While often considered to be the role of the pharmaceutical industry, drug discovery in academia is not a new concept. Indeed, the assembly of research teams in academia, wherein biologists and chemists work together towards a common therapeutic goal, has led to a number of important discoveries and treatments. Over one hundred years ago, Paul Ehrlich, the father of chemotherapy, was developing his work on the “side-chain theory” of how antibodies worked at the Royal Institute for Experimental Therapy in Frankfurt, Germany. To further his efforts, Ehrlich assembled a research team comprised of chemists, pharmacologists, and toxicologists. Ehrlich and his co-workers tried hundreds of chemicals on the microbes that caused syphilis. In 1909, Ehrlich’s new colleague Sahachiro Hata brought with him a method of producing syphilis infections in laboratory rabbits, and discovered that drug no. 606 worked. 606 or salvarsan, (“The Magic Bullet”) was the first drug to be discovered through rational design. Thereafter, Salvarsan became the most effective and widely prescribed drug for treating syphilis. Salvarsan was later replaced by penicillin, which became widely available in the 1940s.
Ironically, penicillin, itself, is an excellent example of how academia has bridged the gap between basic biology and industry know-how. Originally noticed by Ernest Duchesne in 1896, penicillin was re-discovered by Alexander Fleming, who was working at St. Mary’s Hospital in London in 1928. In 1929, Fleming published his research results, noting that his discovery might have therapeutic value if it could be produced in quantity. Fleming attempted to garner interest from the pharmaceutical industry to produce penicillin, but he was unsuccessful. It was not until 1939, after a ten year gap, that Florey (a pathologist), Chain (a biochemist), Heatley (a biologist/biochemist), and their colleagues at Oxford University were able to produce enough penicillin to experiment with its effects on mice and to demonstrate its ability to kill infectious bacteria. Like so many other academic researchers, Florey’s team struggled to persuade British drug companies to manufacture penicillin. Eventually, after forming a partnership with the Peoria Lab in Illinois, the Florey team at Oxford University was able to mass-produce penicillin. The value of this life-saving discovery is immeasurable, as this academia/industry collaboration resulted in the drug’s being available worldwide, most notably to countless Allied soldiers wounded in the Second World War and to millions and millions of more people since. Indeed, the importance and impact of academic research and collaboration in the field of drug discovery was, perhaps, best expressed by Sir Henry Harris, who, in 1998, said:
“without Fleming, no Chain or Florey; without Florey, no Heatley; without Heatley, no penicillin.”
Unfortunately, the model of academia working with an industry partner to take basic discoveries through to commercial production has diminished over the years. Arguably, this coincided with industry’s target-driven reductionist approach that prevailed in the pharmaceutical industry during this time and its increased focus on low-hanging fruits of well-validated drug discovery targets, such as the GPCRs and ion channels. While it is easy to blame industry for the prolonged delay in significant progress in the CNS drug discovery field, academics must shoulder some of the blame, as well. Indeed, there is much that could be done to improve collaboration and co-production of research. Despite the need for academia to shift towards having a willingness to share research and collaborate with industry, significant institutional pressure to publish in the right places still remains.
It is clear that the discovery of disease-modifying drugs for neurodegenerative diseases will require a commitment to research models that are not dependent upon big pharma. Without such a commitment, and without major advances in new medical entities, the suffering of those affected by these crippling neurodegenerative diseases will continue unabated. While pharma, obviously, will continue to be the major developer of new drugs, there is a compelling argument that academia needs to become more directly involved in the translation of fundamental science into therapeutics. University laboratories are uniquely situated to provide the appropriate climate for creative and innovative science. Indeed, they possess intellectual diversity, flexibility, originality, and expertise in a multitude of disciplines, such as the biological, medical, chemical, computational, engineering, and mathematical sciences, and they understand the value of individual freedom. Unlike in big pharma, in academia, with a relatively small amount of well-placed investment, scientists can transform academic research into translational drug discovery and, in the process, bring enormous added value to their parent institutions, their funding agencies, and, ultimately, to healthcare. By increasing the diversity of approaches to drug discovery, both in technologies and thought processes utilized, greater technological innovation will result.