Comment

Kevin Rogers says pharma overlooks bench chemists at its peril

In the past few months, pharmaceutical giant AstraZeneca has announced it will cut the jobs of hundreds of UK chemists and bioscientists working in the field of small molecules. Despite promises to increase productivity in research and increasing pressure on researchers there has been little to show for the past 10 years’ efforts, a problem common to all the major pharmas. 

Why can the pharmaceutical industry no longer rely on new compounds reaching the market every few years? Although the requirement to demonstrate safety to regulatory authorities has become more stringent, and litigation has made companies risk averse, these do not account for the dearth of new chemical entities reaching the market. Are the remaining targets too difficult? Possibly some, but many of those successfully tackled in the past seemed daunting at the time and yet succumbed to diligence, inspiration and perseverance. 

What went wrong? Historically there was room to manoeuvre. When things didn’t go as fast as predicted you persevered until you got the quality of compound required. Stopping a project that was moribund might be difficult but sometimes something unexpected would crop up and be pursued to advantage. In these days of targets and time lines there is no allowance for investigation of sidelines. With an approaching deadline there is always pressure to go with what you’ve got and achieve your targets. With target driven culture you get exactly what you asked for, which is not necessarily what you wanted. Researchers may be motivated by higher things, but penalising them for quality work and rewarding them for filling more notebook pages is ultimately destructive.

If n  thousand compounds give one drug then 2n  thousand gives two. This dubious logic led to vast investment in compound libraries. Large scale investment in compound factories in developing countries propagates this myth. The temptation is always to make the things that can be made easily.  

Most people come into a job in pharmaceutical research hoping to make a difference. Chemists find it dispiriting just playing the numbers game. There is a tendency to talk down the work of the synthetic chemist. ’Synthesis is not a problem. We can make anything you can write down,’ so said a well known professor in a radio interview. In reality chemistry is not as predictable as people make out. Every day there are surprises and unexpected problems and lots of retrospective rationalisation. Chemists require insight and invention to overcome problems and are not just technicians following predictable paths.  

Chemistry chiefs used to carry out some bench work themselves. All the intermediate layers of management have now drifted out of the labs to undertake ’more important’ work. To get on you must get out of the lab, so the myth that anyone who does lab work is a second rate scientist has arisen and those who direct projects become increasingly out of touch with the realities of the job. Research managers should recognise that contrary to HR doctrine all jobs are not alike and the tools you use to increase the output of a car factory are clearly not applicable to drug discovery. 

While not abandoning small molecules altogether, the answer to the lack of new drugs seems to be biological agents, whatever the price. For good reasons interest in antibodies has burgeoned. The time to market is short, and toxicity is less of a problem, but they are produced in tiny yields. The cost to the UK national health service (NHS) of maintaining someone on these therapies can easily exceed ?10,000 per year. Can these agents be funded by the NHS?  

Is there a way forward? The current answer is to buy in ideas from small companies and academic groups that work in a less fettered way. Could control of discovery return to scientists? One way forward might be to set up a group within a research department with a completely free remit and see what they achieve in a few years. The future of small molecule research needs to return from the scatter gun numbers game fettered by arbitrary deadlines to synthesis of selected quality compounds. 

Kevin Rogers recently retired after 33 years in the pharmaceutical industry.