[michellechronicles]

Francis deSouza on LinkedIn: This week we celebrate 20 years since the first publication of the

This week we celebrate 20 years since the first publication of the human genome - one of humanity’s greatest scientific achievements. It unl

[michellechronicles]

Crisis Inspiring Innovation

Biotechnology and pharmaceutical companies are constantly developing with job mapping (users as innovators) in mind. While I can’t say all diagnostic tools and drugs are developed toward improving quality of life, I find some of the most important and recent innovations were inspired by the pandemic. The pandemic revealed deep underlying problems in the healthcare system, changed the way we perceive the world and forced scientists to respond by innovating in new directions. By pushing the frontiers of science forward, scientists have reinvented traditional vaccines, manufactured proprietary Valor Glass (vials for vaccines) at Corning, and developed diagnostics in surveillance platforms. In terms of regulations, the FDA responded by adapting its policies, exercising emergency use authorization (EUA) authority, creating Coronavirus Treatment Acceleration Program (CTAP), and launching the Pandemic Recovery and Preparedness Plan (PREPP) initiative to strengthen the nation’s public health protections against chemical, biological, radiological and nuclear (CBRN) threats.

Traditional vaccines inject bits of attenuated or inactivated viruses and take an average of 10 years to progress from lab research to being administered in the hospital. Scientists have to understand the pathogen causing the infectious disease and identify its associated antigen, which activates our immune system to fight the virus. Then, the antigen must be mass produced before becoming integrated into a vaccine. In general, it’s a very lengthy process. 

However, antigens are usually proteins, and human cells are constantly making proteins as building blocks to maintain our bodies. Scientists asked a question: What if we can program our own cells to make these antigens and trigger the same immune response as traditional vaccine, and tried to improve the process? This is the goal of mRNA vaccines. mRNA is the code instructing our cells what proteins to make, and thanks to advances in DNA sequencing, we can quickly identify the code, make the antigenic proteins specific to the disease, and build the mRNA in the lab. In other words, mRNA vaccines deliver a code not in the form of antigenic proteins, but as instructions commanding our bodies to produce antigens. Once the antigen is present in our bodies, it initiates an immune response just like a traditional vaccine.

This technology could represent a paradigm shift in vaccination. mRNA is much simpler to produce than proteins. To synthesize mRNA, scientists insert a sequence corresponding to the mRNA into a plasmid, a small DNA molecule within a cell that can replicate itself. Then, this plasmid is put into a reactor where an enzymatic reaction triggers the synthesis of the mRNA. Finally, mRNAs are purified and encapsulated in a lipid nanoparticle, a shell of precisely formulated fat, which helps carry the mRNA into our cells. Inside the cells, mRNA is translated into the antigenic protein eventually triggering an immune response. Starting with raw materials, mRNA vaccine manufacturing takes about 2-6 weeks to produce a completed vaccine in a vial or syringe.

With vaccines ready for distribution, billions of vials will have to be manufactured, filled, and shipped, at top speed and in some cases under extreme stress (Pfizer’s vaccine must be kept below -90 degree C). Glass used to store vaccine must prove highly stable and chemically inert. Standard medical vials - made of borosilicate - often break as they’re filled, and just one damaged vial can ruin a batch of doses and stop a production line. In response to it, Corning has modified its manufacturing site and reinvented its vails to create an alternative to borosilicate, called Valor Glass. Using platinum-lined ceramic crucibles, heated to more than a thousand degrees F, they combine silica with new ingredients by adding alumina and removing boron to make the glass more resistant to degradation, and therefore less likely to leach contaminant into the contents. Other innovations include the process where converters cut and shape tubes of Valor Glass into vials, which are then submerged in a molten-salt bath. Potassium atoms in the hot mixture swap with smaller sodium atoms embedded in the surface of the glass, creating tension and therefore toughness - this process was first developed for Gorilla Glass, which is used in iPhones and other electronic devices. A vial fortified this way can withstand as much as a thousand pounds of force. Finally, the vials are transferred onto plastic tracks by robotic arms and conveyed through a chamber where they are rinsed, air-dried and coated with a polymer to reduce surface friction on a filling line, generating glass dust that can ruin doses. That said, there are also other companies racing to produce vaccine vials, because there are not enough vials now.

For the purpose of diagnosing, monitoring, screening and prognosis, in vitro diagnostic tests are essential. In an attempt to support global COVID-19 efforts, biotechnology companies like Illumina Inc. (as the gene sequencing leader) have responded by developing and launching its first rapid and scalable COVID-19 detection test under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), where “the FDA commissioner may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose …” The COVIDSeq test is an amplicon-based NGS test featuring primers designed to detect RNA from the SARS-CoV-2 virus in nasopharyngeal, oropharyngeal, and mid-turbinate nasal swabs from patients with signs and symptoms of infection who are suspected of COVID-19. As a quality control, an internal control consisting of 11 human mRNA targets is also included in every sample. In doing so, Illumina’s recent innovation has leveraged and modified existing validated and publicly available ARTIC multiplex PCR protocols to amplify SARS-CoV-2 virus-specific sequences using their proven sequencing technology.

References:

https://www.nature.com/articles/s41541-020-0159-8 (Links to an external site.)

https://www.nature.com/articles/nrd.2017.243 (Links to an external site.)

https://www.newyorker.com/magazine/2020/12/14/countdown-to-a-coronavirus-vaccine (Links to an external site.)

https://www.corning.com/worldwide/en/innovation/materials-science/glass/accelerated-covid-vaccine-preparation.html (Links to an external site.)

https://www.wsj.com/articles/covid-19-vaccines-could-depend-on-the-strength-of-this-vial-11605306378 (Links to an external site.)

https://www.newyorker.com/magazine/2020/12/07/the-race-to-make-vials-for-coronavirus-vaccines

https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization (Links to an external site.)

https://sapac.illumina.com/company/news-center/press-releases/2020/8cd141fb-68d0-4144-8922-45693ac3f453.html

Edited by J.Briggs

[michellechronicles]

Dear 2020

It’s been a whirlwind in my little corner of genomics world. I had the pleasure of participating in the operationalization of COVID-Seq, the first sequencing-based diagnostics EUA for SARS-CoV-2. I continue to feel incredibly blessed to work with an intelligent, supportive, and inspiring team in an amazing company striving to make a positive impact. 

Shout out to my family, friends, all the front-line healthcare workers, essential workers and someone who taught me a valuable life lesson - sorrow of impermanence. For the past few months, I found myself standing at the nexus of dichotomies: hope and fear, love and loss, wholeness and dissolution. I learned how it feels to fall in love, and - in a heartbeat - be heartbroken; I ached in places I didn’t know I had inside me. 

We progressed from text messages and virtual calls to physical dating. Our conversations started out light and easy, eventually becoming insightful and creative. We discussed my development work, my beautiful family, fur baby, colleagues, friends, favorite books, investment philosophies, dream travel destinations, parallel universes, deja vú from a psychological perspective, dental implant materials (biomaterials inspired by Dr. Larry Hench vs. Titanium and Zirconia - those that cause gums to turn grey); and we talked about his dental school classes/finals, his family, his doggo, his friends, his traveling/climbing experiences and his clinical experiences - potentially more in greater depths if I hadn’t run out of energy in this passive aggressive cycle. Before long, we went on a spontaneous trip to Chicago. At the end of October, I had the wonderful opportunity to meet his family and friends. 

I did all this despite knowing he had “commitment issues”. Naively, I wrote off red flags and continued to show affection seeking stability and consistency despite them. Eventually, he gave me the cold shoulder and pushed me away. I want to think maybe we aren’t compatible at this timepoint in life or maybe he did this because he was afraid I would see him truly as he is and be disappointed, but I will never know. 

Regardless, I hope he finds the courage to love and be loved. When he does, I hope he lets her fall in love with his human parts - the battles he can’t fight, the wounds he can’t heal, all the ways in which he is not enough for himself. I hope he gives her his joys and his pain in equal measures, because he is the most brilliant and terrible mixture of both. I hope he shows her things he haven’t lost along the way, and she shows him his own greatest strength in return. 

Meanwhile, I’ll heal and continue to do me - stay ambitious and motivated.

[michellechronicles]

If you’re ever in New York, remember to stop by Corning Museum of Glass and its innovation center. Their collection showcases more than 35 centuries of glass artistry. Go and see how Corning has combined its unparalleled expertise in glass science, ceramics science and optical physics with deep manufacturing and engineering capabilities to develop life-changing innovations and products e.g. Gorilla glass and Valor glass (COVID vaccine vials). 

Happy Holidays!

[michellechronicles]

Slower Forms of Media

In the more than eight months since COVID-19 manifested in the United States, I became frustrated with the quality of information from the mainstream press or so-called processed media. In the fall, I subscribed to the New Yorker featuring journalism, commentary, criticism, assays, fiction, satire, cartoons and poetry. And I must say, the New Yorker did not disappoint. I very much appreciated digesting slower forms of media. The topics that I find particularly interesting surround coronavirus chronicles and entrepreneurship. I’ll be compiling my notes when time allows.

[michellechronicles]

She is always a novelty; for she is never the Chicago you saw when you passed through the last time.

Mark Twain