop into cancer cells.

When we think of the idea behind the Grand Challenges Initiative and solving big problems, how does a digital twin of the immune system make a big impact? What is its future role?

This is years down the road, but I am hopeful that a virtual immune system can be developed for individuals, based on their own environmental, disease, and immune system history, to really personalize care and predict how you might respond to an infection or an immune-related disease.

Also, it takes $1.2 to 2.5 billion and over 10 years to develop a single drug — from idea to market. Only 7% of initial compounds make it to phase one clinical trials. That means there is a 93% failure rate, and there is no other industry that is OK with such a high failure rate. With this virtual immune system, I believe we can help that pipeline.

And on the clinical side, for example, you have some rare diseases that don’t have good treatments because there isn’t a large enough population for clinical trials. With the virtual immune system, or computer models based on the human body, you could possibly do virtual clinical trials to generate the data. The FDA is moving toward using virtual computational models as a way to supplement data to validate provisional treatments. To this end, the Digital Twin Innovation Hub will also work with the Nebraska Drug Discovery and Development Pipeline (led by David Berkowitz and Kenneth Bayles) to accelerate and increase the odds of the development of new therapeutics.

Editor’s note — This conversation has been edited for length and clarity.

Biochemistry Grand Challenges