The Science of Moonshots: Using Evidence to Design Transformative Initiatives
“We choose to go to the moon. We choose to go to the moon in this decade and do the other things, not because they are easy, but because they are hard, because that goal will serve to organize and measure the best of our energies and skills, because that challenge is one that we are willing to accept, one we are unwilling to postpone, and one which we intend to win, and the others, too.” – President John F. Kennedy, announcing the original moonshot in 1962
This piece developed in concert with the Moonshots and Metascience event made possible by the Alfred P. Sloan Foundation.
In 1945, the Federation of American Scientists was founded by a group of physicists that helped to develop the atomic bomb under the Manhattan Project. FAS was born at a critical juncture – the creation of the atomic bomb was the first time the world had seen a coordinated, interdisciplinary effort to harness science for an ambitious goal. FAS’s founders had just witnessed the power and potential impact of transformative science initiatives. Deeply concerned about the potential for harnessing this impact for malice, they came together to ensure that science and technology would promote societal benefit rather than harm.
Eighty years later, we find ourselves at yet another pivotal moment for the scientific enterprise. Americans are asking critical questions about whether publicly funded research is delivering for them, their families, and their communities. To respond to that challenge, we can learn from FAS’s roots by asking: what does it take to design initiatives centered on big, challenging goals that lead us to better science and a better world? After all, whenever the government spearheads such ambitious initiatives, it can lead to tremendous public benefit in terms of completely new technologies and capabilities that serve critical public needs.
Critical to launching such initiatives is understanding the components that make them so successful. To this end, FAS organized a recent event “Moonshots for Metascience and Metascience for Moonshots” to ask hard questions about what has made prior ambitious efforts work, and why some of those efforts failed – building toward a conversation about the types of moonshot-style initiatives needed today. You can get an inside look at one of those conversations, featuring renowned scientist Lee Hood, here.
From those conversations, we’ve identified the key ingredients of successful moonshots that meet the moment, and developed recommendations about what future efforts can and should look like.
Defining the term “moonshot”
The word moonshot was described by a number of attendees as tired, overused, and overhyped. It has evolved into a marketing term for ambitious science, rather than a specific term used to describe a program with discrete structure and objective.
Other, similar terms might get closer to more generalized ambitious science: entrepreneur and founder of the X-Prize Peter Diamandis uses the term “moonshot mindset” for what he calls “10x thinking”; in other words, the type of approach that treats every problem as solvable and aims for an improvement of 1000% over the current state. Economist Mariana Mazzucato centers her work around “mission-oriented innovation”, an approach that leverages frontier knowledge to help solve big challenges. And philanthropy increasingly uses the term “big bet” to describe these types of projects.
Ultimately, whatever you want to call it, our goal is to better understand and promulgate the essential elements of both moonshots and their close cousins: initiatives that set audacious and transformative goals, how those initiatives chart a clear path toward achieving those goals, and the roadmap for stretching beyond the limits and mechanisms of the traditional scientific R&D enterprise.
It’s not enough to know what your “moon” is – you need to know the trajectory of the “shot”, too.
Successful moonshots involve both a clear what and a clear how. If you think about prior moonshot efforts, there are probably a select few that jump to mind: the Apollo Program, the Manhattan Project, and the Human Genome Project are the most notable efforts. What’s something these all have in common?: A “moon”, a goal that anyone can clearly define. This is a critical element of successful moonshots.
But other similar efforts have been tried before to less avail. As an example, consider the Human Brain Project. This project had a clear goal: to simulate the entire human brain on a computer. It concluded in 2023 after 10 years and €1 billion spent. The effort did lead to significant advances in neuroscience, but it failed to accomplish its stated goal. From the jump, scientists were highly critical of this initiative because they did not believe the requisite technology existed, or was even close to existing. In other words, the how was unclear.
This is common for many such initiatives. For example, when the Human Genome Project was launched, we did not have the technology capable of meeting the mission. The project was highly criticized by many in the research community because the traditional method of DNA sequencing could not possibly be scaled to meet the goal. They needed a new way to sequence DNA faster, with longer reads, and for less money. Therefore, the first goal was to drive investment in the development of technology that could answer the how question.
A successful moonshot is one where it’s clear that we are on the precipice of achieving a once-unimaginable goal, if only we make a significant investment toward that end. Think of the original moonshot: when JFK announced this initiative, we had seen a man orbit the Earth. And we knew that putting a man on the moon was challenging, but far from impossible – we just needed to devote the appropriate time, resources, and organization around that goal.
Organizational structure and governance matter
The history of major scientific initiatives suggests that organizational structure and governance are not merely administrative details. They are often the deciding factor between transformational success and expensive stagnation.
The Human Genome Project illustrates this directly. Years of planning preceded the project’s formal launch in 1990. The project was organized using a joint agency structure, partnering the National Institutes of Health (NIH) and the Department of Energy (DOE), with the two agencies signing a memorandum of understanding to coordinate their efforts. NIH instituted a university grant-based program funding multiple genome centers for five-year periods, a deliberate choice to distribute the work across institutions while maintaining central coordination. In this example and others, structure was not the container for science – it shaped what science is possible in the first place and funneled efforts towards a central goal.
Governance matters for a related but distinct reason: it determines who has the authority to make bets and whether an initiative can maintain its ambition as it encounters institutional and technological barriers. The Human Genome Project’s governance was tested early on. Its inaugural director resigned in 1992. Its new director took over nearly a year later, bringing a revised five-year plan. The ability to absorb that leadership transition without losing momentum was itself a governance achievement; it depended on the project having clear enough goals and distributed enough institutional ownership that no single departure could derail it.
Evidence from other successful models like DARPA similarly suggests that concentrated decision-making authority combined with clear accountability to a defined endpoint is strongly associated with the risk tolerance that transformational work demands. Governance structures send signals that shape who joins and how they behave: a structure that punishes failure will produce risk-averse science regardless of how bold the original mandate was. In this sense the organizational choices made at founding are not just operational. They are a statement of values that propagate through every subsequent decision made to drive the initiative forward.
Today’s moonshots can, and should be, informed by metascience
Sometimes it’s more obvious that we are ready for a moonshot. Again, thinking back to the Apollo program: if we can send someone into orbit around the Earth, we can almost certainly find a way to get to the moon. But in many scientific fields, it’s less clear that we are on the verge of a breakthrough. However, new technological advances and a wealth of available data are starting to make it possible to identify signals that we might be on that verge. In a pre-print published in 2025, Davis et al describe an approach using the PubMed database to detect when breakthroughs are on the horizon in biomedical research; Kristine Willis describes how we can apply that framework to science funding in general. This is an example of how we can directly leverage evidence to inform future ambitious efforts, and will be especially useful for moonshots where understanding where science will likely be in 4-5 years can help direct ambitious investments.
The field of academic study that Davis, Willis, and many others contribute to is called metascience, also referred to as the science of science or research on research, which uses the scientific method to study science itself; it seeks to build an understanding of how research is funded, conducted, and published.
Metascience can help us understand not just what topics might be ripe for a moonshot, but also how to best run those initiatives. There is a limited amount of existing evidence on moonshots specifically, but metascientists can offer useful insights. For example, Dashun Wang’s work on the different types of innovations produced by different size teams or his finding that interdisciplinary teams produce research that is more widely-cited can inform the structure of projects funded under a moonshot effort. Or we can look to Pierre Azoulay’s work on funding people vs. projects, or where grant funding is most useful to spur scientific progress to inform when and how government takes the lead in developing moonshots. These insights, all generated in the past 15 years, help us build new moonshot initiatives that are more efficient, allowing us to make the case that we are better positioned to launch ambitious moonshots because we have a strong evidence base for what works.
Metascience expertise should also be embedded within moonshot efforts to help us understand if we’re making the progress that we hope for and to set achievable timelines. Learning from similar efforts in the UK, there have been recent calls to embed metascience teams within U.S. federal agencies to evaluate the effectiveness of their funding approaches. A metascience team, funded as part of a moonshot initiative, can build evidence along the way so we can learn from any successes and failures and adjust strategy to improve output and efficiency.
In short, metascience can help us understand when we’re ready for a moonshot, how to structure it, and evaluate its effectiveness as it proceeds.
What are the next moonshots?
We have the ingredients for successful moonshots and other transformative scientific efforts, a mandate from the public to engage in scientific discovery that will have a positive impact on their lives, and ambitious national priorities that require significant investment in R&D.
At our event, participants imagined a set of possible moonshot efforts that might meet the moment:
These are not just thought experiments. Each proposal represents a domain where we have clear signals that we are on the verge of something transformational, where the public interest is clear, and where the missing ingredient is a coordinated, well-designed effort to close the gap between what we know and what we could achieve. In other words, each has a clear “moon”. The work ahead is designing the “shot.”
Eighty years ago, FAS’s founders emerged from the Manhattan Project having witnessed what science could accomplish when organized around a bold goal, and committed themselves to ensuring that power was directed toward human benefit. Today, we face a different but parallel challenge: not just identifying the right goals for science, but building the institutional capacity to pursue them effectively. The Human Phenome Project, which our Q&A with Lee Hood describes in detail, is one example of what that could look like – an initiative designed from the start with the organizational structure, governance model, and embedded metascience capacity that transformative efforts require.
FAS was founded on the conviction that scientists have a responsibility not just to do science, but to think carefully about how science is organized and to whose benefit. That conviction is as relevant now as it was in 1945. The moonshots we need are within reach. The question is whether we are willing to be as rigorous about how we pursue them as we are about the science itself.
We’ve identified the key ingredients of successful moonshots that meet the moment, and developed recommendations about what future efforts can and should look like.
Complex systems – from ecological to political to socio-technical – rarely change the way we expect.
Federal data is a diverse ecosystem with well over 500,000 datasets – including those tackling Alzheimer’s disease and related dementias (ADRD).
This is a tremendous opportunity to redefine what people expect from government, and in doing so, inspire cities across the country to raise their own ambitions. We are excited to see this initiative lead the way and look forward to cheering your success.