Developing Next Gen Multiple Sclerosis Therapies: Part 4

The following is part of a MStranslate exclusive series which highlights the struggles and obstacles in developing the next generation of therapies and drugs for human disease. Dr. Travis Stiles is a neuroscientist who has worked to develop regenerative therapies capable of reversing neuronal damage caused by disease and trauma, such as multiple sclerosis and spinal cord injury. Part one of this series can be read here, part two is available here and part three is available here.

You can help support his efforts by clicking here.  Every contribution helps move this work closer to these revolutionary discoveries becoming therapeutic realities.

Welcome back! In part III of this series we broke down several unique issues that have hindered the acceleration of medical innovation relative to other fields of technology. In this article, we will discuss the different players involved in medical innovation, including their roles (and how those roles have evolved over time). There is no shortage of misconceptions regarding these institutions and much of this is based on outdated or oversimplified thinking. Today, we will clarify the actual roles these institutions play. Then, in part V, we will dissect public perceptions, overturning some of the major myths that often distort public perception of these institutions.

Before we get started, I want to make something very clear: nothing I say in this series of articles is meant to portray academic science or the pharmaceutical industry in any specific light. My hope is to provide an objective explanation of each institution and what their respective contributions (and limitations) are in drug development. As I highlight their strengths and weaknesses, please don’t misconstrue what I say as glorification or vilification. It is important to understand that despite the flaws each possess, these entities serve an invaluable and necessary purpose. Both institutions are critical to medical advancement.

As academic science and “big pharma” experience increasing pressures and criticisms, it is crucial for us to sort fact from fiction. In the age of sound bites and talking points, this is often a surprisingly difficult task, as the truth is nuanced and complex. That is exactly why having this conversation is imperative if we are to improve our understanding and optimize the impact of these institutions with an eye towards better medicine. Remember, this series is about understanding how we can advocate for better immunizations, therapies, cures, etc. and that begins with an understanding of the players involved.

The Ivory Tower

Academia is commonly referred to as “The Ivory Tower”, which is adapted from a biblical expression that denotes an institution gilded with veracity and shielded from reality. It is meant to highlight the isolation and disconnectedness of science that often accompanies its altruism, focus, and intrinsic value. Within academia exists the “science” most of us are familiar with (shout out to NASA for arguably challenging academia for the title of “Most Famous Science Institution”).

Academia, largely in the form of research efforts from educational or philanthropic institutions, is where fundamental scientific investigation takes place. This is the where the search for knowledge is at its purest, without the need for financial return or desired outcome. Make no mistake, these are the trenches of discovery. This is where the ever-curious scientists work, every day, to evaluate evolving hypotheses and scientific theories towards building on our understanding of the mechanics of health and disease. Yes, such work is noble, even romantic, but it is equally tedious, frustrating, difficult and humbling.

Academic science is commonly referred to as “basic science”. It is designed to promote discoveries, agnostic to the potential application. The fundamental concept of science agnostic of desired outcome is that it is often difficult to know how a basic discovery might be valuable in the future. As such, the search for knowledge shouldn’t be biased by a preconceived intended use. Unlike industrial science, which is purposely designed to promote value creation, a good basic science project only needs to answer questions previously unanswered. The question may be simple, and its answer may not appear to be immediately useful, but as a rule such observations serve as the basis for every ground-breaking discovery.

The obvious beauty of academia is that it is not motivated by profit, only discovery. Now this does not mean that individual research institutions and investigators are not motivated by dollars. They undeniably are. Research costs money, and researchers are always competing for the very scarce resources available to fund scientific inquiry (and this is why public investment in research is so critical…which we will discuss later). Despite this, academia has the unique luxury of being able to work without the necessity of direct financial return. Instead, funds are intended to provide answers, whether those answers can be profited from or not. Without academia, the basic scientific discoveries that serve as the critical foundation for all innovation would suffer.

It is important to understand that despite the tremendous value of basic science, these discoveries, by nature, are immature and raw.  While modern innovations and technologies would not exist without foundational basic science, discoveries at this stage are a far cry from the products, drugs, and systems that are applied to benefitting society. Discovery thrives in the Ivory Tower, but developmental science often does not. Application of novel scientific discoveries to a consumer end (like making the next iPhone or new drug) requires a different mindset, incentive structure, and skill set. That is why industrial science is needed. In the context of medical therapies, this means that biotech/pharma thrives off of academia. So how does pharma build off academic findings?

Big Pharma and Biotech

Typically, academics and universities lack the skill set, capability and incentive structure to develop drugs (although they sometimes discover them). As a result, the translation of academic findings into new treatments and therapies falls to the biotech and pharma sectors.  These institutions possess the unique capabilities, perspective and operations to take translate discoveries into products that impact the lives of patients. In the context of this series, we will be focusing primarily on pharma, so what exactly does pharma do to translate scientific discoveries into human therapies?

While uncovering the complex mechanics of how a disease works is primarily the job of basic science, it is pharma that is best suited to find ways to exploit new discoveries to therapeutic ends. On the pre-clinical side (going all the way back to part II), pharma has vast resources for the screening and testing of potential drugs in different systems. Once viable candidates are identified, pharma has unparalleled experience in further optimizing/modifying agents for improved drug properties. From there, agents must be tested in different disease models.

Academia and pharma are both excellent for animal models of disease. However, pharma has a unique focus on utilizing these models for the specific purpose of translating the application of potential drugs in these models to a human product. Academics largely use animal models for proof of concept pertaining to a specific hypothesis. In contrast, pharma largely uses these models to elucidate drug effects like the response to different doses and frequencies, how long the drug stays in the system, and what potential side effects might be of concern. This focus is what allows pharma to inform the transition from testing drugs in animal models to treating human patients better than anyone else can. That transition is where the design of clinical trials are created.

We have already discussed much of the remaining aspects of the drug development process in part II of this series. To avoid repeating myself too much, suffice it to say that for clinical trials and beyond, pharma is uniquely situated for these activities. Pharma possesses the unique resources and manpower needed to account for the expense and administrative demands of clinical trials, as well as issues surrounding product/channel management.

Anyone else?

While pharma and academia are undeniably the undisputed largest players in the creation of new drugs and treatments, the dynamic of the interplay between the 2 has changed quite a bit over the years. In fact, it is the evolution of how these players are involved that is the crux of the modern nuances of drug development. While these might be the LARGEST players, they are no longer the only ones doing the heavy lifting.

In our next article we will discuss the academic/industrial marriage and how that shapes the way drugs are discovered and developed. We will also discuss how that relationship has evolved and what new players are involved (spoiler alert; these “new players” are going to be a BIG part of things going forward).

As promised, we will also discuss in later posts the myths and realities of science and pharma, which is a topic I am looking forward to a great deal. Partly because we are coming to the end of the background and are about to move into a more critical analysis of the state of things. In other words, if you’ve stuck around this long, it’s about to get interesting….

Progress to Part 5 of Dr Stiles’ series by clicking here.