79th Congregation (2015)

In organisms such as mammals which have many cells, there exists one fundamental type of cell called a stem cell. This is a kind of mother cell, which has not yet differentiated itself as part of the normal cell-division process into one of the more specialised types, such as a bone or blood or organ or skin cell, but which is capable of developing into any of them. Obviously in mammals these stem cells are mainly to be found in embryos, at the beginning of the growth cycle. They can also be found in adults, as cells which maintain and repair tissue. But adult stem cells are not as versatile or potent as the embryonic ones; they are not what is called ‘pluripotent’, which means they cannot turn themselves into any cell type. On the other hand, scientists have been able to create an embryonic-like cell in the lab: embryonic stem (ES) cells, which are pluripotent.

ES cells have enormous potential for regenerative medicine, such as in the transplanting of cells in incurable disease therapy. They also have important applications in drug testing, and in the basic understanding of how certain diseases develop. But the creation of human ES cells requires the use of human embryos, which raises difficult ethical problems as well as practical ones such as rejection by the host’s immune system. Is there an alternative?

It has been known for 50 years, through the work of John Gurdon, Ian Wilmut and others, that the nucleus of an adult cell can be transplanted into an egg which can then grow into a new frog or a sheep, like the famous Dolly. This is known as cloning. But this technique also has limited application; it is extremely inefficient, which means an extraordinary number of eggs are needed. The Holy Grail of stem cell research became to discover a way of reprogramming an ordinary functional adult cell such as a skin cell so as to return it to a pluripotent state: in other words to create the equivalent of an ES cell out of an ordinary adult body cell, called a somatic cell. And that discovery was made only nine years ago.

The man who made it was the son and grandson of hard-working engineers. Their small factory in Osaka designed and manufactured components for sawing machines. The child copied his father. He loved taking clocks and radios to pieces and then usually failing to put them back together again. Meanwhile as a hobby he loved judo and rugby, and his bones often got broken. This aroused his interest in repairing bodies instead of clocks and radios and he decided to become an orthopedic surgeon. He received his MD from Kobe University in 1987 and during his residency was able to treat his own father’s diabetes and hepatitis during the last two years of his life. But in fact he found the exposure to incurable diseases so distressing, maybe like the broken radios he could not fix as a child, that he decided to become a scientist instead, and look for the cures.

He took his PhD in pharmacology at Osaka City University in 1993. He developed an interest in molecular genetics and especially gene targeting in mice: that is, inducing or deleting single genes in order to alter cells. This is a technique pharmacology cannot hope to emulate. In 1993 he moved to the Gladstone Institute of Cardiovascular Diseases in San Francisco to pursue his research. He now had to learn how to culture ES cells in mice as part of his gene targeting work. By now he was married with a family of his own, but when his wife and two daughters returned to Japan he went back to the Osaka City University’s Pharmacology Department.

ES cells were now his main research interest. After several setbacks he finally got his own laboratory at the Nara Institute of Science and Technology in 1999. He was becoming more interested in human ES cells than in mice; but given the ethical and practical problems, and building on the older frog and sheep genetic research, he was determined to find ways of generating ES cell-like pluripotent cells directly from ordinary somatic cells through genetic engineering. He brought his lab over to Kyoto University’s Institute of Frontier Medical Sciences, and there from 2005 to 2007, he and his colleagues finally succeeded in converting skin cells into induced pluripotent stem (iPS) cells, first in mice and then in humans, by the addition of just four genes.

Of course those iPS cells can be derived from a patient’s own skin, making them specific to him or her, and thus much more effective for studying and treating disease without immunological resistance, as well as for developing chemical and natural products to make medicines. Conditions as varied as sickle cell anaemia, Parkinson’s disease, Alzheimer’s disease, Lou Gehrig’s disease, cancer and diabetes, the disease our scientist’s own father had, are potentially all treatable by iPS cell technology.

The team had indeed found that Holy Grail of stem cell research, and in 2008 their leader was made director of the newly created Center for iPS Cell Research and Application (CiRA), at Kyoto University. Prizes and awards followed thick and fast on that breakthrough success. They included two of the world’s top three awards in medicine, the Wolf Prize in Israel in 2011 and the Albert Lasker Basic Medical Research Award in the US in 2009, as well as the Millennium Technology Award in Finland in 2012, and Hong Kong’s own Shaw Prize in Life Science and Medicine in 2008. He has been named a member of several national science academies including the US National Academy of Sciences, the Pontifical Academy of Sciences and the Japan Academy. Along with remaining director of CiRA, currently he is also a senior investigator at the Gladstone Institutes in San Francisco. He is no stranger to CUHK either, since he gave the Dr Lui Che Woo Distinguished Professor Public Lecture here last year.

That little boy who wanted to fix radios, clocks and broken bones, who loved judo and rugby and still runs marathons to raise money for cell research, has ended up by transforming human cell technology and revolutionizing medical research. He is of course Shinya Yamanaka. In 2012, jointly with Sir John Gurdon, he was awarded the Nobel Prize in Physiology or Medicine, and while of course his father was not present at the ceremony, his mother was.

For his remarkable and ongoing contribution to stem cell research, molecular biology and biotechnology, with its vast implications for regenerative medicine, it gives me great pleasure, Mr Vice-Chancellor, to present to you Professor Shinya Yamanaka, for the award of the degree of Doctor of Science, honoris causa.

This citation is written by Professor Simon Haines