Developing Next Gen Multiple Sclerosis Therapies: Part 5

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, part three is available here and part four 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.

In part IV we outlined the roles of academia and pharma in the drug discovery and development process. To this point, these articles have been largely descriptive, but from here on, we are going to get critical. We are going to parse out myth vs. reality, explain how we address the innovation gap, and how we can improve the system to make the best possible drugs for the future. 

This is the important stuff. Being informed and aware is what facilitates the type of advocacy that leads to change. If our shared goal is to work towards the best possible outcomes for patients, we need to be operating from the best information available and not waste time on flawed concepts. Fundamentally, being informed allows for constructive criticism as opposed to destructive stigma. Breaking down myths and realities allows us to focus our energies on improving the system and takes us away from feeding into destructive narratives that are often designed more to vilify than to motivate. Throughout this series I’m going to give you my most honest portrayal of truth as I see it, and as such, I’m going to say things here that will anger some people and delight others. In either case, whether you love or hate what I say, I urge you to keep an open mind and be critical of these discussions. I encourage everyone to vet my statements before coming to specific conclusions. Accordingly, I welcome any feedback you may have. 

Myth vs Reality – Academia

In recent years there has been a troubling trend in public perception of science. While scientists have been historically revered for their contributions to society and pursuit of knowledge, we are now experiencing a shift towards the framing of experts and the educated as aloof and misaligned with practical concerns of the “average Joe”. This is reflected in the growing adoption of terms like “coastal-” and “academic elitists” to describe the general scientific and expert communities. To be fair, academia is not perfect, and there are legitimate and specific concerns that can be addressed. However, this elitist portrayal of science is not one of them. In fact, these oversimplified assertions often demonize the most beneficial aspects of academic science and leave the true inefficiencies unaddressed. 

Unfortunately, the majority of these harsh narratives are effectively misleading and specifically crafted to serve the interests of those who promote them. As the world drifts further and further into political extremism, it is important to not allow science to be collateral damage. 

Myth #1: Scientists tailor their findings for profit

I know this has already been said but let me reiterate, you do NOT become a scientist for the money. Academia is appealing for the freedom of exploration, but that freedom comes at the cost of relatively meager earning potential. A newly-minted Ph.D. in the biomedical sciences can expect to make around $45k/year in what are called “post-doctoral fellowships”. In case you didn’t catch that, someone who is legally considered a doctor can expect to make less than $50k/year in academia. The academic dogma is that new Ph.D.’s need 4-6 years in such positions before they are considered good candidates for more prestigious jobs. Even after such time, most won’t get faculty positions, but will largely move into academic science staff positions where the earning potential is still shamefully low for the experience and education required. In fact, for most scientists with Ph.D.’s, it can take 5-10 years to get a faculty position, and many never do. Even then, if you are lucky enough to get that tenure track position, starting salaries for an assistant professor average at just under $60k/year! What other field can boast such meager income for such an arduous journey?

(NOTE:  The career path mentioned above is US specific, reflecting Travis’ own experiences.  Whilst a lot of the terms are different in Australia and around the world, the journey described is similar.  That is, the theme that is common for researchers in any location is that they spend extended years studying, followed by a professional life that finds them being underpaid and with little job security.) 

Despite this grim reality, the path described above is the aspiration of most graduate trainees! “Why would anyone want that?”, you may ask. The answer is simple: because the post-doctoral position is the first opportunity for a scientist to be independent and carve out their niche in science. No one wants to be impoverished, but as a scientist, the opportunity to flex your science brain and work on your own ideas is often more appealing than a large salary (the other option being industry where you aren’t given the option of what to work on but are compensated much better). Of course, there are always exceptions to these generalities, but typically, academic scientists are not in this career for the money. The idea that scientists pursue science for fame and fortune is, quite frankly, laughable. 

Myth #2: Unlike pharma, Academic science is pure and without bias

We touched on this in part IV, so I will be brief. Academia is fortunate to remain uninfluenced by profit bias, which is a major benefit. However, while the research pursuits of academia are essentially well-intentioned, at times, the pursuit of funding for these efforts may lead to confirmation bias. For example, if I get a million dollar grant to show that a protein does X, my funding and prestige grows largely by proving that true. If my theory is proven false, as valuable as that knowledge might be, the absence of sex appeal makes additional funding in this line of research difficult to come by. As such, one fundamental flaw in academic research is the disproportionate value placed on positive, hypothesis confirming, findings. In a system that should be agnostic in its interpretation of results, confirmation bias can convolute the findings of academic research.

Fortunately, academic science is beholden to the scientific method and peer-review system, which are potent checks on confirmation bias. Additionally, technical critique by peers and the necessity for replication of findings are inescapable means by which we keep science moving forward and away from the unproductive tangents of biased results. Even in the most extreme cases of bias, such as corruption, the mechanisms academia has in place will always bring things back toward truth. Be that as it may, this does not mean it happens quickly or as efficiently as we might prefer. There is certainly room for improvement in these areas but these checks serve as sources of unbiased accountability and structure. 

In summary, it is important to be aware of the perils of confirmation bias and lack of reproducibility. The scientific system must adapt to incentivize scientists to conduct good science, not just produce new findings. Negative data is just as valuable as positive, and reproducibility is critical to innovation. 

Myth #3: special interests drive scientific findings and consensus builds reputation

This is important!

Make no mistake, undue influence from private groups funding research can happen. However, the beauty of science done well is that hyperbole and opinion cannot persist unsubstantiated. In other words, if a finding is wrong, it will be discovered. It doesn’t matter how big your payday was, you will not escape the fallout of bad science. While it may be easy for opportunists to paint scientists as aligned conspirators with a shared goal of skewed information for personal gain, the reality is that as an idea gains traction, proving that idea WRONG is the perfect way to build a career. As such, the stronger a consensus grows, the harder people will try to disprove it because doing so will allow you to stand out and make your mark on science. In short, no one ever became famous for being the second person to lend support to a finding. Scientific consensus does not self-perpetuate, it does the opposite. The more consensus is derived, the greater the potential for career advancement that can result from proving that consensus wrong. Consequently, the academic system promotes a sense of healthy pessimism and a powerful check against groupthink.

The narratives used by skeptics of climate change are a perfect example of the implementation of this myth. The generic portrayal of climate scientists by those in opposition to their findings are; 1) that they are unduly influenced by the financial incentives for their work and people are making money off directing their findings towards proving climate change to be real, and 2) that there is sufficient dissent amongst them to be unable to conclude what the science is telling us. Neither is true. As discussed, the compensation in academic science is humble, and being contrarian builds a reputation and can bring in more funding than piling on to a specific conclusion. However, this is only true when the contradictory science can stand up to criticism. This is the beauty of scientific disagreement. Competing hypotheses universally result in a refining of our scientific understanding. Despite the political commentary to the contrary, complete scientific consensus is exceedingly rare, largely because of the incentive to disprove existing beliefs. This incentive to challenge paradigms is healthy and insures that our understanding will continue to evolve rather than rest on an illusion of consensus. Regardess, the narrative that incomplete consensus means not enough is known to justify action is, frankly, absurd. Science is never binary and no reputable scientist would ever present their own findings as irrefutable fact. Scientists are inherently skeptical, and in terms of the climate debate, there are few issues with more consensus on one side of an issue, which historically has been sufficient to motivate positive and fruitful action.

Myth vs Reality – Pharma

In terms of pharma, there is really only 1 myth worth addressing, and that is the concept of Big Pharma being “evil”. This type of hyperbole is appealing in its simplicity, and it gives those frustrated with the pace of medical innovation a prominent villain to be the target of their frustration. To be fair, the realities behind slowed biomedical innovation are complex, and in an era of 140-character (now 280) attention spans, it is unsurprising that this narrative would permeate society more readily than the nuanced truths of the issue. Unfortunately, narratives such as this are often perpetuated by those with justifiable frustrations that simply lack the nuanced understanding of how the system works. Make no mistake, while I empathize for those in such situations, the absence of critical understandings that lead to propagation of these oversimplifications actively undermines the best interests of those that are most likely to feed into these myths. The “evil” big pharma myth is likely the most problematic in terms of hindering positive change. As such, I feel the need to take some time here and fully explain my point.

At one time or another, most of us have heard the accusation that the pharmaceutical industry “doesn’t want to cure things” (I hear it a LOT). While there have always been variations of this particular theme, the last decade has experienced an exceptional uptick in this particular implication, which is often pushed in the form of the ultimate oversimplification; memes (like the one shown here).

Regardless of its form, the insinuation is that companies are holding back medical advances because next generation cures or treatments may not be as profitable as existing revenue streams, which may compromise their profit margins. For example, I often hear that it’s more profitable to keep a patient reliant on chronic therapies because if you cure a disease, that person is no longer a customer. 

Where is this coming from?

This myth has always existed, but really gained traction in the last decade. I believe a major factor causing this is the growth of the marijuana industry and the large financial interests pushing for marijuana legalization. Full disclosure, I have no problem with responsible adults partaking of marijuana. However, I do have a problem with the way that pro-legalization groups have pushed a flimsy narrative of “medical” marijuana to remove stigma and move towards legalization. This medical narrative carries with it a sinister bit of secondary propaganda; the idea that marijuana is safe. Granted, marijuana is nowhere near as dangerous as it has been portrayed, but it isn’t a miracle plant without consequences. While it has been unfairly demonized as a gateway drug and more, the truth about cannabis, contrary to what legalization advocates will tell you, is that it is both addictive (not as bad as cigarettes) and can cause cancer (mostly because smoking anything is carcinogenic). More importantly, marijuana is a major trigger of psychosis in susceptible persons and is a potent suppressor of brain development (kids should NOT use the stuff unless its medically necessary). Marijuana is not safe for children—this is particularly vital because more and more well-meaning but uninformed parents, of the same ilk as anti-vaxxers, have taken to self-medicating kids with marijuana. Most relevant to this article, marijuana is no more a “medicine” than poppy plants or willow bark. Poppy seeds are the source for opiates. Willow bark gives us aspirin. While morphine and aspirin are amazing drugs, their crude origins are NOT for MANY reasons. 

Bottom line, marijuana businesses make money off people smoking marijuana. As such, they have created a narrative of miraculous and safe cannabis, while simultaneously slandering pharma and making it difficult for them to create actual DRUGS derived from the plant (in the same way we made morphine from poppy). And that brings me back to my main point: Big Pharma is not evil, sinister, or conspiring to unethically profit from chronic human suffering. Both pharma and the marijuana industry want to make money. If pharma develops real cannabis-based drugs, it could potentially cut into the recreational/medicinal marijuana market. As such, the perception of pharma as the bad guy is in the best interests of marijuana retailers. Neither group is evil. This is just the nature of capitalism. It’s our responsibility to be informed above the simplification.

So pharma isn’t bad?

Look, we know corporations exist to make money and corporate greed can lead to bad behavior. However, this might be one of the few cases where capitalism actually HELPS prove this myth wrong!

The fundamental flaw in logic behind the demonization of Big Pharma is idea that the incentive for profit is inherently at odds curing disease and that keeping people sick is more profitable than curing them. Frankly, this might be true in a vacuum (meaning if only 1 pharma company existed). However, capitalism does not exist in a vacuum, but rather in a complex and competitive market. The beauty of healthy capitalism is competition, and competition is what fundamentally mitigates the idea that greed would prevent the creation of new cures. Without competition (and very important regulatory factors), I have no doubt companies would devolve into an endless stream of “snake oil” products marketed as disease cures because real cures would be too expensive to be worth developing. 

Because competition makes the myth of evil pharma problematic, the brilliance in this narrative is the portrayal of the pharmaceutical industry as one entity (hence the use of simple, singular, and catchy terms like “pharma” as opposed to the more accurate terms, “pharmaceutical companies”). Because the competitive nature of capitalism is so central to how we debunk this myth, it makes sense that those who wish to push the more sinister narrative would do so by creating a perception of pharma as one evil foe. With only one pharma company, it’s easy to see how lack of competition would almost certainly result in no real incentive to improve on the treatments already in the market. But the reality is, this just isn’t how it works.

Summary

I know this was a long read, but this is important stuff. Understanding the myths and realities surrounding the perception of science allows us to direct our efforts towards positive change and overall improved outcomes for patients.