HBR IdeaCast – Future of Business: Moderna’s Founder on Innovation That Breaks Through

Date: December 4, 2025
Host: Alison Beard (Harvard Business Review)
Guest: Noubar Afeyan (Founder & CEO, Flagship Pioneering; Co-founder & Chair, Moderna)

Episode Overview

This episode is a part of HBR’s “Future of Business” CEO interview series and features an in-depth conversation with Noubar Afeyan, the innovative mind behind Flagship Pioneering and Moderna. Afeyan explores what it takes to generate “breakthrough innovation”—not just in biotech, but in any industry—discussing the structural, philosophical, and practical elements required. He also shares his perspective on the interplay of human and artificial intelligence, nature-inspired experimentation, the challenges of commercialization, and the current threats to scientific advancement and immigration in the United States.

Key Discussion Points & Insights

1. Defining Breakthrough Innovation

Timestamps: [01:44]–[02:36]

• Continuous (adjacency-oriented) vs. Discontinuous (breakthrough) Innovation:
  Afeyan distinguishes between incremental advances (iteration over what’s come before) and leaps that are hard to connect to the past but redefine what’s possible.

• Predictability:
  Breakthroughs are difficult to forecast and initially their value is often not understood.

  “Once in a while you have discontinuous innovation… that’s much harder, much less predictable, but often is categorized as a breakthrough because people neither expected it nor could they in the beginning assess its value.” – Noubar Afeyan, [01:51]

2. Why Both Incremental and Breakthrough Innovation Matter

Timestamps: [02:36]–[04:31]

• Thinking from “future-back” vs. “present-forward”:
  Encourage pursuing both adjacencies and radical leaps at the same time—improving current offerings, while also envisioning and planning for disruptive possibilities.

• Risks of Incrementalism:
  Solely focusing on adjacencies leads to commoditization and difficulty sustaining advantage.

  “The disadvantage of adjacency-oriented innovation only is that it can quickly become commoditized... The problem is everybody else is doing the same thing.” – Noubar Afeyan, [03:50]

3. Structuring Organizations for Innovation

Timestamps: [04:31]–[06:49]

• Don’t Expect Everyone to Pursue Breakthroughs:
  Breakthrough focus isn’t feasible or sustainable for all. Organizations should dedicate specialized groups to high-uncertainty projects, with different incentives and philosophies from classic R&D.

• Risk vs. Uncertainty:
  Breakthrough innovation operates in an “uncertainty” domain—unknown probabilities—distinct from calculable risks.

  “This is a space that, I would propose, is more about uncertainty than risk. Uncertainty being about unknown probabilities, risk being about known probabilities... What you need to do is to take multiple approaches and persist long enough to see if you can make them real…” – Noubar Afeyan, [05:40]

4. The New Frontier: Augmenting Human Intelligence with AI

Timestamps: [06:49]–[09:51]

• AI as Augmented Imagination/Intelligence:
  Flagship Pioneering harnesses AI to generate novel ideas at massive scale—what Afeyan sometimes calls “alien intelligence.”

• Early AI Adoption and Evolutionary Algorithms:
  Even in the early 2000s, Afeyan’s teams used evolutionary algorithms for product innovation; now, generative AI and agent-based systems open new frontiers (e.g., 150,000 simultaneous agents assessing millions of objects).

• Scale and “Unimaginable” Possibility:
  Today’s AI lets organizations compete by augmenting and accelerating creativity far beyond individual human capacity.

  “One person’s hallucination is another person’s kind of leap. And so applying it into novel spaces is a very interesting way to prospect for things that a given human may not be able to think of.” – Noubar Afeyan, [07:43]
  “It’s almost unimaginable that you could compete without deploying these significant augmentation capabilities in doing innovation and breakthroughs.” – Noubar Afeyan, [09:38]

5. Learning from Nature: Evolution as a Model for Innovation

Timestamps: [09:51]–[16:38]

• Variation, Selection, Iteration:
  Flagship implements processes inspired by Darwinian evolution—generating many ideas, exposing them to “selection” (feedback), and repeatedly iterating.

• Value of Ecosystem Thinking:
  Analogy between natural selection and market feedback (e.g., mobile phones, running shoes, cars) as drivers of continuous improvement and leaps.

• Poly-Intelligence:
  Proposes viewing not just humans and AI, but also nature (ecosystems, cells) as different “intelligences” capable of adaptation and anticipation.

• Not Just Metaphor, but Operation:
  Methodologies inspired by biology can be directly applied to R&D (e.g., the way RNA vaccines mimic natural viral behaviors).

  “What makes somebody an expert is ... ownership of the best ideas today. And those are not usually the next ones to come along. It’s a rare expert who is humble enough to allow for the possibility that they’re wrong, which is the essence of an unexpected disruptive innovation.” – Noubar Afeyan, [10:26]
  “There’s a lot, not just metaphorically to learn, but also operationally” from nature, especially in how rapidly feedback and iteration evolve solutions – Noubar Afeyan, [16:38]

6. The Challenge of Commercializing Breakthroughs

Timestamps: [18:36]–[22:18]

• Timeframes and Cost:
  Breakthrough innovation can be prohibitively risky and long-term, especially in low-margin industries.

• Strategic Opportunism and Open-Endedness:
  Organizations must accept open-ended, opportunistic searches for new value, iterating until something resonates.

• Not Always a Genius Affair:
  Success is less about genius and more about the persistence to recognize value and iterate constantly.

  “Most people who make breakthroughs describe them as though they were the result of genius... in my experience... it’s got very little to [do] with genius. It’s got to do with opportunism, value orientation and the propensity to iterate.” – Noubar Afeyan, [20:52]

7. Intrapreneurship and Incentivizing Innovation

Timestamps: [22:18]–[24:54]

• Corporate Venture Creation:
  At Flagship, “intrapreneurship” is the entire business—launching new ventures internally and aligning rewards to outcomes, rather than process.

• Avoiding the “Reasonableness” Filter:
  Traditional R&D often selects for safe ideas, but the disruptive ones are “unreasonable” by nature.

• Variable Compensation:
  Advocates for risk-based reward structures—sales may earn more than CEOs, innovation should follow similar flexible models.

  “Intrapreneurship, in my view, allows for that, provided you don’t force it to be entirely commensurate with everything else in the R&D organization, which in my view is prospecting for different value pools in different ways and therefore should be rewarded in a very different way.“ – Noubar Afeyan, [23:38]

8. Science, Immigration, and America’s Future

Timestamps: [24:54]–[28:28]

• Threats to Progress:
  Both anti-science and anti-immigrant policies threaten America’s status as a globally adaptive, innovative leader.

• Value of Openness:
  U.S. societal strength lies in continuous renewal through immigration and scientific exploration, mirroring evolutionary principles.

• Scientific Process as a Bulwark:
  The scientific method, with its focus on hypothesis falsification, remains essential in distinguishing fact from opinion.

  “This country has been a hyper-evolutionary, hyper-adaptive place because of the constant influx of new thoughts, new risk taking appetite, new levels of desperation of people coming here and trying to make it work, which I think has made for a great society.” – Noubar Afeyan, [25:50]
  “The special place we found ourselves, where we welcome uncertainty in science and knowledge and we embrace it and we recognize that at any given time we may be wrong about what we thought we were certain about. But ultimately over time we’ll get it right.” – Noubar Afeyan, [26:35]

Notable Quotes & Memorable Moments

• On the Unpredictability of Breakthroughs:
  “It’s very hard to get money in R&D budgets for truly unpredictable things.” [05:20]

• On the Scale of AI-Driven Discovery:
  “Literally watching 150,000 agents representing humans interacting with millions of objects is quite a scene to behold.” [08:47]

• On the Limits of Expertise:
  “It’s a rare expert who is humble enough to allow for the possibility that they’re wrong, which is the essence of an unexpected disruptive innovation.” [10:26]

• On Commercializing Innovation:
  “If you search for the problem and the solution at the same time, you might be able to matchmake... in a way that if you insisted on owning the solution space or the problem space to be your point of departure, you will miss out on all things that essentially would be matched in the journey.” [19:49]

• On the Evolutionary Nature of America:
  “This country has been a hyper-evolutionary, hyper-adaptive place because of the constant influx of new thoughts, new risk taking appetite, new levels of desperation of people coming here and trying to make it work, which I think has made for a great society.” [25:50]

Key Timestamps

• Defining breakthrough innovation: [01:44]–[02:36]
• Present-forward vs. future-back innovation: [02:36]–[04:31]
• How to organize for breakthrough innovation: [04:31]–[06:49]
• AI, augmented intelligence, and examples from Flagship: [06:49]–[09:51]
• Nature/evolutionary models for innovation: [09:51]–[16:38]
• Timeframes, costs, and the commercialization challenge: [18:36]–[22:18]
• Intrapreneurship vs. entrepreneurship: [22:18]–[24:54]
• Science, immigration, and America’s future: [24:54]–[28:28]

Episode Takeaways

• Sustainable innovation requires balancing incremental evolution with bold, future-facing bets.
• Effective breakthrough innovation demands new structures, incentives, and mindsets oriented toward uncertainty, not mere risk.
• AI and nature-inspired thinking radically accelerate the search for new ideas; learning from ecosystems and evolutionary systems can inform how organizations innovate and adapt.
• Commercializing breakthroughs requires open-ended, iterative, and opportunistic approaches, as well as novel ways to align incentives.
• Societal progress and organizational renewal depend on openness—to both scientific revision and immigration—which are fundamental drivers of adaptation and growth.

Tone

Afeyan’s tone is thoughtful, humble, and occasionally provocative, always questioning orthodoxy and encouraging organizations—and societies—to remain open, adaptive, and evolutionary in their thinking and practice.