The Future of Large-Scale ScienceBack to table of contents
Opportunities for major new scientific discoveries are on the horizon. To name just a few: gravitational wave observation technologies that will drive innovation; particle physics facilities that will enable breakthroughs in studies of the building blocks of matter itself; and advancements in brain science that will unlock treatments for some of the most devastating diseases and disorders on the planet.
The Future of Gravitational Wave Observations
Advanced long-baseline interferometer construction around the world will provide new capabilities to observe gravitational waves. With the three interferometers (two based at LIGO in the United States and one at Virgo in Italy), localization is provided for about half of all possible locations on the sky; a fourth detector operating simultaneously with these three will allow directional determination of sources for all possible sky locations, thereby facilitating follow-up observations by astronomical telescopes. The United States and India are currently working together to build a detector in India, a collaboration between LIGO and three Indian institutes.64 The United States is providing hardware, data, training, and assistance, while India is providing the site, infrastructure, labor, and materials. The lead agency for India is the Indian Department of Atomic Energy, which is cofunding the construction with the Indian Department of Science and Technology.65 Japan completed construction of its interferometer, KAGRA, in October 2019 and began initial observations in February 2020. With five interferometers located around the world, it becomes much more likely that there will be four operating observatories at any one time.66
The international scientific community is also developing capabilities for considerably more advanced next-generation gravitational wave observatories that could observe gravitational waves from sources all the way back to the Big Bang itself.67 For example, Europe is considering building the Einstein Telescope, for completion in the late 2020s at a cost of between $1 billion and $2 billion; the NSF is providing early design study funding for a third-generation observatory study based in the United States.68 The European Space Agency is also leading development of LISA (Laser Interferometer Space Antenna), a space-based gravitational wave observatory, in partnership with NASA and an international consortium of scientists.69 LISA will operate at low frequencies that cannot be accessed from the ground, thus providing a new capability for discovery. The technical demands of this instrumentation will drive the development of innovating technologies, such as microNewton thrusters to provide precise control of spacecraft position and pointing.
- 64LIGO, “LIGO-India: A Planned Joint India-US Detector.”
- 66Ibid.; CERN Courier, “KAGRA Complete,” January 10, 2020; LIGO, “KAGRA Begins Initial Observations,” March 3, 2020; and B. P. Abbott, R. Abbott, T. D. Abbott, et al., “Exploring the Sensitivity of Next Generation Gravitational Wave Detectors,” Classical and Quantum Gravity 34 (4) (2017).
- 67M. Coleman Miller and Nicolas Yunes, “The New Frontier of Gravitational Waves,” Nature 568 (7753) (2019): 469–476.
- 68Lee Billings, “The Future of Gravitational Wave Astronomy,” Scientific American, February 12, 2016.
- 69European Space Agency, “LISA;” and NASA, “LISA.”
The Future of Particle Accelerators
Advances in particle physics facilities are taking place around the world. The CERN Council, in collaboration with the United States, Canada, and Japan, is working to complete the High-Luminosity LHC within the next ten years. This instrument will achieve luminosity that is ten times greater than that of the current LHC.70 In 2019, the Council also authorized development of the design of a next-generation Future Circular Collider, intended to be the most powerful particle collider in the world.71 Japan is considering hosting the International Linear Collider, which would allow for more in-depth exploration of the Higgs boson, and is discussing collaborative options with the United States and European countries for cost-sharing. China has unveiled planning for a future electron-positron collider that would have a circumference over three times that of the LHC. After ten years of operation, China plans to upgrade the facility to a proton-proton collider with more than seven times the energy of the LHC at its peak energy, similar in concept and scientific reach to the CERN Future Circular Collider.72 The cost estimate for the initial collider is ¥30 billion, or $4.3 billion. Given the significant cost of future high-energy colliders, these facilities will likely require significant international partnership on a scale that exceeds CERN. In this regard, CERN provides a successful model of openness and cooperation among nations.
The Future Circular Collider, currently under study by CERN, would use the existing Large Hadron Collider as an injector accelerator. © by Panagiotis Charitos and the European Organization for Nuclear Research.
Fourth-generation facilities have been built in Brazil, France, and Sweden, with additional synchrotrons planned for China, Japan, and the United States.73 These facilities are investments that can enable diverse and international user communities to advance the frontiers of science over the course of decades. These circular sources are augmented by X-ray free electron lasers, driven by linear accelerators, that produce nine-to-ten orders of magnitude greater peak power in extremely short pulses, enabling structural studies of atomic motion. There are also plans for a multinational African Light Source, which would be the first synchrotron light source on the African continent.74
- 70CERN, “High-Luminosity LHC.”
- 71Davide Castelvecchi, “Next-Generation LHC: CERN Lays Out Plans for €21-Billion Supercollider,” Nature, January 15, 2019; and CERN, “Future Circular Collider.”
- 72Elizabeth Gibney, “Inside the Plans for Chinese Mega-Collider that Will Dwarf the LHC,” Nature, November 23, 2018.
- 73Davide Castelvecchi, “Next-Generation X-Ray Source Fires Up,” Nature 525 (7567) (2015); Herman Winick, “Fourth Generation Light Sources,” Proceedings of the 1997 Particle Accelerator Conference 1 (1997): 37–41; Brazilian Synchrotron Light Laboratory, “History of the Synchrotron Light Sources;” and Robert P. Crease, “China’s Next Big Thing: A New Fourth Generation Synchrotron Facility in Beijing,” Physics World, August 2019.
- 74The African Lightsource, Towards a Lightsource for the African Continent.
The Future of Brain Science
Treatments for neurological diseases and disorders are sorely needed. Stroke and neurodegenerative diseases represent leading causes of death, with 270,000 deaths reported from stroke and Alzheimer’s disease in the United States in 2017.75 However, pharmaceutical companies, initially drawn to neurological research in the 1990s by profitable discoveries of antidepressants and antipsychotics, have been shuttering their neuroscience divisions due to ongoing failures to identify novel therapeutics.76 Federal and philanthropic funding in the United States and international funding for open basic and applied research have generated enthusiasm and promise for a greater understanding of the human brain, as well as the potential for future development of cures and therapeutics for brain-based diseases and disorders.77
As a field more broadly, brain science is undergoing a revolution that will have major implications for networks of international collaborators. The development of groundbreaking technologies is allowing researchers to peer into the workings of the brain like never before. This includes neuroimaging technologies such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and positron emission tomagraphy (PET).78 Guided by theoretical insights in behavioral and cognitive science, the increasing accessibility and accuracy of such technologies is increasing our understanding of the complex neural circuitry supporting reading, learning, action, and emotion.79 Brain-computer interfaces permit people with paralysis to operate machines with just a thought.80 Genome editing, through technologies including CRISPR, allows for precise alterations of cellular function at different developmental times and in distinct cell populations.81 Optogenetic approaches give researchers the ability to control neuronal signaling with the flash of a light, and ongoing clinical trials are attempting to use this technology to restore field of vision.82 Single-cell sequencing has revealed new neuronal cell types never before known to exist.83 Neuronal organoids, which approximate minibrains in a petri dish, can now be easily grown from human skin cells and used for personalized therapeutics and mechanistic studies.84
However, each of these technologies and developments requires a common acceptance of protocols and approaches if researchers are to understand and build upon their colleagues’ discoveries. Further, the use of these technologies remains labor-intensive enough that no one scientist or laboratory can develop a full data set for the entire brain using them; researchers must be able to directly compare their results and pool analyses in order to move forward in a holistic manner.
International networks of brain scientists will need to develop innovative ways of establishing these standards and openly pooling data to advance the field’s understanding. The Brain Cell Data Center (BCDC) at the NIH brings multiple research centers, laboratories, and data repositories together to provide a reference of diverse brain cell types from multiple animal models and humans.85 Although its mission extends beyond the brain to all cell types, the Human Cell Atlas provides an example of an international network of scientists using single-cell sequencing to build another repository.86 Brain scientists have long worked in consortia to advance their studies; this approach will only become more critical in the years to come.
Beyond the challenge of collaborating to leverage a single novel technology, many scientists within the brain science community are simultaneously attempting a second shift: moving toward interdisciplinary research that will bring disparate fields together to understand the brain as a system of systems. For experimentalists, a true understanding of how neurons communicate with each other and give rise to the mind requires contributions from molecular biologists, anatomists, immunologists, bioengineers, psychologists, and experts in brain vasculature, among others. Some research questions require the combined approaches of theorists and experimentalists to find success.
To this end, the United States, through the NIH, NSF, DOE, Defense Advanced Research Projects Agency, Intelligence Advanced Research Projects Activity, and Food and Drug Administration, has crafted a vision for unlocking the mysteries of the brain by means of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative.87 It coordinates awards across ten institutes of the NIH alone.88 The initiative encourages international communication and collaboration at all stages, particularly on areas of shared interests like compatible data sharing approaches.89 In the first five years of the initiative, the NIH invested over $559 million and funded more than five hundred scientists.90 The NSF’s investments have also expanded considerably through their Understanding the Brain activities.91 These investments have led to major breakthroughs, including the development of advanced imaging tools that allow direct measurement of neuronal activity, smarter deep brain stimulation to treat diseases such as Parkinson’s disease, and brain-machine interfaces that allow paralyzed people to operate computers.92
In addition to working through the U.S. government, the BRAIN initiative has partnered with NGOs such as the Allen Institute, the Howard Hughes Medical Institute, the IEEE, and the Kavli and Simons Foundations and with firms including Google and General Electric (GE) to advance its goals.93 The initiative currently has several international partners in Australia, Canada, and Denmark. International scientists are eligible to apply for funding, which has so far totaled $1.8 billion through 2020.94 Long term, the initiative has identified the establishment of international collaborative networks as a key goal, including partnerships with other brain science coalitions such as the Human Brain Project, an EU Flagship program, the China Brain Project, the International Brain Initiative, and the International Neuroethics Society.95
Working across silos can enable scientists to unlock the mysteries of the brain and the mind more rapidly and fully and thus enable new discoveries. Such an approach requires careful collaboration and organization that brings scientists of multiple disciplines together to solve common problems, valuing diverse perspectives. Although interdisciplinary brain science will certainly take place at the level of individual domestic institutions and U.S. initiatives, it will also occur among international endeavors, and the United States should work to partner with these efforts as they develop.
- 75Centers for Disease Control and Prevention, National Center for Health Statistics, “Leading Causes of Death;” and “Stroke as a Neurological Disease,” Nature Reviews Neurology, June 29, 2018.
- 76Jacob Bell, “Big Pharma Backed Away from Brain Drugs. Is a Return in Sight?” BioPharma Dive, January 29, 2020; Ben Adams, “As Amgen Zeroes in on Cancer, Neuroscience Pipeline under the Ax,” Fierce Biotech, October 30, 2019; and Colin Dwyer, “Pfizer Halts Research Into Alzheimer’s and Parkinson’s Treatments,” NPR, January 8, 2018.
- 77For instance, the BRAIN Initiative, the Kavli Foundation, the Human Brain Project, and the China Brain Project.
- 78John W. Krakauer, Asif A. Ghazanfar, Alex Gomez-Marin, et al., “Neuroscience Needs Behavior: Correcting a Reductionist Bias,” Neuron Perspective 93 (3) (2017): 480–490.
- 79Lisa Feldman Barrett and Ajay Bhaskar Satpute, “Large-Scale Brain Networks in Affective and Social Neuroscience: Towards an Integrative Functional Architecture of the Brain,” Current Opinion in Neurobiology 23 (3) (2013): 361–372; and Brian A. Wandell and Rosemary K. Le, “Diagnosing the Neural Circuitry of Reading,” Neuron 96 (2) (2017): 298–311.
- 80BrainGate, “Front Page.”
- 81Angela She, “CRISPR in Neuroscience: How Precision Gene Editing May Unravel How the Brain Works (and Why it Sometimes Doesn’t),” Science in the News, April 6, 2016; and Jon Cohen, “CRISPR, the Revolutionary Genetic ‘Scissors’ Honored by Chemistry Nobel,” Science, October 7, 2020.
- 82Karl Deisseroth, “Optogenetics: 10 Years of Microbial Opsins in Neuroscience,” Nature Neuroscience 18 (9) (2015): 1213–1225; Yi Shen, Robert E. Campbell, Daniel C. Cote, and Marie-Eve Paquet, “Challenges for Therapeutic Applications of Opsin-Based Optogenetic Tools in Humans,” Frontiers in Neural Circuits, July 15, 2020; U.S. National Library of Medicine, clinicaltrials.gov, “RST-001 Phase I/II Trial for Advanced Retinitis Pigmentosa;” and U.S. National Library of Medicine, clinicaltrials.gov, “Dose-escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa (PIONEER).”
- 83Eszter Boldog, Trygve E. Bakken, Rebecca D. Hodge, et al., “Transcriptomic and Morphophysiological Evidence for a Specialized Human Cortical GABAergic Cell Type,” Nature Neuroscience 21 (9) (2018): 1185–1195.
- 84Madeline A. Lancaster and Juergen A. Knoblich, “Generation of Cerebral Organoids from Human Pluripotent Stem Cells,” Nature Protocols 9 (10) (2014): 2329–2340.
- 85National Institutes of Health, The Brain Initiative, “BICCN: Brain Cell Data Center (BCDC).”
- 86Human Cell Atlas.
- 87National Institutes of Health, The BRAIN Initiative, “Overview;” Franklin Orr, “What’s Energy Got to Do With It? New MOU Will Strengthen and Expand Collaborations in Medicine and Public Health,” energy.gov, January 19, 2017; and The BRAIN Initiative, “The BRAIN Initiative: Three Years at the Frontiers of Neuroscience.”
- 88National Institutes of Health, “New NIH BRAIN Initiative Awards Accelerate Neuroscience Discoveries,” October 18, 2019.
- 89National Institutes of Health, “BRAIN 2025 A Scientific Vision,” June 5, 2014; and Thomas R. Insel, Story C. Landis, and Francis S. Collins, “The NIH BRAIN Initiative,” Science 340 (6133) (2013): 687–688.
- 90The BRAIN Initiative, “BRAIN Investment Pays Off.”
- 91National Science Foundation, “Understanding the Brain: The National Science Foundation’s Role in the BRAIN Initiative;” and National Science Foundation, “Understanding the Brain.”
- 92BrainGate; The Picower Institute, “CLARITY;” and The BRAIN Initiative, “BRAIN Investment Pays Off.”
- 93The BRAIN Initiative, “BRAIN Initiative Participants.”
- 94National Institutes of Health, The BRAIN Initiative, “Overview;” and Senate Appropriations Committee, “Summary of H.R. 1865: FY2020 Consolidated Domestic and International Assistance Package.”
- 95Human Brain Project; Mu-min Poo, Jiu-lin Du, Nancy Y. Ip, et al., “China Brain Project: Basic Neuroscience, Brain Diseases, and Brain-Inspired Computer,” Neuron 92 (3) (2016): 591–596; International Brain Initiative; International Neuroethics Society; and S4D4C, “International Dimensions of the EU’s FET Flagships: Large Scale Strategic Research Investments as a Site of De-Facto Science Diplomacy.”