or tool—that makes the breakthroughs possible Digging into the data and papers of science's major discoveries across fields and over time, we find a striking and consistent trend. Each discovery-making paper relied on a new method or tool—and the study, including usually experiments, could only be conducted by using it. The strong link is remarkable: analysing science's major discoveries, we find that new breakthroughs are enabled by applying a new method or instrument for the first time to a problem. That is what commonly makes it a breakthrough—it reveals something we could not see, detect, develop or test before, without that method. Let us look first at the turn of the 20th century. At the time, physicists focused on the fascinating newly detected subatomic world. The first subatomic particle discovered was in 1897—the electron. Joseph Thomson unexpectedly detected it using an instrument he improved the previous year: a cathode ray tube. At first, many physicists relied heavily on mathematics—using abstract equations to describe the electron. That changed in 1911 with the invention of the first particle detector that could visually show particle trails: the cloud chamber. For the first time, we could actually see and measure the trails left by charged particles. It was built by Charles Wilson working at Cambridge. With this one groundbreaking instrument, we introduced an entirely new kind of evidence to physics: launching particle physics as an observational science (Picture 1.1 ). Then in 1929, Ernest Lawrence—at just 28—made another extraordinary invention: the first particle accelerator. Working at Berkeley, he designed this new instrument that could propel charged particles to high speeds using electromagnetic fields. Before it, we did not know that many subatomic particles even existed. And without this invention, we would not have discovered the antiproton or uncovered the weak force—that changed how we understand matter and the forces governing physical reality. So even particle physics—often seen as one of science's more theoretical fields—has deep roots in powerful tool innovations that helped make the field possible and transform it into a precise experimental science. S Picture 1.1 The world's first particle detector that visualised particle tracks—Wilson's cloud chamber, 1911. Reproduced from Rolf Kickuth via Wikimedia Commons. Another great leap came in 1952, when Donald Glaser constructed an entirely new kind of particle detector: the bubble chamber. Built at the University of Michigan, it allowed studying particles at much higher energies than before. Together with particle accelerators, this tool was instrumental in the theoretical discovery of quarks in 1964—fundamental particles that make up protons and neutrons. Our ability to observe and measure the smallest units of matter—atoms—was revolutionised with these powerful discovery tools: particle detectors and accelerators. They opened up new layers of reality that were invisible, unknown and unimaginable before—using our bare mind. With them, we could see the evidence unfold before our eyes. And without them, none of these breakthroughs could have been possible. In fact, a range of powerful tools and methods that have made discoveries possible were awarded a Nobel prize for their creation: from particle detectors and accelerators, to x-ray methods, spectroscopes and centrifuges; from advanced microscopes, electrophoresis and statistical methods, to chromatography, the laser, the PCR method and many others. Each of these remarkable tools enabled multiple discoveries—experimental, theoretical and methodological—that in turn won a Nobel, as we see in Figure 1.1 (and Appendix Figure 1.3). Each was designed in one field—like physics—but then triggered discoveries in different fields—like biology, chemistry and medicine. We next zoom further out on this puzzle of how new methods and tools spark breakthroughs. To study it, we trace science's major discoveries—spanning from 1575 to the present—and compare the year each new method or tool was developed with the year the discovery was made using it. It is straightforward to visualise: each new method or tool is shown as a vertical line (│), and each breakthrough made using that method or tool is shown as a dot ( ●) on the same horizontal line—see Figure 1.2. If a new tool triggered multiple discoveries, we see a cluster of dots aligned with that tool's timeline. Take the first particle detector that visualised particle tracks invented in 1911—marked as a vertical line│. It enabled the discovery of the positron in 1932— appearing as a subsequent dot● on the same horizontal line. Or take the invention of x-ray crystallography in 1913 that led to the discovery of DNA's double-helix structure in 1953. The history of science reveals a pattern: discoveries cluster after major new tool innovations that are applied for the first time. Over time, the gap between new Legend Methods and tools (in bold) Resulting discoveries made using them (not in bold) Nobel prize in: Physics Chemistry Medicine Particle accelerator (1929) Particle accelerators for studying atomic nuclei (1932) Transuranium elements (1940) Methods for nuclear magnetic precision measurements (1946) Antiproton (1955) Deep inelastic scattering (1969) Stochastic cooling method (1972) Tau particle (1974) J/psi particle (1974) Weak force (1983) Ultracentrifuge (1924) Catalytic conversion of glycogen (1929) Human leukocyte antigens (1952) Lysosomes (1955) Reverse transcriptase (1970) Regulation of cholesterol metabolism (1973) Particle detector cloud chamber (1911) Coincidence method (1925) Neutron (1932) Positron (1932) Particle detector - Wilson cloud chamber (1932) Synthesis of new radioactive elements (1934) Particle detector - bubble chamber (1952) Particle detector - hydrogen bubble chamber (1959) Neutrino beam method (1962) Symmetry violation in decay of neutral K-mesons (1964) Particle detector - multiwire proportional chamber (1968) X-rays (1895) Characteristic Röntgen radiation (1906) X-ray diffraction by crystals (1912) X-ray spectroscopy (1913) Improved X-ray spectroscopy (1916) Exclusion (Pauli) principle (1925) Mutations via x-ray radiation (1927) Diffraction of electrons by crystals (1927) Nature of the chemical bond (1939) Structure of penicillin and vitamin B12 (1946) Structure of DNA molecule (1953) Structures of globular proteins (1959) X-ray telescope and cosmic x-ray sources (1962) Spectrograph (1859)*Doppler effect in canal rays (1905) Nature of isotopes (1913) Stark effect (1914) Mass spectrography and isotopes (1919) Molecular orbitals (1925) Neutron spectroscopy (1955) Method of crossed molecular beams (1972) NMR spectroscopy for protein structure (1985) Femtochemistry (1988) First exoplanet (1995) Frequency comb technique in spectroscopy (2000) Supermassive compact object at centre of galaxy (2002) 1850 1900 1925 1950 1975 2000 Figure 1.1 New central methods and tools bring about new discoveries The technical notes below the figures throughout the book are just that—technical notes. They only offer additional details but can be skipped to stay with the main story. The data shown in this figure highlight nobel-prize-winning methods and tools developed before 1930, and each has led to at least four later nobel-prize discoveries. (Those developed after 1930 are shown in Appendix Figure 1.3.) The year listed refers to when the tool was created and when the resulting discoveries emerged. ∗One exception is the spectrograph, invented in 1859 to study the spectrum of light; although it did not receive a Nobel prize, it was used to make five discoveries and more advanced spectroscopes that were later awarded a Nobel. Due to space limitations, a number of nobel-prize discoveries made using x-ray methods and spectrometers could not be included in this figure; but they are included in all other relevant figures throughout the book. S tools and new discoveries is reducing. (The horizontal lines are getting shorter over time in Figure 1.2.) We explain why later in the chapter. But this time dimension is important: the earlier we develop transformative tools, the sooner we catalyse new breakthroughs. Surprisingly, we find this key pattern across science—that new methods drive new discoveries by making novel findings possible. We find that the pattern is consistent across science's major discoveries spanning throughout fields—from physics and chemistry to medicine and economics—and it is consistent across history— from past centuries to contemporary science (Appendix Figure 1.5). It holds across experimental discoveries, such as uncovering the hepatitis A virus with an electron microscope. It applies across theoretical breakthroughs, such as developing Planck's quantum hypothesis based on experiments using spectrometers and bolometers, and on mathematical methods. And it holds across method discoveries, such as creating gas chromatography that vastly extended chromatography. As we move through the chapter, we will unpack this key finding. 1600 1700 1800 1900 2000 Year that main method/instrument was developed 1600 1700 1800 1900 2000 Year that discovery was made using it telescope, 1608 distance to sun, 1672 motion of stars, 1719 galaxies, 1750 thermometer, 1714 ideal gas law/Charles's law, 1787 nature of heat, 1786 particle detector - cloud chamber, 1911 positron, 1932 Methods and instruments developed ( ), and the discoveries made using them ( ) Figure 1.2 We trigger new discoveries by using a new central method or tool needed to make the breakthrough The data reflect science's 734 major discoveries since 1575—including all nobel-prize discoveries across science. Examples are shown for three tools. Each new method or tool is marked as a vertical line (│) that all fall along the diagonal 45-degree line. The year a new method or tool is created is closely linked to the year a discovery followed—with a correlation of 92%. When we split and compare the data—exploring only nobel-prize discoveries and only major non-nobel discoveries over the same time period—the pattern remains strong: a correlation of 88% and 81%, respectively. This highlights that the pattern is not driven by just nobel-prize discoveries but is consistent for both groups of discoveries. 30 T HE ENGINE OF SCIENTIFIC DISCOVERY Few tools have transformed science as drastically as the microscope—our prime example of a powerful discovery tool. Microscopes have uncovered about 7% of science's major discoveries—an enormous contribution to scientific progress from a single kind of instrument. This spans from the first microscope in 1590, which inspired later ones such as the achromatic (colour-corrected) microscope in 1841, to scanning tunneling microscopes in the 20th century. Each generation of microscopes are not just technical upgrades, they are scientific catalysts—each one revealing deeper layers of reality. It all started with Zacharias Janssen—a Dutch eyeglass maker who created the first microscope using a simple converging lens of glass beads. This groundbreaking invention marked a turning point in tool-driven science: we had—for the first time ever—a tool in our hands that enabled us to look through its lens to uncover an invisible world. Cells, bacteria and mitochondria were revealed without even searching for them. No one hypothesised or imagined they could even exist. But these unexpected discoveries changed how we understand human life itself. Take the British Robert Hooke who uncovered cells in 1665. By looking through his new 300-power microscope, designed in 1662, he observed a honeycomb-like pattern in a piece of cork: he discovered cells. His book Micrographia—the first important work on microscopy—launched and popularised the microscope into wider scientific use. It also helped establish a concept at the core of biology today: the cell as the basic unit of life. As lens systems improved and magnification increased, optical bottlenecks were broken—again and again. The Nobel prize has since been awarded for developing different powerful microscopes—from the crystallographic electron microscope developed in 1962 and the scanning tunneling microscope in 1982 to an advanced single-molecule microscope in 2006. Take the scanning tunneling microscope—that allows observing and manipulating matter at the level of individual atoms, like no instrument could before. This breakthrough helped launch nanotechnology. Such powerful tools do not just extend our sight—they reset the boundaries of what is observable and thinkable. And they are not isolated advances. So far, about 30 nobelprize discoveries have been sparked using a nobel-prize-winning microscope as the central tool. The electron microscope alone makes up about half of them: from the discovery of cell structure in 1945 to the discovery of ribosomes in 1955. This pushes the electron microscope—as a unifying tool—into the foreground of these breakthroughs it made possible across fields; while it pushes a particular theory, research team or largescale funding into the background of these microscope-driven breakthroughs —Box 1.1 (Appendix Figure 1.3). Box 1.1 How Ernst Ruska built the electron microscope—catalysing breakthroughs across biology, medicine and physics Only a handful of breakthrough inventions are as exciting and transformational as the electron microscope. It is one of the ten central methods and tools most used to make nobel-prize discoveries. Before it, many microorganisms, molecules, S v iruses and nanoparticles were often beyond the reach of any lens—and a mystery. After it, we could observe, study and begin to understand these hidden worlds in the extraordinary detail it offered. The story traces back to the German Ernst Ruska. Ruska said that as a child, he was inspired by his 'father's big Zeiss microscope … [who] sometimes demonstrated to us interesting objects under the microscope' . So how did he exactly develop the electron microscope? The design is straightforward: he realised that improved magnetic coils can be used as a lens for electron beams—and such an electron lens can be applied to depict images of miniscule objects on a fluorescent screen by pointing the lens towards them. In other words, irradiating extremely small objects with electrons. He then linked two electron lenses to create a primitive microscope—that he kept improving (Picture 1.2). Picture 1.2 Ruska's instrument, 1933. Reproduced from Nobel Prize 1986a. This new tool could magnify—for the first time—far beyond any conventional light microscope: achieving magnification of up to 12,000 times. When Ruska designed the first prototypes between 1931 and 1933, he was an unpaid PhD student at the Technical University of Berlin. He did get a modest stipend of 100 Reichsmarks a month in the second half of 1933 to improve its design—and he completed it in November. It turned out to be a highly efficient and very lowcost instrument at 500 Reichsmarks in 1933 (about 2800 US$ in 2025 prices). Remarkably, he built the most powerful microscope yet invented at the time without large funding, a large team or a large research lab—a pattern we will see across a number of science's most important methods and tools. After its creation, Ruska went to work at Siemens, where he spent two decades developing commercial electron microscopes. In the meanwhile, his extraordinary tool unlocked over a dozen major discoveries—and it completely transformed biology. Despite the impact, 32 T HE ENGINE OF SCIENTIFIC DISCOVERY R uska received delayed recognition: he was awarded the Nobel in 1986—53 years after his breakthrough. An astonishing fact for 'one of the most important inventions' not just of the century but the history of science. After zooming in on this powerful instrument, we now zoom back out to explore the broad patterns across science. Next, when we trace science's biggest discoveries over time, a clear trend emerges: in the decades when we develop more major new methods and tools, more major discoveries follow using them. It is not random. It is a consistent pattern that holds across time periods—as visualised in Figure 1.3. Around the turn of the 20th century, the pace of tool innovation accelerated quickly. In fact, the first half of the 20th century stands out as an extremely productive era for major method advances across fields—spanning everything from x-ray crystallography to new statistical methods that transformed fields (explored in more detail in Appendix Figure 1.6). 0 20 40 60 # of new methods/tools and discoveries 1800 1820 1840 1860 1880 1900 1920 1940 1960 1980 2000 2020 Methods/tools developed to make the discoveries Discoveries Figure 1.3 Trends in new central methods and tools closely follow trends in discoveries The data show science's 653 major discoveries made since 1800—and include all nobel-prize discoveries—and track how many central methods/tools and discoveries emerged in each time period. In fact, across all Nobel prizes, there is an average 21-year delay between making the prize-winning discovery and receiving the award. New methods and new discoveries are not decreasing in the past few decades—but trends reflect the delay in the scientific community recognising major discoveries (Figure 1.3). Take biology. The entire human genome—made up of three billion letters of our genetic code— was mapped in 2003. This enormous feat was made possible by powerful new tools such as automated DNA sequencing and sequence-tagged site maps. Then the groundbreaking new method for gene editing, CRISPR, was discovered in 2012 by the French Emmanuelle Charpentier and American Jennifer Doudna. With it, we can S change the DNA of plants, animals and even human cells with precision—offering new hope and solutions for treating genetic diseases and cancers. Or take physics. We detected gravitational waves for the first time in 2015 after upgrading the Laser Interferometer Gravitational-Wave Observatory (LIGO), a massive laser interferometer, in the same year. This proved that space can vibrate and show ripples in spacetime. In astronomy, new high-magnification telescopes have discovered thousands of planets beyond our solar system since 1995—increasing the possibility of finding other life in our universe. Then there is particle physics: the world's biggest particle accelerator, the large hadron collider, was built by CERN on the French-Swiss border, 175 metres underground. In 2012, it revealed a new particle, the Higgs boson, deepening our understanding of the nature of matter. With many new discoveries across fields, we do not see new breakthroughs slowing down—a topic we return to later.