Highlights of Fred Hutch science in 2021

photo of a woman wearing a surgical mask and holding up a vial in a lab setting — Emily Park works on the new Sony ID 7000 machine, one of the most advanced cell analyzers in the world, on Feb. 9, 2021, in the Flow Cytometry shared resource in the newly opened Steam Plant Building at Fred Hutch. Photo by Robert Hood / Fred Hutch News Service

In 2021, the continuing COVID-19 pandemic challenged our daily lives but also sparked incredible scientific advancements as researchers worked to understand the evolving SARS-CoV-2 virus and develop ways to stop the disease.

Throughout the year, Fred Hutchinson Cancer Research Center scientists were at the forefront of COVID-19 research, publishing important results from COVID-19 vaccine trials and insights about the virus’s evolution and potential immune escape. Meanwhile, Hutch research on cancer and other diseases proceeded in office, lab and clinic — safely, thanks to on-campus vaccination clinics and other science-informed safety measures that allowed zero on-campus transmission of the COVID-19 virus.

Here is a look back at Fred Hutch research advances over the year, pulled from scientific journals and our scientists’ Twitter feeds.

Left: Arlyce Coumar, in red, who normally works to educate nurses at Seattle Cancer Care Alliance, distributes COVID-19 vaccine packets to injection nurses on Jan. 22, 2021, at Fred Hutch's brand-new vaccination clinic in the Arnold Building on the Fred Hutch campus. Right: Licensed practical nurse Yuka Urano waits through her 15 minute observation after receiving the Pfizer COVID-19 vaccine at the Fred Hutch vaccine clinic on Jan. 19, 2021.

Top: Arlyce Coumar, in red, who normally works to educate nurses at Seattle Cancer Care Alliance, distributes COVID-19 vaccine packets to injection nurses on Jan. 22, 2021, at Fred Hutch's brand-new vaccination clinic in the Arnold Building on the Fred Hutch campus. Bottom: Licensed practical nurse Yuka Urano waits through her 15 minute observation after receiving the Pfizer COVID-19 vaccine at the Fred Hutch vaccine clinic on Jan. 19, 2021.

Photos by Robert Hood / Fred Hutch News Service

Advances in COVID-19

In 2020, Fred Hutch scientists were among the first to raise the alarm about the SARS-CoV-2 virus’s spread and stepped up to help lead the nation’s vaccine development enterprise. That scientific leadership continued in 2021. While viral variants spread and vaccines rolled out across the U.S. and much of the world, Fred Hutch scientists continued to make new discoveries that can not only help us respond to the COVID-19 virus as it evolves, but also other threats in the future.

Tweet from Trevor Bedford (@trvrb) from 9:43 a.m. on Jan. 14, 2021: After ~10 months of relative quiescence we've started to see some striking evolution of SARS-CoV-2 with a repeated evolutionary pattern in the SARS-CoV-2 variants of concern emerging from the UK, South Africa and Brazil. 1/19 — With nearly 2,500 retweets by mid-December, this thread from Dr. Trevor Bedford is one of the top three most-shared Tweets from Fred Hutch scientists in 2021. Click to view on Twitter

Over the course of the year, researchers in the nationwide COVID-19 Prevention Network, headquartered at Fred Hutch, published the results of their huge trial of the Moderna mRNA vaccine against the COVID-19 virus, demonstrating its safety and efficacy in more than 30,000 participants. Meanwhile, Fred Hutch scientists involved in the historic undertaking offered more insights from the trials:

Lead CoVPN biostatistician Dr. Peter Gilbert and colleagues defined measurements of immune responses, called correlates of protection, for the Moderna vaccine. By using these measurements, tests can quickly show how well future COVID-19 vaccines are working, scientists would not need to wait months for results or enroll such extraordinary numbers of people.
Dr. Michele Andrasik, who is director of social and behavioral sciences and community engagement for the network and a senior staff scientist at the Hutch, co-authored a perspective piece on how to build trust, partnership and reciprocity between vaccine researchers and Black, Indigenous and people of color, or BIPOC, communities, with a special focus on the work of the CoVPN toward equitable inclusion in its vaccine trials.

photo of Peter Gilbert, in a mask, sitting at a conference table and talking with two other people — Dr. Peter Gilbert (left) talks with U.S. Rep. Marilyn Strickland, from Washington state's 10th Congressional District, and Fred Hutch President and Director and Raisbeck Endowed Chair holder Dr. Thomas J. Lynch Jr., on Oct. 7, 2021 at Fred Hutch. Photo by Robert Hood / Fred Hutch News Service

“There has been discourse stating that it is challenging and there are too many barriers to engaging with BIPOC communities,” Andrasik said. “We are hoping that this shows these are surmountable barriers, and it is possible to overcome them through long-term investments in relationships within the community and building reputations of trustworthiness as researchers and institutions.”

Other Hutch researchers analyzed samples from vaccine trials to gain more insights about the vaccines’ effects. In March, a team led by Drs. Leo Stamatatos, Joel D. Meyers Endowed Chair holder Julie McElrath and Andrew McGuire found laboratory evidence that patients who have been infected with the COVID-19 virus and are subsequently vaccinated against it with an mRNA vaccine mount a stronger immune defense than those who were vaccinated but never infected with the virus.

CoVPN researchers, including Dr. Michele Andrasik (pictured) discuss how the network worked with communities to achieve equitable inclusion and better health.

Video courtesy of the COVID-19 Prevention Network

Another active area of COVID-19 research at the Hutch in 2021 was on mutations in the virus and the effect of these mutations on neutralization by antibodies, the targeted immune proteins elicited by infection and vaccination. This research aims, ultimately, at understanding how the virus could escape our immunity and thus informing the design of future vaccines and antibody treatments. (Read more about this research, including several of the studies described below, in the Fred Hutch News Service story: How studies of coronavirus immunity can inform better vaccines, treatments)

In March, Endowed Chair for Graduate Education holder Dr. Julie Overbaugh’s team examined the interaction between antibody binding and viral mutations in regions along the stem of the SARS-CoV-2 spike protein using antibodies produced by infected people. The findings illustrated how antibodies can target a variety of locations on the spike protein. Thus, vaccine designs that prompt a broad, not-too-focused, antibody response may be harder for the virus to escape than those that generate strong, but overly focused immunity.
In January, Drs. Tyler Starr and Allison Greaney on Dr. Jesse Bloom’s team mapped mutations in the virus that allowed it to escape the monoclonal antibodies used in treatments for COVID-19. Later, in July, Starr and his teammates examined how different monoclonal antibodies interact with the spike protein in SARS-related coronaviruses. In one paper, they described the ability of 12 monoclonal antibodies to bind the virus’s spike protein in 45 different SARS-related coronaviruses, and mapped which mutations would allow them to escape neutralization. They identified one particular antibody that has the unusual ability to bind a key region of the spike protein from multiple coronaviruses, even when separated by sometimes hundreds of years of evolution — including a divergent group in bats that has never spilled into humans. A second study examined another monoclonal antibody that also neutralizes many distantly related coronaviruses — but recognizes a separate region of the spike protein. The researchers noted that important regions like these could inform the design of vaccines and antibody therapies that protect against a wide array of SARS-related coronaviruses.

photo of Tyler Starr working in a laboratory — Dr. Tyler Starr, a postdoctoral research fellow, works in the Bloom Lab at Fred Hutch on May 21, 2019. Photo by Robert Hood / Fred Hutch News Service

Outside of these studies in his lab, Bloom was active in another area of coronavirus research: the question of where SARS-CoV-2 came from. In late spring 2021, the evolutionary biologist became one of the leading scientific voices calling for a more thorough investigation of SARS-CoV-2’s origins.

“Greater clarity about the origins of this pandemic is necessary and feasible to achieve. We must take hypotheses about both natural and laboratory spillovers seriously until we have sufficient data,” Bloom and coauthors wrote.

A Tweet from the Bloom Lab account (@jbloom_lab) at 2:09 p.m. on June 22, 2021 that reads: In a new study, I identify and recover a deleted set of #SARSCoV2 sequences that provide additional information about viruses from the early Wuhan outbreak: https://biorxiv.org/content/10.1101/2021.06.18.449051v1 (1/n) — This Tweet from Dr. Jesse Bloom from June was one of the top three most-shared Tweets from a Hutch scientist in 2021 with more than 2,600 retweets by mid-December. Click to view on Twitter

Other Hutch scientists played a prominent role in raising concerns that summer about coronavirus evolution in immunosuppressed patients. Dr. Larry Corey, who co-leads the CoVPN’s vaccine testing pipeline, and computational biologist Dr. Trevor Bedford and colleagues called for heightened precautions in the treatment of people with weakened immune systems and better, more intensive therapies to help them recover from their disease in the wake of findings that virus variants are more likely to spring from such individuals.

Chronic infection in an immunocompromised person could, in fact, have been what led to the emergence of the omicron variant in late November, though scientists can’t yet know for sure. As 2021 closed, the highly mutated variant began to sweep the globe. And, once again, Fred Hutch scientists were on the case, tracking and modeling its spread, evaluating its ability to escape immunity, and advising officials on how to respond.

Tweet from Trevor Bedford (@trvrb) from 1:59 p.m. on Nov. 26, 2021: There have been a number of overview threads on the emerging variant designated as @PangoNetwork lineage B.1.1.529, @nextstrain clade 21K and @WHO Variant of Concern Omicron. I'm not going to attempt to be comprehensive here, but will highlight a few aspects of the data. 1/16 — This late-November Tweet from Dr. Trevor Bedford about the omicron variant was one of the top three most-shared Tweets from a Fred Hutch scientist in 2021, with more than 2,500 retweets in just three weeks. Click to view on Twitter

As it becomes clear that SARS-CoV-2 will always be with us, Fred Hutch scientists at the Hutch’s COVID-19 Clinical Research Center are helping to develop new treatments for infection. In October, Hutch researcher Dr. Adrienne Shapiro was a lead author on the publication of interim results of a Phase 3 trial of the monoclonal antibody treatment sotrovimab, which found that compared to the placebo group, COVID-19 patients who received sotrovimab had a significantly reduced risk of hospitalization or death and that the outpatient IV treatment was safe.

“As long as people are getting COVID-19, there is a need for effective treatment to prevent serious illness and death,” Shapiro said.

a patient sits in a chair in a clinical room with a health care worker standing alongside with medical equipment — In the COVID-19 Clinical Research Center Fred Hutch file

For more highlights of Fred Hutch COVID-19 research in 2021, read the Hutch’s COVID-19 timeline featuring prominent media coverage and review this wrap-up of the latest Hutch research on COVID-19.

Cancer therapy

Cancer did not slow down for the pandemic, and Hutch researchers published several key studies in 2021 they hope will lead to improved treatments for people with many forms of cancer.

In June, Dr. Robert Bradley and collaborators published research demonstrating how RNA-altering drugs might improve cancer immunotherapy. Their work in petri dishes and mice shows that drugs that trigger errors in mRNA codes can cause tumor cells to sprout — sort of like adding eyes on a potato — lots of new and varied surface proteins called neoantigens. The body’s immune cells read these odd little protein displays as foreign, and they respond by attacking the tumor cells that carry them.

Dr. Rob Bradley, wearing a white lab coat and disposable gloves, looks at something he is holding in a laboratory — Dr. Robert Bradley works in his Fred Hutch lab. In addition to his own research, Bradley is the scientific director of the Hutch's Translational Data Science Integrated Research Center. Photo by Robert Hood / Fred Hutch News Service

“We normally think of mutations as a bad thing that are a cause for a tumor to start. But once a tumor is there, if it has a lot of mutations it can be a good thing, because it lets us use these new, transformative therapies,” said Bradley, who holds the McIlwain Family Endowed Chair in Data Science.

The potential role of neoantigens in immunotherapy was also the focus of research published in July by Dr. Evan Newell and colleagues. These researchers are exploring why checkpoint inhibitors, drugs that “take the brakes” off immune responses, do not work in most patients. Using advanced techniques, they studied a failed response to such checkpoint inhibitors in mice with lung tumors. They found the mice generated plenty of killer T cells against a particular neoantigen, but the tumors did not shrink. Instead, the T cells showed traits of immune exhaustion, an unexplained weakening of their cell-killing functions. The work provides clues for further research on anticancer drugs and vaccines.

Dr. Evan Newell looks at data and colorful charts on a large computer screen — Dr. Evan Newell works in his Eastlake Building office at Fred Hutch in April 2019. Fred Hutch file

In September, Dr. Taran Gujral and teammates demonstrated how machine learning, deep neural networks and other artificial intelligence tools can screen, identify and validate compounds, including some approved drugs, that could provide benefit to patients with advanced prostate cancer and other serious conditions. They identified two compounds that acted in a specific way against key molecules involved in prostate cancer growth and progression and suppressed prostate tumor growth in the lab.

“Our goal was to determine if FDA-approved drugs available for clinical use might forestall drug development and deliver timelier solutions,” Gujral said.

Two people look at a computer screen together — Dr. Taran Gujral (standing) and graduate student Thomas Bello, who was the first author of the 2021 prostate cancer paper, work in the Gujral Lab at Fred Hutch on July 1, 2019. Fred Hutch file

HIV and other infectious diseases

Fred Hutch’s leadership in COVID-19 research is built off the Hutch’s decades of expertise in infectious disease research, especially in HIV. Much of this HIV expertise lies in the HIV Vaccine Trials Network. Headquartered at the Hutch, the HVTN is the world’s largest publicly funded, multi-disciplinary international collaboration facilitating the development of vaccines to prevent HIV/AIDS. In 2021, HVTN researchers published the results of large clinical trials of HIV prevention strategies:

A large international study — the Antibody Mediated Prevention, or AMP, trials — showed that it is possible to prevent some HIV infections with infusions of a particularly potent protein known as a broadly neutralizing antibody, but it will likely take a combination of different and more potent proteins to block all strains of the shape-shifting virus. The results, published in early 2021, are an “important proof of concept” that demonstrated the feasibility of blocking HIV with bimonthly infusions of such antibodies, according to trial leader Dr. Larry Corey. The trials were conducted by HVTN and its sister network, the HIV Prevention Trials Network.
In March, HVTN researchers published the results of the HVTN 702 trial, which had been halted a year before when an early look at the data showed that the experimental vaccine showed no efficacy. Researchers are closely analyzing the trial data to find out why this vaccine did not prevent HIV infection, information that could help in the development of better vaccines in the future.

Drs. Trevor Bedford and Allison Black were among the co-authors of a report over the summer about the case of a man in the Democratic Republic of Congo who died from a relapse of Ebola virus disease. The 25-year-old contracted Ebola in June 2019, even though he had been vaccinated during a local outbreak six months earlier. He was treated with monoclonal antibodies and appeared to be cured, but in late November 2019 he had a fatal recurrence. The scientists tracked the infection by tracing small mutations in the viral genome — the same technology they use to track the evolution of SARS-CoV-2. The study confirmed that the man’s second bout was a relapse of his prior illness, six months earlier, and concluded that the recurrence set off a chain of transmission that subsequently infected 91 people. The case revealed a rare failure of an effective vaccine and demonstrated such cases can lead to onward transmission.

Some final numbers

The Fred Hutch News Service team works to cover the scientific advances by our researchers and translate them for a general audience. Here are the numbers behind our efforts in 2021:

97 articles published on Fred Hutch News
More than 2.7 million views of News articles
2,800 posts to our primary social channels
Nearly 20,000 website visits from the Hutch Newsletter
Hundreds of conversations with Hutch researchers

Thank you for being part of the Hutch mission and supporting Fred Hutch science in 2021. Check out our look ahead to next year with Fred Hutch scientists' predictions and hopes for the advancements that 2022 will bring.

And enjoy a few more of our favorite photos from the year: