Basic Science: The 98% We Still Don’t Know

There is a growing sense not only in academia but also in industry that in many therapeutic areas we simply don't know enough about the basic biology of disease to effectively pursue treatments for them. Drug development in areas such as HIV/AIDS and Alzheimer's have been brought up short by a sense that we may be shooting in the dark at unclear targets – that we're wasting ammunition, so to speak. At a Partnering for Cures panel, we took a step back to look at the fundamental building blocks of our R&D enterprise to see what questions remain unanswered and why.

Moderator Cecilia Arradaza of FasterCures opened the discussion by noting that too many breakthroughs go far enough along in the development process but don’t see the light of day. Turning to panelists representing key sectors of the medical research enterprise, she focused the discussion on identifying tools, technologies, or approaches that will allow us to get to some of these vital answers.

“We know much less than we really need to know about almost every single disease, from rare diseases to very common diseases, because we don’t know enough about what causes diseases and also about heterogeneity of expression,” explained William Chin of Harvard Medical School. Chin reinforced the need for a systems approach to understanding disease. Thomas Insel of the National Institute of Mental Health agreed, and pointed out that “there are lots of reasons why studies fail… there is often unpublished data that could lead others to know that what they are doing is a dead end.” Insel said that forums such as http://clinicaltrials.gov were ways of disseminating valuable information, but that competition may inhibit some scientists from publishing critical data.

Matthias von Herrath of the Type 1 Diabetes Research and Development Center at Novo Nordisk elaborated on the issue: “It is important to work together and break down silos and sequestered areas. Where we fall short is in understanding negative data. This is a fundamental problem in both academia and industry.” Von Herrath further emphasized the value of sharing failures and realizing that difficulties arise when there are only incentives for successes.

Brian Mansfield of the Foundation Fighting Blindness described his perspective on animal models, which are a critical link in the translation of basic science to clinical practice, but are not predictive for all diseases. He cited the example of mouse models, which are easy to breed and cost-effective, but can be very different from humans. Mansfield also said “there are lots of constraints on gene therapy.” For example, many people think they can get gene therapy once the gene that is causing their illness has been identified, but that is not always the case.

Panelists agreed that an overwhelming list of questions remains unanswered. Insel noted that we may only actually know about 2 percent of what we should – an optimistic view, according to other panelists. To improve upon this, facilitating a culture change was necessary, they said. Mansfield argued that the basic science culture needs to be changed in a way that would definitively help patients, and suggested that grant-awarding organizations should make it mandatory to publish both positive and negative data as a condition of accepting the grant. Both Insel and Chin agreed that creating teams of individuals with several different perspectives would help advancement in the field. Insel added that collaboration is key, but ultimately, most discoveries are driven because of one individual investigator taking the lead. Von Herrath pushed for the necessity of “tangible incentives” and a cooperative culture that can accelerate translation of basic knowledge into effective therapies.

In all, the panel noted the importance of striking the balance of investing in basic science that allows us to understand the biology of disease while also creating an environment that allows serendipitous paths that lead to new therapeutics.