George Washington’s leadership during the American Revolution was marked by strategic foresight, perseverance, and adaptability—qualities essential for overcoming challenges in drug discovery as well. He was known more for brilliant tactical retreats than outright wins. He knew that the American War of Independence, just like the long march toward a marketed drug, was a marathon and not a sprint. It is an interesting thought exercise to draw parallels between Washington's qualities of patience, resourcefulness, and collaboration and the development of new drugs that similarly demand inspired leadership in the form of long-term vision, resilience in the face of failure and innovative thinking. Below, we’ll explore five lessons from Washington’s military campaigns, applying them to the high-stakes world of drug discovery with some concrete examples.
1. Strategic Patience and Long-term Vision: Washington's Fabian Strategy vs. HIV Drug Development
Washington’s military success was often defined by his Fabian strategy—a war of attrition and avoidance of large-scale confrontations that allowed the Continental Army to conserve strength and gradually wear down the British forces. One of the clearest examples was his decision to avoid the direct engagement in New York in 1776, focusing instead on smaller, targeted strikes. While this strategy initially led to a disastrous retreat across the river to New Jersey, Washington and his troops regrouped, leading to their famous crossing of the Delaware. Washington's patience ultimately paid off with victories at Trenton and Princeton, where the tide of the war began to shift.
In drug discovery, strategic patience is essential, as breakthroughs rarely come overnight. A breakthrough drug famously has less than 1% odds of success and takes billions of dollars and several years to hit the market and treat patients. Consider the development of antiretroviral drugs for HIV/AIDS. When HIV was first discovered in the early 1980s, treatments were non-existent. Early drug trials failed to yield effective results, and scientists faced constant setbacks. However, researchers took a long-term approach, gradually improving upon early, promising but toxic drugs like AZT through years of clinical trials and development. By 1997, the introduction of highly active antiretroviral therapy (HAART) was a turning point, transforming HIV from a fatal disease to a manageable condition. This mirrors Washington’s long-term vision—victory wasn’t immediate, but patience and persistence eventually led to success. HIV drug development also mirrors Washington's ability to learn from his mistakes and build on his successes. After the Battle of Long Island, Washington realized the importance of intelligence, logistics and preparedness. Similarly, when attacking the HIV virus, researchers recognized the value of building on their knowledge of viral mutations to effect combination therapy and attacking different stages of the virus's lifecycle - the equivalent of an attack on multiple fronts.
2. Managing Limited Resources: Valley Forge vs. Orphan Drug Development
One of the most famous episodes of Washington’s leadership was during the harsh winter at Valley Forge in 1777-1778. The Continental Army suffered severe deprivations because of food, clothing, supply and personnel shortages. Washington’s ability to maintain morale and use limited resources efficiently for everything from building shelter to clothing his men, while relying on men like Baron von Steuben to train the troops, was pivotal in turning the army into a more effective fighting force that emerged from this trial by fire (or cold) stronger and more determined.
In drug discovery, managing limited resources is often critical, especially for diseases that don’t attract significant funding or attention. The development of orphan drugs—those that treat rare diseases—often faces the same kind of scarcity. An example is the development of Spinraza (nusinersen), a drug for spinal muscular atrophy (SMA), a rare genetic disease. Biotech firm Ionis Pharmaceuticals faced significant financial challenges, as developing a treatment for a rare disease didn’t seem commercially viable. However, through careful allocation of resources, partnerships with larger pharmaceutical companies (like Biogen), and perseverance, Spinraza became the first FDA-approved treatment for SMA in 2016. Like Washington at Valley Forge, the success of this drug was the result of making the most out of limited resources while keeping the long-term goal in sight.
3. The Importance of Collaboration and Alliances: French Alliance vs. COVID-19 Vaccines
The United States would likely have lost the Revolutionary War without critical assistance from France. In the pivotal Saratoga campaign, for instance, up to 90% of arms and gunpowder carried by American soldiers came from France. French support, particularly in the form of naval power and troops, played a decisive role in the eventual victory at Yorktown in 1781.
A modern parallel in drug discovery is the unprecedented collaboration seen in the development of COVID-19 vaccines. The global pandemic spurred collaborations between pharmaceutical companies, academic institutions, and governments on a scale never seen before. Pfizer and BioNTech’s partnership is a prime example—BioNTech provided the mRNA technology, while Pfizer’s resources and expertise enabled rapid scaling and distribution. This alliance was crucial in delivering one of the world’s first effective vaccines in less than a year. Just as Washington couldn’t win the war alone, drug discovery often depends on strategic alliances to achieve breakthroughs. Often these strategic alliances are between smaller companies that invent a new drug or technology and larger companies that scale and develop it. Sometimes they are between unlikely bedfellows, such as government and the private sector; for instance, HIV drug success was founded upon productive collaborations between government, private companies and activists.
4. Adaptability and Learning from Failure: Battle of Monmouth vs. Alzheimer’s Drug Failures
Washington’s ability to adapt to failure is best exemplified by the Battle of Monmouth in 1778. After the disastrous retreat ordered by General Charles Lee, Washington rallied the troops and turned the battle into a stalemate, avoiding what could have been a significant defeat. Initially goaded by Lee's retreat, British General Henry Clinton declined to attack when he found Washington in a formidable defensive position. This ability to adapt under pressure and recover from failure was a hallmark of his leadership.
In drug discovery, a parallel can be drawn with the development of gefitinib (Iressa), a targeted cancer therapy for non-small cell lung cancer (NSCLC). Initially approved in 2003, gefitinib showed promise in early clinical trials for a subset of lung cancer patients. However, in 2005, the FDA limited its use after post-approval studies failed to show a significant survival benefit in the broader patient population. This was a major setback for AstraZeneca, the drug’s developer.
Despite this failure, researchers did not abandon gefitinib entirely. Reanalysis of the patient response revealed that the drug was highly effective in patients with specific mutations in the EGFR gene—a critical insight that had not been fully understood during the initial trials. By identifying the right patient population, gefitinib regained relevance as a precision medicine for a subgroup of NSCLC patients. In 2015, gefitinib was reapproved in the U.S. for use in patients with EGFR-mutated lung cancer, a prime example of how learning from early failures can lead to a more targeted, effective approach in drug development.
Like Washington at Monmouth, the researchers behind gefitinib adapted to early setbacks by recalibrating their approach, identifying a more precise target, and ultimately turning a potential failure into a success.
5. Endurance and Moral Leadership: Valley Forge vs. Cystic Fibrosis Drug Development
Washington’s moral leadership during Valley Forge was crucial in keeping the Continental Army together during one of its darkest periods. His decision to stay with his men, sharing their hardships, and his constant encouragement gave them the endurance needed to persevere. By the time they emerged from Valley Forge, the army was stronger and better trained. Another example of Washington's leadership was his assumption of a frontline position at Assunpink Creek near Princeton, when his army was in disarray. Again and again, Washington inspired his troops with his quiet inner strength, battlefield bravery, unwavering focus on the end goal and democratic management of his army in which every man's opinion was valuable.
In the drug discovery world, long-term battles against chronic and deadly diseases often require similar moral leadership. One such example is the decades-long effort to develop treatments for cystic fibrosis (CF), a genetic disease that severely affects the lungs. Adopting a program from Aurora Biosciences and shepherding it through significant doubts and uncertainty, Vertex Pharmaceuticals led the charge, working tirelessly through failed attempts and incremental progress. Like Washington with his war council, the company carefully weighed the opinions of both enthusiasts and critics. Their efforts finally culminated in the development of Kalydeco and, later, Trikafta, drugs that significantly improve lung function and quality of life for CF patients. The leadership of Vertex’s researchers and executives, many of whom remained committed to finding a solution even when success seemed elusive and the mechanism of the drug (a potentiator rather than a more traditional inhibitor) appeared unconventional and novel, mirrors Washington’s leadership at Valley Forge. They persevered against severe odds, driven by a belief in the importance of their mission.
Final thoughts
The cause of complex drug development, just like the cause of the American Revolution, is mired in great cost and uncertainty. The odds of success are slim, the obstacles formidable, the naysayers many. Washington's quiet, dogged endurance, leadership from the front, patience and unwillingness to despair for long sustained the American cause long after purely rational analysis would have concluded that it was lost. Similarly, drug discovery depends on the right combination of leadership, resources and just plain good luck. But there is little doubt that dogged perseverance, adaptability in the face of new data, smart resource management and the spirit of collaboration can cause a step change in the odds of success, whether in war against a recalcitrant enemy or war against a recalcitrant disease. As Washington pithily put it, "Perseverance and spirit have done wonders in all ages."