1922 - Banting and Best successfully treat first diabetic patient with natural animal insulin in Toronto, Canada.

1980 - On 15 July the first 8 volunteers received injections of ' biosynthetic human insulin' in the UK.

1981 - Science News, June 27, 1981, volume 119 page 119 and also in a report of a workshop held March 13 - 15 1981 entitled 'The Techniques of Recombinant DNA': Two Eli Lilly scientists reported on several aspects of their process for making human insulin using recombinant DNA ... The two researchers agreed that the clinical trials were progressing rapidly with only one minor surprise: it appears that human insulin is absorbed slightly faster after under-the-skin injections than earlier beef and pork insulin. This can be linked with a report in the Sunday Times Supplement in 1992: While working for Novo Nordisk the medical director wrote about it 'supressing hepatic glucose output and causing counter-regulatory hormonal response'. 'In lay terms', he says 'this means that patients could get hypos on human insulin which they might not get on pork insulin, and that warning symptoms may be different.'

Insulin manufacturers knew that there could be problems with hypoglycaemia and hypoglycaemia unawareness with 'human' insulin. These companies were duty bound to inform the Medicines Control Agency and the FDA prior to marketing approval being given and did so. The Department of Health and FDA granted approval to market 'human' insulin in September / October 1982 and were aware of potential problems of hypoglycaemia (low blood glucose) which could lead to temporary mental impairment akin to the McNaughton rules and behavioural problems of patients biochemically induced by treatment with 'human' Insulin. In November / December 1982 reports were published of reduced adrenal response in 'human' insulin.

1987 - 12 August - 'Hypoglycaemia unawareness in diabetics transferred from Beef/Porcine Insulin' by A Teuscher and W G Berger published in 'The Lancet'. The paper includes details of diabetic coma and death of a 20 year old student in September 1986 two weeks after being transferred to hospital on 9 September 1986 in unconcious diabetic coma with no warning signs of hypoglycaemia (blood glucose 1.7mmol/l measured in hospital). Two weeks later the patient suffered a second hypoglycaemic attack late morning and was found unconcious by his mother at 5.00pm (blood glucose 1.0mmol/l). He remained in deep coma in hospital for 4 days on a life support machine. Assisted ventilation was stopped after 4 days at the request of the parents and the patient died.

1988 - August - British Diabetic Association (BDA) report that 53% of diabetic patients who changed to 'human' insulin but did not modify their regime felt worse.

1988 - August - Insulin manufacturers notify Department of Health of change to data sheets to warn of possibility of lack of warning signs of hypoglycaemia.

1989 - Claims published that 'human insulin' increased the number of unexpected deaths in young people.

1989 - 80% of UK diabetics on 'human' insulin. Manufacturers add warnings about hypoglycaemic unawareness to data sheets.

1990s - A media company is hired to media train UK doctors to state that 'human' insulin has an excellent safety record.

1990's - Many patients continue to suffer hypoglycaemia unawareness when treated with 'human' insulin.

1993 - DCCT Diabetes Control and Complications Trial published.

1996 - Bellagio review published.

2000's - New analogue insulins introduced

2002 - Cochrane Review published