Towering figure brought relief to millions

PHARMACOLOGIST

22-2-1924 8-11-2011

SIR David Jack, who was the scientific brain behind the rise of the pharmaceuticals company Glaxo, and credited with the discovery of seven important drugs, has died, aged 87.

Among these drugs are salbutamol (marketed as Ventolin), which has saved the lives of millions of asthmatics, and Zantac, used to treat peptic ulcers.

From unglamorous beginnings as a producer of powdered milk for infants ("Glaxo builds bonnie babies"), Glaxo transformed itself into one of the world's largest and most profitable manufacturers of prescription medicines. The company's corporate success is often attributed to Sir Paul Girolami, the company's financial controller from 1965, then chief executive and chairman during the 1980s. But he would not have been able to effect the transformation in the company's fortunes without the scientific ingenuity of Jack and his team.

A Scottish pharmacologist, Jack joined Allen and Hanburys (famous for its blackcurrant pastilles, which had been acquired by Glaxo) as head of research in 1961. Operating from a small laboratory in Ware, he created and led what proved to be an extraordinarily productive group of research scientists who concentrated on treatments for respiratory, cardiovascular and alimentary tract diseases.

The Ware team embraced all the latest advances in drug "design", especially receptor theory (by which drugs are used to influence the body's chemical messenger system) but they also used well-established techniques and were quite happy to improve on the work of others.

Their first big success came in 1966 with the development of a new treatment for asthma the bronchiodilator salbutamol. Launched as Ventolin in 1969, the drug was an instant success, and the product (with its successors) still turns over nearly $1 billion a year for GlaxoSmithKline, as the company later became.

Encouraged by this success, Jack began looking at the market for duodenal and gastric ulcers, which in those days had no treatment but surgery. He made little progress until 1972, when James (later Sir James) Black, another brilliant Scottish-born scientist working for the British arm of the American company Smith Kline and French (SKF), published a paper in Nature that showed how a chemical known as a histamine H2 antagonist could switch off acid secretions in the stomach.

Jack assembled a team of 12 chemists and pharmacologists to investigate H2 antagonists. But it was a race that SKF appeared to have won when, in 1976, Black (who would win a Nobel Prize for his drug research) came up with the first effective anti-ulcer drug (called cimetidine), which went on to huge commercial success after it was launched as Tagamet in 1978.

In May 1976, however, Jack's team produced a compound that appeared to outperform Tagamet in tests on animals. The compound, known as Ranitidine hydrochloride, was launched as Zantac in 1981 after passing its toxicity and clinical trials.

Helped by a clever marketing strategy that proved especially effective in America, Zantac soon overtook Tagamet and became the first drug to notch up sales of more than $1 billion a year. Glaxo won approval for a twice-daily dose of Zantac, compared with Tagamet's four-times-a-day dose, and at a lower overall total dose in milligrams. The inference was obvious: Zantac appeared to be a more potent and longer-acting agent.

Jack said Zantac was the result of "a simple piece of applied medical chemistry it's not necessary to shake the earth on its axis to make money in this industry. We simply improved on James Black's product by choosing a substance with a cleaner reaction."

The youngest of six children of a coalminer, Jack was born at the Fife mining village of Markinch and educated at Buckhaven High School. He began his career as an apprentice in pharmacy at Boots the Chemists in Cupar, then took a joint honours degree in pharmacy and pharmacology at Glasgow University and the Royal Technical College (now Strathclyde University). After a brief appointment as an assistant lecturer at Glasgow University, followed by National Service, when he taught at the Army School of Health, in 1951 he joined the pharmacy research department of Glaxo at Greenford.

Two years later he moved on to the pharmaceutical company Menley and James, which was later taken over by Smith Kline and French. There he worked on the product development side, formulating waxes used in coating drugs. But a developing interest in chemistry led him to take a part-time PhD at London University, and in 1961 he was appointed research director of Glaxo's subsidiary Allen and Hanburys.

Jack remained at Glaxo until his official retirement, serving as Glaxo's research and development director from 1978 to 1987.

As well as Ventolin and Zantac, Jack's research team developed several further treatments for asthma and other respiratory ailments, including beclomethasone dipropionate (an anti-inflammatory steroid inhalant launched as Becotide in 1972 its concurrent use with Ventolin has transformed the treatment of asthma) salmeterol (a version of salbutamol with a longer duration of action, launched as Serevent in 1990) and fluticasone propionate, a synthetic Corticosteroid marketed under a variety of names, which is used in inhalant form to treat asthma and hay fever and (as a cream) eczema and psoriasis.

Exploiting developments in receptor theory, Jack's team went on to develop new drugs to treat migraine and the side effects of chemotherapy, notably the anti-emetic ondansetron (launched as Zofran in 1991), which works by reducing the activity of the vagus nerve and blocking certain serotonin receptors, and has proved highly effective in preventing chemotherapy-induced nausea and vomiting and sumatriptan (launched in 1991 as Imigran), the first truly specific treatment for migraine, which works by activating receptors that cause constriction of the intracranial arteries.

Jack continued to carry out research work after his retirement from Glaxo. In August this year the drug development company Verona Pharma announced that it was seeking commercial licensing agreements for RPL554, a new anti-asthma and hay fever treatment developed by Jack as an alternative to conventional steroids and beta-agonists. The drug has nearly completed a program of clinical trials.

Jack was appointed CBE in 1982 and knighted in 1993. He won numerous scientific prizes, including the Royal Society's Mullard Medal. He was elected a Fellow of the Royal Society in 1992, having been elected a Fellow of the Royal Society of Edinburgh in 1978.

Jack married, in 1952, Lydia Downie Brown, with whom he had two daughters.