A year of research dominated by the coronavirus

For many of us, 2020 was the Year of Coronavirus. That was also true for many researchers around the world, including those at Fred Hutchinson Cancer Research Center. While a remarkable volume of papers, preprints, insights about the SARS-CoV-2 virus and the COVID-19 disease were posted this year, across science — and Fred Hutch — work continued to find cures for cancer, HIV and related diseases.

We looked back at some of the most significant science of the year, combing through key journals and preprint servers, plus media coverage, social conversations and web analytics to highlight the work happening at Fred Hutch.

A vaccine effort at unprecedented scale

In May,  former Fred Hutch President and Director Dr. Larry Corey co-authored in the journal Science a call for collaboration between academia, government and industry to develop potential vaccines for COVID-19. With Dr. John Mascola, director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases, Dr. Anthony Fauci and Dr. Francis Collins, Corey wrote:

To return to a semblance of previous normality, the development of SARS-CoV-2 vaccines is an absolute necessity. To achieve this goal, all the resources in the public, private, and philanthropic sectors need to participate in a strategic manner. The ACTIV public-private partnership and collaborative harmonized efficacy trials are enabling models to achieve our common goal. —Corey et al. Science. May 2020. A strategic approach to COVID-19 vaccine R&D

Shortly afterward, NIAID and partners announced the creation of the COVID-19 Prevention Network, or CoVPN. In an interview, Corey talked about the challenges and opportunities ahead as the network’s operations center at the Hutch ramped up to optimize and run the huge COVID-19 vaccine trials that ultimately had at least 30,000 participants each.

Six months later, the first two COVID-19 vaccines were given emergency authorization for use in the U.S. — illustrating the value of building the CoVPN on top of the infrastructure that Corey and colleagues had created for HIV vaccine trials.

On Feb. 29, evolutionary biologist Dr. Trevor Bedford shared preliminary research — via Twitter — that led him to conclude that the SARS-CoV-2 virus was circulating in Washington state and that the region was “facing an already substantial outbreak” of the recently named COVID-19 disease that had not been detected because public health officials were focused only on people who had traveled from China.

At that point, Bedford had been following the virus for weeks using the Nextstrain disease-tracking platform he had developed with Dr. Richard Neher of the Max Planck Institute for Developmental Biology in Germany. Meanwhile, another research project, the Seattle Flu study, created an opportunity for Bedford and the rest of the study team to collaborate with public health officials to run genetic sequencing on study volunteer samples. Bedford and teammates found SARS-CoV-2 infections that “appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread.” The team posted a preprint of their research in April and the paper was updated to publish in Science in September.

In the weeks following Bedford’s discovery, hundreds of researchers across Fred Hutch would shift or pivot their focus to better understanding COVID-19 and helping efforts to stop the growing pandemic.

Delving into coronavirus biology

Dr. Jesse Bloom, an evolutionary biologist, led an effort to understand how a part of the spike protein on the coronavirus called the receptor-binding domain, or RBD, binds to a molecule called ACE2 on human cells to let the virus slip inside. Understanding how mutations affect the RBD has helped guide the design of vaccines. This work is also important for understanding the virus’s evolution and, eventually, for understanding whether this virus can evolve to evade our immune defenses.

Drs. Leo Stamatatos, Andrew McGuire and Marie Pancera focused on which of the tiny, Y-shaped immune proteins in our blood called antibodies are most effective at fighting SARS-CoV-2. They have continued to illuminate the immune response against the coronavirus, even using X-ray crystallography to map the nanoscale structure of the antibody blocking the coronavirus spike.

Advances against herpes

SARS-CoV-2 wasn’t the only virus that Fred Hutch researchers were focused on in 2020. Drs. Keith Jerome and Martine Aubert published a paper in the journal Nature Communications demonstrating how they had destroyed up to 95% of herpes virus lurking in certain nerve clusters of mice using an updated version of a gene-editing tool developed 10 years ago.

“This is the first time that anybody has been able to go in and actually eliminate most of herpes in a body,” said Jerome. The study offered new potential for a future cure for herpes, which afflicts billions of people around the globe.

Exploring fundamental cell biology

New cures, treatments and vaccines like these are built on the foundation of discoveries in basic biology — an area Fred Hutch scientists continued to explore in 2020.

In work published early in 2020 in the Proceedings of the National Academy of Sciences, a team of researchers led by Nobel Prize-winner Dr. Linda Buck described a new technique they dubbed Connect-seq, which makes it possible to map neural connections and gather information about the signals individual neurons send within a circuit. By integrating two technologies previously used by researchers, each of which provides incomplete information about the brain’s circuitry, Buck and team created a guidebook of sorts to navigating the brain.

Progress against cancer, from bench to bedside

Researchers working in the lab and the clinic made critical discoveries in 2020 that are improving care for cancer patients today and may lead to more new treatments in the future.

Researchers led by Dr. Kevin Cheung sought to map the “secret space” between the cells in tumor cell clusters where the signal to grow is co-opted and miscommunicated to other cells — giving the cancer cells a 500-fold increase in their ability to metastasize, or spread beyond the initial tumor site. The team is now working in the lab on new ways to block that signal — call it growth factor “fake news” — in order to stop metastasis in its tracks.

A very exciting, even "practice-changing,” clinical trial evaluated the immunotherapy drug avelumab for patients with advanced urothelial cancer showing that those who received the immune-boosting drug after chemotherapy lived longer than those who didn’t. Dr. Petros Grivas presented the results of the Phase 3 JAVELIN Bladder 100 study in a plenary session at the American Society of Clinical Oncology annual meeting in June, and later published it in the New England Journal of Medicine.

Infection with high-risk strains of human papillomavirus, or HPV, is one of the major risk factors for developing head and neck squamous cell carcinoma, a major cause of cancer deaths worldwide. New research from the lab of Rosput Reynolds Endowed Chair holder Dr. Bruce Clurman, led by postdoctoral fellow Dr. Ahmed Diab, shows that a critical vulnerability in HPV-positive HNSCC tumors renders them sensitive to an experimental drug known as AZD1775 that is currently in clinical trials for a variety of cancers. The initial observation that lay the ground for the discovery was made by the late Dr. Eddie Méndez, whose work and commitment to supporting early-career scientists — particularly those from underrepresented racial and ethnic backgrounds — led to the creation of the Eddie Méndez Award, which Diab won in 2019.