Foreword

A book discussing the collaboration between industry, government, disease foundations, and academia (or the lack thereof) is important, timely, and welcome.

European pharmaceutical companies have generally been more active and public in their collaboration with academic laboratories. The effectiveness and transparency of their collaborations are evidenced by the frequent coauthorship of the resulting publications and the support provided to the investigator's laboratories.

The collaboration of American pharmaceutical companies with university laboratories has been much more variable and probably less productive for drug discovery and development than it could be. The relationships are often much less transparent. Projects and collaborations function more like contracts, with industry having sole ownership of the data and intellectual property. Data are often not mutually shared and there can even be elements of secrecy, with only some company data being shared with the academic scientists. For example, the structures of related compounds from a focus chemical library may not be shared, in order to decrease the risk that company information is leaked to competitors. I have learned years ago that good research ideas do not last long before your competitors are working on related projects.

Industry usually wants the option to review manuscripts before publication. Large multinational pharmaceutical companies are generally opposed to early publication of the work they are supporting. They tend to publish their work at two periods in the life of a project: when it has been terminated, in order to provide some recognition and reward to the project team; and most companies will also encourage publication with opinion leaders in the field before launching a product on the market, in order to influence physicians and promote sales.

If we review the current processes in drug discovery, it is usually the academic laboratory that identifies the interesting molecular targets that are important enzymes and proteins in various biochemical and physiological processes. Occasionally, the academic scientists may also identify chemical leads (drug leads) that function as agonists or antagonists with these molecular targets. More often, this process occurs in industry with high-throughput screening assays of large chemical libraries. The chemical leads then result in chemical focus libraries designed by medicinal chemists to identify the pharmacophores and more potent analogues of the leads; to identify design molecules through the use of computer modeling; and, using physicochemical studies, to identify compounds with more favorable pharmacokinetic properties, formulation requirements, easy low-cost synthesis and process chemistry, and, hopefully, low toxicity. Industry certainly has the appropriate staff to accomplish these difficult tasks. Most of the talented individuals necessary to accomplish this work cannot be found in academic laboratories. Medicinal chemists, computer modelers, process chemists, and toxicologists are usually not found in most medical centers, although some are found in pharmacy schools.

Today the biomarkers of disease identified in genomics, proteomics, and biochemical studies are generally coming from academic laboratories. They have been extremely important in identifying critical molecular targets and have provided important clues for drug discovery and development to both biotechnology companies and large multinational pharmaceutical companies.

Interestingly, about 20–25 years ago, the large multinational pharmaceutical companies in the United States were on average spending about 17% of their total revenue on R&D and about 30–35% on marketing and sales. They are now spending about 11% on research and development (R&D), while marketing and sales budgets have increased. How can technology-based companies decrease investments in technology? Furthermore, most of the R&D budgets is spent on clinical development and phase four marketing studies, which have less risk and are thought to have a greater and more rapid return on investment. As a result, there have been fewer novel molecular targets and novel drugs. So why are the large companies surprised that the pipelines have dried up and that they are having to pay premiums to acquire technology from other pharmaceutical and biotechnology companies?

About 20 years ago, some of us predicted that the big pharmaceutical companies would begin to have problems. Today, many pharmaceutical companies are merging with one another to fill their pipelines, decrease their costs, and presumably increase their profits. They are also acquiring biotechnology companies as a strategy to offset expiring patents on many of their multi-billion-dollar products. What is often not appreciated is that most of the technology in biotechnology companies has come from academic laboratories. Investments in collaborative research projects between pharmaceutical companies and academic research programs would have been needed at a much earlier stage, with greater risk and perceived cost to develop. Since time is money, and senior management in companies usually changes every few years, the acquisition of later-stage technology is generally preferred, as that permits senior management to enhance their equity positions and compensation.

Very often, academic scientists discover and patent a technology and license it to biotechnology companies. While this may also happen with multinational drug companies, it is probably less common. Many large companies often have the philosophy that if the technology is not invented in their company, it has less value or is suspect. Large companies also tend to prefer later stage technology that has less risk and less development time to reach the market.

Not only have many of the novel drug leads come from academic laboratories, but also much of the fundamental technology and discoveries has come from academic programs. Examples include physiochemical studies of molecular targets, genomics, proteomics, computer modeling, identification of new messenger molecules and their receptors, and identification of new biomarkers for various diseases, including cancers.

We are learning that many diseases, such as diabetes, hypertension, atherosclerosis, cancer, and other syndromes with multifactor causes, are heterogeneous diseases. In the future this will lead to personalized therapy for each patient, leaving little room for blockbuster drugs with multi-billion-dollar markets. Designing the most effective personalized treatment requires genomic and proteomic information for each patient. As only physicians and academic programs can provide the patient populations for study, a collaboration between industry and academia would be required to take this step forward.

Markets will be much smaller for these new generation therapies; however, clinical trials could also be smaller and target the most appropriate therapy, saving considerable amounts of clinical development time and cost. Currently, with heterogeneous populations of patients the benefit from an effective therapy is diluted among the larger pool of nonresponders. This requires extremely large numbers in clinical trials in order to see significant drug effects.

I realize that collaborations are often very difficult. Industry wants maximum ownership, control, and profit from the research. Academics, on the other hand, must demonstrate independence for their promotion and grant support. Thus, our current system tends to discourage collaborations between industry and academic programs.

In European countries, professors’ research is often funded by university departmental budgets. Perhaps the collaborations in European countries between universities and industry are more effective because professors and their laboratories are less dependent on funding from research grants. Awards from companies are usually discretionary funds that are often used to supplement salaries. There is also a sense of co-ownership of the research. The competitiveness in the United States for funding and research recognition may be hindering effective collaborations between academics and industry. In the United States, the collaboration between academics and biotechnology companies is much more apparent, perhaps because the technology originated from the academic laboratories. Biotechnology companies have little or no revenue and smaller research budgets and staff, and therefore require collaborations for their research and product development. They often use stock options to reward their advisors and collaborators; this is rarely the case with large companies. Furthermore, outside of clinical studies, which require access to patients, large pharmaceutical companies often believe they are much less dependent on collaborations.

I believe the difficulties in collaborations between industry and academics can be summarized as the parties’ concerns over ownership and profit, fear of the competitors, and lack of trust. These are common problems in many business relationships. Over the past 40 years I have been asked on numerous occasions to collaborate with others. As some of the collaborations could have been very important, I have often agreed. However, on only several occasions did a collaboration occur and did the collaboration lead to some exciting and important discoveries that affected my subsequent research. Most of the collaborations never materialized, usually because the other party committed very little effort to the project. The take-home message that comes across quite vividly and glaringly as you read through the chapters in this fascinating book is that the collaborating parties must plan carefully, take the project...