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Educating Chemists for Medicinal Chemistry Educating Chemists for Medicinal Chemistry C. Robin Ganellin Department of Chemistry, Christopher Ingold Laboratories, University College London, U.K. [email protected] Medicinal chemists gists, and able to use the tools avai- for drug discovery research lable for relating chemical structure and properties to biological activities. Medicinal chemistry has been This probably represents the core of defined1 as: “a chemistry-based disci- their requisite abilities. It does not pline, also involving aspects of bio- represent the limit of their functions, logical, medical and pharmaceutical however. Medicinal chemists must be sciences. It is concerned with the conversant with the requirements for invention, discovery, design, identifi- patents in order to protect their Educating Chemists for Medicinal Chemistry cation and preparation of biological- inventions; they should appreciate ly active compounds, the study of the needs of chemical development their metabolism, the interpretation to assist the scale up of their pro- of their mode of action at the mole- ducts; they ought to understand the cular level and the construction of drug development process, to com- structure-activity relationship.” municate effectively and work effi- ciently in a team composed of scien- The above definition from the tists with different training and back- Medicinal Chemistry Section of the grounds. International Union of Pure and Applied Chemistry (IUPAC) in 1998, This composite of abilities repre- aims to cover the many varied activi- sents a mixture of what was imparted ties of medicinal chemists. The pur- during the formal education in uni- pose of this article, however, is to versity, what has since been learned concentrate on the major employ- “on the job” or acquired by experi- ment of practising medicinal chemists ence, and the chemist’s own charac- outside of academia. This is surely in ter. In terms of the latter, for exam- the pharmaceutical industry where ple, some will hardly need to be told medicinal chemists are mainly con- how to communicate whereas others cerned with the design and synthesis may have to work very hard to learn of novel organic compounds for bio- do this. Obviously too, they must be logical evaluation in the discovery excellent scientists. The question phase of researching for potential arises as to what should be provided new drug therapies. They have to be as formal education and training in a excellent organic chemists, able to university setting. converse with biochemists and biolo- EFMC - Yearbook 2005 - 2006 21 The views It is surprising to find that such of pharmaceutical companies little value is attached to chemists having received some formal educa- Some years ago, the IUPAC tion in a biological topic. It seems Medicinal Chemistry Section (now part logical to employ such chemists since of Division VII, Chemistry and Human it should help them to be effective as health) canvassed the views of indus- medicinal chemists form the outset, try for their preference in hiring the instead of having to spend quite a new employees who will become their few years acquiring the additional medicinal chemists. A questionnaire understanding necessary to enable was sent out in 1996 and 1997 to them to be effectively involved in leading medicinal chemists and drug design as well as in drug syn- research directors in the major inter- thesis. national pharmaceutical companies engaged in research and develop- The foregoing certainly accords ment. The responses were very similar with my personal experience. I and over 90% of the replies indicated trained as an organic chemist and a preference for well trained synthetic entered the pharmaceutical industry organic chemists rather than with no knowledge of medicinal medicinal chemists. The results were chemistry or pharmacology. It took reported in a series of publications me many years to learn about these relating to different countries2-4. disciplines even though I had studied Educating Chemists for Medicinal Chemistry biology at school and for one year at The very strongly expressed opi- university as part of my undergradua- nion was that the most important edu- te course. The knowledge of some cational background required of the biology at least made me receptive to new chemists was excellent training the subsequent research discussions in synthetic organic chemistry. with pharmacologists, but I had to Preferably they should possess a PhD undertake a considerable amount of and postdoctoral experience from private study to learn what was laboratories of well known synthetic needed for drug discovery research. organic chemists. Little interest was expressed for having chemists with A bachelor degree in medicinal formal academic training in medicinal chemistry – a proposition chemistry, or for chemists trained in organic synthesis but also having The above observations are rele- knowledge of biological subjects. The vant to a discussion I once had when I industrial view was that most of the was employed as a medicinal chemist medicinal chemistry aspects, other at SmithKline & French Laboratories than organic synthesis, could be (SK&F) with James Black (later Sir learned on the job or through short James Black, Nobel laureate for courses during employment. In con- Medicine or Physiology) seeking to trast, synthesis cannot be learned define histamine H2 receptors and to effectively in a practical sense through design a suitable antagonist as a useful short courses during employment drug (the work which led to the anti- although, of course, short courses are ulcer drug, cimetidine). During this a valuable way of extending know- particular conversation he was very ledge and, particularly of keeping critical of some of the chemists with abreast of recent developments. whom he had previously collaborated. 22 EFMC - Yearbook 2005 - 2006 To him, they were hidebound in Degrees in medicinal chemistry their thinking and also too ready to treat biological results as if they were The medicinal chemistry degree at precise numbers. He felt that they did UCL has endured and, over thirty years not appreciate the problem of bio- later, it still continues as a three-year logical variation and the need to B.Sc. or four-year M.Sci. (Master of understand the statistical nature of Science). The number of students bioassays. For him, the chemists varies each year but this degree course wanted to treat values from bioassay has provided 20-30% of the annual in the manner in which they consi- undergraduate entrants to the dered melting points, that is as inva- Chemistry Department. The students riant numbers. Unfortunately he felt take the same core lectures for chemis- unable to change this situation by try as do the chemists except for the dialogue with the chemists because, more advanced inorganic chemistry. as he saw it, they were no longer fle- Thus, they are given the same physical xible in their thinking. Therefore, he chemistry and organic chemistry; saw that a possible solution would be indeed they take the courses together. to get at the chemists in their early training, during the period in which Table 1. they were undergoing mental The non-chemical subjects studied by students imprinting. His solution was to have taking the medicinal chemistry degree in chemists study medicinal chemistry at University College London university for their first degree. Educating Chemists for Medicinal Chemistry Year 1: Mammalian physiology; Cellular and Molecular Biology. James Black left SK&F in 1973 to take the Chair of Pharmacology at Year 2: Statistics; General and Systematic University College London (UCL), as Pharmacology; Topics in Biochemistry. Head of Department, from which Professor Heinz Schild had just Year 3: Principles of Drug Design; Molecular Pharmacology; Receptor Mechanisms. retired. Whilst at UCL, he tried out Optional subject. his idea of training medicinal chemists on the Chemistry Department. He found that In addition to the chemistry to- Professor Charles Vernon, a biologi- pics, the medicinal chemists take the cal chemist, was receptive to this subjects outlined in Table 1 for the proposal and between them they first three years, which are taught by initiated a B.Sc. in medicinal chemis- the corresponding departments. try. It was an opportune time to They do this at the expense of being start a new degree in chemistry able to select other optional topics because the number of students but this is acceptable because they applying to study “pure” chemistry have opted to take a medicinal was falling and medicinal chemistry chemistry degree course. In the sounded attractive to some students fourth year, the students undertake leaving school who wished to com- a research project, which involves bine their chemistry with an interest 50% of their course, and can choose in a medicine-related subject. James to also study four optional subjects. Black was only at UCL for four years The latter can be selected from, for but, like all great men, he left his example: natural products chemistry, mark on the place. biological chemistry, advanced spec- EFMC - Yearbook 2005 - 2006 23 troscopy, more-advanced organic In the third year of the medicinal synthesis, chemical computation, or chemistry degree course, the lectures a specialist biological topic. The on the principles of drug design are organic chemistry content of this particularly relevant to a future medi- course is very high since, in the cinal chemist; the stated objectives of second and third years, 25% of the these lectures are: “to understand how teaching time involves organic syn- to relate chemical structure to biologi- thesis and in the fourth year, it is cal activity and how to conduct a struc- possible to again spend 25% of the ture-activity analysis”, and “to appreci- time on organic lecture courses, and ate the various approaches to drug dis- 50% of the time on a synthetic covery and be able to exemplify organic research project. them”. The structure of this lecture course is given in Table 2.
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