Protein “Big Bang” Reveals Molecular Makeup for Medicine and Bioengineering Applications
Protein “Big Bang” Reveals Molecular Makeup for Medicine and Bioengineering Applications
Gustavo Caetano-Anollés Surrounded by Depiction of Molecular Networks

Research by Gustavo Caetano-Anollés and Fayez Aziz, University of Illinois, reveals a “big bang” during evolution of protein subunits known as domains. The team looked for protein relationships and domain recruitment into proteins over 3.8 billion years across all taxonomic units. Their results could have implications for vaccine development and disease management. Credit: Fred Zwicky, University of Illinois

Proteins have been quietly taking over our lives since the COVID-19 pandemic began. We’ve been living at the whim of the virus’s so-called “spike” protein, which has mutated dozens of times to create increasingly deadly variants. But the truth is, we have always been ruled by proteins. At the cellular level, they’re responsible for pretty much everything.

Proteins are so fundamental that DNA – the genetic material that makes each of us unique – is essentially just a long sequence of protein blueprints. That’s true for animals, plants, fungi, bacteria, archaea, and even viruses. And just as those groups of organisms evolve and change over time, so too do proteins and their component parts.

A new study from University of Illinois researchers, published in Scientific Reports, maps the evolutionary history and interrelationships of protein domains, the subunits of protein molecules, over 3.8 billion years.

“Knowing how and why domains combine in proteins during evolution could help scientists understand and engineer the activity of proteins for medicine and bioengineering applications. For example, these insights could guide disease management, such as making better vaccines from the spike protein of COVID-19 viruses,” says Gustavo Caetano-Anollés, professor in the Department of Crop Sciences, affiliate of the Carl R. Woese Institute for Genomic Biology at Illinois, and senior author on the paper.

Caetano-Anollés has studied the evolution of COVID mutations since the early stages of the pandemic, but that timeline represents a vanishingly tiny fraction of what he and doctoral student Fayez Aziz took on in their current study.

The researchers compiled sequences and structures of millions of protein sequences encoded in hundreds of genomes across all taxonomic groups, including higher organisms and microbes. They focused not on whole proteins, but instead on structural domains.

“Most proteins are made of more than one domain. These are compact structural units, or modules, that harbor specialized functions,” Caetano-Anollés says. “More importantly, they are the units of evolution.”

After sorting proteins into domains to build evolutionary trees, they set to work building a network to understand how domains have developed and been shared across proteins throughout billions of years of evolution.

“We built a time series of networks that describe how domains have accumulated and how proteins have rearranged their domains through evolution. This is the first time such a network of ‘domain organization’ has been studied as an evolutionary chronology,” Fayez Aziz says. “Our survey revealed there is a vast evolving network describing how domains combine with each other in proteins.”

Each link of the network represents a moment when a particular domain was recruited into a protein, typically to perform a new function.

“This fact alone strongly suggests domain recruitment is a powerful force in nature,” Fayez Aziz says. The chronology also revealed which domains contributed important protein functions. For example, the researchers were able to trace the origins of domains responsible for environmental sensing as well as secondary metabolites, or toxins used in bacterial and plant defenses.

The analysis showed domains started to combine early in protein evolution, but there were also periods of explosive network growth. For example, the researchers describe a “big bang” of domain combinations 1.5 billion years ago, coinciding with the rise of multicellular organisms and eukaryotes, organisms with membrane-bound nuclei that include humans.

The existence of biological big bangs is not new. Caetano-Anollés’ team previously reported the massive and early origin of metabolism, and they recently found it again when tracking the history of metabolic networks.

The historical record of a big bang describing the evolutionary patchwork of proteins provides new tools to understand protein makeup.

“This could help identify, for example, why structural variations and genomic recombinations occur often in SARS-CoV-2,” Caetano-Anollés says.

He adds that this new way of understanding proteins could help prevent pandemics by dissecting how virus diseases originate. It could also help mitigate disease by improving vaccine design when outbreaks occur.

Reference: “Evolution of networks of protein domain organization” by M. Fayez Aziz and Gustavo Caetano-Anollés, 8 June 2021, Scientific Reports.
DOI: 10.1038/s41598-021-90498-8

The work was supported by the National Science Foundation and the U.S. Department of Agriculture.

The Department of Crop Sciences is in the College of Agricultural, Consumer and Environmental Sciences at the University of Illinois.

NASA’s NEOWISE Asteroid-Hunting Space Telescope Gets Two-Year Mission Extension
NASA’s NEOWISE Asteroid-Hunting Space Telescope Gets Two-Year Mission Extension
Wide field Infrared Survey Explorer

Artist’s concept of NASA’s WISE (Wide-field Infrared Survey Explorer) spacecraft, which was an infrared-wavelength astronomical space telescope active from December 2009 to February 2011. In September 2013 the spacecraft was assigned a new mission as NEOWISE to help find near-Earth asteroids and comets. Credits: NASA/JPL-Caltech

NEOWISE has provided an estimate of the size of over 1,850 near-Earth objects, helping us better understand our nearest solar system neighbors.

For two more years, NASA’s Near-Earth Object Wide-field Infrared Survey Explorer (NEOWISE) will continue its hunt for asteroids and comets – including objects that could pose a hazard to Earth. This mission extension means NASA’s prolific near-Earth object (NEO) hunting space telescope will continue operations until June 2023.

“At NASA, we’re always looking up, surveying the sky daily to find potential hazards and exploring asteroids to help unlock the secrets of the formation of our solar system,” said NASA Administrator Bill Nelson. “Using ground-based telescopes, over 26,000 near-Earth asteroids have already been discovered, but there are many more to be found. We’ll enhance our observations with space-based capabilities like NEOWISE and the future, much more capable NEO Surveyor to find the remaining unknown asteroids more quickly and identify potentially-hazardous asteroids and comets before they are a threat to us here on Earth.”

Originally launched as the Wide-field Infrared Survey Explorer (WISE) mission in December 2009, the space telescope surveyed the entire sky in infrared wavelengths, detecting asteroids, dim stars, and some of the faintest galaxies visible in deep space. WISE completed its primary mission when it depleted its cryogenic coolant and it was put into hibernation in February 2011. Observations resumed in December 2013 when the space telescope was repurposed by NASA’s Planetary Science Division as “NEOWISE” to identify asteroids and comets throughout the solar system, with special attention to those that pass close to Earth’s orbit.

“NEOWISE provides a unique and critical capability in our global mission of planetary defense, by allowing us to rapidly measure the infrared emission and more accurately estimate the size of hazardous asteroids as they are discovered,” said Lindley Johnson, NASA’s Planetary Defense Officer and head of the Planetary Defense Coordination Office (PDCO) at NASA Headquarters in Washington. “Extending NEOWISE’s mission highlights not only the important work that is being done to safeguard our planet, but also the valuable science that is being collected about the asteroids and comets further out in space.”

Comet NEOWISE Tucson

Comet NEOWISE—which was Discovered on March 27, 2020, by NASA’s Near-Earth Object Wide-field Infrared Survey Explorer (NEOWISE) mission—captured on July 6, 2020, above the northeast horizon just before sunrise in Tucson. Credit: Vishnu Reddy

As asteroids are heated by the Sun, they warm up and release this heat as faint infrared radiation. By studying this infrared signature, scientists can reveal the size of an asteroid and compare it to the measurements of observations made by optical telescopes on the ground. This information can help us understand how reflective its surface is, while also providing clues as to its composition.

To date, NEOWISE has provided an estimate of the size of over 1,850 NEOs, helping us better understand our nearest solar system neighbors. As of March 2021, the mission has made 1,130,000 confirmed infrared observations of approximately 39,100 objects throughout the solar system since its restart in 2013. Mission data is shared freely by the IPAC/Caltech-led archive and the data has contributed to over 1,600 peer-reviewed studies. The University of Arizona is also a key partner of the NEOWISE mission as the home institution of the NEOWISE principal investigator, Amy Mainzer, who is a professor of planetary science at the University’s Lunar and Planetary Laboratory.

Among its many accomplishments after its reactivation, NEOWISE also discovered Comet NEOWISE, which was named after the mission and dazzled observers worldwide in 2020.

NEOWISE’s replacement, the next-generation NEO Surveyor, is currently scheduled to launch in 2026, and will greatly expand on what we have learned, and continue to learn, from NEOWISE.

“NEOWISE has taught us a lot about how to find, track, and characterize Earth-approaching asteroids and comets using a space-based infrared telescope,” said Mainzer. “The mission serves as an important precursor for carrying out a more comprehensive search for these objects using the new telescope we’re building, the NEO Surveyor.” Mainzer is also the lead of the NEO Surveyor mission.

The NEOWISE project is managed by NASA’s Jet Propulsion Laboratory in Southern California, a division of Caltech, and the University of Arizona, supported by NASA’s PDCO.

Diet Rich in Omega 3 Fatty Acids May Help Reduce Migraine Headaches
Diet Rich in Omega 3 Fatty Acids May Help Reduce Migraine Headaches

Food Rich in Omega 3

Trial provides ‘grounds for optimism’ for many people with persistent headaches and those who care for them.

Eating a diet rich in omega 3 (n-3) fatty acids reduces the frequency of headaches compared with a diet with normal intake of omega 3 and omega 6 (n-6) fatty acids, finds a study published by The BMJ today (June 30, 2021).

Modern industrialized diets tend to be low in omega 3 fatty acids and high in omega 6 fatty acids. These fatty acids are precursors to oxylipins — molecules involved in regulating pain and inflammation.

Oxylipins derived from omega 3 fatty acids are associated with pain-reducing effects, while oxylipins derived from omega 6 fatty acids worsen pain and can provoke migraine. But previous studies evaluating omega 3 fatty acid supplements for migraine have been inconclusive.

So a team of US researchers wanted to find out whether diets rich in omega 3 fatty acids would increase levels of the pain-reducing 17-hydroxydocosahexaenoic acid (17-HDHA) and reduce the frequency and severity of headaches.

Their results are based on 182 patients at the University of North Carolina, USA (88% female; average age 38 years) with migraine headaches on 5-20 days per month who were randomly assigned to one of three diets for 16 weeks.

The control diet included typical levels of omega 3 and omega 6 fatty acids. Both interventional diets raised omega 3 fatty acid intake. One kept omega 6 acid intake the same as the control diet, and the other concurrently lowered omega 6 acid intake.

During the trial, participants received regular dietary counseling and access to online support information. They also completed the headache impact test (HIT-6) — a questionnaire assessing headache impact on quality of life. Headache frequency was assessed daily with an electronic diary.

Over the 16 weeks, both interventional diets increased 17-HDHA levels compared with the control diet, and while HIT-6 scores improved in both interventional groups, they were not statistically significantly different from the control group.

However, headache frequency was statistically significantly decreased in both intervention groups.

The high omega 3 diet was associated with a reduction of 1.3 headache hours per day and two headache days per month. The high omega 3 plus low omega 6 diet group saw a reduction of 1.7 headache hours per day and four headache days per month, suggesting additional benefit from lowering dietary omega-6 fatty acid.

Participants in the intervention groups also reported shorter and less severe headaches compared with those in the control group.

This was a high quality, well designed trial, but the researchers do point to some limitations, such as the difficulty for patients to stick to a strict diet and the fact that most participants were relatively young women so results may not apply to children, older adults, men, or other populations.

“While the diets did not significantly improve quality of life, they produced large, robust reductions in frequency and severity of headaches relative to the control diet,” they write.

“This study provides a biologically plausible demonstration that pain can be treated through targeted dietary alterations in humans. Collective findings suggest causal mechanisms linking n-3 and n-6 fatty acids to [pain regulation], and open the door to new approaches for managing chronic pain in humans,” they conclude.

These results support recommending a high omega 3 diet to patients in clinical practice, says Rebecca Burch at the Brigham and Women’s Hospital, in a linked editorial.

She acknowledges that interpretation of this study’s findings is complex, but points out that trials of recently approved drugs for migraine prevention reported reductions of around 2-2.5 headache days per month compared with placebo, suggesting that a dietary intervention can be comparable or better.

What’s more, many people with migraine are highly motivated and interested in dietary changes, she adds. These findings “take us one step closer to a goal long sought by headache patients and those who care for them: a migraine diet backed up by robust clinical trial results.”

References:

“Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial” 30 June 2021, The BMJ.
DOI: 10.1136/bmj.n1448

“Dietary omega 3 fatty acids for migraine” 30 June 2021, The BMJ.
DOI: 10.1136/bmj.n1535

Funding: National Institutes of Health (NIH); National Center for Complementary and Integrative Health (NCCIH)

Making Seawater Drinkable in Minutes: A New Alternative Desalination Membrane
Making Seawater Drinkable in Minutes: A New Alternative Desalination Membrane
Co Axial Electrospinning Device Schematic

Schematic of co-axial electrospinning device. Credit: Elsevier

A new alternative seawater desalination membrane to produce drinking water.

According to the World Health Organization, about 785 million people around the world lack a clean source of drinking water. Despite the vast amount of water on Earth, most of it is seawater and freshwater accounts for only about 2.5% of the total. One of the ways to provide clean drinking water is to desalinate seawater. The Korea Institute of Civil Engineering and Building Technology (KICT) has announced the development of a stable performance electrospun nanofiber membrane to turn seawater into drinking water by membrane distillation process.

Membrane wetting is the most challenging issue in membrane distillation. If a membrane exhibits wetting during membrane distillation operation, the membrane must be replaced. Progressive membrane wetting has been especially observed for long-term operations. If a membrane gets fully wetted, the membrane leads to inefficient membrane distillation performance, as the feed flow through the membrane leading to low-quality permeate.

A research team in KICT, led by Dr. Yunchul Woo, has developed co-axial electrospun nanofiber membranes fabricated by an alternative nano-technology, which is electrospinning. This new desalination technology shows it has the potential to help solve the world’s freshwater shortage. The developed technology can prevent wetting issues and also improve the long-term stability in membrane distillation process. A three-dimensional hierarchical structure should be formed by the nanofibers in the membranes for higher surface roughness and hence better hydrophobicity.

Co-Axial Electrospun Nanofiber Membrane

Merits of co-axial electrospun nanofiber membrane. Credit: Elsevier

The co-axial electrospinning technique is one of the most favorable and simple options to fabricate membranes with three-dimensional hierarchical structures. Dr. Woo’s research team used poly(vinylidene fluoride-co-hexafluoropropylene) as the core and silica aerogel mixed with a low concentration of the polymer as the sheath to produce a co-axial composite membrane and obtain a superhydrophobic membrane surface. In fact, silica aerogel exhibited a much lower thermal conductivity compared with that of conventional polymers, which led to increased water vapor flux during the membrane distillation process due to a reduction of conductive heat losses.

Most of the studies using electrospun nanofiber membranes in membrane distillation applications operated for less than 50 hours although they exhibited a high water vapor flux performance. On the contrary, Dr. Woo’s research team applied the membrane distillation process using the fabricated co-axial electrospun nanofiber membrane for 30 days, which is 1 month.

The co-axial electrospun nanofiber membrane performed a 99.99% salt rejection for 1 month. Based on the results, the membrane operated well without wetting and fouling issues, due to its low sliding angle and thermal conductivity properties. Temperature polarization is one of the significant drawbacks in membrane distillation. It can decrease water vapor flux performance during membrane distillation operation due to conductive heat losses. The membrane is suitable for long-term membrane distillation applications as it possesses several important characteristics such as, low sliding angle, low thermal conductivity, avoiding temperature polarization, and reduced wetting and fouling problems whilst maintaining super-saturated high water vapor flux performance.

Dr. Woo’s research team noted that it is more important to have a stable process than a high water vapor flux performance in a commercially available membrane distillation process. Dr. Woo said that “the co-axial electrospun nanofiber membrane have strong potential for the treatment of seawater solutions without suffering from wetting issues and may be the appropriate membrane for pilot-scale and real-scale membrane distillation applications.”

Reference: “Co-axially electrospun superhydrophobic nanofiber membranes with 3D-hierarchically structured surface for desalination by long-term membrane distillation” by Yun Chul Woo, Minwei Yao, Wang-Geun Shim, Youngjin Kim, Leonard D. Tijing, Bumsuk Jung, Seung-Hyun Kim and Ho Kyong Shon, 4 January 2021, Journal of Membrane Science.
DOI: 10.1016/j.memsci.2020.119028

The Korea Institute of Civil Engineering and Building Technology (KICT) is a government-sponsored research institute established to contribute to the development of Korea’s construction industry and national economic growth by developing source and practical technology in the fields of construction and national land management.

This research was supported by an internal grant (20200543-001) from the KICT, Republic of Korea. The outcomes of this project were published in the international journal, Journal of Membrane Science, a renowned international journal in the polymer science field (IF: 7.183 and Rank #3 of the JCR category) in April 2021.

Analysis of Thousands of Drugs Reveals Potential New COVID-19 Antivirals
Analysis of Thousands of Drugs Reveals Potential New COVID-19 Antivirals

Doctors Science Defeating Coronavirus

Researchers at the Francis Crick Institute and University of Dundee have screened thousands of drug and chemical molecules and identified a range of potential antivirals that could be developed into new treatments for COVID-19 or in preparation for future coronavirus outbreaks.

While COVID-19 vaccines are being rolled out, there are still few drug options that can be used to treat patients with the virus, to reduce symptoms and speed up recovery time. These treatments are especially important for groups where the vaccines are less effective, such as some patients with blood cancers.

In a series of seven papers, published today (July 2, 2021) in the Biochemical Journal, the scientists identified 15 molecules which inhibit the growth of SARS-CoV-2 by blocking different enzymes involved in its replication.

The researchers developed and ran tests for around 5,000 molecules provided by the Crick’s High Throughput Screening team to see if any of these effectively blocked the functioning of any of seven SARS-CoV-2 enzymes. The tests were based on fluorescent changes with a special imaging tool detecting if enzymes had been affected.

They then validated and tested the potential inhibitors against SARS-CoV-2 in the lab, to determine if they effectively slowed viral growth. The team found at least one inhibitor for all seven enzymes.

Three of the molecules identified are existing drugs, used to treat other diseases. Lomeguatrib is used in melanoma and has few side-effects, suramin is a treatment for African sleeping sickness and river blindness and trifluperidol is used in cases of mania and schizophrenia. As there is existing safety data on these drugs, it may be possible to more quickly develop these into SARS-CoV-2 antivirals.

John Diffley, lead author of the papers and associate research director and head of the Chromosome Replication Laboratory at the Crick, said: “We’ve developed a chemical toolbox of information about potential new COVID-19 drugs. We hope this attracts attention from scientists with the drug development and clinical expertise needed to test these further, and ultimately see if any could become safe and effective treatments for COVID-19 patients.”

The 15 molecules were also tested in combination with remdesivir, an antiviral being used to treat patients with COVID-19. Four of these, all which target the SARS-CoV-2 enzyme Nsp14 mRNA Cap methyltransferase, were found to improve the effectiveness of this antiviral in lab tests.

The scientists now plan to run tests to see if any pairing of the 15 molecules they identified decrease the virus’ growth more than if they are used alone. Targeting enzymes involved in virus replication could also help prepare for future viral pandemics.

“Proteins on the outside of viruses evolve rapidly but within different classes of viruses are well conserved proteins that change very little with time,” adds John.

“If we can develop drugs that inhibit these proteins, in the situation of a future pandemic, they could provide a valuable first line of defense, before vaccines become available.”

References:

“Identification of SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of the nsp14 RNA Cap Methyltransferase” by Basu, S. et al., 2 July 2021, Biochemical Journal.
DOI: 10.1042/BCJ20210219

“Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of nsp5 Main Protease” by Milligan, J. et al., 2 July 2021, Biochemical Journal.
DOI: 10.1042/BCJ20210197

“Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp12/7/8 RNA-dependent RNA Polymerase” by Bertolin, A. et al., 2 July 2021, Biochemical Journal.
DOI: 10.1042/BCJ20210200

“Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp13 Helicase” by Zeng, J. et al., 2 July 2021, Biochemical Journal.
DOI: 10.1042/BCJ20210201

“Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp3 Papain-like Protease” by Lim, CT. et al., 2 July 2021, Biochemical Journal.
DOI: 10.1042/BCJ20210244

“Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp15 Endoribonuclease” by Canal, B. et al., 2 July 2021, Biochemical Journal.
DOI: 10.1042/BCJ20210199

“Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp14/nsp10 Exoribonuclease” by Canal, B. et al., 2 July 2021, Biochemical Journal.
DOI: 10.1042/BCJ20210198

The Francis Crick Institute is a biomedical discovery institute dedicated to understanding the fundamental biology underlying health and disease. Its work is helping to understand why disease develops and to translate discoveries into new ways to prevent, diagnose and treat illnesses such as cancer, heart disease, stroke, infections, and neurodegenerative diseases.

An independent organization, its founding partners are the Medical Research Council (MRC), Cancer Research UK, Wellcome, UCL (University College London), Imperial College London, and King’s College London.

The Crick was formed in 2015, and in 2016 it moved into a brand new state-of-the-art building in central London which brings together 1500 scientists and support staff working collaboratively across disciplines, making it the biggest biomedical research facility under a single roof in Europe.

Hawking’s Black Hole Theorem Confirmed Observationally for the First Time
Hawking’s Black Hole Theorem Confirmed Observationally for the First Time
Two Black Holes Collide Merge

An artist’s impression of two black holes about to collide and merge.

Study offers evidence, based on gravitational waves, to show that the total area of a black hole’s event horizon can never decrease.

There are certain rules that even the most extreme objects in the universe must obey. A central law for black holes predicts that the area of their event horizons — the boundary beyond which nothing can ever escape — should never shrink. This law is Hawking’s area theorem, named after physicist Stephen Hawking, who derived the theorem in 1971.

Fifty years later, physicists at MIT and elsewhere have now confirmed Hawking’s area theorem for the first time, using observations of gravitational waves. Their results appear today (July 1, 2021) in Physical Review Letters.

In the study, the researchers take a closer look at GW150914, the first gravitational wave signal detected by the Laser Interferometer Gravitational-wave Observatory (LIGO), in 2015. The signal was a product of two inspiraling black holes that generated a new black hole, along with a huge amount of energy that rippled across space-time as gravitational waves.

If Hawking’s area theorem holds, then the horizon area of the new black hole should not be smaller than the total horizon area of its parent black holes. In the new study, the physicists reanalyzed the signal from GW150914 before and after the cosmic collision and found that indeed, the total event horizon area did not decrease after the merger — a result that they report with 95 percent confidence.

Collision of Two Black Holes GW150914

Physicists at MIT and elsewhere have used gravitational waves to observationally confirm Hawking’s black hole area theorem for the first time. This computer simulation shows the collision of two black holes that produced the gravitational wave signal, GW150914. Credit: Simulating eXtreme Spacetimes (SXS) project. Credit: Courtesy of LIGO

Their findings mark the first direct observational confirmation of Hawking’s area theorem, which has been proven mathematically but never observed in nature until now. The team plans to test future gravitational-wave signals to see if they might further confirm Hawking’s theorem or be a sign of new, law-bending physics.

“It is possible that there’s a zoo of different compact objects, and while some of them are the black holes that follow Einstein and Hawking’s laws, others may be slightly different beasts,” says lead author Maximiliano Isi, a NASA Einstein Postdoctoral Fellow in MIT’s Kavli Institute for Astrophysics and Space Research. “So, it’s not like you do this test once and it’s over. You do this once, and it’s the beginning.”

Isi’s co-authors on the paper are Will Farr of Stony Brook University and the Flatiron Institute’s Center for Computational Astrophysics, Matthew Giesler of Cornell University, Mark Scheel of Caltech, and Saul Teukolsky of Cornell University and Caltech.

An age of insights

In 1971, Stephen Hawking proposed the area theorem, which set off a series of fundamental insights about black hole mechanics. The theorem predicts that the total area of a black hole’s event horizon — and all black holes in the universe, for that matter — should never decrease. The statement was a curious parallel of the second law of thermodynamics, which states that the entropy, or degree of disorder within an object, should also never decrease.

The similarity between the two theories suggested that black holes could behave as thermal, heat-emitting objects — a confounding proposition, as black holes by their very nature were thought to never let energy escape, or radiate. Hawking eventually squared the two ideas in 1974, showing that black holes could have entropy and emit radiation over very long timescales if their quantum effects were taken into account. This phenomenon was dubbed “Hawking radiation” and remains one of the most fundamental revelations about black holes.

“It all started with Hawking’s realization that the total horizon area in black holes can never go down,” Isi says. “The area law encapsulates a golden age in the ’70s where all these insights were being produced.”

Hawking and others have since shown that the area theorem works out mathematically, but there had been no way to check it against nature until LIGO’s first detection of gravitational waves.

Hawking, on hearing of the result, quickly contacted LIGO co-founder Kip Thorne, the Feynman Professor of Theoretical Physics at Caltech. His question: Could the detection confirm the area theorem?

At the time, researchers did not have the ability to pick out the necessary information within the signal, before and after the merger, to determine whether the final horizon area did not decrease, as Hawking’s theorem would assume. It wasn’t until several years later, and the development of a technique by Isi and his colleagues, when testing the area law became feasible.

Before and after

In 2019, Isi and his colleagues developed a technique to extract the reverberations immediately following GW150914’s peak — the moment when the two parent black holes collided to form a new black hole. The team used the technique to pick out specific frequencies, or tones of the otherwise noisy aftermath, that they could use to calculate the final black hole’s mass and spin.

A black hole’s mass and spin are directly related to the area of its event horizon, and Thorne, recalling Hawking’s query, approached them with a follow-up: Could they use the same technique to compare the signal before and after the merger, and confirm the area theorem?

The researchers took on the challenge, and again split the GW150914 signal at its peak. They developed a model to analyze the signal before the peak, corresponding to the two inspiraling black holes, and to identify the mass and spin of both black holes before they merged. From these estimates, they calculated their total horizon areas — an estimate roughly equal to about 235,000 square kilometers, or roughly nine times the area of Massachusetts.

They then used their previous technique to extract the “ringdown,” or reverberations of the newly formed black hole, from which they calculated its mass and spin, and ultimately its horizon area, which they found was equivalent to 367,000 square kilometers (approximately 13 times the Bay State’s area).

“The data show with overwhelming confidence that the horizon area increased after the merger, and that the area law is satisfied with very high probability,” Isi says. “It was a relief that our result does agree with the paradigm that we expect, and does confirm our understanding of these complicated black hole mergers.”

The team plans to further test Hawking’s area theorem, and other longstanding theories of black hole mechanics, using data from LIGO and Virgo, its counterpart in Italy.

“It’s encouraging that we can think in new, creative ways about gravitational-wave data, and reach questions we thought we couldn’t before,” Isi says. “We can keep teasing out pieces of information that speak directly to the pillars of what we think we understand. One day, this data may reveal something we didn’t expect.”

Reference: “Testing the Black-Hole Area Law with GW150914” by Maximiliano Isi, Will M. Farr, Matthew Giesler, Mark A. Scheel and Saul A. Teukolsky, 1 July 2021, Physical Review Letters.
DOI: 10.1103/PhysRevLett.127.011103

This research was supported, in part, by NASA, the Simons Foundation, and the National Science Foundation.