ON December 10, 2023, the Nobel Prize in Medicine or Physiology was awarded in Stockholm, Sweden, to Dr Katalin Kariko and Dr Drew Weissman jointly “for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19.” The citation said these “were critical for developing effective mRNA vaccines against COVID-19 during the pandemic that began in early 2020 and contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times.” Presumably, this satisfied the condition in Alfred Nobel’s will, which is the foundation for the Nobel Prize, that the work “has conferred the greatest benefit to humankind.” But does it?

No doubt the award is to be welcomed as recognition of the importance of basic research. It is also heartening that Kariko is a woman, an immigrant from Hungary to the US, and one who was marginalised by mainstream academia. Kariko was forced to emigrate to the US in 1985 when she lost her job in Hungary where she was born, educated and obtained her PhD. But all along she had a singular focus on unleashing the power of mRNA to fight disease. (Note: mRNA or messenger RNA is a nucleic acid which carries information in the DNA code to the protein-making machinery in the cell, thus shaping the living organism itself.) After working many years at the University of Pennsylvania, USA, Kariko was demoted because she was not securing grants, and was made to work alone without lab space. While photocopying research papers, Kariko by chance met Drew Weissman from the same university who was working on HIV therapeutics. This led to collaboration between the two. Kariko agreed to create mRNA for Weissman, who needed it to develop vaccines for diseases like HIV. In return, Weissman introduced her to immunology. Each provided expertise the other lacked, and the result was the remarkable discovery.

Yet, there was considerable deficiency and bias involved in the process of recognition in the Nobel process and the science establishment in general, and large economic forces played a significant role in the award of the Nobel Prize in Medicine or Physiology in 2023.

WHAT IS THE WORK ABOUT?

DNA or deoxyribonucleic acid has nucleic acid bases that are used to make mRNA or messenger ribonucleic acid in the nuclear of the human cell, which then uses the mRNA to make proteins. Kariko and Weissman found, through their research and publications in 2005 and 2008 that the cells did not have any inflammatory response to naturally occurring mRNA in the body for a specific reason, namely that the natural RNA contained chemically modified nucleic acid bases. So they worked to also introduce synthetic mRNA with modified bases and codes which the cells used to make the spike protein of the Covid virus. This the body could use to generate an immune response, triggering an attack on the invading Covid virus. Way back in 1988, another scientist Malone had put forward the pioneering proposal that mRNA could be used for therapeutic purposes, but success in the field came only after Kariko and Weissman’s discovery.

COVID mRNA VACCINES

Four types of vaccines were developed against Covid-19.  The inactive SARS-Cov2 virus used in Covaxin, the modified adenovirus (a type of virus causing flu-like symptoms) carrying the optimised DNA of the spike protein of SARS-Cov2 as in Covishield, the receptor binding domain of the spike protein of SARS-Cov2 used in Corbevax, and the mRNA vaccine using the modified base mRNA of the SARS-Cov2 spike protein. The US based pharma giants Moderna and Pfizer in collaboration with Germany based BioNTech are the only two groups that could at that point make these mRNA vaccines.

Starting from the discovery of mRNA in 1961, there has been a tangled history of research in public funded laboratories to understand the way mRNA works, the immune response mechanisms involving mRNA, and the development of therapeutics and vaccines. Research groups had developed mechanisms to put the mRNA in a bubble of oil-like lipid (insoluble in water) molecules for efficient delivery into cells.

As Kariko remarked after the award announcement in October, “Everyone just incrementally added something – including me.” The Nobel Prize can be given to up to three persons for any particular discipline. The question then arises as to why no one else involved in the development of using mRNA for COVID vaccine was included along with the well deserved Kariko and Weissman. In fact, earlier, Spain’s prestigious Princess Asturias Award for Technical and Scientific Research recognised others involved in mRNA therapeutics development, such as Felgner, Şahin, Türeci and Rossi, along with Sarah Gilbert, the vaccinologist behind the COVID-19 vaccine (Covishield) developed by the University of Oxford, UK, and the drug firm AstraZeneca.

When Covid-19 struck, the stage was ready, mostly based on publicly funded research work, for Pfizer and Moderna to pick up the mRNA baton and run for the vaccine. Of course the companies did earlier invest some amount of their own money and infrastructure for production of synthetic mRNA and encapsulating it in the lipid bubble mechanism that had been developed by others. All through this process, numerous interconnected patents had come up for different parts of these processes and battles of ownership were already taking place.

Once the SARS Cov2 virus genome was sequenced and made publicly available by scientists from China, the analysis of the genome by several independent scientists from public institutions almost overnight helped identify the part of the genome that was coding for the important spike protein, mainly by comparison with the previously known information for the earlier SARS Cov variants. Based on these, the groups at Pfizer/BioNTech and Moderna were able to quickly synthesize the mRNA corresponding to the spike protein part. They incorporated modified bases into the mRNA following the work of Kariko and Weissman. The mRNA could then be put into a lipid bubble for delivery as had been already determined. The companies then used their infrastructure for large scale manufacturing and packaging into vials.

The required round of trials for vaccine testing were speeded up thanks to generous US government funding, and by the US Food & Drugs Administration (FDA) regulator allowing parallel processing of trials without waiting for each stage to finish. A retrospective study published in the British Medical Journal in 2023 has said “the US government invested at least USD 31.9 billion to develop, produce, and purchase Covid-19 vaccines, including sizeable investments in the three decades before the pandemic.”

So the unprecedented fast rate of development of mRNA vaccine was essentially made possible by the push from by the governments using public money and the regulatory agencies.

FOR WHOM?

In 2021 Moderna reaped revenues of USD 18 billion and Pfizer USD 37 billion from mRNA vaccines alone.  Even more astonishing than the sales turnover is the profit Moderna made.  They brought in USD 13 billion in pre-tax profits. That comes to USD 36 million a day in  2021 making for a profit margin of around 70 per cent. It is the kind of margin which one would perhaps find on luxury consumables, not essential medicines.

Moderna sold most of its vaccines to the rich world. Earlier in November 2020, before a single vaccine had been authorised, Moderna had already sold advance orders of 78 per cent of the doses it expected to produce by the end of 2021 to rich countries, home to just 12 per cent of the global population. Nearly a year later, in September 2021, 85 per cent of Moderna’s total supply had been delivered to the richest countries, and almost no doses at all going to low-income countries. While the company has sold a tiny three per cent to the international distribution mechanism Covax, it failed to deliver even this in time.

The mRNA vaccines did not reach all of humanity but only those in select richer countries.

As an opinion piece in The Hindu (October 4, 2023) said, “The technology could have benefited everyone during the pandemic, but it did not. So, history should remember what actually happened during the pandemic and what the 2023 Medicine Nobel claims happened differently.”