One day, machines will do all our work for us—even our drug discovery work. What’s more, the machines will do our work better than we ever could. In drug discovery, the machines will eliminate the human inconsistencies and errors that limit the quantity and quality of our drug candidates. They will perceive and exploit efficiencies beyond our understanding. And they will help us develop drug candidates so economically that even the rarest diseases will attract drug discovery investments.
For such a drug discovery utopia to occur, a great change will be needed. Of course, it will happen gradually. Indeed, it has already begun, now that enabling technologies are maturing and becoming more widely available. These technologies include quantum-inspired molecular optimization, target deconvolution via protein painting and advanced mass spectrometry, and end-to-end automation of drug discovery workflows. When these technologies are implemented, small molecule design and lead optimization are accelerated, shortening the drug discovery process by years and saving untold millions of dollars.
Exploring vast chemical libraries
“We want to create as many small molecule drug leads as possible,” says Shahar Keinan, PhD, CEO and co-founder, Polaris Quantum Biotech (PQB), “[by] combining quantum computing, artificial intelligence (AI), and precision medicine.” The company expects to produce up to 100 “drug blueprints” per year while lowering drug development costs and bringing successful leads to market more quickly.
PQB plans to sift through large chemical libraries to identify small molecules that exhibit the properties a drug would need to change the course of disease. This approach poses an optimization problem. To solve it, PQB partnered with Fujitsu to develop a molecular optimization platform that significantly improves the speed and chemical diversity in small molecule lead discovery.
Fujitsu’s quantum-inspired Digital Annealer solves combinatorial optimization problems 10,000 times faster than other currently available alternatives. In less than five minutes, the Digital Annealer can search a virtual library of a billion molecules that are relevant to a protein-binding pocket associated with a particular disease.
“The library is combinatorial and grows very fast,” notes Keinan. “The problem was searching it. If you can take a three- to four-year process and reduce it to eight months, then addressing smaller patient groups becomes financially feasible.”
After the molecules are searched using the quantum-inspired technology to identify a couple of thousand molecules that satisfy basic design criteria, the next set of candidates goes through more elaborate quantum mechanics and molecular mechanics calculations to define the 10–20 best options. These leads are synthesized and tested to identify the optimal candidate.
Since the platform is fast, it needn’t be confined to investigations of known diseases, such as dengue fever. It can also be used to tackle emerging diseases, such as COVID-19, as well as diseases that have exploited mutations to become nonresponsive to current drugs.
“We are open to collaborations with organizations focused on specific diseases to pursue small molecule therapeutics for their area of interest,” Keinan stresses. “We are faster and less expensive, and we are in this business to find a solution for diseases that are currently overlooked.”
Identifying protein-protein interfaces
Using conventional technologies to identify targetable protein-protein interfaces can be difficult and time consuming. One of these conventional technologies is protein crystallography. It provides unparalleled resolution of protein structures, but it confronts users with crystal structures that can take many years to solve. Another conventional technology, hydrogen deuterium exchange mass spectrometry (HDX-MS), poses experimental challenges, such as low pH digestion, as well as interpretive problems that may be impossible to solve without specialized software.
An alternative technology is protein painting. Developed in 2014 by Alessandra Luchini, PhD, Lance A. Liotta, PhD, and Virginia Espina, PhD, as an outgrowth of their dye chemistry work, protein painting uses noncovalent dyes to selectively label solvent-accessible regions of protein complexes—that is, regions other than the solvent-inaccessible protein-protein interface—in native protein conditions.
The dyes block trypsin cleavage, essentially making the solvent-accessible regions “invisible” to mass spectrometry, thus allowing selective identification of the undyed regions. Protein painting uses recombinant proteins similar to crystallography and HDX but takes only a few days to complete.
“We had some experience using dyes as ‘bait’ for proteins in other applications, and we decided to see if we could directly label proteins,” explains Amanda Haymond, PhD, research assistant professor, School of System Biology, Center for Applied Proteomics and Molecular Medicine (CAPMM), George Mason University. “One of the biggest challenges was identifying appropriate dyes or combinations for the reactions.”
To develop a technique that would be accessible, the investigators had to show that it worked with dyes that were either commercially available or simple to synthesize. A dye that Haymond and colleagues described recently interacted primarily with lysine and tyrosine residues, bound nonspecifically to a range of proteins, bound in high numbers to a range of proteins, and protected bound regions of the protein from urea denaturation.1
“We probed the interface between cytokine IL-1B, its receptor IL-1R1, and accessory protein IL-1RAcP,” Haymond reports. “The protein-painting data allowed design of an interfering peptide that disrupted IL-1B signaling, which has therapeutic applications for osteoarthritis. Most recently, we identified a key residue in the PD-1/PD-L1 interface.1 We designed a peptide that mimicked this region and disrupted PD-1/PD-L1 complex formation.”
“We are working on analogs as potential oncology immunotherapeutic agents,” she continues. “We are excited that other groups have adopted protein painting.”2,3
Deconvoluting target strategies
Accurate target deconvolution and understanding on- and off-target effects is of vital importance to the drug discovery process. According to Diarmuid Kenny, PhD, group leader, Integrated Biology, Charles River Laboratories, mass spectrometry–based proteomics stands at the forefront of most unbiased target deconvolution strategies.
The company has developed Capture Compound mass spectrometry (CCMS), a technology that utilizes a photoaffinity label (PAL) to capture and subsequently identify proteins interacting with a small molecule. The PAL generates a covalent bond between the small molecule and the protein of interest, allowing very stringent washing and identification of weak but specific binding proteins. Using a combination of different PALs maximizes the probability of identifying specific binding partners.
Other strategies include the proteome integral solubility alteration (PISA) assay, which incorporates the principles behind thermal proteome profiling to identify specific protein binding partners with an altered temperature stability profile after treatment with a small molecule.
“CCMS is ideal when working with compounds that have good structure-activity relationship (SAR) data,” says Kenny. “We need to modify the compound to incorporate a PAL without abolishing the compound’s activity.
“The PISA assay, which does not rely on modifying the parent compound, is more suitable for in-cell target deconvolution as it can also be used to potentially identify downstream treatment effects. Both CCMS and PISA are functionally agonist, and therefore they can identify both primary and off-target proteins bound by a compound.”
Shotgun proteomics, or data-dependent acquisition, is the traditional methodology for unbiased proteomics workflows. Although robust and widely suitable, this methodology may miss data values. More recently, there has been a movement toward an alternative methodology, namely, sequential window acquisition of all theoretical mass spectra (SWATH-MS), or data-independent acquisition. It is suited to projects that process many samples and need to quantify many proteins in each sample.
Other advanced mass spectrometry technologies include ion mobility–mass spectrometry (IM-MS). It allows for the discrimination of isomers based on differences in their mobility through a gas-filled region while subjected to an electric field. Such technologies can overcome the limitations of conventional technologies to distinguish analytes of the same mass.
When transitioning from clinical work to laboratory research, Martin-Immanuel Bittner, MD, PhD, co-founder and CEO, Arctoris, was surprised to learn how much time was spent on highly repetitive manual experimentation. Simultaneously, he realized that the low productivity in drug discovery could be attributed mainly to low data quality, which also led to research failures and, consequently, additional costs. Reports showed that less than 25% of published results were reproducible.4,5
“Scientific protocols are highly ambiguous, which impacts reproducibility and makes pooling data from different sources near impossible,” Bittner states. But protocols could be more definite. To illustrate this point, Bittner suggests that a protocol that says “mix the sample” could add details, such as the settings used on an automated mixer, where mixing is “clearly defined as x minutes at x speed at x temperature for a fully compliant, highly rigorous, standardized approach. If each protocol step is clearly defined and automated, it brings data to new quality levels.”
Typically, automation is thought of as a tool that accomplishes high-throughput screening by enabling a very small number of assays to be run over and over again. At Arctoris, however, automation is something that can be more versatile, provided it is implemented throughout discovery. Full automation, the company asserts, can run assays down to single-plate experiments, resulting in better quality data and shorter cycle times.
Arctoris uses its automation approach to help biotech companies manage projects more efficiently. Also, the company can perform a range of experiments, including experiments that might be inaccessible to some researchers. Both standardized assays and customized assays (for example, target-based assays) are available.
The fully automated Arctoris research facility can perform a selection of cell biology, molecular biology, and biochemistry experiments in a nonbiased, reproducible way, and it can run concurrent experiments around the clock seven days a week. The facility, which is modular and incorporates large robotic work cells within sterile enclosures, interconnects scientific instruments via a network of conveyor belts and robotic arms.
“There is no lengthy onboarding process,” Bittner asserts. “Instead, [there is] complete transparency about the entire process. Access to raw data is in real time. Price is per experiment and depends on reagent cost as well as degree of customization.”
“In the move toward AI-driven drug discovery,” he continues, “the quality of data becomes even more important because with machine learning, the ‘garbage in, garbage out’ mantra applies. Our automated platform produces high-quality, consistent, and structured data, resulting in quality inputs for the next generation of drug discovery efforts.”
Histological analysis of 3D cultures
Three-dimensional (3D) cell culture techniques are becoming more important as model platforms for drug discovery and biology. To facilitate handling of 3D spheroids and organoids for high-throughput histological analysis, a Purdue University team, consisting of engineering professors Thomas Siegmund, PhD, Bumsoo Han, PhD, and George T.C. Chiu, PhD, has developed a new technology, the collapsible basket array (CBA).
According to Siegmund, in the CBA, the 3D cultures reside in fluid-permeable baskets attached to a flexible grid that is submerged in microplate wells containing the culture media. After culture, the CBA is removed from the well plate and released from the carrier structure. The CBA then collapses, allowing the array to be fitted to a standard histology cassette for microscopy analysis of the 3D cultures. The grid can conform to a microplate of any size. The histology cassette is the limiting factor.
A U.S. patent application has been filed. Now that the technology is attracting interest, the Purdue Office of Technology Commercialization and the inventors hope to license it to an industry partner.
Making the CBA compatible with automated pipetting and robotics systems for end-to-end automation is a top priority, says Siegmund. The Purdue team believes the CBA will address obstacles with laborious, mostly manual, and low-throughput handling and analysis of 3D cultures, thereby streamlining the process of drug development and reducing errors occurring during transfer. Currently, 3D printed, larger scale manufacturing is under development.
1. Haymond A, Dey D, Carter R, et al. Protein painting, an optimized MS-based technique, reveals functionally relevant interfaces of the PD-1/PD-L1 complex and the YAP2/ZO-1 complex. J. Biol. Chem. 2019; 294(29): 11180–11198. DOI: 10.1074/jbc.RA118.007310.
2. Lin X, Ammosova T, Choy MS, et al. Targeting the Non-catalytic RVxF Site of Protein Phosphatase-1 With Small Molecules for Ebola Virus Inhibition. Front. Microbiol. 2019; 10: 2145. DOI: 10.3389/fmicb.2019.02145.
3. Rosa B, Marchetti M, Paredi G, et al. Combination of SAXS and Protein Painting Discloses the Three-Dimensional Organization of the Bacterial Cysteine Synthase Complex, a Potential Target for Enhancers of Antibiotic Action. Int. J. Mol. Sci. 2019; 20(20): 5219. DOI: 10.3390/ijms20205219.
4. Prinz F, Schlange T, Asadullah K. Believe it or not: How much can we rely on published data on potential drug targets? Nat. Rev. Drug Discov. 2011; 10: 712. DOI: 10.1038/nrd3439-c1.
5. Begley, C, Ellis L. Raise standards for preclinical cancer research. Nature 2012; 483: 531–533. DOI: 10.1038/483531a.
Treating Cancer at a Personal Level
The promise of single-cell proteomics
By Khatereh Motamedchaboki, PhD
“Omics” analysis marks a critical breakthrough in our understanding of human biology and disease. Rather than adopting a reductionist, deconstructed view of a biological system, omics disciplines seek a holistic understanding of how systems interact, and they begin their investigations by characterizing the entire set of molecules present within a cell, organ, or organism.
The value of this approach is well demonstrated by genomics, which has become a key element of disease research and drug discovery. However, proteins provide necessary detail about a cell’s current activity that nucleic acids cannot. Analyzing specific proteins gives a more direct view of cell content and behavior than does evaluating by inference based on other biomolecules—an approach that can fail to account for mechanisms such as post-translational modifications and gene silencing. Proteomics is, therefore, necessary to fully understand the biological systems that drive disease, and to turn biological insights into personalized treatments.
Tackling cancer heterogeneity
Omics analysis enables researchers to explore human biology at an individual level. Every disease, from autoimmune disorders to mental health conditions to cancers, has its own vulnerabilities and patterns, and every patient responds differently. Omics tools can help create tailored medical treatments specific to a patient’s molecular profile, removing the need for “trial and error” periods1 and creating opportunities for both early diagnosis and precision treatment.
As analytical techniques improve, life sciences research is moving from bulk sample analysis toward single-cell omics analysis,2 which explores everything occurring at the molecular level within a single cell. This is crucial in exploring cell heterogeneity, a defining issue in oncology3: tumors comprise many cell types acting in concert, and various cell types and differentiation stages define a system’s health or malignancy. As a result, bulk analysis cannot accurately capture tumor heterogeneity.
Advanced methods of proteomic analysis
Using single-cell proteomics, researchers can examine cellular heterogeneity at the protein level. Single-cell proteomic analysis methods rely upon antibodies, cytometry, or—the gold standard—mass spectrometry (MS). Antibody- and cytometry-based methods use fluorescence-activated cell sorting and antibodies to tag proteins of interest and are, therefore, limited by antibody availability. Single-cell MS-based methods, however, have shown wider applicability in identifying and quantifying thousands of proteins in an unbiased way.4
Proteomics researchers can struggle to increase throughput due to limited sample size5: proteins cannot be amplified, and only small amounts of protein exist within a single cell. Advanced technologies are helping to overcome this hurdle. MS-based tools, such as the Thermo Scientific Orbitrap Eclipse Tribrid mass spectrometer with FAIMS Pro Interface, increase sensitivity and selectivity while conserving limited samples. Field asymmetric waveform ion mobility spectrometry (FAIMS) uses differential ion mobility to spatially separate ion species and directs only target species into the MS for sequencing. When used in combination, FAIMS and MS can offer easy selection and accumulation of multiply charged peptides ions only, as well as increased coverage.
Additionally, innovative methods of sample preparation, such as nanoPOTs (nanodroplet processing in one pot for trace samples), can preserve trace samples.4 Isobaric tandem mass tagging has proven able to “boost” low peptide signals,5 whereas targeted quantitation approaches, such as the Thermo Scientific SureQuant Targeted Mass Spec Assay, are designed to characterize many low-level protein targets, while accounting for proteoforms and post-translation modifications.
Toward a fuller understanding of cellular activity
Single-cell proteomics is a promising tool for modern drug discovery, especially for the development of novel disease treatment methods in the form of personalized medicines. The technology summarized here enables a fuller understanding of cellular activity, by shifting from simple profiling and abundance measurements to dynamic examinations of cells as systems that change over time.
Khatereh Motamedchaboki, PhD, is a senior vertical marketing specialist, proteomics, at Thermo Fisher Scientific.
1. Lopez-Ferrer D, Motamedchaboki K. Challenges and emerging directions in single-cell proteomics: Will it go mainstream like genomics? Thermo Fisher Scientific. 2020; White Paper: 65730.
2. Schoof EM, Nicolas Rapin N, Savickas S, et al. A Quantitative Single-Cell Proteomics Approach to Characterize an Acute Myeloid Leukemia Hierarchy. bioRxiv 2019.
3. Bateman, NW Conrads TP. Recent advances and opportunities in proteomic analyses of tumour heterogeneity. J. Pathol. 2018; 255(5): 628–637.
4. Motamedchaboki K, Dou M, Cong Y, et al. High-throughput single-cell proteomics analysis with nanodroplet sample processing, multiplex TMT labeling, and ultra-sensitive LC-MS. Thermo Fisher Scientific. 2020; Application Note: 65714.
5. Yi L, Tsai C-F, Dirice E, et al. Boosting to Amplify Signal with Isobaric Labeling (BASIL) Strategy for Comprehensive Quantitative Phosphoproteomic Characterization of Small Populations of Cells. Anal Chem. 2019; 91(9): 5794–5801.
Base network launches 8-week training course for blockchain developers
Base Bootcamp will offer students weekly meetings with a mentor, a dedicated Discord server, and access to Coinbase and Base engineers, the team stated.
Base Bootcamp will offer students weekly meetings with a mentor, a dedicated Discord server, and access to Coinbase and Base engineers, the team stated.
On October 20, the team behind Ethereum layer-2 Base network announced that it's launching an eight-week training course to turn traditional software developers into blockchain developers. Called “Base Bootcamp,” the new program doesn't cost anything to attend. However, it's designed for “mid to senior level Software Engineering individual contributors” and students must fill out an application and be accepted to enroll. Less than 20 students will be accepted into each “cohort” or class, and the team will stop accepting applications on October 27, the announcement stated.
Introducing Base Bootcamp, an eight-week program designed to turn experienced developers into smart contract developers— Base ️ (@BuildOnBase) October 20, 2023
Base Bootcamp will make learning interactive and collaborative, with support from experienced engineers and dedicated mentorshttps://t.co/gecI1FMpzT
In its announcement, Base claimed the program is necessary because most software developers still do not know how to build Web3 apps. “Today, there are fewer than 30,000 onchain developers,” they stated, “compared to nearly 30 million software developers.” This implies that only 0.1% of software developers work in Web3.
The team released an online training program called “Base Camp” earlier in the year, which was open to anyone. But they decided that this wasn’t enough, as “keeping the momentum to learn a complex new skill alone can be difficult.” They claim that Base Bootcamp will provide more support for developers who don’t want to study alone.
The Base Bootcamp will pair each student with a mentor who they will meet with each week. It will also give them access to a group of Coinbase and Base engineers who will be available during office hours to answer questions. A private Discord server will be created to allow students to communicate with each other and to Base engineers, and additional assignments will be given that will be graded by members of the team. At the end of the program, students will be required to create their own Web3 app and present it to other students.
Although the program does not charge tuition, students are required to put up 1 Ether (ETH) on deposit to ensure that they finish the program. The team claimed that this deposit will be returned to the student upon graduation.
The lack of qualified Web3 developers is a commonly reported problem in the industry. Some Australian educators have suggested teaching Web3 development in high schools as a means of combating the problem. Other companies have tried to create tools to make Web3 development more simple. For example, Circle recently released a set of tools that allow developers to deploy contracts using familiar Web2 methods.ethereum blockchain
Greece establishes AI advisory committee to create national strategy
The Greek prime minister created an AI advisory committee comprising some of the country’s top tech, ethics and science professionals.
The Greek prime minister created an AI advisory committee comprising some of the country’s top tech, ethics and science professionals.
Greek Prime Minister Kryiakos Mitsotakis announced the establishment of an advisory committee to create a national strategy for artificial intelligence (AI) in Greece on Oct. 19.
The Greek government said the “exponential pace” of AI development has created the necessity for an advisory committee under the country’s prime minister. The object of the committee is to prepare Greece for the developments and applications of the technology.
Mitsotakis commented on the establishment of the commission, saying the reception of the technology must be organized before it becomes a daily reality. “This is not about the future but the present,” he said.
The commission will be led by Constantinos Daskalakis, a professor of computer science at MIT, and has professionals in related fields such as technology, ethics, law and science. It also includes Greek researchers and scientists, a part of the diaspora living outside of Greece.
Daskalakis commented on the initiative, saying:
“We will also work in a coordinated manner so that Greece can be a member of the international initiatives for Artificial Intelligence that are being developed within the framework of the International Organization of Artificial Intelligence.”
A central component of the advisory committee will also be formulating policy recommendations and creating guidelines for a long-term national strategy.
According to the announcement, the AI strategy will include considering its impact on the economy and society, improving productivity, increasing innovation and strengthening local infrastructure, among other things.
Greece is among the 27 member states of the European Union that would be subject to the EU’s forthcoming EU AI Act.
Earlier in October, EU officials announced that they are considering even more restrictive regulations for large AI models such as OpenAI’s ChatGPT and Meta’s Llama 2.bitcoin
Delivering aid during war is tricky − here’s what to know about what Gaza relief operations may face
The politics of delivering aid in war zones are messy, the ethics fraught and the logistics daunting. But getting everything right is essential − and…
In response, U.S. President Joe Biden has pledged US$100 million in humanitarian assistance for the citizens of Gaza.
As a scholar of peace and conflict economics who served as a World Bank consultant during the 2014 war between Hamas and Israel, I believe that Biden’s promise raises fundamental questions regarding the delivery of humanitarian aid in a war zone. Political constraints, ethical quandaries and the need to protect the security of aid workers and local communities always make it a logistical nightmare.
In this specific predicament, U.S. officials have to choose a strategy to deliver the aid without the perception of benefiting Hamas, a group the U.S. and Israel both classify as a terrorist organization.
When aiding people in war zones, you can’t just send money, a development strategy called “cash transfers” that has become increasingly popular due to its efficiency. Sending money can boost the supply of locally produced goods and services and help people on the ground pay for what they need most. But injecting cash into an economy so completely cut off from the world would only stoke inflation.
So the aid must consist of goods that have to be brought into Gaza, and services provided by people working as part of an aid mission. Humanitarian aid can include food and water; health, sanitation and hygiene supplies and services; and tents and other materials for shelter and settlement.
Due to the closure of the border with Israel, aid can arrive in Gaza only via the Rafah crossing on the Egyptian border.
The U.S. Agency for International Development, or USAID, will likely turn to its longtime partner on the ground, the United Nations Relief and Works Agency, or UNRWA, to serve as supply depots and distribute goods. That agency, originally founded in 1949 as a temporary measure until a two-state solution could be found, serves in effect as a parallel yet unelected government for Palestinian refugees.
USAID will likely want to tap into UNRWA’s network of 284 schools – many of which are now transformed into humanitarian shelters housing two-thirds of the estimated 1 million people displaced by Israeli airstrikes – and 22 hospitals to expedite distribution.
Since Biden took office, total yearly U.S. assistance for the Palestinian territories has totaled around $150 million, restored from just $8 million in 2020 under the Trump administration. During the Obama administration, however, the U.S. was providing more aid to the territories than it is now, with $1 billion disbursed in the 2013 fiscal year.
But the White House needs Congress to approve this assistance – a process that requires the House of Representatives to elect a new speaker and then for lawmakers to approve aid to Gaza once that happens.
The United Nations Relief and Works Agency is a U.N. organization. It’s not run by Hamas, unlike, for instance, the Gaza Ministry of Health. However, Hamas has frequently undermined UNRWA’s efforts and diverted international aid for military purposes.
Hamas has repeatedly used UNRWA schools as rocket depots. They have repeatedly tunneled beneath UNRWA schools. They have dismantled European Union-funded water pipes to use as rocket fuselages. And even since the most recent violence broke out, the UNRWA has accused Hamas of stealing fuel and food from its Gaza premises.
Humanitarian aid professionals regularly have to contend with these trade-offs when deciding to what extent they can work with governments and local authorities that commit violent acts. They need to do so in exchange for the access required to help civilians under their control.
Similarly, Biden has had to make concessions to Israel while brokering for the freedom to send humanitarian aid to Gaza. For example, he has assured Israel that if any of the aid is diverted by Hamas, the operation will cease.
This promise may have been politically necessary. But if Biden already believes Hamas to be uncaring about civilian welfare, he may not expect the group to refrain from taking what they can.
Security best practices
What can be done to protect the security of humanitarian aid operations that take place in the midst of dangerous conflicts?
Under International Humanitarian Law, local authorities have the primary responsibility for ensuring the delivery of aid – even when they aren’t carrying out that task. To increase the chances that the local authorities will not attack them, aid groups can give “humanitarian notification” and voluntarily alert the local government as to where they will be operating.
Hamas has repeatedly flouted international norms and laws. So the question of if and how the aid convoy will be protected looms large.
Under the current agreement between the U.S., Israel and Egypt, the convoy will raise the U.N. flag. International inspectors will make sure no weapons are on board the vehicles before crossing over from Arish, Egypt, to Rafah, a city located on the Gaza Strip’s border with Egypt.
The aid convoy will likely cross without militarized security. This puts it at some danger of diversion once inside Gaza. But whether the aid convoy is attacked, seized or left alone, the Biden administration will have demonstrated its willingness to attempt a humanitarian relief operation. In this sense, a relatively small first convoy bearing water, medical supplies and food, among other items, serves as a test balloon for a sustained operation to follow soon after.
If the U.S. were to provide the humanitarian convoy a military escort, by contrast, Hamas could see its presence as a provocation. Washington’s support for Israel is so strong that the U.S. could potentially be judged as a party in the conflict between Israel and Hamas.
In that case, the presence of U.S. armed forces might provoke attacks on Gaza-bound aid convoys by Hamas and Islamic jihad fighters that otherwise would not have occurred. Combined with the mobilization of two U.S. Navy carrier groups in the eastern Mediterranean Sea, I’d be concerned that such a move might also stoke regional anger. It would undermine the Biden administration’s attempts to cool the situation.
On U.N.-approved missions, aid delivery may be secured by third-party peacekeepers – meaning, in this case, personnel who are neither Israeli nor Palestinian – with the U.N. Security Council’s blessing. In this case, tragically, it’s unlikely that such a resolution could conceivably pass such a vote, much less quickly enough to make a difference.
Topher L. McDougal does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.white house congress house of representatives trump european