The Eppendorf, CRISPR, Covid, and my medicine origin story

This post is THREE THINGS. A personal origin story, a (brief) book review, and a connection to recent stories on Pfizer and Moderna Covid vaccines. And, when we’re done, it might even tie together!

Image above: Dr. NoFronta Lobe, Mad Scientist. No this is not me in the research lab; this is me, a kindergarten parent at Halloween

My Origin Story (I was a budding molecular biologist in 1985)

I was alone in the brightly-lit sterile-white research lab; having spent 20 hours on a long, multi-day experiment. It was nearly midnight on Saturday in 1985. I was a college junior majoring in molecular biology, with aspirations of a scientific research career. I was studying P4 bacteriophage, a virus that attacks E coli bacteria.

The work sequence, I could now perform by heart: inoculate, incubate, centrifuge, enzyme reaction, pipette (fancy eyedropper tool) into an Eppendorf tube (a tiny plastic tapered tube. From a Q-tip-loaded with a single bacterial colony, I had carefully grown a quart of bacterial culture, then sequentially purified my sample down to 20 drops of a pearlescent white DNA solution.

So: 20 hours for 20 precious drops. 

Eppendorf tube, Fisher Scientific

Exhausted and looking forward to heading home, I was on my last steps before overnight refrigeration, so as I held the open Eppendorf in my left hand and my pipette in the right, I randomly thought: “What time is it? Am I going to miss the last Orange Line train going home?”

So, I moved to look at my watch…

And since my watch is on my left wrist, the Eppendorf tube in my left hand did a 180…

And I watched as all the liquid ran out … and onto the floor. 

I looked at the upside down Eppendorf, and then down at the floor and the drops of liquid there, uncomprehending. 

*How… what… nnnnnNNNNNOOOOOOOOOOO!!!*

My late-night-fogged brain finally registered SHOCK, DENIAL, ANGER, BARGAINING. The lab was deserted, I deemed it safe to express myself:

“F$*&@! S!#%! D&$%!” I said, eloquently.

Desperate, I dropped down and started using the pipette to suck up DIRTY droplets of DNA extract from the floor and replace it into the Eppendorf. After a few minutes I had about 1/3 of the liquid, now brown-tinged, back in the tube. Resigned, I put the tube in the fridge. 

NO time to fret, no time to start over. Nothing else to do. I got on my jacket and faced the Boston winter, and jogged for the Orange Line stop. 

Once on board that last train, I started to sob. There was no way that soiled sample would be any good. This COMPLETELY SUCKED. 

And, I realized, I really did not want to be here. I realized: I could do the scientific work, but, unlike some colleagues who revelled in long hours in pursuit of new knowledge, I was despondent, not very good at this, and missed being around people. 

That was the night I decided that bench research was not for me. I had thought my calling was in pure science, but this DNA catastrophe taught me where I didn’t want to be. I needed Humanism AND Science. So, medical school it was. I’ve never looked back. 

Molecular Biology after 1985 (CRISPR!)

Thirty-five years later after my profanity-laced change of career, Walter Isaacson chronicles the recent successes of genetic research, including the discovery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and CAS9 (CRISPR ASsociated protein #9).

Book review rating? 5/5 stars.

In a nutshell: Jennifer Doudna and Emmanuelle Charpentier, and many others raced to understand these strange “repeating sequences” in DNA and mRNA, realizing that they were bacterial defenses against “phage” viruses.

In this work, they discovered that CRISPR-Cas9, an mRNA plus protein complex could identify attacking virus mRNA and SLICE IT UP, deactivating it. They realized that this ancient protein complex could be taught to identify ANY RNA or DNA. Gene editing, invented by bacteria as a survival mechanism a millenia ago, co-opted by humans. Precise genetic scissors.

I enjoy Isaacson’s writing style. Not only does he clearly explain the adrenaline rush of scientific discovery (and the delicate dance between scientific sharing versus the race against other labs to publish and claim credit), but also the technical details of how CRISPR works.

Isaacson writes about Doudna and the response to Covid-19. What is even more astonishing about Dr. Doudna, the bench researcher and lab leader at Berkeley, is that she had the socio-political skills to bring together 40 leading geneticists across the Bay Area to successfully set up a brain trust to develop Covid-19 testing and vaccine development. This team lays much of the groundwork of the accomplishments of this past year.

Drs. Doudna and Charpentier were, deservedly, awarded the 2020 Nobel Prize in Biology “for the development of a method for genome editing.”

A personal note: my brief journey in molecular biology never quite crosses Dr. Doudna’s path, but I recognize the genetic tools mentioned, and studied the work of the luminaries in the field. I feel like a distant cousin to these scientists.

Highly recommended read, to understand the genetic foundation of our modern age.

Molecular Biology: the Covid fight

Here are 2 stories about Covid Vaccines, from the New York Times and WIRED.com, fascinating glimpses into the genomic-industrial complex. As of May 14th 2021, 36% of US adults are vaccinated against Covid-19. It is highly likely that these speedier and more effective mRNA-based detection tests and vaccines will forever be part of our lives. This could shorten development and improve accuracy of future vaccines.

WIRED.com story on Moderna’s Covid Vaccine trials

https://www.wired.com/story/moderna-covid-19-vaccine-trials/

CMIO’s take? Our modern world is built from advances in scientific method, computing and now genome editing. Despite my early failure in the lab, I feel fortunate, in the field of medical informatics, to be close to all 3.

Author: CT Lin

CMIO, UCHealth (Colorado); Professor, University of Colorado School of Medicine

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