The cutting edge of medicine, as in most branches of science, is an unforgiving place. Challenging the conventional wisdom usually brings criticism from all quarters. Especially damaging is that which comes from the “thought leaders”. They are consulted by investors, edit the leading journals, chair the sessions at the key professional meetings and sit on the grant review committees. Their scorn for new ideas can create extraordinary headwinds for anyone proposing a new mechanism or therapy that breaks with the established understanding of a disease or treatment.
Hostility to new ideas is not without purpose. Most new ideas tossed out are poorly researched, unsupported or contradicted by evidence, or recycled discredited concepts reintroduced by a proponent who never delved deep enough to discover the history. One need only look at the ongoing politicized controversy over the discredited link of vaccines to autism to understand how dangerous misguided medical “discoveries” can be to health and safety of the population. Battling bad science is an appropriate endeavor for the vanguard protecting what has been established through careful experimentation and study.
However, the zeal of those protecting established thinking can cause genuine breakthroughs to be suppressed. In 1958, a Greek physician, John Lykoudis, successfully treated his own gastroenteritis with antibiotics and received a Greek patent in 1960. He subsequently treated an estimated 30,000 Greeks with antibiotics, curing their ulcers. His attempts to publish his findings in JAMA were rejected and he was fined by Greek medical authorities in 1968 for malpractice. It took more than two decades for Barry Marshall and J. Robin Warren to demonstrate that Heliobacter pylori caused gastric ulcers and could be cured by antibiotics, and another decade from their publication of their findings in 1984 in The Lancet to the general acceptance by the NIH in 1994 that evidence supported H. pylori as the cause of peptic ulcer disease. They were eventually lauded with the 2005 Nobel Prize in Medicine while Dr. Lykoudis did not live to see his hypothesis vindicated.
The breakthrough beginnings
Breakthroughs can come from inside or outside the mainstream of scientific thinking. In his early years, Bob Langer struggled with the resistance to his innovations in drug delivery as much as any new investigator, even though he was on the faculty at MIT. Once established however, he has become an incredibly successful and prolific innovator, helping launch more than 100 companies, and with more than 250 companies having licensed or sub-licensed Langer Lab patents. Having been accepted as a mainstream thought leader, he became a powerful advocate for new ideas and technologies.
Truly independent thinkers in medicine are almost always outside the mainstream of scientific dogma. For those toiling outside the main centers of academic achievement and prestige, it can be almost impossible to break into the conversation let alone advance new ideas to a thoughtful consideration and dialog. Many of those that do succeed in making breakthroughs possess some common characteristics.
Characteristics of breakthrough founders
Independence – critical to making genuine breakthroughs is independence of thought. The tyranny of dogma, what we know and teach in textbooks, inhibits those who are not willing to ignore what is “known” and look at old and new evidence with a fresh and unbiased perspective. The quote: “It isn't what we don't know that gives us trouble, it's what we know that ain't so” has been attributed to both Will Rogers and Samuel Clemens and perfectly captures the dilemma in modern science and medicine. Theories become dogma through teaching and repetition even when they fail to account for all the observations in a disease or condition and do not result in effective treatment. A fresh look only occurs to a few and fewer still have the time to devote to interpreting evidence independently without the shortcuts of others’ prior interpretations.
Independence is also required when bucking the conventional wisdom because it is not likely to garner friends and supporters, at least not initially. Someone willing to put forth the effort to re-examine what is already “known” often has to do so alone.
The classic approach of revising our existing explanations is to engage a problem with a new hypothesis. This is useful but invites several forms of bias including confirmation bias where evidence is selected that fits the hypothesis and contradictory evidence is discarded or ignored. As much as we hate to admit it, this happens all the time, and not just in science. One look at my Facebook feed provides dozens of examples of confirmation bias, cherry picking situations that support someone’s cherished idea while disparaging contradictory evidence.
Far more powerful is approaching a “known” as if it were an “unknown” and assembling the evidence, old and new, and listening to it, letting it gobsmack you in the head with that ah-ha! moment that accompanies a genuine insight. An independent mind, who sees things as they are, not as others say they are, is a treasure.
Focus – the ability to stay on task without distractions is a luxury afforded very few. The ability to discipline one’s mental process to a single question over an extended period of time is important in many breakthroughs. For some it comes more naturally than others – the ability to screen out life’s distractions. For most the requirements of managing daily life with dozens of simultaneous problems and issues, completely overwhelms the ability to focus on one problem.
Tenacity and Stubbornness – examining a problem with an independent and open point of view takes a lot of work. Re-examining the old and new evidence without the comfortable framework of the conventional interpretations is like putting together a massive puzzle without the picture on the box. Some pieces fit together but the whole picture can remain elusive for a long time. Even when sections start fitting together, they still might not make a whole picture. And the goal is to have all the pieces fit, rather than leaving out some as previous hypotheses might. Sticking with it when pieces don’t fit or make sense requires inner strength.
Resistance to Criticism – looking at things from an independent and open point of view requires an ability to ignore the conventional wisdom during and after a new idea has emerged. Unless a new idea emerges from someone well established in the field and accompanied by fresh and compelling evidence, it is seldom embraced with enthusiasm. More typical is the hostility and resistance that Dr. Lykoudis endured or even Drs. Marshall and Warren received initially. Enduring and rising above the criticism is an essential ingredient to championing an idea successfully. Those who shrink from the criticism are unlikely to move their insight far enough into the marketplace of ideas that it can gain momentum and support and make a difference.
The breakdown
In medicine, the grueling process through which breakthroughs are vetted includes regulatory authorities such as the FDA, local IRBs (Institutional Review Boards) for clinical studies, and the screening of investors and potential development partners. Among the myriad of critical tasks are securing a supply chain and preparing a consistent product and manufacturing process, documenting quality and performance, conducting appropriate preclinical and clinical safety studies, filing and prosecuting patents, creating agreements for clinical trial sites and contractors, securing appropriate regulatory approval for various development steps, establishing product reimbursement codes and rates and determining how a product will be sold and to whom. These tasks take a team. No product can be developed alone.
The very personality characteristics that enabled an individual to make a significant breakthrough can come back to inhibit their ability to develop that breakthrough into a product. The independence and perseverance through a period of resistance and criticism often inhibits an inventor from trusting anyone else and instills a need for control – to make sure things are done right. Their ability to focus can cause a founder to zero in on one area requiring attention but neglect the rest of the picture. Developing a medical product, be it drug or device, requires many pieces to work together to create the end product, an approvable product that health professionals and patients benefit from, at a cost the system can afford.
First time entrepreneurs seldom know how to do everything involved in successful development of a medical product. “That’s ok” they think, since “I can figure it out just like I figured out my new therapy”. However, there is a big difference – science is independently knowable while the process of developing and approving a product is a known, human process. The regulatory rules are published and people will interpret and judge the information presented based on precedents going back decades. The same applies for Doctors on IRBs interpreting clinical protocols and investors reviewing business plans.
There are people who have done it before, successfully, who know how the people process works. There are people who know how to handle fundraising and manage funds, performing the legal fiduciary duty, protecting the company, investors, Directors and Officers. There are people experienced in purchasing materials, manufacturing products and/or devices, establishing metrics and documenting quality procedures and outcomes. There are people who design final products to meet patients’ needs and situation successfully so the potential can be realized. There are people who design clinical trials to insure patient safety and give the best chance to establish the statistically significant evidence of efficacy necessary to register a product. All of these people and more need to be part of the team to take a breakthrough idea and make it into a product. And just like the founder, all these people want to make each endeavor they participate in a success.
When a first time entrepreneur takes the independent track and sets out to stubbornly develop their breakthrough on their terms and their own way, bad things can start to happen; professional investors don’t invest, experts don’t become advisors, the FDA does not let an IND move ahead or does so with the greatest caution, a few patients at a time. Contractors, consultants and employees are not willing to work just for equity and things can grind to a halt. If the entrepreneur is independently wealthy or the endeavor can be self-sustaining early on, then bootstrapping lets the entrepreneur stay in control and do it his or her way, taking the time to learn as they go. However, if like most medical innovations, tens or hundreds of millions of dollars will be required to bring it to market, obstacles have to go. And when the entrepreneur is an obstacle, through stubborn insistence things have to be their way, an uncomfortable choice occurs – the resources to move ahead without the cherished control or toiling in futility until someone else figures out how to steal or work around the IP or comes up with a better solution, or the whole thing dies.
To first time founders and their friends and family, the painful loss of control feels like a repudiation of their accomplishment. It is nothing of the sort – in fact quite the opposite. When an investor and team thinks an idea is important enough to put money and human capital behind it, that is a tremendous endorsement of the breakthrough. It is also a practical recognition that things will move ahead smoother and faster without the founder at the helm or in control and with the right team driving the efforts in the areas where each is expert.
A tragedy is a play dealing with tragic events and having an unhappy ending, usually involving the downfall of the main character. So many startups end as tragedies from the perspective of the founder. It does not have to be that way, but to avoid it, first time founders need to know when to let go, and that lesson is unfortunately most often learned the hard way.
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Read more of my blog, “Musings on Medical Startups”, at Wit Creek: http://www.witcreek.com/musings-on-medical-startups.html