Academic Institutions and Drug Discovery

The ability to manipulate the chemical composition of matter has led to new products and technologies emanating from almost every sector of industry. Of these sectors, among the most challenging and time-intensive activities is the discovery and development of new therapeutic agents. These challenges stem from:

• our increased need for safer and more effective products
• inherently long timelines from discovery to market
• the desire of the venture community to realize rapid returns on investments.

Examining these points from the perspective of cause and effect, the well justified need for safer and more effective products results in longer timelines from discovery to market. Unfortunately, long timelines are not compatible with rapid returns on investments. As such, investment capital has been shifting from high risk discovery programs to less risky development programs. In fact, it is not uncommon for investors to reserve capital for products already in clinical trials. The unfortunate consequence of this paradigm shift is that reduced capital for discovery programs has led to a reduced number of products transitioning from discovery to development. This transition begs the question FROM WHERE WILL THE NEXT GENERATION OF DRUG CANDIDATES EMERGE?

In previous posts, I highlighted issues relevant to this question including:

• Where big pharmaceutical companies will rebuild their pipeline of new drug candidates
• Large pharmaceutical firms turning to biopharmaceutical companies to fill their discovery pipelines
• Paradigm shifts incorporating outsourced services as replacements for high cost internal capabilities
• Academic institutions must continue to provide solid educational programs and degrees in chemistry - incorporating broad based and generally useful knowledge/skills

With the shrinking volume of venture capital funds available for early stage discovery startups and the continuing trend of large pharmaceutical companies filling their discovery pipeline through small company acquisitions, there is a sector looking to academic institutions to fill this gap. Having both attended graduate school and contributed to industrial drug discovery efforts, I can state with complete certainty that THIS IS A VERY BAD IDEA!!!

Yes, I said it. I mean it and I make no apologies for the frankness of my statement. Academic institutions are not suitable engines for both drug discovery and the training of our next generation of scientists. To qualify this statement, consider that the drug discovery process requires activities including:

• Compound synthesis/purification/analysis
• Enzyme assays
• Cell-based assays
• Animal models of disease
• Pharmacology
• Formulations
• Metabolite ID/bioanalytical

Each one of these activities requires the involvement of highly trained and knowledgeable scientists. Furthermore, each of these areas must be coordinated with one another in order to enable generation of the data required to accurately evaluate all potential drug candidates. In an academic setting - the setting responsible for much of the cutting edge advancements ultimately benefiting the pharmaceutical industry - such activities are not likely to be implementable without a detrimental effect on the training grounds of the next generation of scientists.

Put another way, where are we to generate the next generation of innovative, highly trained and knowledgeable scientists if our educational resources are diverted to commercial interests?

Organic Chemistry vs Medicinal Chemistry

During my undergraduate research activities with Professor Henry Rapoport at UC Berkeley, I found that my greatest interest was in the discovery of new medicines. Recognizing that the career opportunities I sought required an advanced degree, I began asking about which type of graduate program to pursue - organic chemistry or medicinal chemistry. The input I received overwhelmingly favored a PhD in organic chemistry. The rationale behind this bias was quite simple - the most important skill for a chemist in drug discovery is the mastery of organic chemistry.

Education in organic chemistry programs is not limited solely to reactions. The diverse set of skills, generally applicable to drug discovery (and other industries) are:

• Synthetic organic chemistry technique
• Practice in hundreds of different reactions
• Exposure to many more reaction types
• Scales from mg to multigram
• Training in the logic behind synthetic pathway selection
• Training in all spectroscopic/analytic/purification techniques

While organic chemistry and medicinal chemistry programs both teach organic chemistry, medicinal chemistry programs tend to dilute the breadth of chemistry exposure with the biological aspects of drug discovery activities. These biological aspects, as my colleagues explained to me, are skills that can be learned on the job. However, the on-the-job expansion of organic chemistry knowledge is considerably more difficult to accomplish. From this philosophy, it is not surprising that at every company I worked, the most successful job candidates had degrees in organic chemistry with a strong focus on synthesis.

In my August 21 post, I pointed out that in order to motivate our next generation of scientists,

• Industry must work to prevent chemistry, a discipline requiring intensive education/training, from evolving into a service
• Academic institutions must continue to provide solid educational programs and degrees in chemistry - incorporating broad based and generally useful knowledge/skills

I am, and always have been, enthusiastically in favor of graduate and undergraduate level curricula focusing on the practical and philosophical aspects of the pharmaceutical industry. Such coursework can only serve to prepare students for what will be expected of them as they progress through their professional development. However, replacing or diluting the development of core skills can only compromise our next generation's ability to maintain a competitive edge in a global marketplace. Industry must look elsewhere for its discovery pipeline lest the current trickle of new drug candidates dries up completely.