The Biggest Lesson From Theranos’s Elizabeth Holmes? Self-Doubt Is Underrated

Elizabeth Holmes is not the first businessperson for whom ruthless ambition untethered from reality resulted in a fraud conviction. Nor will she be the last. What, then, is the startup community to make of the spectacular rise and fall of the Theranos founder?

It’s tempting to draw a definitive conclusion from the verdict handed down in a federal court in San Jose on January 3: Theranos will forever change biotech. Theranos is a referendum on Silicon Valley culture. Or, the flip side: Holmes, her company, and her slate of investors–who notably had no experience in healthcare or diagnostics–are outliers rather than representing a condemnable trend in entrepreneurship.

Setting aside the question of long-term implications from the Theranos trial, I think there’s a fascinating post-mortem discussion to be had around the inner turmoil of the entrepreneur who pursues the path of outsize ambition.

Startup culture celebrates the founders who conceive of and effectively sell the most inspiring visions. Hence the glut of startup advice, including on, focused on that first crucial step: the pitch. Without the vision, you have no team, no financial support, no partners, and arguably not enough reason to persevere every morning trying to create something from nothing. So you need the spark that comes from hoping you’ll be the exceptional person who will achieve what others before you have not. You’ll be the one who will revolutionize the healthcare industry with a few drops of blood.

But when reality conflicts with your vision, there’s a psychological dance required to keep working at it. Let too much self-doubt creep in, and you’ll get nowhere, say many successful entrepreneurs. And so unwavering belief in oneself and in one’s idea is paramount. Keep going when everyone tells you ‘no.’ Forget your critics. As Holmes put it in a 2015 interview in an attempt to respond to Theranos skeptics: “First they think you’re crazy, then they fight you, then all of a sudden you change the world.”

To succeed, you must effectively walk the line between projecting hope and inspiration, and responding to the obstacles that are inevitably thrown in your face. But how?

To explore this question, I reached out to entrepreneurs and investors in biotech and healthcare, spheres known for long innovation cycles. And while their perspective most closely reflects what it’s like to operate in these industries, their advice is relevant for ambitious startup founders in any industry.

Adam de la Zerda is a scientist first, and then an entrepreneur. He is the founder and CEO of Visby, a biotech company that has played a pivotal role in the pandemic response by making the world’s first portable PCR machine that can test for Covid in 30 minutes. While the Covid-specific test was brought to market in about six months, de la Zerda had been working on the idea for years leading up to Visby’s FDA emergency-use authorization in September 2020.

When he reflects on what Holmes says she was trying to do at Theranos, de la Zerda–who is also on the faculty at Stanford’s School of Medicine, where he teaches in the structural biology and electrical engineering department–immediately thinks of his scientific training. “The verdict reminds us of what we knew all along, what’s fundamental as scientists: All that matters is truth and data,” he says. “Doubting yourself, others, the data, everything–that’s intrinsic to someone’s identity as a scientist.”

At Stanford, he says, faculty spend enormous amounts of time training students to remove their conscious and unconscious biases in their experiments. Good scientists learn good techniques for asking questions, especially when they get the result they were hoping for. How might they have influenced the outcome? In science, external structures such as peer review and clinical trials are in place to remove the bias and conflicts of interest inherent to the process. (Theranos, it must be noted, did not did not subject its research to the same scrutiny that most biotech companies do.) In other words, applying caution–even doubt–is crucial to the scientific process and to proving the validity of breakthroughs.

When I asked de la Zerda if self-doubting was at odds with his identity as an entrepreneur, he paused. Perhaps in some moments, it might be, he said, pointing to the big pitch moment. But at the same time, he says, “in science, doubt doesn’t take us away from being willing to pursue high-risk, high-reward projects.” Perhaps it needn’t do so in startups either.

De la Zerda’s point easily could be reframed to be more palatable for the non-scientific founder, the same person who believes too much self-doubt is antithetical to the success of a startup entrepreneur. What de la Zerda is talking about is the importance of maintaining a learning mindset. The humility to know what you don’t know, question your assumptions, and change your beliefs in the face of convincing evidence. In short, everything Holmes was unwilling to do. It sounds basic, and yet plenty of business leaders operate with a similar mindset, if not to the extent where they commit fraud. They limit their own growth due to overconfidence in their own ideas and an inability to adapt. For more on that topic, read organizational psychologist Adam Grant’s recent book, Think Again: The Power of Knowing What You Don’t Know (Viking, 2021).

When Menlo Ventures partner and biotech investor Greg Yapp thinks of the task of staying grounded in the pursuit of outsize goals, he puts it another way: “How do you eat an elephant? The answer is one bite at a time.” You absolutely need to preach the long-term vision so your partners, investors, and employees stay excited on the journey, he says. But then your work is about “identifying the de-risking moments along the way to know you’re going in the right direction.” You need to make incremental, tangible progress toward your goal.

Cheryl Cheng, a health tech investor and founder of investment firm Vive Collective adds: “Founders have to be very careful with the claims they make. What you can do today is different from the aspirations of what you think you will do,” she says. “I expect my founders to be dreamers and visionaries. But if along the way you have doubts about whether something is going to work, you also have to have the courage to share that.”

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