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Welcome to Science Simplified, a newsletter which Unlocks the Wonders of Science, One Simplified Concept at a Time!
Each year, the month of October heralds the announcement of Nobel Prizes, a momentous occasion to honor the exceptional contributions of scientists whose work has profoundly benefited humanity. Traditionally, the Nobel Prize journey commences with Physiology or Medicine. Subsequently, over the course of a week, the Nobel Assembly at Karolinska Institutet announces the laureates in Physics, Chemistry, Literature, Peace, and Economic Sciences. The prizes carry a cash award of 11 million Swedish kronor (US$ 1 million). The money comes from a bequest left by the prize’s creator, Swedish inventor Alfred Nobel, who died in 1896.
This year, on Oct 2, the Nobel Prize in Physiology or Medicine was jointly awarded to Katalin Karikó and Drew Weissman for their groundbreaking work on nucleoside base modifications, which paved the way for the development of highly effective mRNA vaccines against COVID-19.
mRNA vaccines or messenger RNA vaccines are a novel type of vaccine. They use small piece of mRNA to instruct the cells in the body to produce a harmless piece of the target virus (such as spike protein of SARS-CoV-2, the virus that cause COVID-19). This viral protein is harmless (does not infect individual) but it trains the immune system to “remember” the viral protein. So, next time when you encounter the virus, your defence system immediately gets into action, eliminating the virus quickly, as it has pre-trained and reserved army of immune cells ready for attack.
mRNA Vaccines, once a groundbreaking concept, are now a household term. Developed and tested at unprecedented speed, within a year, to stop the pandemic. In less than two years, billions received the life-saving jabs from either BioNtech/Pfizer or Moderna, followed by millions opting for mRNA vaccine boosters. In our next edition of Science Simplified, we’ll delve into the intricacies of mRNA vaccines. But for now, let’s turn the spotlight into the remarkable individuals who made this mRNA vaccines a reality.
This article recounts a story of two young scientists whose research paths converged one day around a photocopier. To pass the time time, they talked, and yes they talked about science, each one enthusiastically shared about their research, this conversation resulted in a fruitful collaboration, which would go on to revolutionise how we make vaccines. But wait, there's more! We're not just diving into their scientific pursuits. Get ready to discover the quirks, passions, and dreams that make these scientists tick. What inspires them? What do they envision for the future? It's like getting a backstage pass to the minds behind the science.
Through this article, my aim is to ignite a spark of inspiration in you. There's a treasure trove of wisdom waiting to be uncovered from their journey. And let's not forget, it's high time we put scientists in the spotlight, alongside our beloved athletes and movie stars.
From our Science Simplified Community, a resounding congratulations to both the laureates! Your relentless enthusiasm and dedication for research have not only advanced science but saved countless lives during the COVID-19 pandemic. We celebrate your achievements with great pride and admiration!
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Meet Katalin Karikó
Katalin Karikó is a Hungarian-American Biochemist, was born on January 17, 1955, in Szolnok, Hungary. Her childhood was happy, raised by a butcher father and her mother was a bookkeeper.
Her journey into science was sparked in high school when she read a book by Hans Selye, a Hungarian-Canadian endocrinologist. Hans Selye was first to discover the role of stress in humans in 1930s, before that, the term stress was only used in Physics!! Hans Selye’s writing left a big impression on young Katalin’s mind, it taught her the ways to handle stress positively. This valuable lesson, learned in her school days, continues to guide her today: focus on what you can change, not what you can't. This book changed her and it still helps her to be very optimistic naturally.
Biology was where Katalin’s heart truly was, she loved the problem solving aspect of biology! In fact, she excelled nationally in a biology competition during her elementary years, earning her third place across the entire country. She describes herself as very inspired and competitive. This tenacity of hers was not liked by everyone, but Katalin had a simple philosophy: “some people have power that they can crush you and they try to use it. But you just don’t have to think about too much”.
The Journey into RNA Research
Katalin’s research journey began in Biological Research Center, delving into lipids. Then in 1978, she started working in the RNA Lab in Hungary. She learned a lot about RNA, but was kicked out of lab as the funding was cut from the RNA study. She then moved to USA.
Before going further in her research journey, which gets more exciting, let’s first understand a little about RNA.
What is RNA? RNA stands for ribonucleic acid. There are different types of RNAs: messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA, 80-90% of total RNA, part of protein synthesis machinery). We will focus on mRNA here, as this was the focus of Katalin’s research. As the name suggests, mRNA is the messenger which carries information of our genetic code (that is DNA), to the protein manufacturing machinery of our cells (ribosomes) which then decode the information to produce proteins. Proteins are the functional unit of the cells, they could be enzymes, hormones, antibodies, etc. This unidirectional flow of information from DNA to RNA to Proteins is called Central Dogma.
DNA stores information of what kind of protein it is coding for, it is double stranded, and quite stable. On the other hand, RNA is single stranded, very unstable, and prone to self-destruction. RNA is very labile, it degrades so fast, this is the reason why palaeontologists could extract DNA but never recover RNA from excavated dinosaur bones. This is the reason why RNA-based therapies are particularly challenging.
After coming to the US, she spent time at Temple University and in Bethesda, delving deeper into mRNA research. In 1989, she landed at the University of Pennsylvania, determined to unravel the potential of mRNA. Her focus shifted to not only delivering mRNA into cells but also directing them to manufacture proteins they wouldn't produce otherwise.
A String of Setbacks
At University of Penn, Dr, Karikó joined as a research-assistant professor, a non-tenured position requiring continuous grant funding. In the first two years at Penn, Dr. Karikó wrote a grant every month, but every time her grant proposal was rejected. Use of RNA for therapeutics was completely new thing, RNA is so labile that grant committee was critical of this idea. Her pioneering work with RNA faced resistance. Grant after grant was rejected, as the concept was met with skepticism.
Most would have wavered, considering a change in research focus or university. Not Katalin. She asked herself, “What can I do?” and set to work improving her writing, generating more data. Yet, despite her relentless efforts, she secured no grants in five years and was demoted.
The Never Give-Up Spirit
Undeterred, Katalin continued her research at Penn as a Molecular Biologist in the Neurosurgery Department for 17 years. She continued working at bench, conducting experiments herself. Without students to assist, she tackled every aspect.
Her response to those who pitied her struggles? "I was happy. I was at the bench, all the way. When I was 58 years old, I still did my own experiments, I did every part."
While grants eluded her, she cherished her lab and the autonomy it afforded. Empowered, she relished full control over her experiments, discovering, reading, implementing – a researcher's dream.
A Fateful Encounter at the Photocopier
Destiny had some plans, while using photocopier at the Dept of Medicine, she encountered a new guy. They both started talking about their work, this new guy was Dr. Drew Weissman, who at the time was working with Dr. Anthony Fauci. At that time Dr. Fauci was working on HIV research and Dr. Weissman wanted to develop a prophylactic or a therapeutic vaccine for HIV. Katalin proposed to test the idea of using mRNA as a vaccine, Drew agreed to give it a shot.
This fortuitous encounter paved the way for a productive partnership that would revolutionise vaccines. Without their innovation, producing a vaccine within a year to combat a global pandemic would have been nearly impossible. Their work also opened doors for mRNA-based therapies to effectively treat a range of diseases. In the next article, we will discuss in detail on the wider applications of mRNA vaccine.
Meet Drew Weissman
Dr. Drew Weissman, an American physician and immunologist born on September 7, 1959, in Lexington, Massachusetts. He was interested in science from a young age. While in high school, Weissman worked for his father’s company, which specialised in making optical mirrors for satellites.
Weissman's educational background is impressive, with both an M.D. and Ph.D. in Microbiology earned from Boston University. His decision to pursue both degrees demonstrates a drive for in-depth understanding and a willingness to delve into multiple facets of medicine and science. After PhD, he continued his research journey in immunology under Dr. Anthony Fauci at the National Institutes of Health. There he carried out research on developing vaccines for HIV.
In 1997, Weissman established his independent lab at University of Penn. He began carrying out studies in dendritic cells, which serve a key role in immune surveillance. Not long after starting at Penn, Weissman met Karikó while using a photocopier, who shared an interest in finding ways to leverage mRNA to stimulate the body to develop immunity against viral pathogens. This shared interest was start of a successful collaborative relationship. It was a collaboration of two experts in different fields, Weissman an expert in immunology and Katalin an expert in mRNA research. They educated each other, this unique situation led to inventions. Such interdisciplinary collaborations pushed the boundaries, you come up with something that you wouldn’t as individuals, think about. Their story reminds us that true innovation often arises from the synergy of diverse perspectives and expertise.
Breakthrough in mRNA-based Vaccines
Together, Weissman and Karikó tackled a crucial challenge: the body's rejection of synthetic mRNA. They devised a groundbreaking method to synthesize mRNA, rendering it non-inflammatory. This modification not only prevented the body's aggressive response but also increased protein production tenfold – a monumental breakthrough.
Their research, initially met with modest reception, eventually gained recognition. Landmark studies in 20051 and 20082 demonstrated the efficacy of their innovations. They conquered the hurdle of mRNA degradation and developed a delivery system using lipid nanoparticles, safeguarding the fragile molecule until it reached its target.
Conclusion
Their story is truly inspiring. It's a tale of never giving up, having the right attitude, and persevering. They didn't begin their research journey with dreams of revolutionising vaccines or winning Nobel Prizes. Instead, they were driven by a genuine passion for what they loved doing every day. Their dedication to finding solutions, constant refining, and unending search for answers allowed them to thrive, even when their work went largely unrecognized.
We salute their love for science. Congratulations, Dr. Karikó and Dr. Weissman! Your journey has not only inspired me but I believe it will inspire many others too. You both showcase the power of scientific curiosity and the impact it can have. You have our utmost respect!
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Coming up in the next edition of Science Simplified: a deep dive into the world of mRNA Vaccines! Stay tuned for an enlightening exploration of this cutting-edge technology.
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Karikó, K., Buckstein, M., Ni, H. and Weissman, D. Suppression of RNA Recognition by Toll-like Receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005).
Karikó, K., Muramatsu, H., Welsh, F.A., Ludwig, J., Kato, H., Akira, S. and Weissman, D. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol Ther 16, 1833–1840 (2008).