When Microsoft co-founder Paul Allen put up $125 million in seed money for a Seattle institute focused on human immunology shortly before his death in late 2018, no one had any inkling a viral pandemic would strike within a year.

The Allen Institute for Immunology’s emphasis was on cancers and diseases linked to a haywire immune system – like inflammatory bowel disorder, rheumatoid arthritis, and multiple myeloma.  Allen himself died of complications of another immune-related cancer, non-Hodgkin lymphoma.

But now, the fledgling institute has taken on a new challenge: Unraveling the immune response to the novel coronavirus in hopes of speeding development of treatments and vaccines. Another goal is understanding why infection is mild for many people, but fatal for others.

“We all agreed there wasn’t anything more important than this to study right now,” said institute director Tom Bumol. “This is exactly the kind of project Paul would have wanted us to take on.”

The Paul G. Allen Family Foundation, led by Allen’s sister Jody Allen, is funding the work with a $2.5 million grant. The project is a collaboration with the Fred Hutchison Cancer Research Center, which will also share in the grant.

While most studies have focused on patients so sick they require hospitalization, the Allen group is targeting people with mild to moderate symptoms. If scientists can figure out how a normal immune response keeps the disease from becoming severe and eliminates the virus from the body, they can use that insight to evaluate vaccines, said Dr. Troy Torgerson, director of experimental immunology for the institute.

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“We felt like this was an area that wasn’t being as thoroughly addressed, even though the overwhelming majority of people actually have a mild to moderate course or are asymptomatic,” Torgerson said.

The Allen team is far from alone in the rush to understand immunity and the novel coronavirus, but they bring a level of scientific firepower to the search that few other labs can match.

Since its founding, the institute has assembled rooms full of high-tech instruments and coupled them with immense computing and data-processing capacity to create what it calls a “pipeline” geared to examine the human immune system in unprecedented detail.

From a single blood sample, an instrument called a flow cytometer can analyze 80 different proteins on each of three million cells. Other instruments examine thousands of genes at a time to determine which are switched on in different types of immune system cells. Every patient’s genome is rapidly sequenced.

“The number of data points we’re generating each time a patient is evaluated is in the tens of millions,” said Torgerson.

The researchers hope to recruit 50 volunteers, soon after they test positive for the virus, and track them throughout the course of the disease and recovery. Some of the volunteers will be monitored for up to two years, to see how long immunity lasts and how it changes over time.

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Only a handful of research facilities in the U.S. have the capability to take such a deep dive into immune response, said Dr. Jim Heath, president of the Seattle-based Institute for Systems Biology. ISB is among them and is conducting a similar study with Swedish Health System.

It’s already clear from their early finding that the disease is “crazy heterogenous”, meaning that it manifests in many different ways, Heath said. “Even in the same family – two kids, two parents – all four people can have different symptoms.”

It’s going to take a lot of research to sort it out, and Heath welcomes the new project. “It’s needed,” he said. “We’ve got to have a lot of big studies going on.”

Hutch scientist Dr. Julie McElrath and her colleagues have already recruited 400 volunteers – almost half of them firefighters and other first-responders – for multiple immune response studies. Some of the volunteers have been monitored for several months now.

McElrath is eager to work with the Allen Institute because of its ability to integrate vast amounts of information, correlating a patient’s symptoms with their immune profile and genetic data and everything that’s known about where and how they were exposed. “It’s bringing as many pieces as we can together to help us understand what is a protective immune response … and how long will that protective response last,” she said.

She also hopes to figure out why some people seem to have symptoms that linger for months. “That was a surprise to us,’ she said. “I think we will get clues about what is driving that from the studies we’re doing.”

In addition to seeking 50 volunteers for the Allen Institute study, McElrath and her team also hope to recruit another 100 volunteers for their ongoing studies – particularly people who have been recently diagnosed and family members of people with COVID-19.

More information on all of the studies is available at https://tinyurl.com/y52sbt5x