The 2023 Nobel Prize for Medicine is a thumbs up for basic science research

Euphoria surrounds this year’s Nobel Prize in Physiology or Medicine awarded to Dr Katalin Karikó and Dr Drew Weissman for their scientific research that made mRNA vaccines a reality. Soon after the Nobel Foundation made the announcement, this writer participated in a large academic gathering comprising mostly biological science researchers and students. Discussions surrounded the tremendous global impact of mRNA vaccines in reducing the number of COVID-19 cases and associated deaths. mRNA vaccines are a powerful weapon against SARS-CoV-2, but more importantly, the discoveries and the approaches Karikó and Weissman enunciated in developing the vaccine hold tremendous promise for other infectious diseases. In fact, the approach is viewed as a true revolution in medicine. Interestingly, much of the discussion surrounded the practical impact of vaccines, emphasising that only applied research—such as the work that resulted in the mRNA vaccine for COVID-19—should be funded by the public. Many discussants even pooh-poohed the need for funded research in the basic sciences.

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mRNA vaccines are a direct product of the basic science research in molecular biology that began in the mid-20th century following the discovery that nucleic acids conferred inheritance (1944) and of the structure of DNA (1953). Many technological advances have indeed been instrumental to the development of mRNA vaccines. One important advance was the packaging of the vaccine in a hollow lipid sphere (for example, an oil bubble) so that it can penetrate the human host cell.

However, the key contribution of Karikó and Weissman was to identify and devise a method, using a series of basic molecular biology experiments, to cheat the human host’s immune system so that it considers the vaccine not as a foreign particle but as intrinsic to the human. Any foreign particle entering the human body meets great resistance from the immune system and is usually discarded from the body. A vaccine cannot afford to meet this fate.

Therefore, identification of the way to cheat the immune system was the fundamental knowledge that Karikó and Weissman generated through painstaking basic science research. Thus, basic science research provided humanity with an option to meet the existential threat COVID-19 posed. This knowledge is, however, deep and broadly applicable; in the coming years, one will witness the availability of mRNA vaccines for many other human diseases and thereby the saving of many more lives.

Unfortunately, the appreciation and even awareness of the critical function of basic sciences seems to be on a downslide, especially in India. Research in the basic sciences is essentially driven by the curiosity of the researcher. But the results of such research serve a fundamental role in our lives and can lead to the understanding of causes and the means and tools to deal with the challenges of hunger, infectious diseases, climate change, environmental pollution, and so on. It is critical to raise awareness of this among policymakers, in business and industry, and the general public.

Basic science research is often motivated by a gap in knowledge about something, while applied research focusses on filling a need. A basic scientist’s questions are usually of the type: Why is this important? Why does it happen this way? An applied scientist usually asks: How can I use this? Can I find a tool to help those in need? A basic scientist may ask: What types of immune cells are found near the site of liver cancer that are not found near a normal liver?

“A basic scientist’s questions are usually of the type: Why is this important? Why does it happen this way? An applied scientist usually asks: How can I use this? ”

Once the basic scientist has an answer to this question, an applied scientist—sometimes also called a translational scientist—may ask: Can I use the knowledge of the specific types of immune cells that are found in large numbers near a liver with cancer to devise a system that will fight the cancer?

More simply, a basic scientist wants to elucidate why component X exists within a particular system and its function, but an applied scientist is usually more interested in figuring out how to use component X to achieve a certain end. Unless the basic scientist generates appropriate knowledge, the applied scientist cannot profitably put the knowledge to use. Both types of scientists are, therefore, important. The visible impact of applied science is strong, but unless basic scientists generate knowledge to apply, there cannot be any impact of applied science. It is critical for everyone to realise these facts.

Highlights

Katalin Karikó and Dr Drew Weissman get the 2023 Nobel Prize in Physiology or Medicine for their research that made mRNA vaccines possible. Using a series of basic molecular biology experiments, they identified and devised a way to cheat the human host’s immune system so that it considers the vaccine not as a foreign particle but as intrinsic to the human.
The results of basic sciences research can lead to the understanding of causes and the means and tools to deal with the challenges of hunger, infectious diseases, climate change, environmental pollution, and so on. Many key scientific advancements would have been impossible without the basic science research that preceded them.

Why is basic science research important?

The prevalent view that applied research is superior to basic research is most unfortunate. Science advances and humanity benefits when scientists carry out research and discover important features of nature and use these discoveries to invent solutions for the benefit of humankind. Scientists require funds to conduct research. Most research funding comes from the government, which in effect is taxpayers’ money. Therefore, public opinion holds sway over the allocation of science funding. Since applied science is visibly more impactful to the common man than basic science, the latter is often perceived as ineffectual or even frivolous. When this perspective is used to influence decision-makers, inevitably funding for basic science is reduced and research suffers and diminishes.

Society does not immediately perceive any negative impact of the decline of basic science research because there is always a backlog of basic science discoveries that remain to be used for translational purposes. However, after a period of time, applied scientists will have no basic scientific discoveries to use; then there will be a sudden negative impact that will continue for a long time. New products will not become available. New diseases will arise, but there will be no way to detect, prevent, or treat them. The ozone layer will break down, but without knowledge of the factors that caused the catastrophe, there will be no way to prevent it.

Government funding agencies insist that even basic science research proposals should state the immediate commercial impact or translational potential of their research. While this may be a good push to foresee possible ways to apply the discoveries basic scientists are seeking, it is impossible to always do so. If such proposals are not funded, no scientist will walk into uncharted territories, and important discoveries will become limited. This leads one to make a critical statement about basic research: While it may not be possible for a basic science researcher to offer clear-cut ways to immediately provide solutions to outstanding problems, basic research is the bedrock for future problem-solving. Many key scientific advancements would have been impossible without the basic science research that preceded them. We have all seen a person delivering a lecture using a laser pointer to highlighting statements or figures projected on a screen. Lasers are also used for various types of surgical procedures. We hardly remember that Albert Einstein established the foundational knowledge of electromagnetic radiation in his theoretical paper in 1917. Theodore Maiman used this knowledge to invent the first functioning laser prototype in 1960. Similarly, most of us are unaware that considerable basic mathematical research on packet-switching theory had to be carried out in the 1960s to enable the establishment of the Internet in the 1990s.

“Breakthrough inventions are never made in a vacuum; they are built upon the basic science work done by others, often decades ago.”

Breakthrough inventions are never made in a vacuum; they are built upon the basic science work done by others, often decades ago. We simply do not understand humans or the world well enough to predict everything we might need; basic scientific research ensures we are equipped to deal with issues beyond the limits of our present-day imagination, should they arise.

Alexander Fleming in his laboratory in London in 1943. In 1928, Fleming discovered some fungus growing in a Petri dish of Staphylococcus bacteria that seemed to be preventing the bacteria around it from growing. He found that the fungus produced a self-defence chemical that could kill bacteria. Fleming named the substance penicillin. | Photo Credit: Wikimedia Commons

Basic and applied research go hand in hand as symbiotic and complementary entities: Without basic research, applied research has no foundation, and without applied research, basic research yields no tools. Also known as discovery research owing to its emphasis on the quest for knowledge rather than commercial applications, basic research has led to breakthroughs that have spawned entirely new fields of science like genomics. Some of these discoveries were actually accidental. Recall that in 1928 Dr Alexander Fleming returned from a holiday to accidentally discover some fungus growing in a Petri dish of Staphylococcus bacteria. He noticed that the fungus seemed to be preventing the bacteria around it from growing. He did some research and found that the fungus produced a self-defence chemical that could kill bacteria. Fleming named the substance penicillin.

“Basic and applied research go hand in hand as symbiotic and complementary entities: Without basic research, applied research has no foundation, and without applied research, basic research yields no tools. ”

The flat screen of television sets or cell phones is the fruit of the accidental discovery of liquid crystals in 1888 by the Austrian botanist Friedrich Reinitzer while he was studying cholesteryl benzoate, an organic chemical, in carrots. Reinitzer observed that when he heated the chemical (to 145°C), it melted and turned into a cloudy fluid. When heating was continued, it changed again (at 179°C), but this time into a clear liquid. The cloudy fluid was a liquid crystal; it flowed like liquid, but under a microscope, Reinitzer could see little crystals (crystallites). Liquid crystals, most commonly known today for their presence in liquid crystal displays (LCDs), have a molecular make-up between a solid and a liquid. It was Reinitzer who observed that the substance reflected polarised light and could also rotate the polarisation direction of light.

Basic research is foundational but is a time-consuming process. The US’ National Institute of Allergy and Infectious Diseases defines basic scientific research more formally as “a systematic study directed toward greater knowledge or understanding of the fundamental aspects of phenomena and of observable facts without specific applications towards processes or products in mind” and says that this helps us understand the principles, mechanisms, and processes that underlie nature and answer fundamental questions about how nature and life work.

The line between discovery and application can be long and hard to trace. The fundamental knowledge gained through basic science often leads to unanticipated breakthroughs. The return on investment from basic research over the long term is significant; most of the gains over the past century could not have happened without basic research. Science is often slow and unpredictable, and it can take years to build up enough basic knowledge to apply it in beneficial ways.

Basic science is always a work in progress. It takes many studies to identify the “most accurate” model; the most accurate model may not be the “right” model. It is a self-correcting process. Sometimes experiments can give different results when they are repeated. At other times, when the results are combined with later studies, the current model can no longer explain all the data and needs to be updated. Basic science looks at a question from many different angles using many different techniques to find an answer.

Why is public support for basic science critical?

We are passing through a phase of fiscal restraint; a phase of so-called mission-critical priorities where tangible outcomes are considered essential for research. Consequently, basic research, whose risk-benefit ratio is unquantifiable, is not encouraged. But if we make this decision, it must be with the full realisation that not taking this risk today poses an equally unquantifiable but inevitable risk for tomorrow.

To build a bridge that extends from the laboratory to the community and to simultaneously close the entrance to the bridge is to forfeit the future of applied or translational science. We should be aware of this and be able to inform those who are unaware of the risks of not supporting basic science research. Humanity’s best insurance policy is a continued investment in basic sciences.

Partha P. Majumder is a National Science Chair, government of India, and a former president of the West Bengal Academy of Science & Technology and the Indian Academy of Sciences.