Science for the common good: a discussion on Covid 19

By Maggie Moore

JAX leaders discussed COVID-19-related research, the origins of the virus, its clinical impacts, and how we can target therapeutics during the first virtual JAXtaposition event, Science for the Common Good: A Discussion on COVID-19.

JAX CEO and President  Edison Liu, M.D.Conducts research focused on the functional genomics of breast cancer through an exploration of the entire genomic space.Edison Liu, M.D. and JAX Scientific Director for Mammalian Genetics Nadia Rosenthal, Ph.D., F.Med.SciGlobal leader in the use of targeted mutagenesis in mice to investigate muscle development, disease and repair.Nadia Rosenthal, Ph.D. , shared their insights about responding to a global pandemic and how research will be utilized to study the disease for treatment in the future.

“Coronaviruses have been around us for a long, long time. And during my medical school days, it was really thought to be only the cause of a form of common cold,” said Liu, who earned the President’s Public Service Medal for leading Singapore's scientific response to the 2003 SARS crisis.

“In 2003, during the time I was establishing the Genome Institute of Singapore, the coronavirus emerged as one of the major deadly pathogens that has swept the Asian continent, Southeast Asia, and then subsequently the world. It's the same family, the same appearance, but is different than the COVID-19 virus that we know of today. It was more virulent, but less transmissible.”

Liu says it is this balance of the virulence and transmissibility that makes SARS, as well as COVID-19, particularly deadly.

Responding to a pandemic

Liu said that there are several fundamental truths that are important to know about this virus in order to organize a response to it:

• SARS-CoV-2 is transmitted via aerosols and is very contagious.
• The mortality rate for those that contract COVID-19 is between four and six percent. Note that the mortality rate is less than one percent for those under 50 years of age, but is between 10% and 40% in those who are more than 70 years old.
• Herd immunity is not feasible until a vaccine is deployed.
• Social distancing works, and needs to be started as early as possible.
• Infectious individuals can be asymptomatic.
• Testing and contact tracing are fundamental to COVID-19 pandemic control.
• We must thread the needle of maintaining safety while jump-starting the economy.

There is no perfect solution to re-starting the economy, Liu said: “Different sectors respond differently. Different countries in different local conditions have different needs. But first and foremost, we have to have adequate testing capability that is coupled with contact tracing. The key for that is really to be able to isolate individuals so they don't pass on the virus to especially vulnerable populations.”

Liu also discussed the Laboratory’s role in providing coronavirus testing capacity of 20,000 tests per day at its Farmington, Connecticut-based clinical laboratory.

“Because of my experience in the SARS crisis in Singapore, I knew very much that testing needed to be in the core of what we are going to do to control the pandemic,” he explained. “And because of our really remarkable capabilities at The Jackson Laboratory, I knew we could stand up these tests, and in relatively short order.”

Finding cures, faster

“The question is how to achieve a therapeutic as fast as possible,” said Rosenthal. “We have to rely on a thorough knowledge of the enemy, and the enemy here is the coronavirus.

Rosenthal explained how the SARS-CoV-2 virus exploits a cellular protein called ACE-2.

“We essentially make a mouse that's humanized by injecting this gene into the embryo of a mouse so that every cell in the adult mouse has a human ACE-2 gene,” she said. This means that the cellular composition of the mouse is now essentially susceptible to viral attack. And these mice, when exposed to the virus, become susceptible and experience the same symptoms that are found in human patients.

Going forward, Rosenthal said, once we make these humanized mice, we can put these genetic changes onto different genetic backgrounds, and more accurately and authentically replicate the variation we see in the human population in terms of their genetics. JAX scientists will also be able to put all of these genetic variations onto the background of a mouse that has a compromised immune system, such that we can recapitulate the human immune system in these mice.

“Essentially this is an extraordinarily complicated and very sophisticated way of turning a mouse as close to a human patient as we possibly can get,” said Rosenthal.

“The reason that we can do this at The Jackson Laboratory is because we have for many, many decades supplied the entire scientific community in the world with highly valuable and extraordinarily complex genetic models of human disease. And we can do this at scale and with the expertise we have.

“We really hope to make major inroads into providing these models to get to faster cures and to be able to understand this new pandemic in all of its different forms and guises,” she concluded.