Comedian, public official Kristina Wong for the win

How the performance artist serves her community and gears up for upcoming ASU Gammage show

May 18, 2020

When California’s shelter-in-place order was issued in March of this year, Los Angeles comedian Kristina Wong had grandiose plans of cleaning her house and sticking to a workout regimen.

Instead, Wong found herself fronting an amateur medical factory right from her living room and becoming “sweatshop overlord” to Auntie Sewing Squad, a group that now includes more than 600 members that dedicate their time and resources to creating face masks for health care professionals and other essential workers.  Kristina Wong's show, "Kristina Wong for Public Office," draws from her experiences as a public official. It will air through ASU Gammage’s Facebook page on May 28. Download Full Image

“This is what we do now as performance artists — create and fix medical equipment,” Wong jokingly said.

The currency the squad deals in is fabric, elastic and the time put into making masks. While most people who are staying at home are on a Netflix-binge marathon, Wong and her crew are on a sewing one. On Thursday, Auntie Sewing Squad sent a van full of supplies, including masks, materials and three sewing machines, to the Navajo Nation, which has been hard hit by the virus. 

“I’m like, ‘How did I go from sewing a few masks to humanitarian aid missions?’ But this is the country we live in,” Wong said. “We have no government that’s functioning, so we have to do what we can.”

Armed with her Hello Kitty sewing machine, Wong said the work she does is not just about making masks; it’s about the community that’s been built and the way its sustained itself to protect the community at large.

“This is where I see my work as an artist,” Wong said. “We’re in the business of making communities and trying to engage people in meaningful ways, so for me, I don’t want people to create a labor farm, but I want people to find friendship, meaning and power in this work.”

Wong said, “If you’re bored at home, think about the power that you do have right now, and how you can be of support to other people.”

Performance artist turned politician

Besides being a performance artist, Wong is an actual elected representative from Koreatown’s Wilshire Center Neighborhood Council. Her new show, “Kristina Wong for Public Office,” draws from her experiences as a public official to highlight a campaign-based performance of satire and political commentary.The show began its tour in February 2020 before being halted due to COVID-19. 

Even so, that hasn’t stopped Wong from continuing her show, which will be available through ASU Gammage’s Facebook page at 6 p.m. May 28. “Excerpts from Kristina Wong for Public Office” will be Wong’s first attempt at shifting her show to a virtual format.

READ MORE: More information on “Excerpts from Kristina Wong for Public Office” and other upcoming virtual events

“I have to dust off this old show — which isn’t even that old — but my mind and body have been in such a different place that I’ll have to integrate some of these new stories I have and still give it that ‘rally’ feel from my living room,” Wong said.

Wong said that although she wishes things were different, she’s happy to see artists try to embrace performing in a virtual format.

“The bar is so low — I don’t think anyone is expecting Zoom theater to blow them away — so there’s a lot of discovery to be made.”

Wong said she thinks people have felt helpless over the last few years, and her show aims to empower the audience.

“I ended up running for office because even as an artist, I couldn’t outdo the spectacle of real life anymore,” Wong said. “I thought, ‘If they’re going to take my job, I’m going to take theirs.’ A lot of what I’m discovering now during this time is just how inept the system is, the one that’s supposed to protect us, because it’s so slow, because it’s so mired in approvals and politics and filibusters, that citizens who take direct action can actually get more done.”

In the world of government, Wong said that a lot of what politicians do is not that much different from artists; they create a lot of symbolic gestures and are actors in a public space.

“All we have right now are symbols, because we don’t have soap apparently, or vaccines and stuff like that,” she said. “So that’s power to me, and where our art is power. Putting symbols and culture and messages out into the world, but also action.”

Wong said she encourages folks to run for office, vote and not totally give up on the system when action can be taken.

“I feel like I’ve done more work in the last few months to help my community than I have as an elected official, and that’s a big question of the show: Am I more powerful as an elected official than as an artist?”

Marketing Communications Assistant, ASU Gammage

Mutational meltdown: Can we push SARS CoV-2 off an evolutionary cliff?

May 18, 2020

From New York to Luxembourg, Namibia, Iceland and Bhutan, the novel coronavirus SARS CoV-2 has turned the modern world into a crisis zone. An unprecedented global effort is underway to understand the elusive pathogen and find effective therapies.

An intriguing approach to treating COVID-19, the disease caused by the novel coronavirus, has recently been suggested by Arizona State University faculty members Jeff Jensen from the Center for Evolution and Medicine and Michael Lynch from the Biodesign Center for Mechanisms of Evolution. Mutational meltdown This graphic shows a series of viral replication cycles for a hypothetical viral population within a patient — with four representative virus genomes shown at each time point. At the time of infection, no mutations are present. Over time, mutations accumulate, and if natural selection fails to eliminate these harmful mutations, each generation may become less fit than the preceding. In this way, the most fit genome carries more and more deleterious mutations over time. This phenomenon, known as Muller’s ratchet, sets the viral population on a one-way path to extinction. Graphic courtesy of Shireen Dooling Download Full Image

The strategy they describe for vanquishing SARS CoV-2 is rooted in evolutionary theory. The basic idea is simple: If a particular drug could sufficiently boost the virus’ rate of mutation, it may be possible to saddle the pathogen with so many harmful genetic errors that the viral population within a patient collapses.

The phenomenon, known as mutational meltdown, was first described by Lynch three decades ago in the context of preventing extinction in small or endangered populations.

In the new research, the goal instead is to encourage extinction in large viral populations, through a ruinous accumulation of viral mutations. (The concept is similar to a later-described phenomenon known as lethal mutagenesis.)

“This is a great example of well-established principles in evolutionary theory being repurposed for solving significant practical problems,” Lynch said.

In addition to providing a hopeful candidate for the treatment of SARS CoV-2, mutational meltdown could offer a new blueprint for treating a broad range of infectious diseases. The method is particularly attractive as it holds the potential to deliver a knockout blow to infectious agents, causing such widespread damage to their genomes that they are unable to develop antiviral or antibiotic drug resistance.

Lynch and Jensen recently outlined the strategy in the journal Heredity.

In earlier proof-of-concept research, Jensen, his postdoctoral associate Claudia Bank, now a faculty member at the University of Berne, Switzerland, and their colleagues at the University of Massachusetts Medical School demonstrated that the drug favipiravir, if given at sufficiently high dosage, could effectively induce mutational meltdown in laboratory populations of the influenza A virus.

New killer on the block

As of May 14, 2020, confirmed cases of COVID-19 number over 4.5 million globally. Over 300,000 have died and the numbers almost certainly represent a significant undercount.

The success of SARS CoV-2 in invading human cells and rapidly disseminating through the global population is due to the virus likely having undergone specific mutations, allowing it to make a leapSuch species-straddling pathogens are called zoonotic. from some reservoir species to humans.

Genetic mutations are nature’s ultimate double-edged sword. They provide the raw material for evolution to act upon and account for the astonishing diversity observed across species, including humans. Through natural selection, mutations conferring an adaptive advantage in nature’s great game can become fixed in a population and transmitted to offspring through generations.

Most genetic mutations, however, are deleterious and these account for a dizzying range of diseases, from mild to lethal. Over successive generations, natural selection can act on these errors, increasing the probability of ultimate fixation for mutations that are advantageous, and decreasing the probability for those that are deleterious, owing to the reduced biological fitnessFitness is a measure of an organism’s ability to grow to adulthood and successfully contribute progeny to the next generation. of organisms carrying these harmful mutations.

While harmful mutations can wreak havoc in individuals who acquire them, over time, populations tend to shed the majority of detrimental mutations. In organisms that reproduce sexually, this purging process is helped along by the recombination of genetic elements provided to offspring from two genetically distinct parents.

Ratchet of doom

Although evolution acts to remove deleterious mutations from the population through purifying selection, there are limits to this cleansing process. Should the overall population number fall below a certain threshold, purifying selection can’t keep pace with the accumulation of bad mutations.

professor's portrait

Michael Lynch directs the Biodesign Center for Mechanisms of Evolution and is a professor in ASU's School of Life Sciences.

“This is because the efficiency of selection is reduced in small populations, owing to the increased noise in the transmission process across generations,” Lynch said.

In this case, biological fitness in the remaining population will be continually degraded, placing the organism on a one-way path to extinction.

For example, a population initially bearing no harmful mutations will eventually degrade to a population with all members bearing at least 1 bad mutation, later, 2, then 3 and so on. Such populations grow successively sicklier over time, further reducing population size, in a snowball effect.

This irreversible mechanism, long recognized by evolutionary biologists, is known as Muller’s ratchet, for the ratchet-like, one-way accumulation of harmful mutations in a population. This process is traditionally viewed as being the result of genetic drift, a random evolutionary process, but under high mutation rate regimes these "clicks of the ratchet" may be driven by mutation itself.

Hacking the viral genome

Typically, single-stranded RNA viruses have a 100- to 1000-fold higher mutation rate per replication than humans do per human generation. Coronaviruses like SARS CoV-2, however, are unique among RNA viruses as they possess a proofreading domain used to reduce mutational accumulation.

The strategy outlined seeks to target this proofreading apparatus through drug therapy, damaging its functionality. If the virus could be induced to pick up deleterious mutations at an accelerated pace, Muller’s ratchet may begin clicking, eventually reducing population fitness to the point of no return: mutational meltdown.

professor's portrait

Jeff Jensen is a population geneticist and professor in the Biodesign Center for Mechanisms of Evolution, the Center for Evolution and Medicine, and ASU's School of Life Sciences.

"Practically, a key question here is how much the mutation rate must be turned up to achieve this effect," Jensen said, "as one certainly doesn't want to run the risk of an insufficient rate increase that may generate adaptive mutations without generating a sufficient deleterious mutational load to ensure extinction."

If a viral invader like SARS CoV-2 were treated with a mutation-boosting drug at sufficient dosage, the result would be to shower the entire viral genome with mutations, which could make it very hard for the virus to evolve resistance.

The drug favipiravir is one such mutation-enhancing candidate, which has already shown promise in this regard in a number of RNA viruses, including Ebola, yellow fever, chikungunya, enterovirus and notovirus.

In the previous work on influenza A virus, Jensen and colleagues accurately predicted the subtle dynamics of mutational meltdown due to favipiravir, which involved a linear rate of mutational accrual leading to a fatal transition point, beyond which harmful mutations rapidly accumulated prior to the collapse of the viral population.

Recently, another drug, remdesivir, has shown promise against a clinical isolate of SARS-CoV-2. Like favipiravir, the treatment appears to confuse the virus’ genetic proofreading system. As Lynch notes, “anything we could do to muck up the proofreader would increase the mutation rate around 20-fold.”

Such therapies could be used in conjunction with other drugs targeting different aspects of viral assembly or replication, further increasing the likelihood of achieving effective meltdown. Much more work is needed however — both experimental and theoretical — to determine if the strategy can be safely and effectively applied to treat COVID-19, or indeed be used as a general antiviral strategy in future unknown pandemics.

Richard Harth

Science writer, Biodesign Institute at ASU