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Particle physicists propose stripped-down ventilator to help combat COVID-19

A preliminary CAD model of the HEV unit. Credit: HEV Collaboration.

As part of the global response to the COVID-19 pandemic, a team led by physicists and engineers from the LHCb collaboration has proposed a design for a novel ventilator. The High Energy Ventilator (HEV) is based on components which are simple and cheap to source, complies with hospital standards, and supports the most requested ventilator-operation modes, writes the newly formed HEV collaboration. Though the system needs to be verified by medical experts before it can enter use, in the interests of rapid development the HEV team has presented the design to generate feedback, corrections and support as the project progresses. The proposal is one of several recent and rapidly developing efforts launched by high-energy physicists to help combat COVID-19.

The majority of people who contract COVID-19 suffer mild symptoms, but in some cases the disease can cause severe breathing difficulties and pneumonia. For such patients, the availability of ventilators that deliver oxygen to the lungs while removing carbon dioxide could be the difference between life and death. Even with existing ventilator suppliers ramping up production, the rapid rise in COVID-19 infections is causing a global shortage of devices. Multiple efforts are therefore being mounted by governments, industry and academia to meet the demand, with firms which normally operate in completely different sectors – such as Dyson and General Motors – diverting resources to the task.

There are many proposals on the market, but we don’t know now which ones will in the end make a difference, so everything which could be viable should be pursued
Paula Collins

HEV was born out of discussions in the LHCb VELO group, when lead-designer Jan Buytaert (CERN) realised that the systems which are routinely used to supply and control gas at desired temperatures and pressures in particle-physics detectors are well matched to the techniques required to build and operate a ventilator. The team started from a set of guidelines recently drawn up by the UK government’s Medicines and Healthcare products Regulatory Agency regarding rapidly manufactured ventilator systems, and was encouraged by a 3D-printed prototype constructed at the University of Liverpool in response to these guidelines. The driving pressure of ventilators — which must be able to handle situations of rapidly changing lung compliance, and potential collapse and consolidation — is a crucial factor for patient outcomes. The HEV team therefore aimed to produce a patient-safety-first design with a gentle and precise pressure control that is responsive to the needs of the patient, and which offers internationally recommended operation modes.

As the HEV team comprises physicists, not medics, explains HEV collaborator Paula Collins of CERN, it was vital to get the relevant input from the very start. “Here we have benefitted enormously from the experience and knowledge of CERN’s HSE [occupational health & safety and environmental protection] group for medical advice, conformity with applicable legislation and health-and-safety requirements, and the working relationship with local hospitals. The team is also greatly supported from other CERN departments, in particular for electronic design and the selection of the best components for gas manipulation. During lockdown, the world is turning to remote connection, and we were very encouraged to find that it was possible in a short space of time to set up an online chat group of experienced anesthesiologists and respiratory experts from Australia, Belgium, Switzerland and Germany, which sped up the design considerably.”

Prototyping the HEV buffer-concept at CERN to demonstrate “breathing” and flow capabilities of the device. The demonstrator is built with in-house parts and looks mechanically very different to the final system. Control is provided via LabView, whereas the final system will use an embedded controller. Credit: HEV Collaboration.

Conceptual design of the HEV ventilator. Credit: HEV Collaboration.

Stripped-down approach
The HEV concept relies on easy-to-source components, which include electro-valves, a two-litre buffer container, a pressure regulator and several pressure sensors. Embedded components — currently Arduino and Rasbperry Pi — are being used to address portability requirements. The unit’s functionality will be comprehensive enough to provide long-term support to patients in the initial or recovery phases, or with more mild symptoms, freeing up high-end machines for the most serious intensive care, explains Collins: “It will incorporate touchscreen control intuitive to use for qualified medical personnel, even if they are not specialists in ventilator use, and it will include extensive monitoring and failsafe mechanisms based on CERN’s long experience in this area, with online training to be developed.”

The first stage of prototyping, which was achieved at CERN on 27 March, was to demonstrate that the HEV working principle is sound and allows the ventilator to operate within the required ranges of pressure and time. The desired physical characteristics of the pressure regulators, valves and pressure sensors are now being refined, and the support of clinicians and international organisations is being harnessed for further prototyping and deployment stages. “This is a device which has patient safety as a major priority,” says HEV collaborator Themis Bowcock of the University of Liverpool. “It is aimed at deployment round the world, also in places that do not necessarily have state-of-the-art facilities.”

Complementary designs
The HEV concept complements another recent ventilator proposal, initiated by physicists in the Global Argon Dark Matter Collaboration. The Mechanical Ventilator Milano (MVM) is optimised to permit large-scale production in a short amount of time and at a limited cost, also relying on off-the-shelf components that are readily available. In contrast to the HEV design, which aims to control pressure by alternately filling and emptying a buffer, the MVM project regulates the flow of the incoming mixture of oxygen and air via electrically controlled valves. The proposal stems from a cooperation of particle- and nuclear-physics laboratories and universities in Canada, Italy and the US, with an initial goal to produce up to 1000 units in each of the three countries while the interim certification process is ongoing. Clinical requirements are being developed with medical experts, and detailed testing and qualification of the first prototype is presently underway with a breathing simulator at Ospedale San Gerardo in Monza, Italy.

Sharing several common ideas with the MVM principle, but with emphasis on further reducing the number and specificity of components to make construction possible during times of logistical disruption, a team led by particle physicists at the Laboratory of Instrumentation and Experimental Particles Physics in Portugal has also posted a proof-of-concept study for a ventilator on arXiv. All ventilator designs are evolving quickly and require further development before they can be deployed in hospitals.

“It is difficult to conceive a project which goes all the way and includes all the bells and whistles needed to get it into the hospital, but this is our firm goal,” says Collins. “After one week we had a functioning demonstrator, after two weeks we aim to test on a medical mechanical lung and to start prototyping in the hospital context. We find ourselves in a unique and urgent situation where there are many proposals on the market, but we don’t know now which ones will in the end make a difference, so everything which could be viable should be pursued.”

The Human Condition: Reality, Science and History

“Homo has much work left to become Sapiens,” is Gregory Loew’s catchphrase in The Human Condition: Reality, Science and History. An accelerator physicist with an illustrious 50-year-long career at the SLAC National Accelerator Laboratory in California, Loew also taught a seminar at Stanford University that ran the gamut from psychology and anthropology to international relations and arms control. His new book combines these passions.

This reviewer must admit to being inspired by the breadth of Loew’s polymathic ambition, which he has condensed into 200 colourful pages. The author compares his work to noted Israeli historian Yuval Harari’s hefty tomes Sapiens and Homo Deus, but The Human Condition is more idiosyncratic, and peppered with fascinating titbits. He points out the difficulties in connecting free will with quantum indeterminacy. He asks what came first: the electron or the electric field? Neglecting to mention the disagreement with the long-accepted age of the universe inferred from fits to the cosmic microwave background, he breathlessly slips in a revised-down value of 12.8 billion years, tacitly accepting the 2019 measurement of the Hubble constant based on observations by the Hubble Space Telescope. He even digresses momently to note the almost unique rhythmic awareness of cockatoo parrots.

But this is not a scenic drive through the nature of existence. Loew wants to be complete. He reverses from epistemology to evolution and the nature of perception, before pulling out onto the open road of mathematics and the sciences, both fundamental and social, via epigenetics, Thucydides and the Cuban missile crisis. The final chapter, which looks to the future, is really a thoughtful critique of Harari’s books, which he discovered while writing. It’s heartening to join Loew on an expansive road trip from metaphysics and physics to economic theory and realpolitik.

No scientific knowledge or mathematical training is necessary to enjoy The Human Condition, which will entertain and intrigue physicists and lay audiences alike. While some subjects, such as homosexuality, are treated with inappropriate swiftness, in that case with a rapid and highly questionable hop from Freud to Kinsey to Schopenhauer to Pope Francis, in general Loew writes with a refreshing élan. His final thought is that “if all Homo Sapientes became wiser, they would certainly be happier.” Here, he flirts with contradicting Kant, a philosopher he frequently esteems, who wrote that the cultivation of reason sooner leads to misery than happiness. But perhaps the key word is “all Homo Sapientes”. If every one of us became wiser, perhaps through the utopic initiatives advocated by Loew, we would indeed be happier.

Fiction, in theory

Irène Jacob reads an excerpt from *Big Bang*. Credit: SJ Hertzog / CERN-PHOTO-202002-036-2

French actor Irène Jacob rose to international acclaim for her role in the 1991 film The Double Life of Véronique. She is the daughter of Maurice Jacob (1933 – 2007), a French theoretical physicist and Head of CERN’s Theory Division from 1982 to 1988. Her new novel, Big Bang, is a fictionalised account of the daughter of a renowned physicist coming to terms with the death of her father and the arrival of her second child. Keen to demonstrate the artistic beauty of science, she is also a Patron of the Physics of the Universe Endowment Fund established in Paris by George Smoot.

When Irène Jacob recites from her book, it is more than a reading, it’s a performance. That much is not surprising: she is after all the much-feted actor in the subtly reflective 1990s films of Krzysztof Kieślowski. What did come as a surprise to this reader is just how beautifully she writes. With an easy grace and fluidity, she weaves together threads of her life, of life in general, and of the vast mysteries of the universe.

The backdrop to the opening scenes is the corridors of the theory division in the 70s and 80s

Billed as a novel, Big Bang comes across more as a memoir, and that’s no accident. The author’s aim was to use her entourage, somewhat disguised, to tell a universal story of the human condition. Names are changed, Irène’s father, the physicist Maurice Jacob, becomes René, for example, his second name. The true chronology of events is not strictly observed, and maybe there’s some invention, but behind the storytelling there is nevertheless a touching portrait of a very real family. The backdrop to the opening scenes is CERN, more specifically the corridors of the theory division in the 70s and 80s, a regular stomping ground for the young Irène. The reader discovers the wonders of physics through the wide-open eyes of a seven-year-old child. Later on, that child-become-adult reflects on other wonders – those related to the circle of life. The book ties all this together, seen from the point in spacetime at which Irène has to reconcile her father’s passing with her own impending motherhood.

For those who remember the CERN of the 80s, the story begins with an opportunity to rediscover old friends and places. For those not familiar with particle physics, it offers a glimpse into the field, to those who devote their lives to it, and to those who share their lives with them. The initial chapters open the door to Irène Jacob’s world, just a crack.

The atmosphere soon changes, though, as she flings the door wide open. More than once I found myself wondering whether I had the right to be there: inside Irène Jacob’s life, dreams and nightmares. It is a remarkably intimate account, looking deep in to what it is to be human. Highs and lows, loves and laughs, kindnesses and hurts, even tragedies: all play a part. Irène Jacob’s fictionalised family suffers much, yet although Irène holds nothing back, Big Bang is essentially an optimistic, life affirming tale.

Science makes repeated cameo appearances. There’s a passage in which René is driving home from hospital after welcoming his first child into the world. Distracted by emotion, he’s struck by a great insight and has to pull over and tell someone. How often does that happen in the creative process? Kary Mullis tells a similar story in his memoirs. In his case, the idea for Polymerase Chain Reaction came to him at the end of hot May day on Highway 128 with his girlfriend asleep next to him in the passenger seat of his little silver Honda. Mullis got the Nobel Prize. Both had a profound impact on their fields.

Bohr can be paraphrased as saying: the opposite of a profound truth is another profound truth

Alice in Wonderland is a charmingly recurrent theme, particularly the Cheshire cat. Very often, a passage ends with nothing left but an enigmatic smile, a metaphor for life in the quantum world, where believing in six impossible things before breakfast is almost a prerequisite.

Big Bang is not a page turner. Instead, each chapter is a beautifully formed vignette of family life. Take, for example, the passage that begins with a quote from Niels Bohr taken René’s manuscript, Des Quarks et des Hommes (published as Au Coeur de la Matière). Bohr can be paraphrased as saying: the opposite of a profound truth is another profound truth. As the passage moves on, it plays with this theme, ending with the conclusion: if my story does not stand up, it’s because reality is very small. And if my story is very small, it is because reality does not stand up.

Whatever the author’s wish, Big Bang comes across as an admirably honest family portrait, at times uncomfortably so. It’s a portrait that goes much deeper than the silver screen or the hallowed halls of academia. The cast of Big Bang is a very human family, and one that this reader came to like very much.

European strategy update postponed

The European strategy for particle physics. Credit: CERN.

During its 197^th session, which took place for the first time by videoconference on 19-20 March, the CERN Council addressed the impact of the current COVID-19 situation on the update of the European strategy for particle physics (ESPPU).

The ESPPU got under way in September 2017, when the CERN Council appointed a European Strategy Group (ESG) – headed by Halina Abramowicz of Tel Aviv University and comprising a scientific delegate from each of CERN’s member and associate-member states, plus directors and representatives of major European laboratories and organisations and invitees from outside Europe – to organise the process. Following two years of discussions and consultation with the high-energy physics and related communities, the ESPPU entered its final stages in January with a week-long drafting session in Bad Honnef, Germany. Afterwards, the ESG released a statement reporting convergence on recommendations to guide the future of high-energy physics in Europe. These were due to be submitted for final approval at an extraordinary session of the CERN Council on 25 May in Budapest, Hungary, before being publicly released.

Discussing with various stakeholders in the Member States will take more time
Ursula Bassler

Acknowledging that the COVID-19 outbreak threatens the lives and health of hundreds of thousands of people, and affects the everyday lives of millions, the CERN Council has now agreed that it would not be appropriate to release the ESG update (and an accompanying deliberation document) to a wider audience, nor for the Council to make any further comment on the contents of the documents for the time being. The Budapest event has been cancelled and replaced by a new extraordinary session, to be held by videoconference on the same date, at which the Council will further discuss how to proceed.

“In these exceptional circumstances it is not the right time to release the strategy, and discussing with various stakeholders in the Member States will take more time,” says Ursula Bassler, president of the CERN Council. “Even though this will come as a disappointment to many physicists after all the effort put into the ESPPU, everyone can understand, that in this situation, the process will last longer.”

Yerevan hosts early-career accelerator internship

The inaugural joint German-Armenian internship in accelerator physics was held at the CANDLE Institute in Yerevan, Armenia, from 29 September to 5 October. In this first round, twelve undergraduates at Universität Hamburg joined eleven students from Yerevan State University to form eight small teams. Each team worked its way through an experiment under the supervision of experts from both nations, interacting with physicists in a laboratory setting for the first time in many cases. The goal of the programme of week-long internships, which was supported by the German Federal Foreign Office, is to integrate accelerator physics and technology into undergraduate courses and provide students with an early experience of international cooperation. It will make use of eight experimental stations recently set up to foster young academics learning accelerator technology in Armenia.

CANDLE is the Armenian synchrotron-radiation storage-ring project. As a first step towards its realisation, AREAL, an ultrafast laser-driven electron accelerator, has been constructed. The next steps are S-band linac acceleration up to 20-50 MeV and the generation of coherent and tunable THz-radiation in an undulator.

Ascent commemorates cosmic-ray pioneers

A hot-air balloon commemorating the discovery of cosmic rays — **For the love of physics** The balloon shortly after taking off, showing CAEN’s Cosmic Hunter inside a heated box attached to the basket and passenger Hans Peter Beck with pilot Nicolas Tièche. Credit: M Hoch

On 25 January, a muon detector, a particle physicist and a prizewinning pilot ascended 4000 m above the Swiss countryside in a hot-air balloon to commemorate the discovery of cosmic rays. The event was the highlight of the opening ceremony of the 42nd Château-d’Oex International Balloon Festival, attended by an estimated 30,000 people, and attracted significant media coverage.

In the early 1900s, following Becquerel’s discovery of radioactivity, studying radiation was all the rage. Portable electrometers were used to measure the ionisation of air in a variety of terrestrial environments, from fields and lakes to caves and mountains. With the idea that ionisation should decrease with altitude, pioneers adventured in balloon flights as early as 1909 to count the number of ions per cm³ of air as a function of altitude. First results indeed indicated a decrease up to 1300 m, but a subsequent ascent to 4500 m by Albert Gockel, professor of physics at Fribourg, concluded that ionisation does not decrease and possibly increases with altitude. Gockel, however, who later would coin the term “cosmic radiation”, was unable to obtain the hydrogen needed to go to higher altitudes. And so it fell to Austrian physicist Victor Hess to settle the case. Ascending to 5300 m in 1912, Hess clearly identified an increase, and went on to share the 1936 Nobel Prize in Physics for the discovery of cosmic rays. Gockel, who died in 1927, could not be awarded, and for that reason is almost forgotten by history.

ATLAS experimentalist Hans Peter Beck of the University of Bern, and a visiting professor at the University of Fribourg, along with two students from the University of Fribourg, reenacted Gockel’s and Hess’s pioneering flights using 21st-century technology: a muon telescope called the Cosmic Hunter, newly developed by instrumentation firm CAEN. The educational device, which counts coincidences in two scintillating-fibre tiles of 15 × 15 cm² separated by 15 cm, verified that the flux of cosmic rays increases as a function of altitude. Within two hours of landing, including a one-hour drive back to the starting point, Beck was able to present the data plots during a public talk attended by more than 250 people. A second flight up to 6000 m is planned, with oxygen supplies for passengers, when weather conditions permit.

The view from inside the hot-air balloon — **Flying high** The view from above. Credit: M Hoch

“Relating balloons with particle physics was an easy task, given the role balloons played in the early days for the discovery of cosmic rays,” says Beck. “It is a narrative that works and that touches people enormously, as the many reactions at the festival have shown.”

The event – a collaboration with the universities of Bern and Fribourg, the Swiss Physical Society, and the Jungfraujoch research station – ran in parallel to a special exhibition about cosmic rays at the local balloon museum, organised by Beck and Michael Hoch from CMS, which was the inspiration for festival organisers to make physics a focus of the event, says Beck: “Without this, the festival would never have had the idea to bring ‘adventure, science and freedom’ as this year’s theme. It’s really exceptional.”

AMS detector given a new lease of life

Checking the installation of the Upgraded Tracker Thermal Pump System for AMS — **Out of this world** (Top) Luca Parmitano checking the installation of the Upgraded Tracker Thermal Pump System for AMS (seen above his head), while AMS spokesperson Sam Ting watches from CERN. Credits: NASA; N Caraban/CERN.

On 25 January, European Space Agency astronaut Luca Parmitano stepped outside a half-million-kilogramme structure travelling at tens of thousands of kilometres per hour, hundreds of kilometres above Earth, and, tethered by a thin cord, ventured into the vacuum of space to check for a leak.

It was the fourth such extravehicular activity (EVA) he’d been on in two months. All things considered, the task ahead was relatively straightforward: to make sure that a newly installed cooling system for the Alpha Magnetic Spectrometer (AMS), the cosmic-ray detector that has been attached to the International Space Station (ISS) since 2011, had been properly plumbed in.

Heart-stopping spacewalks

The first EVA on 15 November saw Parmitano and fellow astronaut, NASA’s Drew Morgan, remove and jettison the AMS debris shield, which is currently still spiralling its way to Earth, to allow access to the experiment’s cooling system. The CO₂ pumps, needed to keep the 200,000-channel tracker electronics at a temperature of 10 ± 3 °C, had started to fail in 2014 – which was no surprise, as AMS was initially only supposed to operate for three years. During the second EVA on 22 November, the astronauts cut through the cooling system’s eight stainless-steel lines to isolate and prepare it for removal, and a critical EVA3 on 2 December saw Morgan and Parmitano successfully connect the new pump system, which had been transported to the ISS by an Antares rocket the previous month. Then came a long wait until January to find out if the repair had been successful.

“EVA4 was the heart-stopping EVA because that’s where we did the leak tests on all those tubes,” says Ken Bollweg, NASA’s AMS project manager. The success of the previous EVAs suggested that the connections were going to be fine. But Parmitano arrived at the first tube, attached one of 29 bespoke tools developed specially for the AMS repair, and saw that the instrument had issued a warning signal. “I see red,” he reported to anxious teams at NASA’s Johnson Space Center’s Mission Control Center and the AMS Payload Operations Control Centre (POCC) at CERN’s Prévessin site, from where spokesperson Sam Ting and his colleagues were monitoring proceedings closely. Though not huge, the leak was serious enough not to guarantee that the system would work, jeopardising four years of preparation involving hundreds of astronauts, engineers and scientists. Following procedures put in place to deal with such a situation, Parmitano tightened the connection and waited for about an hour before checking the tube again. A leak was still present. Then, after re-tightening the troublesome connection again, while the team was preparing a risky “jumper” manoeuvre to bypass the leak and make a new connection, he checked a third time: “No red!” Happy faces lit up the POCC.

NASA has learned a lot of new things from this
Ken Bollweg

AMS was never designed to be serviceable, and the repair, unprecedented in complexity for a space intervention, required the avoidance of sharp edges and other hazards in order to bring it back to full operational capacity. The chances of something going wrong were high, says Bollweg. “NASA has learned a lot of new things from this. We really pushed the envelope. It showed that we have the capabilities to do even more than we have done in the past.” EVA4 lasted almost six hours. Five hours and two minutes into it, Parmitano, who returned safely to Earth on 6 February, broke the European record for the most time spent spacewalking (33 hours and nine minutes). It’s not a job for the fainthearted. During a spacewalk in 2013, while wedged into a confined space outside the ISS, a malfunction in Parmitano’s spacesuit caused his helmet to start filling with water and he almost drowned.

“Building and operating AMS in space has been an incredible journey through engineering and physics, but today it is thanks to the NASA group that in AMS we can continue this journey and this is amazing. An enormous thanks to the EVA crew,” said AMS integration engineer Corrado Gargiulo of CERN. The day after EVA4, the POCC team spent about 10 hours refilling the new AMS cooling system with 1.3 kg of CO₂ and started to power up the detector. At noon on 27 January, all the detector’s subsystems were sending data back, marking a new chapter for AMS that will see it operate for the lifetime of the ISS.

Into the unknown

The 7.5 tonne AMS apparatus has so far recorded almost 150 billion charged cosmic rays with energies up to the multi-TeV range, and its percent-level results show clear and unexpected behaviour of cosmic-ray events at high energies. A further 10 years of operation will allow AMS to make conclusive statements on the origin of these unexpected observations, says Ting. “NASA is to be congratulated on seeing this difficult project through over a period of many years. AMS has observed unique features in cosmic-ray spectra that defy traditional explanations. We’re entering into a region where nobody has been before.”

AMS has observed unique features in cosmic-ray spectra that defy traditional explanations
Sam Ting

The first major result from AMS came in 2013, when measurements of the cosmic positron fraction (the ratio of the positron flux to the flux of electrons and positrons) up to an energy of 350 GeV showed that the spectrum fits well to dark-matter models. The following year, AMS published the positron and electron fluxes, which showed that neither can be fitted with the single-power-law assumption underpinning the traditional understanding of cosmic rays. The collaboration has continued to find previously unobserved features in the measured fluxes and flux ratio of electrons and positrons, publishing the results in several high-profile papers during the past couple of years.

Figure 1. The positron spectrum measured by AMS (yellow), showing that low-energy positrons mostly come from cosmic ray collisions (shaded area). Unexpectedly, there is a continuous excess starting at 25 GeV. The spectrum reaches a maximum at around 284 GeV followed by a sharp drop-off with a finite energy cutoff established at 99.99% confidence.

Figure 2. Comparison between 0.6 million antiprotons (blue, right axis) with 1.9 million positrons (yellow, left axis) using the latest AMS data.

Last year, AMS reaffirmed the complex energy dependence exhibited by the positron flux: a significant excess starting from 25 GeV, a sharp drop-off above 284 GeV and a finite energy cutoff at 810 GeV (figure 1). “In the entire energy range the positron flux is well described by the sum of a term associated with the positrons produced in the collision of cosmic rays, which dominates at low energies, and a new source term of positrons, which dominates at high energies,” says Ting. “These experimental data on cosmic-ray positrons show that, at high energies, they predominantly originate either from dark-matter annihilation or from other astrophysical sources.” Although dark-matter models predict such a cut off, the AMS data cannot yet rule out astrophysical sources, in particular pulsars. Further intrigue comes from the latest, to-be-published, AMS result on antiprotons, which, although rare at high energies, exhibit similar functional behaviour as the positron spectrum (figure 2). “This indicates that the excess of positrons may not come from pulsars due to the similarity of the two spectra and the high mass of antiprotons,” says Ting.

Thanks to the successful installation of the new AMS cooling system, the expected positron spectrum by 2028, in particular the high-energy data points, should enable an accurate comparison with dark-matter models (figure 3). High-energy (>TeV) events are also expected to provide insights into the origins of cosmic electrons, the latest results on which show that the electron flux exhibits a significant excess starting from 42 GeV.

Figure 3. Comparison between the projected positron spectrum (light blue) and the prediction from a dark-matter model (Phys. Rev. D 88 076013).

Figure 4. The electron spectrum (light blue points) fitted with the sum of two power laws (green curve) in the energy range 0.5–1400 GeV. The two power-law components a and b are represented by the grey and blue areas, respectively. The minute contribution of electrons from cosmic-ray collisions is also shown (green area). — Figure 4. The electron spectrum (light blue points) fitted with the sum of two power laws (green curve). The two power-law components a and b are represented by the grey and blue areas, respectively. The minute contribution of electrons is also shown (green area).

Unlike the positron flux, which has an exponential energy cutoff at 810 GeV, the electron flux does not have a cutoff (at least not below 1.9 TeV). Also: in the entire energy range the electron flux is well described by the sum of two power law components (figure 4), providing “clear evidence”, says Ting, that most high energy electrons originate from different sources than high energy positrons.

Novelties in nuclei

Unexpected results continue to appear in data from cosmic nuclei, which make up the bulk of cosmic rays travelling through space. Helium, carbon and oxygen nuclei are thought to be mainly produced and accelerated in astrophysical sources and are known as primary cosmic rays, while lithium, beryllium and boron nuclei are produced by the collision of heavier nuclei with nuclei of the interstellar matter and are known as secondary cosmic rays.

New properties of primary cosmic rays – helium, carbon and oxygen – have been observed in the rigidity range 2 GV to 3 TV; at high energies these three spectra also have identical rigidity dependence, all deviating from a single power law above 200 GV. Similar oddities have appeared in measurements of secondary cosmic rays – lithium, beryllium and boron – in the range 1.9 GV to 3.3 TV (figure 5). The lithium and boron fluxes have an identical rigidity dependence above 7 GV, all three fluxes have an identical rigidity dependence above 30 GV, and, unexpectedly, above 30 GV the Li/Be flux ratio is approximately equal to two.

Figure 5. The rigidity dependences of the spectra of primary cosmic rays (helium, carbon and oxygen) compared to the spectra of secondary cosmic rays (lithium, beryllium and boron), all scaled to the helium flux at 30 GV. — Figure 5. The rigidity dependencies of the spectra of primary cosmic rays (helium, carbon and oxygen) compared to the spectra of secondary cosmic rays (lithium, beryllium and boron), all scaled to the helium flux at 30 GV.

The ratio of secondary fluxes to primary fluxes is particularly interesting because it directly measures the amount and properties of the interstellar medium. Before AMS, only the B/C ratio was measured and was assumed to be proportional to R^Δ with Δ a constant for R > 60 GV. The latest AMS results on secondary (Li, Be, B) to primary (C, O) flux ratios show that Δ is not a constant, but changes by more than 5σ between the two rigidity ranges, 60 < R < 200 GV and 200 < R < 3300 GV. As with electron and positron fluxes, none of the current AMS results can be explained by existing theoretical models. By 2028, says Ting, AMS will extend its measurements of cosmic nuclei up to Z=30 (zinc) with sufficient statistics to get to the bottom of these and other mysteries. “We have measured many particles, electrons, positrons, antiprotons and many nuclei, and they all have distributions and none agree with current theoretical models. So we will begin to create a new field.”

Synchrotrons on the coronavirus frontline

Representation of the 3D structure of the main SARS-CoV-2 protease, obtained using Diamond Light Source. The coils represent “alpha” helices and the flatter arrows are “beta sheets”, with loops connecting them together. The organisation of alpha helices and beta sheets is often referred to as the secondary structure of the protein (with the primary sequence being the amino acid sequence and the tertiary structure being the overall 3D shape of the protein). Credit: D Owen/Diamond Light Source.

At a time when many countries are locking down borders, limiting public gatherings, and encouraging isolation, the Diamond Light Source in Oxfordshire, UK, has been ramping up its intensity, albeit in an organised and controlled manner. The reason: these scientists are working tirelessly on drug-discovery efforts to quell COVID-19.

It is a story that requires fast detectors, reliable robotics and powerful computing infrastructures, artificial intelligence, and one of the brightest X-ray sources in the world. And it is made possible by international collaboration, dedication, determination and perseverance.

Synchrotron light sources are particle accelerators capable of producing incredibly bright X-rays, by forcing relativistic electrons to accelerate on curved trajectories. Around 50 facilities exist worldwide, enabling studies over a vast range of topics. Fanning out tangentially from Diamond’s 562-m circumference storage ring are more than 30 beamlines equipped with instrumentation to serve a multitude of user experiments. The intensely bright X-rays (corresponding to flux of around 9 × 10¹² photons per second) are necessary for determining the atomic structure of proteins, including the proteins which make up viruses. As such, synchrotron light sources around the world are interrupting their usual operations to work on mapping the structure of the SARS-CoV-2 virus.

Knowing the atomic structure of the virus is like knowing how the enemy thinks

Knowing the atomic structure of the virus is like knowing how the enemy thinks. A 3D visualisation of the building blocks of the structure at an atomic level would allow scientists to understand how the virus functions. Enzymes, the molecular machines that allow the virus to replicate, are key to this process. Scientists at Diamond are exploring the binding site of the main SARS-CoV-2 protease. A drug that binds to this enzyme’s active site would throw a chemical spanner in the works, blocking the virus’ ability to replicate and limiting the spread of the disease.

By way of reminder: Coronavirus is the family of viruses responsible for the common cold, MERS, SARS, etc. Novel coronavirus, aka SARS-CoV-2, is the newly discovered type of coronavirus, and COVID-19 is the disease which it causes.

Call to arms

On 26 January, Diamond’s life-sciences director, Dave Stuart, received a phone call from structural biologist Zihe Rao of ShanghaiTech University in China. Rao, along with his colleague Haitao Yang, had solved the structure of the main SARS-CoV-2 protease with a covalent inhibitor using the Shanghai Synchrotron Radiation Facility (SSRF) in China. Furthermore, they had made the solution freely and publicly available on the worldwide Protein Data Bank.

During the phone call, Rao informed Stuart that their work had been halted by a scheduled shutdown of the SSRF. The Diamond team rapidly mobilised. Since shipping biological samples from Shanghai at the height of the coronavirus in China was expected to be problematic, the team at Diamond ordered the synthetic gene. A synthetic gene can be generated provided the ordering of T, A, C and G nucleotides in the DNA sequence is known. That synthetic gene can be genetically engineered into a bacterium, in this case Escherichia. coli, which reads the sequence and generates the coronavirus protease in large enough quantities for the researchers at Diamond to determine its structure and screen for potential inhibitors.

Eleven days later on 10 February, the synthetic gene arrived. At this point, Martin Walsh, Diamond’s deputy director of life sciences, and his team (consisting of Claire Strain-Damerell, Petra Lukacik, and David Owen) dropped everything. With the gene in hand, the group immediately set up experimental trials to try to generate protein crystals. In order to determine the atomic structure, they needed a crystal containing millions of proteins in an ordered grid-like structure.

Diamond Light Source, the UK’s national synchrotron facility, located at the Harwell Science and Innovation Campus in Oxfordshire. Credit: Diamond Light Source.

X-ray radiation bright enough for the rapid analysis of protein structures can only be produced by a synchrotron light source. The X-rays are directed and focused down a beamline onto a crystal and, as they pass through it, they diffract. From the diffraction pattern, researchers can work backwards to determine the 3D electron density maps and the structure of the protein. The result is a complex curled ribbon-like structure with an intricate mess of twists and turns of the protein chain.

The Diamond team set up numerous trials trying to find the optimum conditions for crystallization of the SARS-CoV-2 protease to occur. They modified the pH, the precipitating compounds, chemical composition, protein to solution ratio… every parameter they could vary, they did. Every day they would produce a few thousand trials, of which only a few hundred would produce crystals, and even fewer would produce crystals of sufficient quality. Within a few days of receiving the gene, the first crystals were being produced. They were paltry and thin crystals but large enough to be tested on one of Diamond’s macromolecular crystallography beamlines.

Watching the results come through, Diamond postdoc David Owen described it as the first moment of intense excitement. With crystals that appeared to be “flat like a car wind shield,” he was dubious as to whether they would diffract at all. Nevertheless, the team placed the crystals in the beamline with a resignation that quickly turned into intense curiosity as the results started appearing before them. At that moment Owen remembers his doubts fading, as he thought, “this might just work!” And work it did. In fact, Owen recalls, “they diffracted beautifully.” These first diffraction patterns of the SARS-CoV-2 virus were recorded with a resolution of 1.9 Angstrom (1.9 × 10⁻¹⁰ m) — high enough resolution to see the position of all of the chemical groups that allow the protease to do its work.

By 19 February, through constant adjustments and learning, the team knew they could grow good-quality crystals quickly. It was time to bring in more colleagues. The XChem team at Diamond joined the mission to set up fragment-based screening – whereby a vast library of small molecules (“fragments”) are soaked into crystals of the viral protease. These fragments are significantly smaller and functionally simpler than most drug molecules and are a powerful approach to selecting candidates for early drug discovery. By 26 February, 600 crystals had been mounted and the first fragment screen launched. In parallel, the team had been making a series of sample to send to company in Oxford called Exscientia, which has set up an AI platform designed to expediate candidates in drug discovery.

Drug-discovery potential

As of early March, 1500 crystals and fragments have been analysed. Owen attributes the team’s success so far to the incredible amounts of data they could collect and analyse quickly. With huge numbers of data sets, they could pin down the parameters of the viral protease with a high degree of confidence. And with the synchrotron light source they were able to create and analyse the diffraction patterns rapidly. The same amount of data collected with a lab-based X-ray source would have taken approximately 10 years. At Diamond, they were able to collect the data in a few days of accumulated beamtime.

A close up view of some residues in the active site of the protein, where the sticks represent the protein molecules and the mesh represents the electron density. Credit: D Owen/Diamond Light Source.

Synchrotron light sources all over the world have been granting priority and rapid access to researchers to support their efforts in discovering more about the virus. Researchers at the Advanced Photon Source in Argonne, US, and at Elettra Sincrotrone in Trieste, Italy are also trying to identify molecules effective against COVID-19, in an attempt to bring us closer to an effective vaccine or treatment. This week, the ESRF in Grenoble, France, announced that it will make its cryo-electron microscope facility available for use. The community has a platform called www.lightsources.org offering an overview of access and calls for proposals.

Synchrotron light sources all over the world have been granting priority and rapid access

In addition to allowing the structure of tens of thousands of biological structures to be elucidated – such as that of the ribosome, which was recognised by the 2009 Nobel Prize in Chemistry — light sources have a strong pedigree in elucidating the structure of viruses. Development of common anti-viral medication that blocks the actions of virus in the body, such as Tamiflu or Relenza, also relied upon synchrotrons to reveal their atomic structure.

Mapping the SARS-CoV-2 protease structures bound to small chemical fragments, the Diamond team demonstrated a crystallography- and fragmentation-screen tour de force. The resulting and ongoing work is a crucial first step in developing a drug. Forgoing the usual academic root of peer-review, the Diamond team have made all of their results openly and freely available to help inform public heath response, limit the spread of the virus with the hope that this can fast-track effective treatment options.

Rolf Widerøe: a giant in the history of accelerators

The betatron is an early type of MeV-range electron accelerator which uses the electric field induced by a varying magnetic field to accelerate electrons, or beta particles. It operates like a transformer with the secondary winding replaced by a beam of electrons circulating in a vacuum tube. It was invented by pioneering Norwegian accelerator physicist Rolf Widerøe when a student in 1925. Since the construction failed at the time, he had to find another theme for his thesis, and so in 1927 he constructed the first linear accelerator (50 keV), before later proposing the principle of colliding beams to fully exploit the energy of accelerated particles. Through these innovations, Rolf Widerøe decisively influenced the course of high-energy physics, with betatrons shaping the landscape in the early days, and linear accelerators and colliding beams becoming indispensable tools today.

Aashild Sørheim, a professional writer, now presents a new biography of this visionary engineer, who had a seminal impact on accelerator physics. Her book covers Widerøe’s whole life, from 1902 to 1996, and from his childhood in a well-to-do family in Oslo to his retirement in Switzerland. Certainly, many who read Pedro Waloscheck’s 1994 biography, The Infancy of Particle Accelerators: Life and Work of Rolf Widerøe, will be curious how this new book will complement the former. Sørheim‘s new offering is based on new documentary evidence, the result of painstaking sifting through archives, and a large number of interviews. She has opened new perspectives through her interviews, and the access she has gained in several countries to hitherto restricted archives has provided a wealth of new material and insights, in particular in relation to the second world war. Sørheim’s book focuses not on physics or technology, but on Widerøe himself, and the social and political environment in which he had to find his way. In particular, it gravitates to the question of his motivation to work in Germany in the troubled years from 1943 to 1945, when he constructed a betatron, the accelerator he had invented two decades earlier while a student in Karlsruhe.

Occupied Oslo

In the most interesting parts, the book provides background information about the entanglement of science, industrial interests and armament, and in particular the possible reasons for the “recruitment” of Rolf Widerøe in occupied Oslo in the spring of 1943 by three German physicists mandated by the German air force, who insinuated that willingness to cooperate might well help to improve the conditions of his brother Viggo, who was in prison in Germany for helping Norwegians escape to England. The apparent motivation was that a powerful betatron could produce strong enough X-rays to neutralise allied bomber pilots. Though leading German scientists quickly discovered this to be nonsense, the betatron project was not interrupted. The book describes the difficult working conditions in Hamburg, and the progress towards a 15 MeV betatron. Among the key players was Widerøe’s assistant Bruno Touschek, who was finally arrested by the Gestapo in 1945 as his mother was Jewish. It was during this time that Widerøe patented his idea to use colliding beams to maximise the energy available, against the advice of Touschek, who found the idea too trivial to publish. It was the Touschek though, who in 1961 used first used this principle in ADA, the e⁺e^– ring in Frascati which was the first collider of the world.

Widerøe faced official prosecution on the ludicrous charge of having helped develop V2 rockets

After Widerøe’s return to Oslo in March 1945, when the betatron was operational and the advancing English army made a study of a 200 MeV betatron illusionary, he faced official prosecution on the ludicrous main charge of having helped develop V2 rockets, explains Sørheim. Released from prison after 47 days, he got away without trial, but had to pay a substantial fine. Unemployed, seeing no basis for pursuing his dream of further developing betatrons in his home country, and with the stigma of a collaborator in the understandably overheated atmosphere of the time, he moved his family to Switzerland in 1946. One chapter, strangely put near the beginning of the book, describes how Widerøe then became a successful leader of the betatron production at Brown-Boveri in Switzerland, a respected lecturer at the ETH in Zurich and a promoter of radiation therapy until late into his retirement. He was a CERN consultant in the early days, and worked with Odd Dahl and Frank Goward in Brookhaven 1952 where they became acquainted with the alternating-gradient focusing principle which was then boldly proposed to the CERN Council as basis for the design of the 25 GeV Proton Synchrotron.

The book leaves the reader somehow overwhelmed by the amount of material presented, the non-chronological presentation, and the many repetitions of the same facts, conveying the impression that the author had difficulty in putting the information in a coherent order. However, the many interviews and new documentary evidence, including a hitherto unknown letter from his brother Viggo, open novel perspectives on this extraordinary engineer and scientist who, besides receiving many honours abroad, finally also received recognition in his home country, after a lengthy reconciliation process.

A unique exercise in scientific diplomacy

The International Thermonuclear Experimental Reactor — now simply ITER — is a unique exercise in scientific diplomacy, and a politically driven project. It is also the largest international collaboration, and a milestone in the technological history of mankind. These, I would say, are the main conclusions of Michel Claessens’ new book ITER: The Giant Fusion Reactor. He unfolds a fascinating story which criss-crosses more than 40 years of the history of nuclear fusion in a simple, but not simplistic, way which is accessible to anyone with a will to stick to facts without prejudices. The full range of opinions on ITER’s controversial benefits and detriments are exposed and discussed in a fair way, and the author never hides his personal connection to the project as its head of communications for many years.

Why don’t we more resolutely pursue a technology that could contribute to the production of carbon-free energy? ITER’s path has been plagued by rivalries between strong personalities, and difficult technical and political decisions, though, in retrospect, few domains of science and technology have received such strong and continuous support from governments and agencies. Claessens’ book begins by discussing the need for fusion among other energy sources — he avoids selling fusion as the “unique and final” solution to energy problems — and quickly brings us to the heart of a key problem humanity is facing today. Travelling through history, the author shows that when politicians take decisions of high inspiration, as at the famous fireside summit between presidents Reagan and Gorbachev in Geneva in November 1985, where the idea for a collaborative project to develop fusion energy for peaceful purposes was born, they change the course of history — for the better! The book then goes through the difficulties of setting up a complex project animated by a political agenda (fusion was on the agenda of political summits between the USA and the USSR since the cold war) without a large laboratory backing it up.

The author shows that when politicians take decisions of high inspiration they change the course of history

Progress with ITER was made more difficult by a complex system of in-kind contributions which were not optimised for cost or technical success, but for political “return” to each member state of ITER (Europe, China, Japan, Russia, South Korea, the US, and most recently India). Claessens’ examples are striking, and he doesn’t skirt around the inevitable hot questions: what is the real cost of ITER? Will it even be finished given its multiple delays? How much of these extra costs and delays are due to the complex and politically oriented governance structures established by the partners? The answers are clear, honestly reported, and quantitative, though the author makes it clear that the numbers should be taken cum grano salis. Assessing the cost of a project where 90% of the components are in-kind contributions, with each partner having its own accounting structures, and in certain cases no desire to reveal the real cost, is a doubtful enterprise. However, we can say with some certainty that ITER is taking twice as long and likely costing more than double what was initially planned — and as the author says on more than one occasion, further delays will likely entail additional costs. By comparison, the LHC needed roughly an additional 25% in both budget and time compared to what was initially planned.

Price tag

Was the initial cost estimate for ITER simply too low, perhaps to help the project get approved, or would a better management, with a different governance structure, have performed better? Significantly, I have not met a single knowledgeable person who did not strongly express that ITER is a textbook case of bad management organisation, though in my opinion the book does not do justice to the energetic action of the current director general, Bernard Bigot. His directorate has been a turning point in ITER’s construction, and has set the project back on track in a moment of real crisis when many scientists and mangers expected the project to fail. A key question surfaces in the book: is the price tag important? ITER’s cost is peanuts compared to the EU’s budget, for example, and the cost is not significant by comparison to the promise it delivers: carbon-free energy in large quantities, at an affordable cost to environment, and based on widely distributed fuel.

Michel Claessens’ book explores different points of view without fanaticism

Though there is almost no intrinsic innovation in ITER, Claessens shows how the project has nevertheless pushed tokamak technology beyond its apparent limits by a sheer increase in size, though he neglects some key points, such as the incredible stored energy of the superconducting magnets. An incident similar to that suffered by the LHC in 2008 would be a logistical nightmare for ITER, as it contains more than three times the stored energy of the entire LHC and its detectors in an incomparably smaller volume. Comparisons with CERN are however a feature throughout the book, and a point of pride for high-energy physicists — clearly, CERN has set the standard for high-tech international collaboration, and ITER has tried to follow its example (CERN Courier October 2014 p45). Having begun my career as a plasma scientist, before turning to accelerators at the beginning of the 1980s, I know some of the stories and personalities involved, including CERN’s former Director General, and recognised father of ITER, Robert Aymar, and ITER’s head of superconductor procurement, my close friend Arnaud Devred, also now of CERN.

I recommend Michel Claessens’ well written and easy-to-read book. It is passionate and informative and explores different points of view without fanaticism. Interestingly, his conclusion is not scientific or political, but socio-philosophical in nature: ITER will be built because it can be, he says, according to a principle of “technological necessity”.

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