Nuclear stability for all put at risk by Putin's speech Explainer NCapeling 22 February 2023

Explaining the risks of Russia’s decision to suspend the New START nuclear treaty with the US, and the wider implications for international relations.

Why is New START important?

Following the collapse of the Intermediate-range Nuclear Forces treaty (INF), New START is the only remaining nuclear arms control treaty between the US and Russia.

This means that without it there would be no limits on numbers or the type of Russian and US deployed nuclear warheads. The limits set under New START are lower than those set under its predecessor, the Strategic Arms Reduction Treaty (START).

It is also important for maintaining some form of strategic arms control between Russia and the US. The treaty provides the US and Russia with mechanisms for transparency and confidence-building, for instance through regular biannual data exchanges, as well as measures for verification.

What is Russia able to do next after suspending participation?

President Vladimir Putin’s decision to suspend its participation could pave the way for Russia to increase the number of deployed warheads, delivery vehicles and launchers, potentially exceeding the limits placed on numbers under the new START.

Putin stated he would resume testing of nuclear weapons if the US resumed – Russia is a full state party to the nuclear Comprehensive Test Ban Treaty (CTBT) negotiated in 1996, as is the UK and France. The US has signed, as has China, but neither state has yet ratified the treaty.

Other countries required to ratify the treaty for it to enter into force include Egypt, India, Iran, Israel, North Korea, and Pakistan.

Although the US is modernizing its nuclear weapons forces, there is no need – or plan – for the US to test nuclear warheads, and it is the same for the UK and France.

Concerns are now rising that Russia could point to no-fissionable yield experiments – which are allowed under the treaty and which the US and other nuclear weapons possessors conduct primarily for safety purposes – and then falsely declare those to be nuclear weapons tests, thus paving the way for a narrative to justify the resumption of nuclear testing by Russia.

Conducting a nuclear weapons test would be seen clearly as a further step on the escalation scale towards nuclear use for Russia.

While inspections of nuclear weapons sites had not resumed since COVID-19, Russia’s suspension of its participation could result in the further halting of other transparency and verification measures under New START, including the regular mutual data exchanges between the US and Russia – for example on warhead numbers, locations, and technical information on weapons systems and their sites – which are conducted through the Bilateral Consultative Commission (BCC).

What is the difference between withdrawing from New START and ‘suspending’ participation?

In his speech, Putin announced the suspension of Russian participation in New START. While this does not mean Russia has formally withdrawn from the treaty, the suspension could enable Russia to continue preventing the US from inspecting its nuclear weapons sites and halt Russia’s participation in other obligations, such as the routine reporting and data exchanges on nuclear weapons as well as meetings of the BCC.

The decision to suspend participation rather than withdraw from the treaty means Russia retains the option to return to compliance at a later point. However, it is not yet clear under what conditions Russia would opt to return to compliance with the treaty, or whether this means the US will, in turn, suspend their own obligations.

The treaty text itself does not provide for a suspension of participation by parties to the treaty. However, the Vienna Convention on the Law of Treaties does address the mechanisms for suspension of participation in a treaty. Russia is a full state party to the Vienna Convention, but the US has remained a signatory without ratification since 1970.

There is a precedent of Russia suspending its membership in arms control treaties rather than withdrawing, which is when Russia suspended its participation in the original Treaty on Conventional Armed Forces in Europe (CFE) in 2007.

The US does not recognize Russia’s suspension of its participation in the CFE treaty, but this does not make a material difference to Russian actions.

What does the suspension mean for the wider international treaty regime?

Russia’s suspension of the New START could signal the end of strategic arms control between the two countries. There is now virtually no regular scheduled arms control communication between the two countries bilaterally – this is a dangerous position to be in, especially in times of crisis.

The suspension of New START further erodes limited recourse for communication between the two countries, by suspending information exchange and meetings of the BCC under the treaty.

This is likely to have wider implications for progress on nuclear non-proliferation under the Treaty on the Non-Proliferation of Nuclear Weapons (NPT), as well as the wider international security treaty regime.

Will this increase the nuclear threat or the likelihood of nuclear use?

New START provides both the US and Russia with a degree of transparency surrounding nuclear weapons systems. Without an avenue for regular data exchange and notification, and mechanisms for verification through mutual nuclear weapons site inspections, the risk of misperception or misunderstanding could increase and fuel uncertainty which could increases the perception of threat between Russia and the US.

What are Putin’s reasons for suspending Russia’s participation?

Putin and various members of his government have been linking the future of New START to the war in Ukraine rhetorically for several months now, threatening that Russia may not be willing to negotiate a follow-on treaty for when New START expires in Feb 2026 because of US support for Ukraine.

By announcing Russia’s suspension of the treaty in his main address on the anniversary of the invasion of Ukraine, Putin is sending a signal about Russia’s intent for the future.

Russia’s new hypersonic glide vehicle Avangard was already counted under New START and it is likely follow-on negotiations would have focused on some of Russia’s other hypersonic capabilities or other new nuclear systems.

Without the treaty, Russia might be less inhibited in its development of new nuclear systems.

Have both the US and Russia been compliant with the treaty until now?

Both the US and Russia have remained within the central limits of the treaty since its entry into force in 2011. Following the outbreak of COVID-19, both sides agreed to suspend in-person inspections due to restrictions on travel, and attempts to recommence in-person inspections in 2022 were unsuccessful.

In August 2022, Russia prevented US on-site inspections under New START and a November 2022 meeting of the BCC was called off by Russian officials. Russia has blamed both the ongoing COVID-19 pandemic and the sanctions burden on Russia as reasons for not wanting to resume inspections.

SVB collapse shows interest rate financial stability threat Expert comment LJefferson 15 March 2023

Governments must resist pressure to relax post-financial crisis regulation, while central banks should moderate their attack on inflation if financial stability is at risk.

The collapse of California’s Silicon Valley Bank (SVB) on 10 March has triggered a wave of volatility in global bank equity prices, raised questions about whether US bank regulation and its tech industry funding model are fit for purpose, and forced a rethink on the extent and pace of monetary policy tightening appropriate for the US and other advanced economies.

SVB was the US’s 16th largest bank with total assets of $212bn at the end of 2022 and a presence in eight countries around the world, including the UK. Since it was founded 40 years ago, it has maintained a strong focus on the technology sector, claiming recently that nearly half of all US venture-backed technology and life science companies banked with it. Partly as a consequence, some 95 per cent of its deposits came from corporates and hedge funds, far higher than the one-third typical of similarly sized banks.

What led to SVB’s collapse?

Ironically, SVB’s failure did not result from its core business model of serving a relatively high-risk and fast-growing sector, but rather from a dramatic failure in liquidity management. During the pandemic, SVB saw a very large inflow of corporate deposits. But rather than disincentivizing depositors or investing the funds attracted in assets of matching maturity, it chose to invest them in low credit risk, but long maturity bonds attracted by a small pick-up in return over shorter-term assets. 

When US interest rates began to rise rapidly in 2022 following Russia’s invasion of Ukraine, the value of SVB’s long-term bond portfolio declined sharply. It was left facing a large capital loss of some $15bn, roughly equivalent to its total shareholder funds. The management attempted to repair SVB’s balance sheet last week by crystalizing some of the loss and raising new capital.

But when this failed, the US supervisory authorities had no choice but to step in and close the institution.  This action was quickly followed by emergency action from other regulators vis-a-vis SVB subsidiaries and offices around the world.

The US entity has formally been taken over by the FDIC and a bridge bank established. All depositors have had their funds guaranteed, going beyond the normal federal deposit insurance limit of $250,000 per customer. However, bond holders and equity holders have been wiped out. The authorities have said that any loss will be covered by the industry as a whole via the FDIC.

In the UK, the Bank of England was able to sell the ring-fenced UK subsidiary of SVB to HSBC for £1 over the weekend, so that all its depositors and other liability holders have effectively had their funds guaranteed. In contrast to previous Bank of England rescues (such as Johnson Matthey Bank in 1984, the ‘small banks’ crisis in 1991 and the global financial crisis in 2008-9) no public money has been put at risk.

Four key questions

SVB’s rapid collapse raises four central questions:

First, how was it that the bank was able to take on such a risky interest rate maturity mismatch in its US operations? Maturity transformation is standard banking industry practice, but it is usually closely monitored by regulators who place limits on the extent of interest rate maturity mismatch and require liquidity buffers to offset the risk of deposit flight and forced asset sales.

SVB’s very high concentration of corporate deposits as compared to ‘sticky’ retail deposits, means that the risk of deposit flight was unusually high and so the bank should have been more, not less, cautious in its liquidity policy. SVB was classed as a regional bank in the US which means that it did not have to meet international regulatory standards under Basle III. And in 2018, the Trump administration approved legislation removing the post-financial crisis requirement that banks with assets under $250bn submit to stress testing and relaxing liquidity buffer requirements.

But it is still hard to understand why regulators allowed SVB to commit such a classic banking error. On Monday, the Federal Reserve ordered an inquiry into what it has correctly described as a regulatory failure. This should look at the role played by all the elements of the oversight system including the auditors, KPMG.

Second, does SVB’s failure reflect a much bigger underlying risk in the US banking sector, and potentially other banking systems around the world, built up over the prolonged period of ultra-low interest rates? SVB’s collapse was followed by the failure of the $110bn Signature Bank in New York, as well as sharp falls in US regional bank stock prices – by close of play on 14 March, the S&P Regional Bank Index was down 22 per cent on a week before, with some individual bank stocks seeing much sharper falls.  

To the extent that banks have been covered by international bank regulatory requirements, the risk of a much broader problem should be limited because stress testing and other regulatory tests would have looked at precisely the scenario that has happened. Even where large market losses have been incurred, capital buffers should be sufficient to cover them. But as SVB has shown, there are some large banks that are seemingly not required to follow international rules, while the latest developments at Credit Suisse indicate that market concerns may still arise when other factors are in play.

Third, how far, in the light of the potential vulnerability in banking systems, should central banks in advanced countries moderate their efforts to squeeze out inflationary pressures? While inflation already appears to have peaked in many economies and the pace of interest rate rises was expected to slow, inflation is far from vanquished, as recent data in the US has demonstrated.

Fourth, does the failure of SVB tell us something new about the financial risks facing the high technology sector?  It was remarkable that a single (and not particularly large, by international standards) financial institution could have played such a central role in the tech sector in both the US and UK. 

Why was this the case and does it reflect special features of the tech/start-up sector (e.g. the need for substantial cash deposits to cover relatively large negative cash flows in the early years of operation, or the need for highly specialized lending expertise). If so, should governments take steps to mitigate such risks, given the outsized importance of this sector in many national economic strategies? 

Steven A. Carr
Mar 1, 2014; 13:907-917
Technological Innovation and Resources

Ivan Matic
Jan 1, 2008; 7:132-144
Research

Mitsunori Fukuda
Jun 1, 2008; 7:1031-1042
Research

Tamar Geiger
Mar 1, 2012; 11:M111.014050-M111.014050
Special Issue: Prospects in Space and Time

Sebastian A. Wagner
Oct 1, 2011; 10:M111.013284-M111.013284
Research

Joris J. Benschop
Jul 1, 2007; 6:1198-1214
Research

Christian Tagwerker
Apr 1, 2006; 5:737-748
Research

Ignat V. Shilov
Sep 1, 2007; 6:1638-1655
Technology

Ulrich Rothbauer
Feb 1, 2008; 7:282-289
Research

Jesper V. Olsen
Dec 1, 2005; 4:2010-2021
Technology

Eiji Kinoshita
Apr 1, 2006; 5:749-757
Technology

Staphylococcus aureus adhesion to the host's skin and mucosae enables asymptomatic colonization and the establishment of infection. This process is facilitated by cell wall-anchored adhesins that bind to host ligands. Therapeutics targeting this process could provide significant clinical benefits; however, the development of anti-adhesives requires an in-depth knowledge of adhesion-associated factors and an assay amenable to high-throughput applications. Here, we describe the development of a sensitive and robust whole cell assay to enable the large-scale profiling of S. aureus adhesion to host ligands. To validate the assay, and to gain insight into cellular factors contributing to adhesion, we profiled a sequence-defined S. aureus transposon mutant library, identifying mutants with attenuated adhesion to human-derived fibronectin, keratin, and fibrinogen. Our screening approach was validated by the identification of known adhesion-related proteins, such as the housekeeping sortase responsible for covalently linking adhesins to the cell wall. In addition, we also identified genetic loci that could represent undescribed anti-adhesive targets. To compare and contrast the genetic requirements of adhesion to each host ligand, we generated a S. aureus Genetic Adhesion Network, which identified a core gene set involved in adhesion to all three host ligands, and unique genetic signatures. In summary, this assay will enable high-throughput chemical screens to identify anti-adhesives and our findings provide insight into the target space of such an approach.

Despite its major importance in human health, the metabolic potential of the human gut microbiota is still poorly understood. We have recently shown that biosynthesis of Ruminococcin C (RumC), a novel ribosomally synthesized and posttranslationally modified peptide (RiPP) produced by the commensal bacterium Ruminococcus gnavus, requires two radical SAM enzymes (RumMC1 and RumMC2) catalyzing the formation of four Cα-thioether bridges. These bridges, which are essential for RumC's antibiotic properties against human pathogens such as Clostridium perfringens, define two hairpin domains giving this sactipeptide (sulfur-to-α-carbon thioether–containing peptide) an unusual architecture among natural products. We report here the biochemical and spectroscopic characterizations of RumMC2. EPR spectroscopy and mutagenesis data support that RumMC2 is a member of the large family of SPASM domain radical SAM enzymes characterized by the presence of three [4Fe-4S] clusters. We also demonstrate that this enzyme initiates its reaction by Cα H-atom abstraction and is able to catalyze the formation of nonnatural thioether bonds in engineered peptide substrates. Unexpectedly, our data support the formation of a ketoimine rather than an α,β-dehydro-amino acid intermediate during Cα-thioether bridge LC–MS/MS fragmentation. Finally, we explored the roles of the leader peptide and of the RiPP precursor peptide recognition element, present in myriad RiPP-modifying enzymes. Collectively, our data support a more complex role for the peptide recognition element and the core peptide for the installation of posttranslational modifications in RiPPs than previously anticipated and suggest a possible reaction intermediate for thioether bond formation.

HIV Type 1 (HIV-1) and simian immunodeficiency virus (SIV) display differential replication kinetics in macrophages. This is because high expression levels of the active host deoxynucleotide triphosphohydrolase sterile α motif domain and histidine-aspartate domain–containing protein 1 (SAMHD1) deplete intracellular dNTPs, which restrict HIV-1 reverse transcription, and result in a restrictive infection in this myeloid cell type. Some SIVs overcome SAMHD1 restriction using viral protein X (Vpx), a viral accessory protein that induces proteasomal degradation of SAMHD1, increasing cellular dNTP concentrations and enabling efficient proviral DNA synthesis. We previously reported that SAMHD1-noncounteracting lentiviruses may have evolved to harbor RT proteins that efficiently polymerize DNA, even at low dNTP concentrations, to circumvent SAMHD1 restriction. Here we investigated whether RTs from SIVmac239 virus lacking a Vpx protein evolve during in vivo infection to more efficiently synthesize DNA at the low dNTP concentrations found in macrophages. Sequence analysis of RTs cloned from Vpx (+) and Vpx (−) SIVmac239–infected animals revealed that Vpx (−) RTs contained more extensive mutations than Vpx (+) RTs. Although the amino acid substitutions were dispersed indiscriminately across the protein, steady-state and pre-steady-state analysis demonstrated that selected SIVmac239 Vpx (−) RTs are characterized by higher catalytic efficiency and incorporation efficiency values than RTs cloned from SIVmac239 Vpx (+) infections. Overall, this study supports the possibility that the loss of Vpx may generate in vivo SIVmac239 RT variants that can counteract the limited availability of dNTP substrate in macrophages.

Candida albicans and Aspergillus fumigatus are dangerous fungal pathogens with high morbidity and mortality, particularly in immunocompromised patients. Innate immune-mediated programmed cell death (pyroptosis, apoptosis, necroptosis) is an integral part of host defense against pathogens. Inflammasomes, which are canonically formed upstream of pyroptosis, have been characterized as key mediators of fungal sensing and drivers of proinflammatory responses. However, the specific cell death pathways and key upstream sensors activated in the context of Candida and Aspergillus infections are unknown. Here, we report that C. albicans and A. fumigatus infection induced inflammatory programmed cell death in the form of pyroptosis, apoptosis, and necroptosis (PANoptosis). Further, we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as the apical sensor of fungal infection responsible for activating the inflammasome/pyroptosis, apoptosis, and necroptosis. The Zα2 domain of ZBP1 was required to promote this inflammasome activation and PANoptosis. Overall, our results demonstrate that C. albicans and A. fumigatus induce PANoptosis and that ZBP1 plays a vital role in inflammasome activation and PANoptosis in response to fungal pathogens.

Lys234 is one of the residues present in class A β-lactamases that is under selective pressure due to antibiotic use. Located adjacent to proton shuttle residue Ser130, it is suggested to play a role in proton transfer during catalysis of the antibiotics. The mechanism underpinning how substitutions in this position modulate inhibitor efficiency and substrate specificity leading to drug resistance is unclear. The K234R substitution identified in several inhibitor-resistant β-lactamase variants is associated with decreased potency of the inhibitor clavulanic acid, which is used in combination with amoxicillin to overcome β-lactamase–mediated antibiotic resistance. Here we show that for CTX-M-14 β-lactamase, whereas Lys234 is required for hydrolysis of cephalosporins such as cefotaxime, either lysine or arginine is sufficient for hydrolysis of ampicillin. Further, by determining the acylation and deacylation rates for cefotaxime hydrolysis, we show that both rates are fast, and neither is rate-limiting. The K234R substitution causes a 1500-fold decrease in the cefotaxime acylation rate but a 5-fold increase in kcat for ampicillin, suggesting that the K234R enzyme is a good penicillinase but a poor cephalosporinase due to slow acylation. Structural results suggest that the slow acylation by the K234R enzyme is due to a conformational change in Ser130, and this change also leads to decreased inhibition potency of clavulanic acid. Because other inhibitor resistance mutations also act through changes at Ser130 and such changes drastically reduce cephalosporin but not penicillin hydrolysis, we suggest that clavulanic acid paired with an oxyimino-cephalosporin rather than penicillin would impede the evolution of resistance.

Time to accelerate the sustainability pivot Expert comment NCapeling 26 May 2021

Higher stakes make it more important than ever to safeguard the integrity of sustainability commitments, and ensure high quality in delivery and implementation.

Regular headlines reaffirm the rise of sustainability on the global stage. Political momentum behind climate action has not been derailed by COVID-19, sustainability is increasingly central to national political debates, and what once might have been confined to scientific pursuits and UN conferences has now percolated through to international financial affairs and the wider political summits.

Much is made of the scale of the challenge, from climate change, water stresses, and biodiversity loss to the looming spectre of environment-induced societal breakdown triggering unprecedented civilizational challenges on the back of decades of systemic neglect over the true cost of social and environmental imbalances and unencumbered consumption.

But the good news is that talk of sustainability solutions is picking up pace and growing in its reach into the mainstream. The Wall Street Journal recently charted the shift of sustainable finance from being a niche interest of socially conscious investors into a sustainable ‘gold rush’, further bolstering its financial credentials with trillions of dollars designated for the global energy transition.

Assets in investment funds with links to the environment came to almost $2 trillion globally in the first quarter of 2021, more than tripling in just three years, and investors are putting some $3 billion a day into these funds while bonds and loans worth $5 billion looking to bankroll green initiatives are issued every day.

Climate ambitions and power diplomacy

Should the number of zeros fail to persuade, other signs of a sustainability pivot abound. Climate ambition was the driving force in major power diplomacy as France, Germany, China, and the US jostled for leadership positions in a high octane theatre of ‘climate one upmanship’ in the run-up to the Climate Summit hosted by US president Joe Biden. The G7 has agreed to stop international financing of coal projects, and an International Energy Agency report says delivering net zero emissions by 2050 means no new coal, oil, or gas development from now on.

Governments are sending unmistakable policy signals which are redrawing multiple frontiers of the real economy, such as the banning of single use plastic in multiple jurisdictions from Europe, China, and more than 30 African states as well as New York and California. The sale of internal combustion engine vehicles is also set to end by 2035 or sooner in the EU, the UK, and California, and China is expected to follow suit with similar plans. France has proposed a ban on domestic flights when there are less carbon intensive alternatives on the ground.

But these signals did not spring out of a political vacuum. A global climate poll conducted by the United Nations (UN) in 50 countries showed two-thirds of the 1.2 million people polled thought there is a global climate emergency, and most indicated their support for stronger climate action even in countries with strong fossil energy interest.

Real economy responses to noticeable changes in risk calculus and political appetite will likely underpin further rapid shifts in market sentiment as investors begin to fully factor in the scale of the challenge and escalate their interrogation of company-level climate action plans.

Rapid pace of change still needed

But despite this ever-clearer direction of travel and growing availability of new technology and policy options, the need for speed remains. The rationale for moving fast in the next decade and a half to avoid the clear and present threats of environmental and breakdown is increasingly clear.

Getting up to scale is an ongoing and daunting challenge not least because exponential growth has brought growing pains. The recent spat over the definition and the usefulness of net zero targets for corporations and investors as seen in the shareholder votes over the climate plans put forward by Shell and other companies are all testimony to the challenge of mainstreaming.

While some have characterized these debates as political infighting, the reality is higher stakes simply mean it is more important than ever to safeguard the integrity of sustainability commitments as well as the quality of their delivery and implementation.

The move from ‘what’ to ‘how’ points to a clear demand for new, innovative collaborative efforts to help mitigate myriad political economy challenges associated with the upcoming great transition and ensure this sustainability pivot will deliver the promised outcomes. Launching the Chatham House Sustainability Accelerator in support of these once-in-a-generation efforts is a proud moment for the institute, and a clear sign that this pivot to sustainability is here to stay.

The Platinum Jubilee of Her Majesty Queen Elizabeth II News release NCapeling 1 June 2022

The staff, associate fellows and Council of the Royal Institute of International Affairs at Chatham House send congratulations and warmest wishes to Her Majesty Queen Elizabeth II on the occasion of her momentous Platinum Jubilee.

As the Patron of the institute since her accession to the throne in 1952, HM The Queen has underpinned Chatham House’s independence for seven decades and thereby strengthened the impact of our work on the critical issues facing the world.

HM The Queen lent her personal support to the establishment of the annual Chatham House Prize in 2005 and has presented the award in person on behalf of the institute’s members on three occasions.

Among her other direct engagements with Chatham House, HM The Queen has helped us engage the next generation by supporting and then attending the launch of the Queen Elizabeth II Academy for Leadership in International Affairs in 2014, when she met the first intake of Academy fellows.

We are enormously grateful for her continued involvement as Patron of the institute and wish her and the Royal Family a memorable Platinum Jubilee.

Robin Niblett awarded knighthood in Queen's Birthday Honours News release NCapeling 1 June 2022

Chatham House director Dr Robin Niblett CMG receives a knighthood for services to international relations and to British foreign policy.

Chatham House Council and staff congratulate the institute’s director Robin Niblett, who has been appointed as a Knight Commander of the Order of St Michael and St George (KCMG) by HM The Queen in her Birthday Honours list.

The citation for the KCMG, awarded at the recommendation of the UK foreign secretary, recognizes Dr Niblett’s ‘outstanding personal contribution to British soft power and influence in his role as director of Chatham House over the last 15 years’.

The citation also states: ‘With exceptional energy and talent, he has greatly enhanced the research reputation of the Institute, strengthened its international convening power, finances and staffing, and modernised its premises, image and diverse outreach’.

Dr Niblett is standing down in the summer and will be replaced by Bronwen Maddox, who joins from the Institute for Government.

Dr Niblett says: ‘I am deeply honoured by this award, which is as much a recognition of the tireless and selfless work of my colleagues at Chatham House throughout my tenure as director.

‘Together, and through challenging times, we have offered a vital source of independent debate and analysis. And, with the engagement of our supporters and a new generation of thinkers and actors, I know the institute will continue to provide creative ideas for a better future.’

Independent Thinking: Biden and the Republicans, AUKUS Audio NCapeling 9 February 2023

Episode 14 of our weekly podcast examines the Chinese balloon saga, the State of the Union address, and updates on the AUKUS deal 18 months after it was signed.

This week saw US president Joe Biden address an unruly joint session of Congress, during which he discussed America’s place in the world, China, Ukraine, and the state of the US economy.

As a new presidential cycle begins at the mid-point of Biden’s presidency, the panel analyses how Biden is doing and the challenges that lie ahead for him.

Also it is now 18 months since the announcement of the AUKUS partnership between the UK, US and Australia to develop nuclear hunter killer submarines. What does AUKUS mean for Australia, non-proliferation, and the Indo-Pacific more broadly?

Finally, the panel discusses China’s balloon over Montana in the US. Was it a signal from Beijing and what was it trying to photograph?

Joining guest host John Kampfner this week from Chatham House are Dr Leslie Vinjamuri, director of the US and the Americas programme and Dr Patricia Lewis, director of the International Security programme. They are joined by Dr Euan Graham, Shangri-La Dialogue senior fellow for defence and strategy at the International Institute for Strategic Studies (IISS).

About Independent Thinking

A weekly podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

Accumulation of the microtubule-associated protein tau is associated with Alzheimer's disease (AD). In AD brain, tau is abnormally phosphorylated at many sites, and phosphorylation at Ser-262 and Ser-356 plays critical roles in tau accumulation and toxicity. Microtubule affinity–regulating kinase 4 (MARK4) phosphorylates tau at those sites, and a double de novo mutation in the linker region of MARK4, ΔG316E317D, is associated with an elevated risk of AD. However, it remains unclear how this mutation affects phosphorylation, aggregation, and accumulation of tau and tau-induced neurodegeneration. Here, we report that MARK4ΔG316E317D increases the abundance of highly phosphorylated, insoluble tau species and exacerbates neurodegeneration via Ser-262/356–dependent and –independent mechanisms. Using transgenic Drosophila expressing human MARK4 (MARK4wt) or a mutant version of MARK4 (MARK4ΔG316E317D), we found that coexpression of MARK4wt and MARK4ΔG316E317D increased total tau levels and enhanced tau-induced neurodegeneration and that MARK4ΔG316E317D had more potent effects than MARK4wt. Interestingly, the in vitro kinase activities of MARK4wt and MARK4ΔG316E317D were similar. When tau phosphorylation at Ser-262 and Ser-356 was blocked by alanine substitutions, MARK4wt did not promote tau accumulation or exacerbate neurodegeneration, whereas coexpression of MARK4ΔG316E317D did. Both MARK4wt and MARK4ΔG316E317D increased the levels of oligomeric forms of tau; however, only MARK4ΔG316E317D further increased the detergent insolubility of tau in vivo. Together, these findings suggest that MARK4ΔG316E317D increases tau levels and exacerbates tau toxicity via a novel gain-of-function mechanism and that modification in this region of MARK4 may affect disease pathogenesis.

Alzheimer's disease (AD) is characterized by neuronal loss and accumulation of β-amyloid-protein (Aβ) in the brain parenchyma. Sleep impairment is associated with AD and affects about 25–40% of patients in the mild-to-moderate stages of the disease. Sleep deprivation leads to increased Aβ production; however, its mechanism remains largely unknown. We hypothesized that the increase in core body temperature induced by sleep deprivation may promote Aβ production. Here, we report temperature-dependent regulation of Aβ production. We found that an increase in temperature, from 37 °C to 39 °C, significantly increased Aβ production in amyloid precursor protein-overexpressing cells. We also found that high temperature (39 °C) significantly increased the expression levels of heat shock protein 90 (Hsp90) and the C-terminal fragment of presenilin 1 (PS1-CTF) and promoted γ-secretase complex formation. Interestingly, Hsp90 was associated with the components of the premature γ-secretase complex, anterior pharynx-defective-1 (APH-1), and nicastrin (NCT) but was not associated with PS1-CTF or presenilin enhancer-2. Hsp90 knockdown abolished the increased level of Aβ production and the increased formation of the γ-secretase complex at high temperature in culture. Furthermore, with in vivo experiments, we observed increases in the levels of Hsp90, PS1-CTF, NCT, and the γ-secretase complex in the cortex of mice housed at higher room temperature (30 °C) compared with those housed at standard room temperature (23 °C). Our results suggest that high temperature regulates Aβ production by modulating γ-secretase complex formation through the binding of Hsp90 to NCT/APH-1.

Will the next US president invest in Middle East stability or walk away? Expert comment LToremark 17 October 2024

Harris and Trump look set to continue US deprioritization of the region, but they would do better to enlist the support of their partners.

When stability in the Middle East feels so distant, it is much to the dismay of America’s partners that conflict management in the region has fallen down the list of US priorities. As Israel’s war in Gaza has reached its tragic one-year milestone, a new front has opened in Lebanon and further direct escalation between Israel and Iran seems imminent, it is hoped that the next US president will take a bolder role.

Namely, leaders in the UK, Europe and the Middle East are looking to whoever is in the White House to do more to restrain Israel, deliver self-determination – if not a peace process – for Palestine, and contain Iran’s interventionist regional role and nuclear programme.

While it is naive to expect either Kamala Harris or Donald Trump to prioritize conflict management in the Middle East above immigration, the economy, the war in Ukraine or competition with China, the past year has shown the danger of ignoring or sidestepping cascading and glaring regional challenges. 

For Harris or Trump to have a more sustainable impact in the region, they must enlist the support of European, British and Middle Eastern partners and work collectively to build multilateral processes that can set a stronger foundation for regional stability.

Repercussions of deprioritization

The Abraham Accords, which normalized relations between Israel, the UAE and Bahrain, led many to believe that a new era of integration was possible in the Middle East. To some, it also vindicated the US decision to deprioritize the region that had started with Barack Obama’s presidency and his drawing down from ‘forever wars’ in Iraq and Afghanistan. Presidents Trump and Biden continued that approach, encouraging America’s partners in the Middle East to assume greater responsibility for regional stability. Notably, neither renewed negotiations with Iran despite both committing to deliver a stronger deal with Tehran.

The shock of the 7 October attacks shattered that view, and the longer overhang of the US decision to deprioritize the region has visibly played out over the past twelve months. 

While the Biden administration marshalled full political and military support for Israel and there is not – yet – a direct regional war with Iran, the US has been unsuccessful in multiple areas: delivering a ceasefire agreement, securing the release of hostages, maintaining regular humanitarian relief and producing a so-called ‘day after’ plan of action.  

Moreover, the US temporary arrangement with Iran to prevent nuclear acceleration in exchange for marginal sanctions relief has also shown the limits of compartmentalization when managing a portfolio of issues with Tehran.  

No new approach

Trump and Harris’s policy approaches to conflict in the region further show their limited intent to change course on the Middle East. Both leaders are aware that Middle East politics, particularly on Israel–Palestine and Iran – the key issues requiring urgent attention – has become a US partisan minefield that could alienate voters. Despite their different plans, with Trump inclined to be more unilateral, they will both continue the trend of gradually deprioritizing conflict management in favour of greater burden sharing by those in the region.  

President Trump has promised a tougher approach aimed at curtailing conflict and advancing US interests. On Iran, Trump has made clear that he would return to a policy of maximum pressure on the Islamic Republic, perhaps to come to new agreement with Tehran or alternatively to constrain Iran even further.  He has championed his administration’s withdrawal from the 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran nuclear deal. Trump has argued that this approach put economic strain on Iran and reduced its ability to fund proxy groups. 

His advisers have also indicated that they would extend this pressure campaign and provide maximum support to the Iranian opposition and activists. Yet without clear goals or a willingness to negotiate with Tehran to contain further nuclear advancements, the result may well be another round of instability.  

Should he return to office, Trump has indicated that he would immediately put an end to the war in Gaza, though how remains unclear. More broadly, he would likely double down on the agreements to promote Israeli–Saudi normalization and attempt to bypass the Palestinian leadership, focusing on broader regional normalization. But sidestepping Palestinian self-determination, which since 7 October has been the condition for broader Arab normalization, will be difficult for Saudi Arabia to sell to its broader, now politicized, public.  

Many Middle East leaders, including those from the Arabian peninsula, might welcome the return of a Trump presidency, but Trump’s ‘America First’ policy did not provide Arab Gulf leaders, especially Riyadh, with protection from Iran’s attack on Saudi oil facilities seen in September 2019.  

Trump also promised without success to deliver a bigger, better Iran deal that would extend the JCPOA and include compromises on Tehran’s support for proxy groups and constraints on its missile programme. Rather than imposing his previous strategy, a second Trump presidency would be more effective if it worked collaboratively with transatlantic and regional partners on regional security issues pertaining to Israel–Palestine and Iran.  

Continuation and reinforcement?

Despite her recent tough talk on Iran, it is expected that Harris will reinforce the current wave of diplomatic efforts to deescalate and manage tensions with Tehran, rather than advocate for ‘maximum pressure’.  

Harris would likely build on efforts to revive a new paradigm that could contain Iran’s nuclear programme. She is expected to emphasize a strategy of engagement combined with pressure to prevent Iran from obtaining a nuclear weapon, while addressing its regional activities.   

Now that Iran has provided missiles and drones to Russia, it is clear that Tehran’s transfer of lethal aid needs an urgent response beyond continued reliance on sanctions. Harris’s team would be wise to pursue a multilateral negotiation process bringing together Europe and the UK, who are already discussing these issues, to collectively engage Tehran on a broader deal.

Moreover, winning support from Israel and the Gulf is a necessary condition to build a more sustainable Iranian agreement. 

The UK needs to address growth and debt problems if it is to match resources to ambitions on international priorities Expert comment LJefferson 5 November 2024

The budget marks the lowest amount in decades the country has spent on development, and it is struggling to fund other international priorities too.

The UK’s Chancellor Rachel Reeves unveiled her much-anticipated budget last week, the first of the new Labour government. Labour is in a difficult place. There are numerous calls on the public purse and public services are not performing well. Meanwhile, public debt remains close to 100 per cent of GDP, and there has been a long run of sluggish growth.
 
Reeves argues with some justification that the previous government left her a challenging inheritance – gaps in this year’s spending plans, and persistent debt questions left unresolved. More importantly, there are longer-term concerns about the sustainability of UK public spending – the country’s Office for Budget Responsibility has warned public debt could triple by the 2070s due to an ageing population, the climate crisis, and security risks. The focus has understandably been on kitchen table questions about tax rises and funding public services.
 
But this picture also has longstanding implications for international policy – on whether the UK can afford to invest in its foreign policy. The Chancellor did announce an increase of £2.9bn for defence. But the question of whether the UK can get on a sustainable path to spending 2.5 per cent of GDP on defence is still being worked through in the ongoing Strategic Review, and remains challenging despite increasingly urgent warnings from parliamentary committees about the UK’s defence readiness.

The budget also marks one of the lowest amounts in recent years the UK will spend on development overseas, despite setting an ambition to reset relations with the Global South and recover the UK’s role as a leader in international development.
  
The UK needs to either match resources to ambition, spend much more efficiently, or, in the case of the aid budget, it could seek to focus on priorities that are less dependent on spending. But even this will still require consistent resources, alongside significant diplomatic attention, intellectual leadership, and focus.

Longer-term, the UK may need to consider larger questions: addressing broader problems with its lack of growth and productivity will be critical to fund an expansive international role.

With this budget, UK aid spent overseas is at a historic low

In 2020 the UK government cut its goal for spending on international development to 0.5 per cent of Gross National Income (GNI), ending a longstanding policy of spending 0.7 per cent. Labour have echoed this, promising to only return to previous levels when fiscal circumstances allow.
 
But this masks a bigger issue. Since 2022, significant amounts of the UK’s aid budget have been spent on accommodation for asylum seekers in the UK. This is within the rules governing aid, but reduces the amount spent on reducing poverty overseas. In 2023 this spending was 28 per cent of the £15.4bn aid budget. In 2016, it was 3.2 per cent. 

Previous Chancellor Jeremy Hunt quietly allowed a top-up of aid spending over the last two fiscal years to offset how much is being spent at home on asylum seeker accommodation. That provided an additional £2.5 billion for 2022–23 and 2023–24.

But Rachel Reeves declined to provide extra funding this time, meaning the amount being spent overseas is likely the lowest its been since 2007 – an effective cut – under a Labour government.

The Minister for Development, Anneliese Dodds, speaking at Chatham House last month, said the government is working on clearing the backlog of asylum claims, which should free up more to spend overseas.

But beyond this there has been little clarity on plans to address the issue. And costs for asylum seeker accommodation have increased significantly – the UK appears to spend much more than comparator countries per head, according to the Center for Global Development, raising questions about how this spending is managed.

Development is not just about money – but money is important

The UK debate about development has often focused on the 0.7 per cent figure, which can distract from larger questions about what development policy is intended to achieve. As many experts have argued, development aid is about more than spending, and the wider, complex process by which the UK contributes to broad-based growth and stability for poorer countries is not about hitting a specific number.
 
There are things the UK can do that aren’t about spending more directly. This might include focusing on priorities like reforming multilateral development banks so they provide more low-cost public finance, and more flexible and agile loans to poorer countries – a priority echoed by Dodds. It might also incorporate focusing more broadly on helping developing countries attract more investment to bolster growth. 

There is also the issue of developing country debt, much of which is held by the private sector. Dodds previously said, when she was shadow chancellor, she might consider changing the law to address this issue. However,  she declined to recommit to this when questioned at Chatham House. 

None of this can be done unilaterally – on debt, for example, the UK has spearheaded some creative policies. Its UK Export Finance body developed climate-resilient debt clauses – agreements that countries can pause debt repayments in the event of a climate shock – but the UK holds limited amounts of developing country debt. Impact will only come by galvanizing and coordinating others to adopt similar approaches.

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