Attracting and Training the Next Generation of Medicinal Chemists

By Steve Carney. Since I’ve been the Editor of Drug Discovery Today, I have made the conscious effort to include articles of interest to medicinal chemists in the Pharmaceutical and Biotech industries. Not least because Medicinal Chemists make up (still) a very significant proportion of the Pharma discovery community, but also because their efforts produce the lifeblood of the Pharma pipelines, although marginally less now with the advent and success of biological therapies.

I think perhaps I’m not the best individual to judge how successful this effort has been, although there have been some notable successes in this period, most obviously the article on “click chemistry” by Kolb and Sharpless, which to date has been cited some 1,837 times (data from Scopus). There have been others that have been major successes, although none to compare with this.

Also, I’ve been keen to highlight various models of how industry and academia can collaborate, interact  or influence drug discovery  for example Rethinking ‘academic’ drug discovery: the Manchester Institute perspective, Collaborative approaches to anticancer drug discovery and development: a Cancer Research UK perspective Practices and collaborations are now well-established and functioning smoothly in the main. What has become perhaps a more worrying trend is the relative lack of provision of appropriate training for future medicinal chemists. With the contraction of the Pharma industry and the now common practice of involving CROs in the day-to-day aspects of synthetic chemistry, the number of medicinal chemists working within the industry in the UK has been estimated to have reduced by perhaps as much as a third in the last 10 years or so according to an Editorial published in Drug Discovery Today by GSK Chief Chemist, Dave Allen. The supply of quality chemists to CROs has, to a great extent, come from the contraction of big Pharma. A fabulous resource to these companies of experienced, well-trained chemists with a background in the ins and outs of every day drug discovery and development.

A major concern, however, is from where will the future crop of such experienced medicinal chemists come? The reduction in size of big Pharma and corresponding reduction in medicinal chemistry headcount will make these positions much harder to come by for applicants and one would expect that people in post will be more likely to stay. Only those with significant experience will have the ability to move between companies. Just how could the newly-qualified chemistry graduate gain the necessary experience in medicinal chemistry?

One such initiative between GSK and Nottingham University has been reported in Drug Discovery Today; they have worked together to provide real-world experience of the nitty gritty of drug discovery in a teaching environment. To date, two separate projects have been jointly developed to introduce Undergraduate students to the skills, approaches and daily routine of developing drugs within a team setting. One of the courses, designed for a group of 20-24 third year undergraduates, dealt with the development of PI3K inhibitors for the treatment of asthma; the second is the option taken by a group of 10 MSci students as their final year research project and deals with the development of αvβ6 integrin antagonists for the treatment of idiopathic pulmonary fibrosis. The structure of the courses were determined to interest, attract and stimulate the brightest chemistry students. The advantages of such an approach and training are of obvious interest and value to the Pharmaceutical industry, but also the Chemistry departments of Universities in that it may help to attract the best students. Moreover, the reviewers of the latest article on the αvβ6 integrin antagonist project showed how impressed they were with the approach: This paper will be of great interest to all academics involved in medicinal chemistry education and I have already been inspired to consider how such a thing might be done in my own institution.” Another highlighted the value to the University and indeed to the Pharma industry in the UK Overall, I think this is a wonderful account. This type of practical teaching is key for future employers and important for elevating the UK job sector in this area of activity. As an aside, it is also fantastic to see Nottingham harnessing this opportunity with GSK and hence bring the Midlands on the map of medicinal chemistry/drug discovery, thereby enhancing the competitiveness in the UK. Comments from other reviewers were equally complimentary, pointing out the value of the course to the students and the wider community: “The whole project has been very well thought out and provides a superb introduction to research that may lead to a new drug. This is a great academic-industrial collaboration led by medicinal chemists with an excellent pharma track record, with input from GSK scientists and a world-leading academic in the area of lung disease. Almost every aspect seems to have been covered and I can hardly fault the philosophy or course content.” and “This article is certainly worthy for publication and would benefit the wider community, I'm sure there are many others who would like to replicate this approach, though without the support of GSK many may have to go with a more streamlined approach to achieve similar learning outcomes

But in all this, did anyone ask the students what they felt about such courses? I went to Nottingham to talk to some of the students that had been through the experience to find out their feelings towards this approach.

Aimie Garces (Undergraduate from 2011 to 2015; studied both the PI3K and the αvβ6 integrin antagonist courses) is currently in the first year of a PhD programme and did both of the courses; she thought that the approach was fresh and interactive and promoted teamwork, as they were placed into small teams composed of people that might not otherwise have interacted. The very active participation of staff from GSK was highly valued, in that this was expertise to which they would not normally have been exposed. In Aimie’s case, this was her first practical exposure to molecular modelling and the enthusiasm of the GSK tutor was a major fillip to her trying it for herself. Doing this course made her much more aware of medicinal chemistry as a discipline and greatly influenced her to go on to do the αvβ6 integrin antagonist programme the following year. Exposure to this course made her think about chemistry in a different way; prior to this, when performing reactions in practical classes, yield was king. Now in this sort of project, it became clear that producing a compound for biological evaluation was the important thing and at this stage, yield was much less significant. Aimie commented that some students were initially apprehensive of the modules, viewing them as scary, due to the synthetic chemistry demands of such a course. She countered this by pointing out that “you shouldn’t be scared of it – because it’s really fun!” Also, it was very useful to Aimie in that “the vocabulary of medicinal chemistry is learned on these modules and that is really useful when you move to the next stage of interaction”.

Fran Smith (Undergraduate from 2011 to 2015; studied the αvβ6 integrin antagonist course) was enrolled on a slightly different course, Medicinal and Biological Chemistry (a course that particularly appealed to her, given its balance between the biological and physical/inorganic chemistry aspects) and, as a result, was more familiar with the biology and drug discovery aspects related to chemistry. She highlighted the value at school of having a motivated and knowledgeable chemistry teacher who gave her good career advice. As part of her course, she had already spent a year in industry, so was perhaps more aware of the mechanics of drug discovery. What she found valuable from the Nottingham – GSK course was the concentration upon synthetic organic chemistry and the opportunity to work in teams. She was impressed with how well the team worked together and she was able to develop strategies to deal with small issues that occurred at the personal level. The introduction to molecular modelling particularly appealed to her and she commented that, in her current course of study, she is keen “to get involved in some sort of molecular modelling”. Taking the course influenced her choice of PhD topic, one that had a well-rounded biological component, and made her realise that she would like to do something similar in her future career.

Finally, I spoke to Jack Sorrell (Undergraduate from 2010 to 2014; studied both the PI3K and the αvβ6 integrin antagonist courses). Jack is currently working with a specialist drug formulation company and had previously worked with another formulation company through the University graduate placement scheme following his degree. Initially, he was attracted by the sound of the PI3K project, which lived up to his expectations. Up until then, his undergraduate course did not have a major focus on medicinal chemistry, but his day-to-day involvement on the project really helped his understanding of the process. What was particularly enjoyable was the feedback from the testing of the group’s compounds. A great departure from the standard chemistry course. Jack thought that the modules was good in that it was “good to be associated with GSK people – it’s great for getting first-hand knowledge”. In common with the other interviewees, Jack really valued the opportunity to work in teams and the experience was very enjoyable for him in that a compound that he synthesised during his MSci project was causing some interest from GSK scientists. He would recommend the courses to future students and commented that it allowed him to hit the ground running when he took up his current job.

In conclusion, in my opinion, this has been a highly-valuable venture for the teaching Staff at the Chemistry Department of the University of Nottingham and the Research Scientists at GSK. All of the students were aware of the efforts of all their mentors in academia and industry; they were particularly keen to point out how much they appreciated the efforts of the industrial mentors – this provided the critical hands-on knowledge that would be difficult to glean from any other source. One of the comments was that the courses provided the appropriate language and mindset to allow meaningful conversations in medicinal chemistry and drug development. This is perhaps something overlooked by drug discovery professionals who have been around the field for many years. All of the students were enthused by working in teams and stimulated by the feedback that came from biological testing of their own compounds. They gained good teamwork skills and were exposed to many techniques (especially analytical techniques) that might only have been dealt with briefly in a standard undergraduate degree course.

I must congratulate the staff of the University Chemistry Department and GSK for their efforts; one cannot underestimate the value of their time and experience. Clearly, this was valued by the students and they seemed to be enthused and motivated to continue in professional science as a result of their, albeit brief, exposure. I hope that such an experiment will continue well into the future, fully aware of the cost implication to the sponsor organisation. Hopefully they will reap the value in the very near future with a crop of talented scientists. The true value of such a venture will only come in the future when we see such undergraduates populating the Medicinal Chemistry departments of major Pharma and Biotech companies. Fortunately, these modules will continue to be funded for at least the next 3 years in the new, GSK part-funded, carbon neutral laboratory, due to open this Summer.

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