2020 Perseverance hasn’t left us for Mars. She’s right here with us.
2020 saw an incredible amount of events both of chaos and order, both of inspiration and gloom. While the chaos of Covid was unleashed, there were quite a lot of moments of inspiration and hope. Be it the breakneck speed at which our scientific community was able to come up with vaccines, the awe-inspiring technology behind mRNA, the huge therapeutic promise it holds beyond covid along with advancements on CRISPR/CAS9 , the incredible advances NeuraLink, DeepMind , autonomous driving made in deep learning and AI, the first private vehicle transporting astronauts to ISS, first LEO satellite communications network connecting the world even more and so on.
One that stood out for me as the face of 2020 is that of the Mars Perseverance Rover. There couldn't have been a more apt name for the rover considering the times, one that rightly embodies the spirit of our species in the face of extreme adversities.
Now that the Perseverance rover has left our planet, I stumbled on the incredible story of a woman, who I think could very well become the face of Earth Perseverance 2020. And the face is that of Katalin Kariko.
The success of all the current mRNA vaccines today can very well be attributed to the breakthrough research of Katalin Kariko and Drew Weissman at the UofPenn.
I was digging into the history and the science behind mRNA. I stumbled along the way on the inspiring story of Katalin Kariko. The breakthrough accomplished by her team’s research when the promise held by the mRNA was slowly fading and was close to hitting a dead end. Instead of going into the fascinating science behind this, which itself would be a brilliantly enlightening piece of information, I would like to focus here on her story.
It would be good to create a timeline of events from her life in relation to the advancements and research on mRNA.
1955- Karikó was born in a tiny town outside Budapest, in a one-room house with no running water and no refrigerator. She got her first taste of biology examining the carcasses of pigs with her father, a Hungarian butcher.
1961 — mRNA discovered.
Here’s my imaginative tale on mRNA. Shameless Plug:)
A well-guarded mystery chamber where the instructions are encoded for the creation of weapons and life-saving functions
(DNA), and the weapons and life-sustaining products factory (protein machinery) where the actual production of these elements takes place. The mystery to solve was who and how are these instructions in DNA getting translated to the factory. A classic impedance mismatch, translation problem for a computer engineer. Enter the mRNA knight. The knight in shining armor, who not only can lift the heavy scroll of DNA , but also read and understand the instructions. One who can take the scroll and ride to the factory, tells the machinery a sweet and easy to digest acid tale on how to mix and match the amino acids to make the required proteins. Well, there's an enzyme intermediary in between but will skip it for the fantasy tale.
1970’s — Imagination by the scientific community on gene therapy and also on the possibilities of using the mRNA as a trojan horse, so that new instructions can be passed to the factory to make proteins not even encoded in the DNA. ie therapeutics and similar scenarios. Turning the body into an antibody, spike protein, medicine factory.
1976 — Kariko fascinated by a lecture on mRNA at a university in her home country. Pursues a PhD on the same topic. No form of artificial mRNA existed when she entered the field.
1984 — Boom in mRNA and DNA research in the US
1985 — Kariko still fascinated and continuing her research decides to move to the US to be closer to the advancements in this space. Hungary had restrictions on money that could be taken abroad. Her family sells their possessions, sews around 1200 $ to her daughter's teddy bear, and flies to the US. Takes up a job at Temple University.
1989 — Had to leave the job due to disagreements with her boss. Almost got deported. But was able to land a job at UofPenn. First artificially synthesized mRNA by researchers elsewhere. She along with the whole scientific fraternity was ecstatic. in Her own words “Suddenly we felt like we could do anything.”
1990s — Synthetic mRNA created severe immune responses when trialed in animals.
The immune system sent its warriors to kill the mRNA, sensing the messenger knight as an intruder. Often the response was so severe resulting in inflammation of the subjects and soon the excitement around mRNA was lessening.
1995 — All her grant applications to continue the mRNA research got rejected. She had a cancer scare and underwent surgery. Her husband stuck in Hungary due to a visa issue for six months. UofPenn demoted her which included a pay cut owing to the lack of funding for mRNA research. Period.
In her words.
“Usually, at that point, people just say goodbye and leave because it’s so horrible, “I thought of going somewhere else, or doing something else. I also thought maybe I’m not good enough, not smart enough.”
In the words of an undergrad student who was under her supervision back at the time
“Still, Karikó was struggling. Her science was fantastic, but she was less adept at the competitive game of science. She tried again and again to win grants, and each time, her applications were rejected.
Eventually, in the mid-1990s, she suffered the academic indignity of demotion, meaning she was taken off the academic ladder that leads to becoming a professor. We never discussed it personally because by the time I joined the lab, Karikó’s history was still only discussed in hushed tones as a cautionary tale for young scientists.”
1997 — Chance meeting with the accomplished immunologist Drew Weissman who had recently moved to UofPenn. Struck a chord and started working together since Weissman had the funding for the experiments.
“My salary was lower than the technician who worked next to me, but Drew was supportive and that’s what I concentrated on, not the roadblocks I’d had to face.”
2005 — Publishes the seminal paper on the breakthrough in modifying the mRNA that would not trigger the immune response. For the layman in me, the technique was replacing one of the four legs of the horse on which the mRNA knight was riding. It was this particular leg that made a lot of noise while invading the cells which triggered the immune response. So the breakthrough involved creating a similar prosthetic leg that made no sound at all. And the experiments on the mice successfully generated the target protein without inciting an immune response. It's a brilliant paper. But it remained brilliant on paper. In her own words
“We realized at that moment that this would be very important, and it could be used in vaccines and therapies. So we published a paper, filed a patent, established a company, and then found there was no interest. Nobody invited us anywhere to talk about it, nothing.”
2008 /2010 — Though the company they established was shut down, licensed their patented technology to a small firm BioNtech founded in 2008 to pioneer cancer immunotherapy leveraging mRNA. , Their breakthrough research also inspired a Stanford Postdoc Derrick Rossi to cofound Moderna in 2010.
In Rossi’s words, “If anyone asks me whom to vote for someday down the line, I would put them front and center,” he said. “That fundamental discovery is going to go into medicines that help the world.”
2013 — UofPenn refused to reinstate her to the faculty position even after her pioneering research. She took up the role of SVP at a company that did not even have a website. A company whose founder was commuting to work on his decade-old mountain bike. The company is a familiar name now. BioNTech.
In her words “ “They told me that they’d had a meeting and concluded that I was not of faculty quality, When I told them I was leaving, they laughed at me and said, ‘BioNTech doesn’t even have a website.’”
30 years of research ever since she was fascinated by mRNA, even in the face of adversities, and when the rest of the world started doubting the practicality of mRNA, culminating in the seminal 2005 breakthrough.
Another 15 years of working and waiting for her research to be put to practical use, to accomplish the primary objective which pushed her into this field 45 years ago in 1976( using mRNA to save lives).
45 years of pursuit and perseverance. And when the world needed it the most there it was.
And the rest, unlike what they say is not history, it's the present and the future. Be it cancer immunotherapy, vaccines, HIV , strains of viruses, it's a brighter future in the making. The mRNA as I would often cite in systems architecture is a “universal platform” and not a particular product design. The trojan horses can be tamed to serve humankind to potentially turn our bodies into mean fighting machines, cluster munition arsenal.
It would be misleading to attribute any particular breakthrough to one single person because as Newton said “ If I have seen further it is by standing on the shoulders of Giants”. But certainly, we could attribute a lot to all those giants and giantesses who redefine humanity through perseverance, inventions, discoveries thereby bringing an infinitude of faith, hope, and inspiration to the species we all belong to.
Hence, I would rather attribute this story in equal measure to her perseverance in addition to her genius. Who, along with her fellow confederate giants and giantesses, has carried us thus far and would inspire us to partake in our own possible ways on the way forward. As Ayn Rand puts in “Atlas Shrugged”, the movers and shakers of the world”.
To the face of Earth 2020 perseverance, Katalin Karikó, to the collage of perseverance 2020 faces, the healthcare workers, researchers, scientists, essential service providers, Thank you.
And here’s how it comes full circle:
Katalin’s daughter is an embodiment of the spirit of perseverance. Fractured ribs. Herniated discs, 2-time Olympic gold medalist, 5-time world champion in her sport.
Guess what that sport is?
ROWER , no not the MARS one. Susan Francia .
Hey Mars 2020 Rover,
Did you know the daughter of Earth 2020 Perseverance is a champion Rower?
Row on to unchartered lands, Perseverance. Godspeed.
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