On a cold winter’s day in February 1997, the world woke to the news that Dolly, a sheep, had been cloned from adult mammalian cells at the Roslin Institute of the University of Edinburgh. Responses varied from amazement at the achievement and vision for the future to the more mundane «Why bother, sheep are quite good at it on their own?» The subsequent award of the Nobel Prize for Physiology or Medicine to Sir John Gurdon in 2012 brought broader awareness of the scientific culture and excellence at Edinburgh and in Scotland. In fact, some 1.5% of all Nobel Prizes have been won by scientists with close associations with Scotland – not bad for a country that boasts only 0.07% of the World’s population.

How has this Tartan powerhouse emerged? Scotland has always had a tradition of academic excellence, and two of its ancient universities (St. Andrews, 1413 and Glasgow, 1451) predate the oldest in Switzerland (Basel, 1460). Edinburgh is a relative newcomer, being founded in 1583. In contrast, medicine at the University of Edinburgh dates to at least 1505, and the Medical School, established in 1726, is among the oldest in the anglophone world. Medicine can be seen as the centre from which excellence in physical and life sciences and medicine developed from the Scottish Enlightenment to the present day.

Strangely enough, Scotland's early history of medicine and the life sciences was one of scientific evolution rather than revolution. Nevertheless, highlights include the discovery of chloroform as an anaesthetic by Sir James Young Simpson (Edinburgh), and the development of antiseptic care, particularly the use of phenol, by Joseph Lister (Glasgow and Edinburgh).

Great contributions were made to chemistry by holders of the position of Professor of Medicine and Chemistry at the University of Edinburgh, particularly by Joseph Black, who identified the gas carbon dioxide (“fixed air”). Another Edinburgh physician, Daniel Rutherford, discovered a new gas in air, nitrogen, that he distinguished from Black’s carbon dioxide (that he called “mephitic air”). With this strongly developed background in gas chemistry, it is unsurprising that Glasgow, Edinburgh, Dublin and London became the hubs of the 18th Century Phlogiston discussions in the anglophone world. Joseph Black believed that phlogiston had negative weight (absolute levity), but by the early 1780s, Black rejected the phlogiston theory, which was replaced by Lavoisier's oxygen combustion model.

What has happened in Edinburgh since Dolly’s first hesitant bleats? Edinburgh remains at the centre of advances in molecular biology and the life sciences, and it has embraced the new technologies and methods that were in their infancy, or non-existent, in the 1990s. Scottish life science recognizes that research should be for societal benefit and finesses the balance between fundamental discovery and application. The intimate relationship between physiological research and molecular biology lies at the heart of developing new diagnostic and therapeutic methods.

Like all laboratories worldwide, the Scottish research community was deeply engaged in COVID-19 research, with the Roslin Institute playing a key role. In addition to fundamental studies at the molecular level, the Institute was involved in developing antiviral strategies, investigating the origin and distribution of the virus and modelling the spread of Covid-19.

The developments in molecular biology in the past quarter of a century are too numerous to mention. Still, two can be identified as having a disproportionate actual or potential societal impact.

The first is the widespread use of the polymerase chain reaction (PCR) in molecular biology, medicine, and well-publicised “real world” applications. At its simplest, the PCR technique generates millions or billions of copies of a single piece of DNA. These copies of clones can then be used to read the genetic code or to manipulate and clone entire genes. The Human Genome Project was designed to read the complete genetic blueprint for a human being and is now essentially complete; PCR methods were one of the core technologies in achieving this success. PCR is now widely used for the diagnosis of diseases and the detection of pathogens. The PCR technique has had a real impact on the way that society and science interact. Reading or watching a “Krimi” that does not use DNA testing to identify or eliminate suspects is almost impossible.

The Jurassic Park movies are based on amplifying ancient dinosaur DNA using PCR methods. During the Covid-19 pandemic, the entire world became aware of the PCR and antigen (rapid) testing methods. In Scottish universities and hospitals, PCR is part of the core methodology used for diagnosing and treating diseases ranging from genetic disorders to cancer and fundamental studies ranging from molecular biology through ecology to archaeology. It is true to say that PCR has become the Swiss army knife of molecular biology.

If PCR represented the multiple uses of the Swiss army knife, the second development centres upon its cutting ability! This is the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology. In brief, this method uses a simple bacterial CRISPR-Cas9 enzyme to act as a pair of molecular-level scissors to cut DNA at a specific point. As DNA is the genetic material that defines individual organisms and is responsible for any genetic defects that they might have, CRISPR technology offers the opportunity to “repair” defective DNA or to modify the DNA of an organism to incorporate specific desired properties. The potential applications are enormous, although not uncontroversial, ranging from genetic modification of foodstuffs, conferring resistance in livestock, pre- or post-natal treatment of genetic disorders to cancer therapy. The first clinical trials on cancer patients were successfully concluded in the United States in 2020. Scottish universities and hospitals are actively involved in utilizing all aspects of the CRISPR methods. One application by Edinburgh scientists that I find particularly interesting is developing CRISPR to enable algae and plants to synthesize new molecules, thus offering new and sustainable methods for producing renewable fuels, pharmaceuticals and medicines, and other high-value small molecules.

We often equate scientific advances with the medical and life sciences in our post-pandemic world. Although their societal impact is beyond dispute, we should not forget that all the comforts of our material world come from advances in engineering, materials science, chemistry, and physics. In 2013, colleagues at CERN’s Large Hadron Collider near Geneva confirmed the existence of the Higgs boson, thereby providing strong support for the Standard Model of the universe. The Higgs boson was originally postulated in 1964 by Peter Higgs of the University of Edinburgh to explain the origin of the mass of elementary particles, an achievement for which he shared the 2013 Nobel Prize in Physics.

Scotland continues to hit above its weight in knowledge creation and dissemination, with societal relevance at the core of research culture. It would be disingenuous to end this article without mention of one applied research body, The Scotch Whisky Research Institute, based in Edinburgh – Slàinte.

 

Edwin «Ed» Constable is a chemist and former vice-rector of the University of Basel. He was born in Edinburgh and recently was elected to Fellowship of the Royal Society of Edinburgh. He is passionate about the history and communication of science.

This article was printed in Die Weltwoche supplement «Sonderausgabe Schottland»