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By Shinya Yamanaka / Special to The Yomiuri Shimbun
10:30 JST, December 29, 2023
The 2023 Nobel Prize in Physiology or Medicine was awarded jointly to Dr. Katalin Kariko and Dr. Drew Weissman.
The awarding committee cited their basic research that led to the development of effective messenger RNA (mRNA) vaccines for the novel coronavirus.
It has now become common knowledge that mRNA can be used to create vaccines. But as mRNA can quickly degrade and cause an inflammatory response in cells to which it is artificially delivered, it was thought, in the nascent stages of development, that it would be difficult to use mRNA in medicine.
Kariko embarked on mRNA research while she was a graduate student in Hungary. In 1985, she moved to the United States, where she applied for federal research funding almost every year, to no avail. At a U.S. university, she even had to agree to a demotion so that she could continue her research there.
One day, Kariko, still in difficulties, had a chance encounter with Weissman while waiting for a copy machine. Several years on, in 2005, she managed to publish a research paper on mRNA, thanks to Weissman’s collaboration. However, the paper received little attention at the time. Several more years passed and she showed her research results to German pharmaceutical startup BioNTech, opening the way for mRNA vaccine development. For more than 25 years, governments and most researchers had failed to see the potential and value of mRNA vaccine technology, which has now contributed so immensely to humankind.
In 2006, one of my colleagues and I published a paper introducing a method for generating induced pluripotent stem (iPS) cells. Based on this paper, I was awarded the 2012 Nobel Prize in Physiology or Medicine, alongside Sir John Gurdon. Some people seemed surprised at how soon — just six years after the publishing of the paper — the Nobel honor was given for iPS cells. In truth, however, iPS cell research had its start 50 years earlier. In 1962 — the year when I was born — Gurdon, then a young researcher in the United Kingdom, reported a crucial discovery: When he removed the nucleus of a frog egg and replaced it with that of a cell from a tadpole’s intestine, the modified egg cell grew into a new frog as a normally fertilized egg cell would do.
In those days, it was thought that no new specimen could be born from the nucleus of a cell with distinct roles already assigned, such as an intestinal cell. I can imagine how enthusiastically the young British researcher must have worked to prove such conventional wisdom wrong, carrying out an experiment using a difficult technique known as somatic cell nuclear transfer. In his research, a tadpole that was born through nuclear transfer matured into an adult frog, and such frogs were able to breed.
Gurdon’s research led to the discovery that even intestinal cells contain a blueprint for creating cells for the rest of the body. After many years of little recognition, his research suddenly took center stage when it was announced in 1997 that a cloned sheep had been birthed from an adult somatic cell, which eventually led to the development of iPS cells in 2006.
The unstinting efforts Kariko and Gurdon made in their youth would greatly impact society after the passage of decades. Despite the clear importance of their research now, even they could hardly have predicted the impact when they started. This shows just how crucial it is to encourage researchers to take on ambitious basic research so that we may have as many scientific breakthroughs as possible.
As basic research, especially ambitious and pioneering research, often requires decades before it produces tangible results, it is generally difficult to assess how promising the work is.
On the other hand, applied research projects, such as for developing new therapies, should obviously have definite goals, as they can take advantage of the pioneering work that has been done already. It is also easier to evaluate such applied projects in a short time span, compared to basic research.
Across the world, research subsidies from governments tend to focus on applied research. Since government leaders and officials usually come and go in a few years’ time, it seems inevitable that they would prioritize such research, whose effects may become tangible during their tenure.
Private funding pivotal
Private sector research funding is one means for promoting ambitious research.
For example, the Howard Hughes Medical Institute (HHMI) in the United States is well-known for turning out Nobel Prize winners. It was founded in 1953 with donations from industrialist Howard Hughes, who had amassed a huge fortune. Though it calls itself an institute, HHMI is focused on providing support to biomedical research — it employs researchers who lead research laboratories at top U.S. universities and other research institutes. It has an endowment of $24.2 billion, and spends about $760 million annually to support medical and biological researchers across the United States.
HHMI is also unique in that it supports individuals — researchers themselves — instead of research projects, as it values people who are creative and who have research competence, as well as the perseverance to overcome difficulties.
At a minimum, it supports researchers for five years. A researcher supported by HHMI can pursue bold projects without worrying about short-term results. Since 2000 alone, 26 current and former HHMI researchers have won Nobel Prizes in physiology or medicine and in chemistry.
In the United States, many private sector funds and donations not only support research efforts but also help ordinary people deepen their understanding of science. The Smithsonian’s National Museum of Natural History in Washington, for instance, has extensive collections of plants, animals, fossils, minerals, rocks, meteorites and cultural artifacts. Its annual revenue stood at $80.3 million in 2022, with donations accounting for 11% of the total and endowment returns for 14%.
In the United Kingdom, the Wellcome Trust is well-known as a charitable foundation focused on health research. It was founded in 1936 by pharmaceutical entrepreneur Sir Henry Wellcome to manage an investment portfolio now totaling £37.8 billion ($47.8 billion). It extends £1 billion annually to research projects related to such core areas as climate change and health, infectious diseases and mental health. The foundation also runs a free library and museum to help people learn about medicine and medical history.
In Japan, there are many grant-offering foundations that support research activities in the medical field. Nevertheless, they are inferior to their U.S. and U.K. peers in terms of grant scale and duration, with the largest foundation having an endowment of about ¥100 billion.
That said, multiple foundations have recently launched new programs for young researchers, providing grants for as long as 10 years. And some have introduced research mentorship programs enabling young researchers to receive advice from senior colleagues. I look forward to seeing young researchers in these programs take on bold basic research — hopefully yielding groundbreaking results.
For my part, when I became an independent researcher, I was granted some research subsidies. When I approached the Japan Science and Technology Agency with a highly risky plan to generate iPS cells, it agreed to subsidize me for five years, providing more than ¥50 million per annum. In retrospect, I had relatively few research achievements, but the opportunity given to me by the agency helped me gain momentum, and lead to the development of iPS cells.
Two years ago, I retired as director of Kyoto University’s Center for iPS Cell Research and Application to concentrate on my own research. This has allowed me to communicate more with young researchers from other institutes. There are many talented researchers, and I feel they will make major breakthroughs once they have the chance to pursue bold research.
In August, some 57,000 people donated ¥920 million to a crowdfunding project by Tokyo’s National Museum of Nature and Science. The museum shot past its goal of ¥100 million in a single day, making headlines. It was good that such a massive sum was donated so quickly. Yet, I feel that the story’s newsworthiness points to a major problem for Japan.
If more donations are made to basic research projects and museums in Japan, such stories could become commonplace. I expect donations to contribute, in tandem with public sector support, to an acceleration of Japan’s scientific and technological development.
Shinya Yamanaka
Yamanaka, winner of the 2012 Nobel Prize in Physiology or Medicine for producing induced pluripotent stem (iPS) cells, is a professor at Kyoto University’s Center for iPS Cell Research and Application, where he was the director until March 2022.
The original article in Japanese appeared in the Dec. 24 issue of The Yomiuri Shimbun.
