The Nobel Prize Medicine 2023

 

Introduction

Katalin Karikó and Drew Weissman shared the 2023 Nobel Prize in Physiology or Medicine, "for their discoveries regarding nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19."

The two Nobel Prize winners' discoveries were essential for creating COVID-19 mRNA medicines that worked during the pandemic that started in early 2020. The prize winners contributed to the exceptional velocity of vaccine development during one of the greatest risks to human health in modern times with their ground-breaking discoveries, which have fundamentally changed our knowledge of how mRNA works with our immune system. 

                                                               

Before the Pandemic, Vaccines 

• A specific pathogen-specific immune response is generated by vaccination. In the event of a subsequent exposure, this gives the body a head start in its fight against disease. 
• The vaccines against polio, measles, and yellow fever are only a few examples of the many existing vaccines based on killed or weakened viruses. For creating the yellow fever vaccine, Max Theiler received the Nobel Prize in Physiology or Medicine in 1951.
• Thanks to the progress in molecular biology in recent decades, vaccines based on individual viral components, rather than whole viruses, have been developed. Parts of the viral genetic code, usually encoding proteins found on the virus surface, are used to make proteins that stimulate the formation of virus-blocking antibodies. 
• Examples are the vaccines against the hepatitis B virus and human papillomavirus. Alternatively, parts of the viral genetic code can be moved to a harmless carrier virus, a “vector.” This method is used in vaccines against the Ebola virus. 
• When vector vaccines are injected, the selected viral protein is produced in our cells, stimulating an immune response against the targeted virus.
• Producing whole virus-, protein- and vector-based vaccines requires large-scale cell culture. This resource-intensive process limits the possibilities for rapid vaccine production in response to outbreaks and pandemics. 
• Therefore, researchers have long attempted to develop vaccine technologies independent of cell culture, but this proved challenging. 

mRNA Vaccines: An amazing idea

• In human cells, messenger RNA (mRNA), which serves as an example for the synthesis of proteins, receives genetic information stored in DNA. In vitro, transcription refers to effective techniques for generating mRNA without cell culture that were developed in the 1980s. 
• This important move boosted the advancement of molecular biology applications across numerous sectors. However, difficulties continued in the use of mRNA technologies for vaccination and medical purposes. 
• It was thought that in vitro transcribed mRNA was unreliable and hard to distribute, necessitating the creation of complex carrier lipids systems. Additionally, mRNA created in vitro resulted in inflammatory responses. As a result, there wasn't much interest in developing mRNA technology for medical uses at first. 
• The Hungarian biochemist Katalin Karikó was committed to creating strategies for using mRNA for therapy and was unfazed by these challenges. Although she had difficulty convincing research funders of the importance of her work in the early 1990s when she was an assistant professor at the University of Pennsylvania, she stayed committed to accomplishing her vision of mRNA as a therapy. 
• Drew Weissman, an immunologist at her university, was a new colleague of Karikó's. Dendritic cells, which play crucial roles in immunological monitoring and the induction of vaccine-induced immune responses, attracted his interest. 
• A productive partnership between the two soon started, concentrating on how various RNA types interact with the immune system and was rapidly inspired by new concepts.

                          

The Discovery

• In vitro-produced mRNA is recognized by dendritic cells as a foreign substance, which causes them to become activated and release inflammatory signaling molecules, as discovered by Karikó and Weissman. 
• They asked why mRNA from mammalian cells failed to produce the same response when it was in vitro transcribed, but did. Karikó and Weissman came to the conclusion that specific characteristics were required to separate the various mRNA types.
• The four bases of RNA are A, U, G, and C, which are shorthand for the genetic code's letters A, T, G, and C in DNA. Karikó and Weissman were aware that in vitro-generated mRNA frequently undergoes chemical modification, although mammalian cell RNA does not. 
• They questioned whether the in vitro transcribed RNA's lack of changed nucleotides could be to blame for the negative inflammatory response. In order to research this, scientists created many mRNA variations and sent them to dendritic cells, each of which had different chemical alterations in its bases. 
• The results were shocking: When base changes were added to the mRNA, the inflammatory reaction was virtually totally eliminated. Our understanding of how cells detect and respond to various types of mRNA was fundamentally altered by this. 
• Karikó and Weissman noticed instantly how important their discovery was for utilizing mRNA as a form of therapy. This ground-breaking research was released in 2005, which was fifteen years before the COVID-19 epidemic. 
• Karikó and Weissman demonstrated in several tests that the administration of mRNA produced with base changes significantly boosted protein production when compared to unmodified mRNA in 2008 and 2010. 
• The lower activation of an enzyme that controls protein synthesis was what caused the effect. Karikó and Weissman have removed significant barriers to the clinical use of mRNA by demonstrating that base changes both decreased inflammatory responses and boosted protein synthesis.

mRNA Vaccines Alternatives were identified

• As interest in mRNA technology increased, more businesses started pursuing its development in 2010. The development of vaccines against the Zika virus and MERS-CoV, which is closely linked to SARS-CoV-2, was pursued. 
• Two base-modified mRNA vaccines encoding the SARS-CoV-2 surface protein were created in a record amount of time after the COVID-19 pandemic broke out. Both vaccinations have already received approval for use in December 2020 and protective effects of about 95% have been documented. 
• The development of mRNA vaccines can be done quickly and with great flexibility, which opens the door to using the novel platform for vaccines against additional infectious diseases. Future applications of the technology could include the delivery of protein therapies and the treatment of certain cancers.

Indian Who Won the Nobel In Biology: Hargobind Khorana (1922–2011)

• An Indian-American biologist named Hargobind Khorana (1922–2011) is recognized for his groundbreaking discoveries in decoding the genetic code.
• He was born in India and later moved to the US, where he produced ground-breaking advances in molecular biology. 
• His contribution to decoding the genetic code and proving how the nucleotide sequence of DNA directs the creation of proteins awarded him the 1968 Nobel Prize in Physiology or Medicine. 
• Our knowledge of how DNA conveys genetic information and translates it into the components of life is largely thanks to Khorana's study. 
• His influence on genetics and biotechnology is still felt today.

Conclusion: The Achievements

• More than 13 billion dosages of the COVID-19 vaccine have been supplied globally as a result of the quick introduction of several more SARS-CoV-2 vaccines based on various techniques. The vaccines prevented serious sickness in many more people and saved millions of lives, allowing countries to come back and resume regular life. 
• The Nobel Prize winners for this year made key findings on the significance of base changes in mRNA, which were crucial to this significant advancement during one of the worst health crises of our time. 

Frequently Asked Questions(FAQ's)

1: What is the significance of Katalin Karikó and Drew Weissman's Nobel Prize in Physiology or Medicine?

• Katalin Karikó and Drew Weissman received the Nobel Prize for their groundbreaking discoveries regarding nucleoside base modifications in mRNA. 
• These discoveries cleared the door for the creation of potent COVID-19 mRNA vaccines, which were vital in halting the pandemic and rescuing numerous lives.

2. How has the research of Katalin Karikó and Drew Weissman altered our perception of mRNA?

• Our understanding of how cells recognize and react to various forms of mRNA has been substantially influenced by Karikó and Weissman's study. 
• They discovered that they could greatly minimize inflammatory reactions while increasing protein output by making particular nucleotide alterations to mRNA. 
• This discovery has revolutionized the use of mRNA in therapy and vaccine development.

3. What challenges did Katalin Karikó and Drew Weissman face in their early research on mRNA?

• In the early 1990s, when Katalin Karikó was an assistant professor at the University of Pennsylvania, she faced difficulties convincing research funders of the importance of her work on mRNA therapy. Additionally, mRNA created in vitro resulted in inflammatory responses, discouraging initial interest in its medical applications.

4: How have mRNA vaccines altered the vaccine development landscape?

• mRNA vaccines, such as those created for COVID-19, have made vaccine development speedier and more flexible. 
• They may be easily developed and customized for various infectious diseases. The pandemic's success with this technique has opened methods for future vaccine research and even the treatment of some ailments, like cancer.

5. How will Katalin Karikó and Drew Weissman's Nobel Prize affect global health more broadly?

• The significance of mRNA technology in the field of medicine is shown by the Nobel Prize acknowledgment of Karikó and Weissman's work. 
• In addition to making an important contribution to the fight against COVID-19, it shows promise for the development of future vaccines against infectious diseases and the administration of protein treatments. 
• Their achievements have the potential to change the world's healthcare system for the better.