Science is a quest to push the boundaries of what we know and reveal fundamental mysteries of the universe, matter, human life and the mind. But how we break and redefine the limits of science is not with conventional methods that produce conventional research—it is with new tools that enable new discoveries. Inventing tools with cutting-edge innovations—sharper resolving power, greater computational strength, more statistical power, greater acceleration, more precise measurement—continually break the boundaries at the frontier. From developing the gene-editing method CRISPR to rewrite genes, to creating quantum computers to solve problems we otherwise could never do, to harnessing machine learning methods to uncover hidden patterns in massive datasets, the power of our tools is enormous. Creating a new generation of toolmakers is one of the single best ways to invest our time in the future of science. So how do we actually push our limits and accelerate discoveries? To break new ground in any field, we generally first have to spot where our tools run into bottlenecks—and tackle them. It is about amplifying our ability to see, measure and theorise about the world with better lenses. Whether better fighting climate change with cutting-edge carbon-capture methods or better mapping the brain's complexity with more advanced neuroimaging and AI analysis, our progress depends on constantly pushing our tools' boundaries. Here we map out the steps we need to take to expand the top ten most influential discovery tools—from x-ray devices to statistical methods. Researchers best equipped at the edge of science are those who can best see the gaps in our tools and what we know—and test new ones to fill these gaps. This principle—that new tools are the engine of discovery—can be widely applied across science. We also explore deeper questions here: are there fundamental limits to what we can discover in some domains? And what can the future of science look like—and how can we power it with new tools, including AI tools?
Breaking the limits of science largely relies on a simple but powerful principle: breaking the current limits of our best tools and methods. Tackling real bottlenecks facing our tools may not seem exciting at first glance. But it is exactly the cutting-edge research that unlocks new ways to see, measure and uncover the world that are not possible without them. It is about sharpening lasers' focus and tuning, overcoming electron microscopes' depth and clarity constraints, and resolving chromatography's resolution and flow bottlenecks. It means pushing past electrophoresis' size-separation limits, addressing statistics' sample size, scale and power challenges, and exceeding centrifuges' separation and speed thresholds. It is about penetrating x-ray imaging's depth and timing barriers, surpassing spectroscopes' resolution and sensitivity boundaries, and bypassing spectrometers' mass accuracy and range restrictions. It involves boosting advanced thermometers' accuracy and sensitivity, solving space telescopes' sharpness and light-gathering obstacles, and expanding particle accelerators' energy and brightness ceilings. It depends on tackling particle detectors' spatial resolution and noise limits, pushing beyond PCR's sensitivity and mixing barriers, and so much more. It is this cutting-edge research that opens extraordinary new lenses to the world that would catalyse more discoveries than other strategies we have. Each major upgrade has unlocked discoveries that were impossible before—from detecting thousands of exoplanets with more precise spectrometers to decoding entire genomes with more advanced DNA sequencing methods. Each major invention—a better sensor, a faster sequencer, a deeper imager—redraws the map of what science can explore, imagine and understand. This is the core of a new way of thinking about discovery: a buildto-discover strategy. With the new methods-driven discovery theory, we can make an important prediction: developing new methods and tools would be the key catalyser for new discoveries across fields. The best way to predict the pace of new discoveries is commonly looking at the pace at which we scale up, recombine and reinvent our tools—and where and when we do so. After all, waiting for serendipity or revising theories is generally more context-specific, and it is not about more funding but better targeting existing funding and researchers towards tool development (Chapter 6). It is crucial we begin directing much more energy to spotting and fixing the blind spots in what our tools can do. When an experiment stalls or fails, we should turn our attention to why and where the method hits a wall—and tackle the bottleneck. Think of better AI-assisted microscopes that not only image but diagnose disease, make predictions or flag anomalies. Think of better sequencing methods that decode entire genomes in minutes. While science's tools are currently still made in a surprisingly scattered and improvised way by individual researchers and teams, a number of remarkable innovations in methods have been made in recent years. Take biology and chemistry that keep pushing their borders. Click chemistry, invented in 2001 by Barry Sharpless and Morten Meldal and—along with Carolyn Bertozzi—awarded the Nobel prize in 2022, lets scientists click (snap) molecular building blocks together like Lego pieces. This vastly simplifies making complex molecules and has been called 'lego chemistry' . At Scripps Research in California, Sharpless discovered it by building on new methods including hydroxylation methods he invented. With this new technology, scientists can now design cancer drugs and advanced industrial materials more efficiently than ever. Take the mapping of ribosomes that was completed by the Indian-born Venkatraman Ramakrishnan and his colleagues in 2000 using sharper electron-density maps and x-ray crystallography to reveal its structure. The discovery opened the door to producing entirely new antibiotics to fight bacterial infections we face. The gene-editing method CRISPR was discovered by Emmanuelle Charpentier and Jennifer Doudna in 2012 leveraging a powerful new differential RNA sequencing technique. Used today by labs around the world, this method revamped the life sciences, our ability to alter the DNA of plants and animals and drastically advance the fight of cancer. The Neandertal genome was sequenced by Svante Pääbo and his colleagues in 2010—and was awarded the Nobel in 2022. This fascinating breakthrough relied on applying new specialised sequencing methods they developed the previous year to deal with the degraded ancient DNA. In the landmark article published in Science, A draft sequence of the Neandertal genome, Pääbo shined new light on our human origins: humans in Eurasia carry about 2–4% Neandertal DNA. Neandertals were more closely related to present-day Europeans and Asians than present-day Africans. The finding changed how we understand human origins. Take also physics that keeps pushing through the outer edges of science. A supermassive object at the centre of our galaxy—orbited by stars—was discovered in 2002. This extraordinary observation was sparked using the Very Large Telescope built on a mountain in Chile and the Keck Observatory on a mountain in Hawaii—coupled with a powerful new adaptive optics spectrometer. It redefined our understanding of our galaxy and our place in it. And in 2015, gravitational waves were detected using a more sensitive laser interferometer. Each of these breakthrough discoveries pushed a field's boundaries—and won a Nobel prize. Yet researchers have not yet explained how we actually push the boundaries of science. Throughout this book, we have been explaining how new discoveries are preceded by tool innovations that enable a leap in the way we see and measure—and are the factor we can most actively shape. Such tool-powered discovery pushes us to think of scientists not just as question-askers or experimenters, but as extraordinary toolmakers who build the very means to ask and answer bigger questions. Yet as science makes remarkable progress, there are in each generation those who think we essentially already solved the big mysteries. Newton revealed the laws of motion and gravitational force and Maxwell uncovered the nature of electricity, magnetism and light. Mendeleev put the elementary pieces of the periodic table together that make up the basis of chemistry. Darwin and Wallace provided evidence of evolution as the reason why we see so many forms of life on earth—and as the driving principle of biology. Smith described the forces behind the Wealth of Nations and the invisible hand of markets: the division of labour, freedom of trade and pursuit of personal interest that can drive societal benefit. These breakthroughs laid the early foundation of physics, chemistry, biology and economics, and many believed that the big questions in these fields were basically settled. At the end of the 1800s, the laws of motion, gravity, electromagnetism, energy conservation and thermodynamics seemed to explain the entire physical world. Physics looked like it had uncovered all the principles that hold physical reality together. In 1900, Lord Kelvin—one of the most renowned physicists at the time—allegedly said at a meeting at the British Association of Science: 'There is nothing new to be discovered in physics now. All that remains is more and more precise measurement' . But then came the vast breakthroughs of relativity and quantum mechanics at the beginning of the 1900s. They revealed that major pieces of the puzzle explaining physical reality on both the largest and smallest scales were missing. Special relativity introduced a different concept of time and space, while quantum theory revealed a probabilistic, counterintuitive world where particles can act like waves, and outcomes are uncertain until measured. These breakthroughs did not add details, they drastically transformed physics. They gave rise to one of the biggest unsolved puzzles: can quantum theory, the physics of the very small, be unified with relativity theory, the physics of the very large? We still do not know how to tie the two into one framework. String theory is an attempt, but no answer has emerged yet. Many scientists in each generation think we have run into a wall, with only finetuning left to do. But history, again and again, shows they are wrong. Every time we think we have hit the limits or are closer to 'completion' , new surprising instruments and experimental findings unveil new mysteries—and hidden layers of reality we never imagined. From the James Webb Space Telescope that spots ancient galaxies to cutting-edge particle accelerators that probe the building blocks of matter.