Before I pursued post-secondary studies, I knew I wanted to do science, real science with a Capital S: pure science, science which aims to further medicine and society without prestige or selfish or financial interests. That’s the idealised desire that led me to years of studies in biology across several universities. Academic research is conducted by professors and students in university and hospital laboratories and is publicly funded in large part.
In my Manichean view, the pharmaceutical industry stood on the opposite side.
The pharmaceutical industry discovers, develops, produces and sales drugs. And as is the case for any industry, it must be viable, competitive and make profits, which, in my opinion, conflicted with seeking progress.
However, I have since realised that there exists an alternative model, crucial today in the development of new drugs: collaboration between academia and the pharmaceutical industry.
The Birth of a New Drug
Historically, the discovery of drugs was often accidental. Such was the case for penicillin, for instance, discovered by Dr. Alexander Fleming, a medical biologist. In 1928, he noticed by chance that a fungus that grew in a forgotten Petri dish left on the work surface secreted a substance which inhibited bacterial growth. This substance would be named penicillin. In other cases, plant extracts with known drug effects would be used to identify the active ingredient (as was done for Taxol, a drug used in some anticancer therapies).
If accidental discoveries are still possible today, drugs are predominantly designed as follows: a new product is developed based on our understanding of biological mechanisms.
When we seek to treat a disease with a new drug, it all starts by the identification of therapeutic targets. Generally, a target is a natural molecule involved in a biological process which drives the disease development. Once the target is identified, it must be validated: we must verify that acting on this target will yield the desired results in diseased cells. Thousands of compounds are then tested to establish if they have an activity on the validated target. That is how we identify one or several candidate molecules (“hits”) representing protodrugs.
Once hits are identified, the work is far from over. Chemists then work to modify those chemical compounds at the basis of future drugs in order to improve their effectiveness, to reduce adverse effects, and to ensure they possess adequate pharmacodynamic (how the molecule affects the body) and pharmacokinetic (how the body affects the molecule) properties to be administered as drugs.
Preclinical studies are conducted in various animal models to test the selected molecule’s toxicity and side effects and to determine the formulation of the drug (the mix of active medication and chemical agents that will make the active molecule capable of acting on diseased cells).
Through those studies, we establish the safe dosage for the first clinical trials. Clinical trials involve human patients and clinicians. A drug that successfully passed all those steps will be produced for the general population.
A Long Journey… And a Slice of Luck!
This is an extremely long process: once a target has been identified, it normally takes 10 to 15 years to end up with a drug. And target identification itself often takes years of research. This also represents a huge financial investment. On average, only one in 5,000 compounds tested in the preclinical phase will become an approved drug and 90% of compounds entering clinical trials will not be approved.
Take for example the development path of Herceptin, a drug indicated for the treatment of some breast cancers, among others.
In 1979, Robert Weinberg discovered gene HER2, which plays a crucial role in cancer progression. Scientist Alex Ullrich from Genentech picked up on the work of Dr. Weinberg with Dr. Dennis Slamon, a medical oncologist at UCLA.
In 1987, they validated the pharmaceutical interest of protein HER2.
In 1988, they received financial support from Genentech to develop a drug targeting HER2.
It’s only in 1998, 19 years after the discovery of this gene involved in cancer progression that Herceptin was approved for commercialization. In addition, luck played a role in this journey with the chance meeting of Ullrich and Slamon at Denver International Airport, and the fact that the mother of a vice-president at Genentech was diagnosed with breast cancer, which influenced the company’s interest in the project.
The Logic of Collaboration
Traditionally, a pharmaceutical company would draw promising targets from scientific publications (the “results” of academic research) and then further the drug discover process. This model entails little to no collaboration between the academic research field and the pharmaceutical industry.
The industry needs academic research…
The dynamics of the pharmaceutical industry have changed tremendously over the last 30 years. Spending has gone up while the return on investment in research and development (R&D) has gone down. Despite the progress made in the understanding of complex biological systems and the sophistication of methods and technologies, productivity has remained constant over the last 60 years with an approximate rate of one new drug a year per company (among the three oldest and biggest pharmaceutical companies: Merck, Eli Lilly, and Roche). The pharmaceutical industry’s business model is a constant challenge. Most of the products commercialized by companies today will no longer generate market profits after a dozen years or so, once the patents expire.
Some companies choose to seek innovation externally. If academic research has always been a source of innovation for the industry, today, it is a critical point. Collaboration between the two protagonists is now active at the identification, modification, and selection of hits and, in some cases, even at the earlier stage of target validation.
… And academic research needs the pharmaceutical industry.
The goal of academic health researchers is to understand biology and discover new avenues for treating or preventing diseases. Often, discoveries made in the academic environment must be transferred to the industry to lead to concrete applications in population health. It is particularly true for drug development in our current system.
In the United States, the Bayh-Dole Act accelerates innovation transfer to avoid leaving publicly funded discoveries gathering dust on the shelves. There is no equivalent legislation in Canada. However, organizations are founded (such as the Institute for Research in Immunology and Cancer — Commercialization of Research — IRICoR at Université de Montréal) with the goal to bridge the gap between academic research and the industry. Governments are also launching initiatives like the Centres of Excellence for Commercialization and Research Program (CECR—at the national level) and previously, the Fonds de partenariat pour un Québec innovant et en santé (FPQIS—at the provincial level). In this way, the academic and industry sectors carry out particularly promising projects in close cooperation.
Funding provided by the industry benefits academic research globally as it supports the acquisition of technologies and reinvestment in early stage projects. This is especially important now with the process to secure public research grants becoming extremely competitive: while 30% of operating grant applications to the Canadian Institutes of Health Research (CIHR) were approved and funded in 2005-06; in 2015-16, that rate dropped to 18%.
A Marriage of Convenience
Collaborating is not always easy. There is a culture shock between the two environments. While their goals are the same, the way to reach them is different. Industrial projects often follow a specific timeline while academic projects are usually less structured and follow a more flexible timeline with hypotheses being restated along the way.
The culture of basic research is well illustrated in the words of Vannevar Bush, the architect of scientific research in the United States during the Second World War. In a 1945 report to President Truman, Bush wrote: “Basic research is performed without thought of practical ends. It results in general knowledge and an understanding of nature and its laws. […] It provides scientific capital. It creates the fund from which the practical applications of knowledge must be drawn. […] Basic research is the pacemaker of technological progress.”
Other obstacles exist. Collaborating with the industry limits academic freedom, especially through control over the dissemination and publication of findings, justified by trade secrets.
Although means of collaboration have greatly evolved, it is crucial for academic researchers and pharmaceutical companies to work together to meet the needs of most medical specialties, including cancer research. Whilst we have made significant progress over the last few decades, we are still a long way from being able to say that we know how to cure cancer.
Michael Rosenblatt, Executive Vice President and Chief Medical Officer at Merck, shared his career between the academic world and the pharmaceutical industry. He explains, “The secret of a true partnership is acting like you have a true partner. This applies to both academia and industry. We need to partner for the sake of modern medicine; we need to do it for the sciences fundamental to medicine; and most of all, we need to do it for our patients.”
Mathilde is studying the role played by protein ERK3 in the development and regeneration of muscle tissue. Her work will allow a better understanding of ERK3 whose physiological function is still unknown. It could lead to the development of new therapies to treat conditions involving muscle damage or atrophy (such as trauma, muscular dystrophy, cachexia associated with cancer or ageing).
About the birth of a drug
- Claude Brezinski. Histoires de sciences : Inventions, découvertes et savants. Éditions L’Harmattan (2006) : 185
- Ezekiel J. Emanuel. “The Solution to Drug Prices.” New York Times: Sept. 2015
- Patty Delaney, “HER-2: The Making of Herceptin, a Revolutionary Treatment for Breast Cancer.” J Natl Cancer Inst, 1999.
About the collaboration between academia and the pharmaceutical industry
- Michael Rosenblatt. “How Academia and the Pharmaceutical Industry Can Work Together.” Annals Am Th Soc, 2013.
- Gabrielle Moisan & François Painchaud. « Bayh-Dole : déjà 30 ans — Le gouvernement doit-il demeurer propriétaire des brevets d’invention découlant de ses subventions ? » 2011.
- Fonds de partenariat pour un Québec innovant et en santé
- Centres of Excellence for Commercialization and Research Program
- Application and Funding Statistics OOGP and Related Programs
- Vannevar Bush. “Science the Endless Frontier: A Report to the President.” United States Government Printing Office, 1945.