Written by Grace Browne
Originally published by WIRED
February 15, 2022

DIGITAL TWINS—VIRTUAL REPRESENTATIONS of real-world things—are already a mainstay in manufacturing, industry, and aerospace: There are digital doppelgängers of cities, ports, and power stations. The term was first introduced in 2010 by NASA researcher John Vickers in a report about the agency’s technology road maps, and industry analysts estimate the market for digital twins could reach nearly $50 billion by the year 2026.

It wasn’t long before the idea crept into biology. In 2016, Bill Ruh, then-CEO of GE Digital, predicted that “we will have a digital twin at birth, and it will take data off of the sensors everybody is running, and that digital twin will predict things for us about disease and cancer and other things.” A digital twin could inform tailored treatments for a patient and predict how their disease might develop. It could even be used to trial potential treatments, rather than testing them on the patient—a process that can be filled with risk.

So far, these projects are mostly in their early stages. A research program called Echoes, involving researchers in Europe, the United Kingdom, and the United States, is working to build a digital heart. Siemens Healthineers, a German medical device company, is aiming to do the same. Dassault Systèmes, a French software company, teamed up with the US Food and Drug Administration to approve what it calls “The Living Heart.” Austrian company Golem is creating digital twins of vulnerable people who live alone. The idea is that the digital twin continuously monitors their health, alerting caregivers if they fall ill and need help.

Now researchers are shooting for the loftiest goal: to twin the brain. Neurotwin, an EU-funded project, wants to design a computerized model of an individual patient’s entire brain.

The Neurotwin team is hoping the model can be used to predict the effects of stimulation for the treatment of neurological disorders, including epilepsy and Alzheimer’s disease. They’re planning a clinical trial that will kick off next year and create digital twins of about 60 patients with Alzheimer’s, who will receive a brain stimulation treatment that has been optimized specifically for their brain. A second clinical trial planned for 2023 will do the same, but for patients with treatment-resistant focal epilepsy. Both are proof-of-concept trials to determine whether the approach works and can improve treatment outcomes for these patients. If successful, the team plans to extend their technology to study other aspects of the brain, such as those involved in multiple sclerosis, stroke rehabilitation, depression, and the effects of psychedelics.

For about a third of epilepsy patients, drugs don’t help. Noninvasive stimulation, in which electrical currents are painlessly delivered to the brain, has been shown to help alleviate the frequency and intensity of seizures. But the technology is still pretty new and needs some refining. This is where a virtual brain could prove useful.

The digital avatar is essentially a mathematical model running on a computer, says Giulio Ruffini, coordinator of the Neurotwin project and chief science officer and cofounder of Neuroelectrics, a Spanish health tech startup that is developing noninvasive therapies for neurological disorders like epilepsy. To make a digital double for a patient with epilepsy, the Neurotwin team takes about half an hour’s worth of MRI data and about 10 minutes of EEG (electroencephalography) readings and uses these to create a computer model that captures the electrical activity of the brain, as well as to realistically simulate the brain’s main tissues, including the scalp, skull, cerebrospinal fluid, and gray and white matter.

The twin will include a network of embedded “neural mass models,” says Ruffini. These, he says, are basically computational models of the average behavior of many neurons connected to each other using the patient’s “connectome”—a map of the neural connections in the brain. In the case of epilepsy, some areas of the connectome could become overexcited; in the case of, say, stroke, the connectome might be altered. Once the twin has been created, the team can use it to optimize stimulation of the real patient’s brain “because we can run endless simulations on the computer until we find what we need,” Ruffini says. “It is, in this sense, like a weather forecasting computational model.”

For example, to improve treatment for an epilepsy patient, the person would wear a headcap every day for 20 minutes as it delivers transcranial electrical stimulations to their brain. Using the digital twin, Ruffini and his team could optimize the position of stimulating electrodes, as well as the level of current being applied.

Digital twinning any organ opens up a whole host of ethical questions. For example, would a patient have the right to know—or to refrain from knowing—if, say, their twin predicts that they’ll have a heart attack in two weeks? What happens to the twin after the patient dies? Will it have its own legal or ethical rights?

On the one hand, virtual body doubles provide us with exciting, revolutionary pathways to develop new treatments, says ​​Matthias Braun, an ethicist at the University of Erlangen-Nürnberg, Germany, who has written about the ethics involved in the use of digital twins in health care. “But, on the other hand, it provides us with challenges,” he continues. For one thing, who should own a digital twin? The company building it? “Or do you have a right to say, well, I refuse the use of specific information or specific predictions with regard to my health insurance or with regard to the use in other contexts? In order to not be an infringement on autonomy or privacy, it is important that this specific person has control of the use [of their digital twin],” he says. Losing that control would result in what Braun dubs “digital slavery.”

Ana Maiques, the CEO of Neuroelectrics, says the company is already grappling with the issue of what happens to the extremely personal data a digital twin is built upon. “When you’re doing these kinds of personalizations, you have to ask difficult questions, right? Who’s going to own that data? What are you going to do with data?” she asks.

The project has enlisted researchers to dissect the ethical and philosophical components of the endeavor, including Manuel Guerrero, a neuroethicist at the University of Uppsala, Sweden. For Neurotwin, a project based out of Europe, the data gathered will be protected by the European Union’s General Data Protection Regulation (GDPR). This means any use of the data requires the consent of its owner, Guerrero says.

Guerrero and his team are also exploring whether the term “digital twin,” which was first coined for manufacturing, is still the most apt term for copying something as intricate and dynamic as a living brain or heart. Could its use lead to misunderstandings or raised expectations within society? “[The brain] is much more complex than other types of twins that are coming from the manufacturing system, so the notion of a twin for the brain is something that, within the neuroscientific community, is being debated,” he says.

And taking on the brain is many orders of magnitude more complex than modeling the heart or kidney, in addition to being potentially more ethically complex. “We are creating fairly sophisticated computational models of the brain,” Ruffini says. “At some stage, I think it will become blurry to what extent this digital twin is a digital twin or it’s a sentient being.”

Braun says it’s time to reckon with these thorny questions. “To me, these are really important challenges we have to face now,” he says. “We know what happens if you just say, ‘Well, just develop a technology—and then we’ll see,’” he adds, warning of the dangers that come with pushing ethical and moral consequences off to a later date.

But the Neurotwin team says that, if done right, this digital twinning could dramatically improve both patient outcomes and what we know about tricky-to-treat brain disorders. “We are working to really help people suffering from brain diseases from a completely different perspective,” says Maiques. “We like to call it a new category of therapeutics, where you’re really using the power of physics and math to decode the brain.”

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