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Iran Crisis: The Impact on Oil Markets

14 January 2020

Professor Paul Stevens

Distinguished Fellow, Energy, Environment and Resources Programme
The assassination of Qassem Soleimani has exacerbated the sensitivity of oil markets to political events and brought geopolitics back into global oil prices.

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Satellite image of the Strait of Hormuz. Photo: Getty Images.

The assassination of General Qassem Soleimani has created much speculation about the possible impact on oil markets and – although any impact will very much depend upon what happens next in terms of political and military responses – theoretically the potential exists for Iran to seriously destabilize oil markets, raising oil prices.

Arguably, it would be in Iran’s interest to do so. It would certainly hurt Trump’s possibility of a second term if higher prices were to last for some time as the 2020 presidential election gets underway. And it would also help shore up Iran’s failing economy. 

The assassination did initially cause oil prices to rise by a few dollars before quickly falling back, and the missile attacks by Iran produced a similar response. However, direct action by Iran to raise prices – for example by trying to close the Strait of Hormuz – is unlikely.

Around one-fifth of the world's oil supplies passes through the Strait of Hormuz, a narrow choke point between Iran and the Arabian Peninsula. Closing it would invite serious military action by the Americans and many of its allies who, so far, have been rather lukewarm over Trump’s actions. It would also possibly limit Iran’s own oil exports.

Similarly, overt attacks on American allies in the region such as Saudi Arabia and the UAE would probably invite too heavy a reaction, although this is uncertain given the lack of response after the alleged Iranian attacks on Abqaiq and Khurais in mid-September.

Indirect action by Iran to affect oil supplies is much more likely as they have many options by using their proxies to affect others’ oil production. This is especially true for Iraq, which is now an important source of global oil supply as Iraqi exports in 2019 averaged 3.53 million barrels per day (Mb/d), a significant amount.

Iraq’s future production has already been damaged as international oil companies are withdrawing staff for safety reasons, anticipating potential attacks by both Iraqi and Iranian sources. It is now very unlikely that the crucial ‘common seawater supply project’ being run by Exxon – essential for expanding production capacity – will go ahead in the near future.

However, one important consequence of the assassination that has attracted little attention is that it has almost fully restored the role of geopolitics into the determination of oil prices. Up to 2014, geopolitics played a key role in determining oil prices in the paper markets where perceptions and expectations ruled.

Prices determined in these markets – NYMEX in New York, ICE in London and other lesser futures markets throughout the world – then influence wet barrel markets where real barrels of oil are traded. 

In 2014, the world was so oversupplied with real oil barrels that the oil price collapsed – the price of Brent crude fell from $110.72 on 23 May to $46.44 eight months later. Thereafter, little if any attention was given to geopolitical events, and geopolitics became marginalized in the determination of crude oil prices.

This began to change in 2019. The market remained physically over-supplied but events in the Gulf began to attract attention. In June, there were a series of attacks on oil tankers close to the Gulf, followed by attacks on Saudi Arabia’s Abqaiq processing facility and the Khurais oil field in September.

The Americans claimed these attacks were launched by Iran, but no convincing evidence for the claim was provided. Both attacks produced an initial price response but it was surprisingly limited and short-lived. However, it did suggest that geopolitics might be creeping back into influencing oil prices.

This became ever more noticeable in the third and fourth quarters as rumours regarding the trade talks between China and US clearly began to affect price – talks going well meant higher oil demand, and prices rose; talks going badly meant lower oil demand, and prices fell.

Meanwhile, the oil market showed signs of tightening towards the end of 2019. Although there was much cheating on the OPEC+ agreement that was trying to restrain production and protect prices, the OPEC meeting last December saw both Iraq and Nigeria agreeing to restrain production. 

US stock levels also began to fall in December and the futures markets began to price in a tightening market towards the end of 2020. Significantly, the tighter the market appears, the greater attention is paid to the level of spare producing capacity.

Just before the attack on Abqaiq, the International Energy Agency (IEA) estimated there was 3.5 Mb/d spare capacity in OPEC which, historically, is quite comfortable. However, 2.5 of this was estimated to be in Saudi Arabia, so how much of this spare capacity still existed after the Abqaiq attack?

The Saudis claimed the Abqaiq capacity was quickly restored but technical experts greeted this with considerable skepticism, not least because the Abqaiq equipment was highly specialized. If spare capacity is tight, this makes the oil price vulnerable to geopolitical scares and rumours, real or imagined. 

Although the assassination of General Soleimani has exacerbated the sensitivity of oil markets to geopolitical events, this becomes irrelevant if a serious shooting war starts in the region. Saudi Arabia, the UAE and Iraq’s oil infrastructure remains highly vulnerable to attack either directly by Iran or one of its many proxies, suggesting oil prices will become increasingly volatile but, at the same time, benefit from a rising geopolitical premium.




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Climate Action in 2020: Time to Focus on Forests

14 January 2020

Alison Hoare

Senior Research Fellow, Energy, Environment and Resources Programme
More ambitious policies to reduce deforestation are key to effective climate policy, but to succeed, they require three big changes in approach.

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Mahogany tree seedlings being taken to be planted out in the Amazon. Photo: Getty Images.

December’s UN climate talks held in Madrid were aptly titled ‘Time for Action’. While little progress was made at the conference in establishing an international framework that would help to instigate this, there is still much scope for action in 2020. The need for this has become all too apparent as the impacts of climate change are increasingly seen around the world.

One of the key areas where progress can be made in 2020 is in increasing the ambition of nationally determined contributions (NDCs), these being governments’ plans to take action in response to climate change. To date, 184 countries have submitted NDCs, yet the commitments that have been made fall far short of what is needed to avert catastrophic climate change.

In 2020, however, many countries will be revising their NDCs, presenting an important opportunity to shift momentum; to date 79 countries have announced that they will be enhancing the ambition of their NDCs.

The forest sector is one area where more ambitious targets are likely to be set, and indeed, at the Climate Action Summit in September 2019, more than 20 countries made new commitments for the conservation, reforestation and restoration of their forests.

This will be essential. As is well documented, reducing deforestation is critical to reducing carbon emissions, while healthy and diverse forests are vital for adapting and increasing resilience to climate change.

However, while it is important that ambitious targets are set, this is relatively easy; the bigger challenge lies in ensuring that these are achievable.

This is all too apparent from experience thus far. In 2014, the New York Declaration on Forests set the goal to halve forest loss by 2020, and to end it by 2030. In addition, it included the goal to restore 150 million hectares of degraded landscapes and forestlands by 2020, and a further 200 million hectares by 2030.

The declaration has been endorsed by over 50 countries, as well as business and civil society organizations, yet the 2020 goals are far from being reached – in the six years since the declaration was launched, it has been found that forest loss increased rather than declined, and only about 27 million hectares of land have been restored.

What then is needed to ensure that the commitments being made by governments in their NDCs will actually be met? Three big changes are required.

Firstly, a shift in perspective is needed in many countries to a more forest-sensitive approach to development, one that gives adequate recognition to the full range of values provided by forests, rather than primarily focusing on their role as a global carbon sink. These include their importance for local and national economies, for livelihoods and the well-being of forest-dependent peoples, and for biodiversity and the regulation of local climate and water systems.

The focus on nature-based solutions at the international level offers potential to support this shift. However, it is critical that these are not seen as ‘niche’ approaches, and that countries identify what nature-based solutions mean for them, and how forests and tree-rich landscapes can best be integrated into their development strategies.

Fundamental to achieving this will be further improvements in governance, and this is the second change that is required. Legal and institutional reforms are needed in many countries as well as significant investments in human and technical resources. This will enable processes to be strengthened, or put in place, so that equitable strategies can be developed and implemented – strategies that reflect a balance of the needs and priorities of the full range of stakeholders, including local and global, rural and urban, women and men, young and old.

Financing will of course be critical for this, and the least developed countries in particular will be hindered in the actions they can take without additional finance. This is the third area of change that is needed, and it is to be hoped that the international community will make better progress on this in 2020. Forest and land-use options are often described as a cost-effective means of tackling climate change, as is noted in the Santiago Call for Action on Forests for example.

This is not to say that these will be easy or cheap – as Chatham House has documented, experience of forest governance reform has shown that it takes significant funding and time to bring about deep-rooted change. However, the huge potential benefits that can result, for the citizens of forest-rich countries as well as for the planet, mean that forests and sustainable land-use are a good investment.




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The Indo-Pacific: Geostrategic Outlook From Now to 2024 - Workshop 5

Invitation Only Research Event

18 February 2020 - 12:00pm to 4:30pm

Langafonua Centre

This roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024. Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.

The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence. The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga).
 

Anna Aberg

Research Analyst, Energy, Environment and Resources Programme
020 7314 3629




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Global aid and faith actors: the case for an actor-orientated approach to the ‘turn to religion’

4 March 2020 , Volume 96, Number 2

Emma Tomalin

In this article, drawing on the work of the development sociologist Norman Long, I make the case for an actor-oriented approach to understanding the ‘turn to religion’ by global aid actors over the past couple of decades. I ask, is the ‘turn to religion’ evidence of the emergence of post-secular partnerships or are faith actors being instrumentalized to serve neo-liberal development goals? I argue that neither option captures the whole story and advocate that the study of religion and development needs to move beyond a binary between the ‘turn to religion’ as either evidence of post-secular partnerships or of the ‘instrumentalization’ of religion by the secular global aid business, and instead to think about how faith actors themselves encounter and shape development discourses and frameworks, translate them into relevant formats and strategically employ them. Alongside the adoption of an actor-orientated approach, I build on the work of Lewis and Mosse, Olivier de Sardan and Bierschenk to view international faith-based organizations (IFBOs) as development brokers and translators. This approach allows me to articulate the distinctive role that many members of IFBOs report they play as intermediaries who shift register between the secular development language and the faith-inspired language of their local faith partners. I take the engagement of faith actors with the new Sustainable Development Goals framework as a case-study to explore this.




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COP26 Diplomatic Briefing: Climate Ambition in Europe and its Potential Global Impact

17 February 2020 - 8:30am to 10:00am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Jacob Werksman, Principal Adviser to Directorate General for Climate Action, European Commission
Imke Lübbeke, Head of EU Climate and Energy Policy, WWF European Policy Office 
Simon Petrie, Head of International Climate Strategy - Europe, UK Department for Business, Energy and Industrial Strategy
Jen Austin, Policy Director, We Mean Business Coalition
Chair: Jill Duggan, Associate Fellow, Chatham House

The President of the European Commission, Ursula von der Leyen, has declared that she wants Europe to become ‘the first climate-neutral continent by 2050’, and in December 2019, the Commission presented the European Green Deal in order to achieve this objective. However, even though greenhouse gas emissions from the EU have fallen by more than 20 per cent since 1990, the Union remains the third largest emitter in the world, after the United States and China.

What are the opportunities and challenges for raising climate ambition in Europe?  Will the EU increase its Nationally Determined Contribution and what impact might this have globally? How might Brexit affect climate action in the EU and the UK?  The second event in the Chatham House COP26 Diplomatic Briefing Series will address these critical questions.

Anna Aberg

Research Analyst, Energy, Environment and Resources Programme
020 7314 3629




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Episode 28: The Place Beyond the Pines/From Up On Poppy Hill

  • The Place Beyond the Pines Review
  • From Up On Poppy Hill Review
  • Movie Homework: Beasts of the Southern Wild/Shame
  • What We Watched: Evil Dead, Game of Thrones, The Staircase & A Dangerous Method

Next Episode: Oblivion/Trance 




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Episode 32: Pacific Rim


  • Pacific Rim Review
  • World War Z mini-review
  • What We Watched: The Lone Ranger, Breaking Bad, Mad Men, Celeste and Jesse Forever, Despicable Me 2, Ruby Sparks, Melancholia, Do The Right Thing, ESPN 30 for 30: Broke, etc.


Next Episode: The Conjuring




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Episode 33: Upstream Color/The Kings of Summer/Blackfish


  • Upstream Color review
  • The Kings of Summer review
  • Blackfish review
  • What We Watched: Fruitvale Station, At World's End, The Spectacular Now, Elysium, Only God Forgives, and The ABCs of Death
  • Grand Theft Auto 5 talk





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Episode 39: American Hustle/The Hobbit 2/Anchorman 2/Out of the Furnace

  • American Hustle
  • The Hobbit: The Desolation of Smaug
  • Anchorman 2: The Legend Continues
  • Out of the Furnace
  • 2014 Bucket List Films
  • What We Watched: Bully, Prisoners, Powwow Highway, Miss Representation, The Spectacular Now, Knuckle, Shut Up And Play The Hits, Mike Birbiglia: My Girlfriend's Boyfriend and The Act of Killing. 


Next Episode: Martin Scorcese's The Wolf of Wall Street and Spike Jonze's Her. 




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Closing the Global Access Gap in Palliative Care and Pain Relief: A Top Priority in Achieving Universal Health Coverage

Invitation Only Research Event

17 July 2019 - 12:30pm to 5:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Tedros Adhanom Ghebreyesus, Director-General, World Health Organization 

The Lancet Commission on Palliative Care and Pain Relief estimated that in 2015, 61 million people experienced serious health-related suffering (SHS) that could have been ameliorated by palliative care. A large proportion of this burden – more than 80 per cent – fell on low- and middle-income countries (LMICs) despite an essential package of palliative care and pain relief services being cost-effective and affordable. As the director general of the World Health Organization (WHO) argues, there cannot be UHC without palliative care and thus, closing this coverage gap should be a top priority for the global UHC movement.

The Centre on Global Health Security at Chatham House, building on the momentum of the Lancet Commission, is hosting a roundtable focused on the global unmet need for palliative care and effective pain relief. The primary purpose of this roundtable is to convene leading experts, palliative care service users and advocates with key figures from the UHC movement and global health to highlight the importance of prioritizing this vital part of the continuum of care in UHC reform processes. The roundtable will serve as a scholarly discourse in translating the recommendations of the Lancet Commission into concrete actions, focusing on the political and economic dimensions.

Alexandra Squires McCarthy

Programme Coordinator, Global Health Programme
+44 (0)207 314 2789




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Acting Early, Saving Lives: Prevention and Promotion

Invitation Only Research Event

9 September 2019 - 9:00am to 5:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Universal Health Coverage (UHC) is driving the global health agenda and is embedded in the Sustainable Development Goals (SDGs). According to the World Health Organization, universal health coverage means that ‘all people and communities can use the promotive, preventive, curative, rehabilitative and palliative health services they need, of sufficient quality to be effective, while also ensuring that the use of these services does not expose the user to financial hardship’.

Despite this comprehensive starting point, it has been observed that UHC efforts to date have focused more on provision of treatment services than promotion and prevention strategies. Not only is this a missed opportunity from a financing perspective (public health interventions often offer better value for money than curative services), without robust health promotion and prevention efforts, UHC may not fulfil its potential towards reducing health inequity.

Primary health care (PHC) is a whole-of-society approach to health that aims to ensure the highest possible level of health and well-being and equitable distribution. PHC has been described as the cornerstone of UHC. As set out in the recent World Health Assembly report by the Director-General Primary health care towards universal health coverage: ‘..with its emphasis on promotion and prevention, addressing determinants and a people-centred approach, primary health care has proven to be a highly effective and efficient way to address the main causes of, and risk factors for, poor health...UHC and the health-related Sustainable Development Goals can only be sustainably achieved with a stronger emphasis on primary health care.’

The 2018 Declaration of Astana has sparked a renewed commitment to PHC. For NCD and mental health advocates there is an opportunity to now build on the foundations of PHC, to deliver more equitable, people-centred and sustainable UHC.

This event sets out why promotive and preventive health services for NCDs and mental health disorders are such an important part of UHC. It will focus on two key dimensions: the role of health promotion and preventative services within UHC in delivering health for all, and sustainable financing through innovative fiscal policy.

As one of the first high level events looking exclusively at prevention in the context of UHC, it will serve as an important reference for those going forward into the High Level Meeting on UHC as well as a unique opportunity for participants from a range of perspectives to discuss the barriers to progress.

The event is convened by Chatham House and the UK Working Group on NCDs – a coalition of over 20 UK-based NGOs with an interest in the inclusion of NCDs as an international development priority.

Objectives

  • To understand how NCD prevention and mental health promotion are a key aspect of universal health coverage.
  • To explore the case for investment in NCD prevention and mental health promotion, for both governments and donors/global health actors.
  • To share experiences of financing and delivering prevention and promotion services, and to reflect on the potential of PHC to support NCD and mental health goals.

Attendance at this event is by invitation only.

Department/project

Alexandra Squires McCarthy

Programme Coordinator, Global Health Programme
+44 (0)207 314 2789




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Tackling Toxic Air Pollution in Cities

Members Event

27 November 2019 - 6:00pm to 7:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Camilla Hodgson, Environment Reporter, Financial Times

Dr Benjamin Barratt, Senior Lecturer in Chinese Environment, KCL

Dr Susannah Stanway MBChB MSc FRCP MD, Consultant in Medical Oncology Royal Marsden NHS Foundation Trust

Elliot Treharne, Head of Air Quality, Greater London Authority

Chair: Rob Yates, Head, Centre on Global Health Security, Chatham House

Air pollution has been classified as a cancer-causing agent with evidence showing an increased risk of lung cancer associated with increasing levels of exposure to outdoor air pollution and particulate matter.

Air pollution is also known to increase risks for other diseases, especially respiratory and heart diseases, and studies show that levels of exposure to air pollution have increased significantly in some parts of the world - mostly in rapidly industrializing countries with large populations.

In coordination with London Global Cancer Week partner organizations, this event outlines the evidence linking air pollution and cancer rates in London and other major cities.

Panellists provide a 360° picture of the impact of the rising incidence of cancer across the world, the challenges the cancer pandemic poses to the implementation of universal health coverage and the existing UK contribution to strengthening capacity in cancer management and research in developing countries.

Department/project

Members Events Team




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The NHS Is Not for Sale – But a US–UK Trade Deal Could Still Have an Impact

29 November 2019

Dr Charles Clift

Senior Consulting Fellow, Global Health Programme
Charles Clift examines what recently leaked documents mean – and do not mean – for healthcare in transatlantic trade negotiations.

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Kings College Hospital in London. Photo: Getty Images.

The leaked record of the five meetings of the UK–US Trade & Investment Working Group held in 2017–18 has led to a controversy in the UK election campaign around the claim that ‘the NHS is up for sale’.

But a careful reading of the leaked documents reveals how remarkably little concerns the NHS – in five meetings over 16 months, the NHS is mentioned just four times. The patent regime and how it affects medicines is discussed in more depth but largely in terms of the participants trying to understand each other’s systems and perspectives. For the most part, the discussions were overwhelmingly about everything else a trade deal would cover other than healthcare – matters such as subsidies, rules of origin and customs facilitation.

But this does not mean there will be no impact on Britain’s health service. There are three main concerns about the possible implications of a US–UK trade deal after Brexit – a negotiation that will of course only take place if the UK remains outside the EU customs union and single market and also does not reach a trade agreement with the EU that proves incompatible with US negotiating objectives.

One concern is that the US aim of securing ‘full market access for US products’, expressed in the US negotiating objectives, will affect the ability of NICE (The National Institute for Health and Care Excellence) to prevent the NHS from procuring products that are deemed too expensive in relation to their benefits. It could also affect the ability of the NHS to negotiate with companies to secure price reductions as, for instance, happened recently with Orkambi, a cystic fibrosis drug.

A peculiarity of the main US government healthcare programme (Medicare) is that it has historically not negotiated drug prices, although there are several bills now before Congress aiming to change that. US refusal to negotiate or control prices is one reason that US drug prices are the highest in the world.  

A second concern is that the US objective of securing ‘intellectual property rights that reflect a standard of protection similar to that found in US law’ will result in longer patent terms and other forms of exclusivity that will increase the prices the NHS will have to pay for drugs.

However, it is not immediately apparent that UK standards are significantly different from those in the US – the institutional arrangements differ but the levels of protection offered are broadly comparable. Recent publicity about a potential extra NHS medicine bill of £27 billion resulting from a trade deal is based on the NHS having to pay US prices on all drugs – which seems an unlikely outcome unless the UK contingent are extraordinarily bad negotiators.

Nevertheless, in an analysis section (marked for internal distribution only), the UK lead negotiator noted: ‘The impact of some patent issues raised on NHS access to generic drugs (i.e. cheaper drugs) will be a key consideration going forward.’

A third concern is that the US objective of providing ‘fair and open conditions for services trade’ and other US negotiating objectives will oblige the UK to open up the NHS to American healthcare companies.

This is where it gets complicated. At one point in a discussion on state-owned enterprises (SOEs) the US asked if the UK had concerns about their ‘health insurance system’ (presumably a reference to the NHS). The UK response was that it ‘wouldn’t want to discuss particular health care entities at this time, you’ll be aware of certain statements saying we need to protect our needs; this would be something to discuss further down the line…’

On this exchange the UK lead negotiator commented:  ‘We do not currently believe the US has a major offensive interest in this space – not through the SOE chapter at least. Our response dealt with this for now, but we will need to be able to go into more detail about the functioning of the NHS and our views on whether or not it is engaged in commercial activities…’

On the face of it, these documents provide no basis for saying the NHS would be for sale – whatever that means exactly. The talks were simply an exploratory investigation between officials on both sides in advance of possible negotiations.

But it is a fact that US positions in free trade agreements are heavily influenced by corporate interests. Their participation in framing agreements is institutionalized in the US system and the pharmaceutical and healthcare industries in the US spend, by a large margin, more on lobbying the government than any other sector does. Moreover, President Donald Trump has long complained about ‘the global freeloading that forces American consumers to subsidize lower prices in foreign countries through higher prices in our country’.

It is when (and if) the actual negotiations on a trade deal get under way that the real test will come as the political profile and temperature is raised on both sides of the Atlantic.




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Strengthening National Accountability and Preparedness for Global Health Security (SNAP-GHS)

The project aims to identify the enablers and barriers to enhance data use by National Public Health Institutes (NPHIs), producing outputs that will facilitate strengthening of the role of NPHIs in monitoring potential public health threats, and in shaping and informing domestic policies on health security and preparedness.

Global health security is underpinned by the actions taken at a national level to ensure capacities exist to sufficiently prepare for and respond to acute threats and crises. In many contexts, National Public Health Institutes (NPHIs) were first established because of, and in response to, specific public health challenges typically related to infectious diseases.

The Strengthening National Accountability and Preparedness for Global Health Security (SNAP-GHS) project evolved from a series of roundtables and discussions hosted by the Centre on Global Health Security at Chatham House, in collaboration with the Graduate Institute of Geneva.

The outcome of the project is a SNAP-GHS Toolkit to support NPHIs in better diagnosing and understanding the challenges to data use within their own institutes, as well as in relation to external stakeholders and agencies. The toolkit is intended to be used for further circulation and dissemination by the International Association of National Public Health Institutes (IANPHI).

The project is led by the Centre on Global Health Security at Chatham House in collaboration with the Ethiopian Public Health Institute, the Nigeria Centre for Disease Control, and the National Institute for Health in Pakistan.




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The Hurdles to Developing a COVID-19 Vaccine: Why International Cooperation is Needed

23 April 2020

Professor David Salisbury CB

Associate Fellow, Global Health Programme

Dr Champa Patel

Director, Asia-Pacific Programme
While the world pins its hopes on vaccines to prevent COVID-19, there are scientific, regulatory and market hurdles to overcome. Furthermore, with geopolitical tensions and nationalistic approaches, there is a high risk that the most vulnerable will not get the life-saving interventions they need.

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A biologist works on the virus inactivation process in Belo Horizonte, Brazil on 24 March 2020. The Brazilian Ministry of Health convened The Technological Vaccine Center to conduct research on COVID-19 in order to diagnose, test and develop a vaccine. Photo: Getty Images.

On 10 January 2020, Chinese scientists released the sequence of the COVID-19 genome on the internet. This provided the starting gun for scientists around the world to start developing vaccines or therapies. With at least 80 different vaccines in development, many governments are pinning their hopes on a quick solution. However, there are many hurdles to overcome. 

Vaccine development

Firstly, vaccine development is normally a very long process to ensure vaccines are safe and effective before they are used. 

Safety is not a given: a recent dengue vaccine caused heightened disease in vaccinated children when they later were exposed to dengue, while Respiratory Syncytial Virus vaccine caused the same problem. Nor is effectiveness a given. Candidate vaccines that use novel techniques where minute fragments of the viruses’ genetic code are either injected directly into humans or incorporated into a vaccine (as is being pursued, or could be pursued for COVID-19) have higher risks of failure simply because they haven’t worked before. For some vaccines, we know what levels of immunity post-vaccination are likely to be protective. This is not the case for coronavirus. 

Clinical trials will have to be done for efficacy. This is not optional – regulators will need to know extensive testing has taken place before licencing any vaccine. Even if animal tests are done in parallel with early human tests, the remainder of the process is still lengthy. 

There is also great interest in the use of passive immunization, whereby antibodies to SARS-CoV-2 (collected from people who have recovered from infection or laboratory-created) are given to people who are currently ill. Antivirals may prove to be a quicker route than vaccine development, as the testing requirements would be shorter, manufacturing may be easier and only ill people would need to be treated, as opposed to all at-risk individuals being vaccinated.

Vaccine manufacturing

Developers, especially small biotechs, will have to make partnerships with large vaccine manufacturers in order to bring products to market. One notorious bottleneck in vaccine development is getting from proof-of-principle to commercial development: about 95 per cent of vaccines fail at this step. Another bottleneck is at the end of production. The final stages of vaccine production involve detailed testing to ensure that the vaccine meets the necessary criteria and there are always constraints on access to the technologies necessary to finalize the product. Only large vaccine manufacturers have these capacities. There is a graveyard of failed vaccine candidates that have not managed to pass through this development and manufacturing process.

Another consideration is adverse or unintended consequences. Highly specialized scientists may have to defer their work on other new vaccines to work on COVID-19 products and production of existing products may have to be set aside, raising the possibility of shortages of other essential vaccines. 

Cost is another challenge. Vaccines for industrialized markets can be very lucrative for pharmaceutical companies, but many countries have price caps on vaccines. Important lessons have been learned from the 2009 H1N1 flu pandemic when industrialized countries took all the vaccines first. Supplies were made available to lower-income countries at a lower price but this was much later in the evolution of the pandemic. For the recent Ebola outbreaks, vaccines were made available at low or no cost. 

Geopolitics may also play a role. Should countries that manufacture a vaccine share it widely with other countries or prioritize their own populations first? It has been reported that President Trump attempted to purchase CureVac, a German company with a candidate vaccine.  There are certainly precedents for countries prioritizing their own populations. With H1N1 flu in 2009, the Australian Government required a vaccine company to meet the needs of the Australian population first. 

Vaccine distribution

Global leadership and a coordinated and coherent response will be needed to ensure that any vaccine is distributed equitably. There have been recent calls for a G20 on health, but existing global bodies such as the Coalition for Epidemic Preparedness Innovations (CEPI) and GAVI are working on vaccines and worldwide access to them. Any new bodies should seek to boost funding for these entities so they can ensure products reach the most disadvantaged. 

While countries that cannot afford vaccines may be priced out of markets, access for poor, vulnerable or marginalized peoples, whether in developed or developing countries, is of concern. Developing countries are at particular risk from the impacts of COVID-19. People living in conflict-affected and fragile states – whether they are refugees or asylum seekers, internally displaced or stateless, or in detention facilities – are at especially high risk of devastating impacts. 

Mature economies will also face challenges. Equitable access to COVID-19 vaccine will be challenging where inequalities and unequal access to essential services have been compromised within some political systems. 

The need for global leadership 

There is an urgent need for international coordination on COVID-19 vaccines. While the WHO provides technical support and UNICEF acts as a procurement agency, responding to coronavirus needs clarity of global leadership that arches over national interests and is capable of mobilizing resources at a time when economies are facing painful recessions. We see vaccines as a salvation but remain ill-equipped to accelerate their development.

While everyone hopes for rapid availability of safe, effective and affordable vaccines that will be produced in sufficient quantities to meet everyone’s needs, realistically, we face huge hurdles. 




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Coronavirus Vaccine: Available For All, or When it's Your Turn?

4 May 2020

Professor David Salisbury CB

Associate Fellow, Global Health Programme
Despite high-level commitments and pledges to cooperate to ensure equitable global access to a coronavirus vaccine, prospects for fair distribution are uncertain.

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Researcher in Brazil working on virus replication in order to develop a vaccine against the coronavirus. Photo by DOUGLAS MAGNO/AFP via Getty Images.

When the H1N1 influenza pandemic struck in 2009, some industrialized countries were well prepared. Many countries’ preparedness plans had focused on preparing for an influenza pandemic and based on earlier alerts over the H5N1 ‘bird flu’ virus, countries had made advanced purchase or ‘sleeping’ contracts for vaccine supplies that could be activated as soon as a pandemic was declared. Countries without contracts scrambled to get supplies after those that already had contracts received their vaccine.

Following the 2009 pandemic, the European Union (EU) developed plans for joint-purchase vaccine contracts that any member state could join, guaranteeing the same price per dose for everyone. In 2009, low-income countries were unable to get the vaccine until manufacturers agreed to let 10 per cent of their production go to the World Health Organization (WHO).

The situation for COVID-19 could be even worse. No country had a sleeping contract in place for a COVID-19 vaccine since nobody had anticipated that the next pandemic would be a coronavirus, not an influenza virus. With around 80 candidate vaccines reported to be in development, choosing the right one will be like playing roulette.

These candidates will be whittled down as some will fail at an early stage of development and others will not get to scale-up for manufacturing. All of the world’s major vaccine pharmaceutical companies have said that they will divert resources to manufacture COVID-19 vaccines and, as long as they choose the right candidate for production, they have the expertise and the capacity to produce in huge quantities.

From roulette to a horse race

Our game now changes from roulette to a horse race, as the probability of winning is a matter of odds not a random chance. Countries are now able to try to make contracts alone or in purchasing consortia with other states, and with one of the major companies or with multiple companies. This would be like betting on one of the favourites.

For example, it has been reported that Oxford University has made an agreement with pharmaceutical company AstraZeneca, with a possibility of 100 million doses being available by the end of 2020. If the vaccine works and those doses materialize, and are all available for the UK, then the UK population requirements will be met in full, and the challenge becomes vaccinating everyone as quickly as possible.

Even if half of the doses were reserved for the UK, all those in high-risk or occupational groups could be vaccinated rapidly. However, as each major manufacturer accepts more contracts, the quantity that each country will get diminishes and the time to vaccinate the at-risk population gets longer.

At this point, it is not known how manufacturers will respond to requests for vaccine and how they will apportion supplies between different markets. You could bet on an outsider. You study the field and select a biotech that has potential with a good production development programme and a tie-in with a smaller-scale production facility.

If other countries do not try to get contracts, you will get your vaccine as fast as manufacturing can be scaled up; but because it is a small manufacturer, your supplies may take a long time. And outsiders do not often win races. You can of course, depending on your resources, cover several runners and try to make multiple contracts. However, you take on the risk that some will fail, and you may have compromised your eventual supply.

On April 24, the WHO co-hosted a meeting with the president of France, the president of the European Commission and the Bill & Melinda Gates Foundation. It brought together heads of state and industry leaders who committed to ‘work towards equitable global access based on an unprecedented level of partnership’. They agreed ‘to create a strong unified voice, to build on past experience and to be accountable to the world, to communities and to one another’ for vaccines, testing materials and treatments.

They did not, however, say how this will be achieved and the absence of the United States was notable. The EU and its partners are hosting an international pledging conference on May 4 that aims to raise €7.5 billion in initial funding to kick-start global cooperation on vaccines. Co-hosts will be France, Germany, Italy, the United Kingdom, Norway and Saudi Arabia and the priorities will be ‘Test, Treat and Prevent’, with the latter dedicated to vaccines.

Despite these expressions of altruism, every government will face the tension between wanting to protect their own populations as quickly as possible and knowing that this will disadvantage poorer countries, where health services are even less able to cope. It will not be a vote winner to offer a share in available vaccine to less-privileged countries.

The factories for the biggest vaccine manufacturers are in Europe, the US and India. Will European manufacturers be obliged by the EU to restrict sales first to European countries? Will the US invoke its Defense Production Act and block vaccine exports until there are stocks enough for every American? And will vaccine only be available in India for those who can afford it?

The lessons on vaccine availability from the 2009 influenza pandemic are clear: vaccine was not shared on anything like an equitable basis. It remains to be seen if we will do any better in 2020.




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SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect FA translocation [Research Articles]

Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focused on sulfosuccinimidyl oleate (SSO), reported to be a competitive inhibitor of CD36-mediated LCFA transport. Using these assays in adipocytes and inhibitor-treated protein-free lipid vesicles, we demonstrate that rapid LCFA transport across model and biological membranes remains unchanged in the presence of these purported inhibitors. We have previously shown in live cells that CD36 does not accelerate the transport of unesterified LCFAs across the PM. Our present experiments indicated disruption of LCFA metabolism inside the cell within minutes upon treatment with many of the "inhibitors" previously assumed to inhibit LCFA transport across the PM. Furthermore, using confocal microscopy and a specific anti-SSO antibody, we found that numerous intracellular and PM-bound proteins are SSO-modified in addition to CD36. Our results support the hypothesis that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter for their transmembrane movement.




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Hepatic monoamine oxidase B is involved in endogenous geranylgeranoic acid synthesis in mammalian liver cells [Research Articles]

Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from 13C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been suggested to be involved in GGOH oxidation. Here, using two human hepatoma cell lines, we investigated whether MAOB contributes to GGA biosynthesis. Using either HuH-7 cell lysates or recombinant human MAOB, we found that: 1) the MAO inhibitor tranylcypromine dose-dependently downregulates endogenous GGA levels in HuH-7 cells; and 2) siRNA-mediated MAOB silencing reduces intracellular GGA levels in HuH-7 and Hep3B cells. Unexpectedly, however, CRISPR/Cas9-generated MAOB-KO human hepatoma Hep3B cells had GGA levels similar to those in MAOB-WT cells. A sensitivity of GGA levels to siRNA-mediated MAOB downregulation was recovered when the MAOB-KO cells were transfected with a MAOB-expression plasmid, suggesting that MAOB is the enzyme primarily responsible for GGOH oxidation and that some other latent metabolic pathways may maintain endogenous GGA levels in the MAOB-KO hepatoma cells. Along with the previous findings, these results provide critical insights into the biological roles of human MAOB and provide evidence that hepatic MAOB is involved in endogenous GGA biosynthesis via GGOH oxidation.




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Slc43a3 is a regulator of free fatty acid flux [Research Articles]

Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. To identify potential membrane proteins that are involved in regulating FA flux in adipocytes, the expression levels of 55 membrane transporters without known function were screened in subcutaneous adipose samples from obese patients before and after bariatric surgery using branched DNA methodology. Among the 33 solute carrier (SLC) transporter family members screened, the expression of 14 members showed significant changes before and after bariatric surgery. One of them, Slc43a3, increased about 2.5-fold after bariatric surgery. Further investigation demonstrated that Slc43a3 is highly expressed in murine adipose tissue and induced during adipocyte differentiation in primary preadipocytes and in OP9 cells. Knockdown of Slc43a3 with siRNA in differentiated OP9 adipocytes reduced both basal and forskolin-stimulated FA efflux, while also increasing FA uptake and lipid droplet accumulation. In contrast, overexpression of Slc43a3 decreased FA uptake in differentiated OP9 cells and resulted in decreased lipid droplet accumulation. Therefore, Slc43a3 seems to regulate FA flux in adipocytes, functioning as a positive regulator of FA efflux and as a negative regulator of FA uptake.




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The grease trap: uncovering the mechanism of the hydrophobic lid in Cutibacterium acnes lipase [Research Articles]

Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. Cutibacterium acnes is known as a major acne-associated bacterium that derives energy from lipase-mediated sebum lipid degradation. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. For example, higher populations of the type IA strains are present in acne lesions with higher lipase activity. In the present study, we examined a conserved lipase in types IB and II that was truncated in type IA C. acnes strains. Closed, blocked, and open structures of C. acnes ATCC11828 lipases were elucidated by X-ray crystallography at 1.6–2.4 Å. The closed crystal structure, which is the most common form in aqueous solution, revealed that a hydrophobic lid domain shields the active site. By comparing closed, blocked, and open structures, we found that the lid domain-opening mechanisms of C. acnes lipases (CAlipases) involve the lid-opening residues, Phe-179 and Phe-211. To the best of our knowledge, this is the first structure-function study of CAlipases, which may help to shed light on the mechanisms involved in acne development and may aid in future drug design.




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The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes [Thematic Reviews]

Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.




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Commentary on SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect fatty acid translocation [Commentaries]




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Membrane domains beyond the reach of microscopy [Commentaries]












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Liberalism’s betrayal of itself—and the way back

Source

The Economist

Release date

14 February 2019

Expert

Hans Kundnani

In the news type

Op-ed

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X-ray structures of catalytic intermediates of cytochrome c oxidase provide insights into its O2 activation and unidirectional proton-pump mechanisms [Molecular Biophysics]

Cytochrome c oxidase (CcO) reduces O2 to water, coupled with a proton-pumping process. The structure of the O2-reduction site of CcO contains two reducing equivalents, Fea32+ and CuB1+, and suggests that a peroxide-bound state (Fea33+–O−–O−–CuB2+) rather than an O2-bound state (Fea32+–O2) is the initial catalytic intermediate. Unexpectedly, however, resonance Raman spectroscopy results have shown that the initial intermediate is Fea32+–O2, whereas Fea33+–O−–O−–CuB2+ is undetectable. Based on X-ray structures of static noncatalytic CcO forms and mutation analyses for bovine CcO, a proton-pumping mechanism has been proposed. It involves a proton-conducting pathway (the H-pathway) comprising a tandem hydrogen-bond network and a water channel located between the N- and P-side surfaces. However, a system for unidirectional proton-transport has not been experimentally identified. Here, an essentially identical X-ray structure for the two catalytic intermediates (P and F) of bovine CcO was determined at 1.8 Å resolution. A 1.70 Å Fe–O distance of the ferryl center could best be described as Fea34+ = O2−, not as Fea34+–OH−. The distance suggests an ∼800-cm−1 Raman stretching band. We found an interstitial water molecule that could trigger a rapid proton-coupled electron transfer from tyrosine-OH to the slowly forming Fea33+–O−–O−–CuB2+ state, preventing its detection, consistent with the unexpected Raman results. The H-pathway structures of both intermediates indicated that during proton-pumping from the hydrogen-bond network to the P-side, a transmembrane helix closes the water channel connecting the N-side with the hydrogen-bond network, facilitating unidirectional proton-pumping during the P-to-F transition.




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RNA helicase-regulated processing of the Synechocystis rimO-crhR operon results in differential cistron expression and accumulation of two sRNAs [Gene Regulation]

The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts.




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Unified approach to critical-contrast homogenisation with explicit links to time-dispersive media

K. D. Cherednichenko, Yu. Yu. Ershova, A. V. Kiselev and S. N. Naboko
Trans. Moscow Math. Soc. 80 (2020), 251-294.
Abstract, references and article information




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On the existence of an operator group generated by the one-dimensional Dirac system

A. M. Savchuk and I. V. Sadovnichaya
Trans. Moscow Math. Soc. 80 (2020), 235-250.
Abstract, references and article information




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An explicit form for extremal functions in the embedding constant problem for Sobolev spaces

I. A. Sheipak and T. A. Garmanova
Trans. Moscow Math. Soc. 80 (2020), 189-210.
Abstract, references and article information




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Spectral analysis and representation of solutions of integro-differential equations with fractional exponential kernels

V. V. Vlasov and N. A. Rautian
Trans. Moscow Math. Soc. 80 (2020), 169-188.
Abstract, references and article information







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GoDaddy – “unauthorized individual” had access to login info

Web hosting behemoth GoDaddy just filed a data breach notification with the US state of California.




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Air gap security beaten by turning PC capacitors into speakers

Researchers have poked another small hole in air gapped security by showing how the electronics inside computer power supply units (PSUs) can be turned into covert data transmission devices.




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Police nab InfinityBlack hackers

Five alleged members of hacking group InfinityBlack got some unexpected visitors last week when Polish law enforcement arrested them.