Message from the Director

July, 2020

How do we navigate in a perfect storm?

We are not alone in suffering the trifecta of the COVID-19 pandemic, the movements responding to the George Floyd murder, and the massive economic recession. Like most of you, each of us is alone at home with Zoom as the main tool of communication and work. But stem cell research is not a theoretical exercise, the COVID-19 agent and our immune and inflammatory response to it are not yet fully knowledge-based, and the inevitable effects of the recession on our personnel and science are looming in the near future. In this message let me make a few comments on how we are responding to these challenges, and how we might get back to the biomedical research and translation that the institute hopes to achieve. 

The pandemic and the institute: We are at the stage of bringing back institute personnel and functions gradually to the labs, I believe the safe return will require learning from the past. While we are fortunate that the rate of COVID-19 infections in institute personnel has been extremely low, and Stanford Medicine clinics and hospitals have been incredibly good at protecting patients and caregivers, the return of students and fellows from homes that are in high infection areas will inevitably bring in many who are infected, often minimally affected or not symptomatic. They can spread the infection, and themselves be unaware that they could even be super spreaders. 

The initial sites of COVID-19 infection are cells in the nose, throat, and mouth; these are also the only sites which spread the infection. The immune response that sterilizes these infected sites is special—immune cells adjacent to the infected surface ‘mucosa’ of nose, throat, and mouth are induced to give rise to antibody-forming cells that home back to these mucosal sites. The operative special antibody against the virus is called secretory IgA, which is secreted from the antibody-forming cells (that had homed back) to neutralize COVID-19.  In experiments done here and elsewhere, vaccination through the skin on the upper arms makes immunity inside the body, but not to the mucosa; vaccination by aerosols (or in sugar cubes, like the Sabin polio vaccine) do make the secretory IgA as well as immunity inside the body that can eliminate the infection. 

When the virus spreads to the lungs and the rest of the body, the actually killing of cells by virus is only part of the dangerous and sometimes lethal disease. Many labs at the institute and elsewhere at Stanford are pursuing this with focus and vigor. For example, Gerlinde Wernig has found that this later stage of the infection in the lungs involves a too-rapid and too-much inflammatory response, as well as the emergence of cells called fibroblasts that are trying to form ’scars’ to wall off infected areas. My own lab is testing whether the blood forming stem cells of young vs old people explain the high susceptibility of us old folks to more severe disease than in the young. Many other institute labs are following their special fields to investigate the pandemic. This level of basic science, and attention to results that could lead to interventions in the pandemic, are critical to generate knowledge applicable to this pandemic, and likely the coming epidemics with other respiratory system viruses. With such a dangerous virus, our laboratory experiments and development of models to test therapeutics require high containment laboratory and mouse barrier facilities which are not now available here. This is especially critical as the availability of animal models that don’t include human cells means that principles learned in mice must somehow be redone in humans. 

What does this mean for our own personnel as they return to work? Because carriers of the infection may be asymptomatic, simply testing for viral infection or for antibodies to the virus in serum is not enough. Roel Nusse in the institute leads our building-wide return to work, and with the University has provided the swab in the nose testing for viral infection for first time returning personnel. Personnel entering the building have to describe symptoms or check for fever, and to practice safe distancing, wearing of masks, and washing hands frequently (even gloved hands). In addition to the current regulations, I advocate weekly mandatory repeat testing of personnel in the building for infection, and also recommend testing for mucosal antiviral IgA antibodies as well as testing serum for other aspects of immunity.

It is impossible to carry out safe public health measures unless every infected person is diagnosed in a timely manner, and when discovered his/her/their contacts traced and tested themselves. Absolute adherence to masking and social distancing and other preventative measures is mandatory in our hospitals and clinics, but will be logistically challenging for institute personnel without verification that all preventive measures are mandatory and enforced as well. And I advocate testing for covid19 specific antibodies in sputum or swabbed areas along with the viral infection tests. 

Approaching the institute and institutional responses to the issues of intended and unintended actions in the era following the tragic death of George Floyd:

Our institute and university are a microcosm of the United States, with faculty, students, trainees, administration, and staff coming from all racial, ethnic, and gender identification groups. In addition to people of color, women, and gender identification diversity, there is little doubt that amongst us are those who harbor racist or other disrespectful opinions and beliefs. Many of us have acted for years to remove these barriers to the full respectful interactions of all, as well as many others who do not identify with those who intentionally act in racist or misogynistic ways. But even those who are not intentionally racist or misogynistic still go home every day safe from being targets of disrespectful and often dangerous behaviors based on prejudice, while the students, trainees, faculty, administrators, and employees who are BIPOC never escape the dangers of racism. The post-George Floyd, Black Lives Matter and associated movements are powerful and informative. At the institute we have allied with the peaceful movements to have means by which the instances and situations and stories of the victims of such oppression can safely, and if wished, anonymously, bring out these stories. It is clear from town halls and other venues that racist behavior here and in the Bay Area happens every day, and that police in our area have profiled BIPOC and stopped them with no evidence of illegal actions. And even well-intended individuals in our community may unintentionally use words or images or phrases that are typical of attitudes of racist perpetrators. 

A group of institute students, administrators, postdoctoral trainees, employees and other staff are leading efforts to reveal and remove such barriers to true equality at Stanford. As they define their missions, including an overt set of actions to recruit faculty, students, trainees, administrative personnel, and other employees of these under-represented communities, we will keep you apprised of our efforts. 

We began our efforts with a series of letters that include my own, one from the institute leadership, and another shocking one from Dr Sam Cheshier, a professor and neurosurgeon MD/PhD who was many times despite his many accomplishments the object of racial profiling and behaviors.  Here are links to these documents: 

Messages from Irv Weissman and the institute about diversity and recent events

On George Floyd: Thoughts from a Black Stanford lifer, by Sam Cheshier, MD, PhD

I have not addressed the economic aspects of the trifecta, as those require the actions of the leadership of the University and our Board of Trustees. 

Yours,

Irv Weissman, Director