Porton Down Research Articles

Sarin exposure, mortality and cancer incidence in UK military veterans involved in human experiments at Porton Down: 52-year follow-up

ObjectivesWe investigated whether UK military personnel exposed to sarin during the ‘Service Volunteer Programme’ at Porton Down had increased rates of mortality or cancer incidence over a 52-year follow-up.MethodsA historical...

Biological Weapons Testing at Porton Down

This article focuses on the use of nonhuman animals for biological weapons testing by military scientists at Porton Down Defence Science and Technology Laboratory, 1948–1955. After the end of the Second World War and the beginning of the Cold War, the British state and its allies invested in new military technologies which could ensure their superiority in times of conflict. My analysis reveals the partial workings of the Porton Down Laboratory through its historical use of nonhuman animals. I demonstrate that nonhuman animals were simultaneously effaced and made visible during biological warfare experiments. This effacement and visibility was dependent on anthropocentric notions of animal subjection whereby their use in experiments made them “seen” as resources for use, yet paradoxically elicited their nonexistence as subjects. I extend the notion of “strategic ignorance” to develop a novel concept of “strategic effacement” to demonstrate this contradictory relationship which both impacted scientific “objectivity” and contributed to the continued exploitation of animals in the laboratory.

Arbovirology and Cold War Collaborations: A Transnational History of the Tick-borne Encephalitis Vaccine, 1930-1980.

This article analyzes the history of immunization against tick-borne encephalitis (TBE) and specifically the processes that led to the creation and application of TBE vaccines in the Soviet Union and Austria. Rather than presenting the development of TBE vaccines from the perspective of national scientific schools, the article investigates their history as a transnational project, focusing on the connections among the Soviet Union, Czechoslovakia, Austria, the United States, and the United Kingdom. It argues that biomedical research on TBE was profoundly intertwined with political and military agendas and depended on civil international cooperation as well as Soviet, American, and British military concerns, infrastructures and funding. The article consists of four parts that discuss (1) the identification of the TBE virus and the creation of the first TBE vaccine in the Soviet Union in the 1930s; (2) the internationalization of TBE research and vaccine development in the 1940s-1960s; (3) the history of TBE research and virology in Austria in the 1930s-1960s and the role of the US military funding; and (4) the cooperation of Austrian virologist Christian Kunz with the Microbiological Research Establishment Porton Down in the UK leading to the development of the Austrian/British vaccine against TBE in the 1970s.

Chemical Weapons: VX Nerve Agents

Abstract: In light of earlier research completed by Dr. Gerhard Schrader, a scientist working for IG Farben in Germany during the 1930s, VX, also known as "venomous specialist X," is one of the most amazing known about the V nerve specialists. It was first discovered at Porton Down in England during the mid-1950s. They are currently a part of a larger V-series of specialists and go by the label of nerve specialists. They have been used as a substance weapon in numerous documented dangerous assaults. VX is more potent than sarin, another nerve agent with a similar component of activity, in that it causes death with exposure to multiple milligramme levels through inhalation or absorption through skin. Such candour has some experts really upset. A delayed neuromuscular bar, limp loss of motion of the relative variety of body muscles, including the stomach, and asphyxiation are the results of these specialists' serious disruption of the body's motioning between the worried and strong frameworks. VX in particular poses a problem because it is relatively non-unpredictable and does not dissipate and circulate as a fume; rather, it remains directly exposed to the chemical specialist where it was initially dispersed. These physical and biological properties of VX make it a weapon that can be used in a wide range of environments. The Chemical Weapons Convention of 1993 forbids the production and storage of VX above 100 grammes (3.53 oz) each year as a substance weapon and classifies it as a weapon of mass destruction. "Examination, clinical or drug purposes outside a single limited scope office in total amounts not exceeding 10 kg (22 lb) each" is the primary exception.

Mortality and cancer incidence in UK military veterans involved in human experiments at Porton Down: 48-year follow-up.

We investigated whether military personnel involved in chemical warfare agent research at Porton Down had increased rates of mortality or cancer incidence. This was a historical cohort study comprising male UK veterans who participated in the 'Service Volunteer Programme', 1941-89, identified from Porton Down experiment books, and a comparison group of similar 'non-Porton Down' veterans identified from military personnel files. Of 19 233 records retrieved for each group, 18 133 (94%) Porton Down and 17 591 (92%) non-Porton Down were included in our analytical sample. Mortality and cancer incidence data were obtained from national registries up to December 2019. Over a median follow-up of 48.1 years, 10 935 Porton Down veterans (60.3%) and 10 658 non-Porton Down veterans (60.6%) had died. After adjustment for age, year of birth and military service characteristics, overall, Porton Down veterans had a 6% higher rate of all-cause mortality compared with non-Porton Down veterans [hazard ratio (HR) = 1.06, 95% confidence interval (CI) 1.03-1.09]. For cause-specific mortality, Porton Down veterans had higher rates of death from genitourinary diseases (HR = 1.34, 95% CI 1.05-1.70) and deaths attributable to alcohol (HR = 1.44, 95% CI 1.07-1.94), with weaker associations observed for deaths from infectious and parasitic diseases (HR = 1.32, 95% CI 0.99-1.78), lung cancer (HR = 1.10, 95% CI 1.01-1.20) and external causes (HR = 1.15, 95% CI 1.00-1.32). Associations with all-cause mortality were stronger for veterans who attended Porton Down between 1960 and 1964 (HR = 1.34, 95% CI 1.19-1.50); likelihood-ratio test, P = 0.006. There was no association between attendance at Porton Down and overall cancer incidence (HR = 1.00, 95% CI 0.95-1.03). Overall, mortality rates were slightly higher in Porton Down veterans, but there was no difference in cancer incidence. Associations for mortality were stronger in Porton Down veterans who attended in the early 1960s.

Mortality and cancer incidence in British military veterans involved in human experiments at Porton Down: 40-year follow-up

Background and aim: To investigate whether veterans involved in chemical warfare agents research at Porton Down have increased rates of mortality or cancer incidence. Methods: The study is a historical cohort study. Participants are male UK veterans who participated in the ‘Service Volunteer Programme’, 1941-1989, identified from Porton Down experiment books, and a comparison group of similar ‘non-Porton Down’ veterans identified from military personnel files. Of 19,233 records retrieved for each group, 18,069 (94%) Porton Down and 17,588 (91%) non-Porton Down are included herein our study sample. The main outcome measures – National Health Service Central Registry Data on mortality and cancer registrations up to December 2019. Results: Over a median follow-up of 48.1 years, 10,889 Porton Down veterans (60.3%) and 10,657 non-Porton Down veterans (60.6%) died. After adjustment for age, year of birth, and military service characteristics, overall, Porton Down veterans had a 7% higher rate of all-cause mortality compared to non-Porton Down veterans. Associations with all-cause mortality were stronger for veterans who attended Porton Down between 1960 and 1964 (1.36, 95% CI 1.20 to 1.54), compared to other periods; likelihood-ratio test, p=0.006. For cause-specific mortality, Porton Down veterans had a statistically significantly higher rates of death from infectious and parasitic disease (5%), genitourinary (45%), circulatory diseases (5%), external causes (23%) and deaths attributable to alcohol (48%). There was no association between attendance at Porton Down and overall cancer incidence (0.99, 0.95 to 1.03). although Porton Down veterans had higher rates of neoplasms of ‘uncertain or unknown behaviour’ (1.26, 1.04 to 1.53), but lower rates of ‘other urinary tract’ neoplasms (0.77, 0.60 to 0.98). Conclusions: Overall, mortality rates were slightly higher in Porton Down veterans, but there was no difference in cancer incidence. Associations were stronger in Porton Down veterans who attended in the early 1960s.

Implementation and Extended Evaluation of the Euroimmun Anti-SARS-CoV-2 IgG Assay and Its Contribution to the United Kingdom's COVID-19 Public Health Response.

ABSTRACTIn March 2020, the Rare and Imported Pathogens Laboratory at the UK Health Security Agency (UKHSA) (formerly Public Health England [PHE]) Porton Down, was tasked by the Department of Health and Social Care with setting up a national surveillance laboratory facility to study SARS-CoV-2 antibody responses and population-level sero-surveillance in response to the growing SARS-CoV-2 outbreak. In the following 12 months, the laboratory tested more than 160,000 samples, facilitating a wide range of research and informing UKHSA, DHSC, and UK government policy. Here we describe the implementation and use of the Euroimmun anti-SARS-CoV-2 IgG assay and provide an extended evaluation of its performance. We present a markedly improved overall sensitivity of 91.39% (≥14 days 92.74%, ≥21 days 93.59%) compared to our small-scale early study, and a specificity of 98.56%. In addition, we detail extended characteristics of the Euroimmun assay: intra- and interassay precision, correlation to neutralization, and assay linearity.IMPORTANCE Serology assays have been useful in determining those with previous SARS-CoV-2 infection in a wide range of research and serosurveillance projects. However, assays vary in their sensitivity at detecting SARS-CoV-2 antibodies. Here, we detail an extended evaluation and characterization of the Euroimmun anti-SARS-CoV-2 IgG assay, one that has been widely used within the United Kingdom on over 160,000 samples to date.

Cohort Profile: The Porton Down Veterans cohort study.

Cohort Profile: The Porton Down Veterans cohort study.

L-Asparaginase and HCP quantification by SWATH LC-MS/MS for new and improved purification step in Erwinia chrysanthemil-asparaginase manufacture

Erwinase® or Erwinaze® are the proprietary names for the L-asparaginase enzyme derived from Erwinia chrysanthemi.L-asparaginase is an integral part of the treatment of Acute Lymphoblastic Leukaemia (ALL) in children and adolescents. E. chrysanthemiL-asparaginase was first developed in the early 1970s at Porton Down and is currently manufactured by Porton Biopharma Ltd. One of the early purification steps during E. chrysanthemiL-asparaginase manufacture, involves use of batch cation exchange carboxymethyl resin, and alternatives to this older technology are currently under investigation using mass spectrometry to understand the impact of resin changes on the impurity profile. In this study, a novel SWATH library was developed for E. chrysanthemi proteome and used to evaluate this potential process change on product yield and host cell protein (HCP) profile and clearance. An ELISA assay is currently used as a quality control release test for quantifying HCPs at the Drug Substance (DS) stage, but these early extract samples are too crude for interference-free analysis by ELISA. Given that ELISA assay could not be used in the assessment of new resin options, SWATH LC-MS/MS analysis proved to be pivotal in selecting a resin for further scale-up and implementation. The data quantified that L-asparaginase from the new process step was 2.28-fold higher in concentration than in legacy-process samples. The new step, using a modern ion exchanger, was at least equivalent and in some cases outperformed the legacy resin step in terms of HCP clearance for 78.2% of total HCPs (528 of 675 total proteins).

Leptospirosis: A Rare Cause of Acute Hepatitis

Leptospirosis is a zoonotic infection caused by the pathogenic Leptospira interrogans. Humans acquire the infection either through direct contact with the urine of infected animals, commonly rats or indirect contact of contaminated water or soil. It is a rare cause of acute hepatitis in the UK with fewer than 100 reported cases a year and hence diagnosis is commonly delayed. A 51-year-old fit Caucasian gentleman was admitted with a one-week history of painless jaundice, dark urine and pale-coloured stools. This was associated with feeling unwell, anorexia, nausea and intermittent epigastric discomfort. He binges on alcohol on a weekend. He works as a telephone engineer which occasionally exposes him to sewage water. On clinical examination, he was icteric with mild right hypochondriac tenderness. Liver biopsy was performed and histologically it was suggestive of leptospirosis. He was started on a five-day course of intravenous ceftriaxone followed by two days course of oral doxycycline. His IgM leptospirosis result finally came back as positive. Due to the rarity of leptospirosis in the UK, the serological testing of leptospirosis is only performed in the Rare and Imported Pathogens Laboratory in Porton Down, Salisbury leading to a delay in getting the result. The patient underwent an invasive procedure which can be avoided if the leptospirosis serology was ordered early and result available quickly. Fortunately, the patient made a full recovery after two months. Leptospirosis should be considered in an individual with acute hepatitis and a history of exposure to sewage.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S22

Letter to the Editor regarding Peto T; UK COVID-19 Lateral Flow Oversight Team: COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay.

It is essential that studies of the accuracy of lateral flow antigen tests (LFTs) to detect SARS-CoV-2 are accurately and completely reported and that data are widely available and freely shared to ensure public and health policy are properly informed [1]. The FDA have raised concerns on the evidence for the Innova LFT [2]. Peto report key studies from Porton Down and the University of Oxford which form the evidence base for use of Innova and its rebranded version (the NHS Test-and-Trace LFT) [3].

COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay: A national systematic evaluation of sensitivity and specificity for mass-testing.

BackgroundLateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour.MethodsLFDs were initially reviewed by a Department of Health and Social Care team, part of the UK government, from which 64 were selected for further evaluation from 1st August to 15th December 2020. Standardised laboratory evaluations, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots were performed (UK COVID-19 testing centres, hospital, schools, armed forces).Findings4/64 LFDs so far have desirable performance characteristics (orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1–6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20–0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists was 78.8% (156/198, 95% CI 72.4–84.3).InterpretationOur results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission.FundingDepartment of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research.

Raman Scattering Techniques for Defense and Security Applications.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTRaman Scattering Techniques for Defense and Security ApplicationsAdam P. ListerAdam P. ListerSchool of Chemistry and Institute for Life Sciences, University of Southampton, Highfield, Southampton SO17 1BJ, United KingdomMore by Adam P. ListerView Biography, William J. SellorsWilliam J. SellorsDstl Porton Down, Salisbury SP4 0JQ, United KingdomMore by William J. SellorsView Biography, Chris R. HowleChris R. HowleDstl Porton Down, Salisbury SP4 0JQ, United KingdomMore by Chris R. HowleView Biography, and Sumeet Mahajan*Sumeet MahajanSchool of Chemistry and Institute for Life Sciences, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom*Email: [email protected]More by Sumeet MahajanView Biographyhttp://orcid.org/0000-0001-8923-6666Cite this: Anal. Chem. 2021, 93, 1, 417–429Publication Date (Web):December 22, 2020Publication History Published online22 December 2020Published inissue 12 January 2021https://doi.org/10.1021/acs.analchem.0c04606Copyright © 2020 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views1275Altmetric-Citations8LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (2 MB) Get e-AlertsSUBJECTS:Bacteria,Lasers,Materials,Raman scattering,Raman spectroscopy Get e-Alerts

Sarah Gilbert: carving a path towards a COVID-19 vaccine

Sarah Gilbert: carving a path towards a COVID-19 vaccine

17. Tick-borne relapsing fever: a fever syndrome mimic

17. Tick-borne relapsing fever: a fever syndrome mimic

Catherine Helen Roberts

Catherine Helen Roberts (“Cathy”) studied preclinical medicine at St Catherine’s College, Oxford, in 1996-99. She gained an MA Hons (Oxon) in physiological sciences before transferring to University College London Medical...

Creating a ‘FatherConfessor’: the origins of research ethics committees in UK military medical research, 1950–1970. Part I, context and causes

Part I provides the historiographical context and examines the causes which led to the creation of the first independent research ethics committee (REC) at Porton Down, Britain’s biological and chemical...

Creating a ‘FatherConfessor’: the origins of research ethics committees in UK military medical research, 1950–1970. Part II, origins and organisation

Using a major ethics crisis as a methodological approach to study secret science environments, part II examines the origins and organisation of the Applied Biology Committee (ABC), the first independent...

Lyme disease in Northern Ireland – a look back on serological testing

Background Lyme disease is an illness caused by the spirochete Borrrelia burgdoferi. NICE guidance suggests an approach to diagnosis resting on clinical presentation, presence in an epidemiologically plausible area, and positive serology. It is however, well documented that serological diagnostics in European Lyme disease is problematic. There is a movement for Lyme advocacy, a voice that emphasises the poor diagnostics in this infection. With the spotlight on Lyme disease, we are increasingly seeing patients presenting in Northern Ireland across a broad range of specialities. Currently there is minimal data looking at the local epidemiology of Lyme disease. We present previously unpublished data looking at the demographics of those testing positive for Borrelia burgdoferi antibodies. Methods We collected data from all patients tested for Lyme disease in Northern Ireland from 2013–2018. We excluded negative results. A randomised selection of 300 cases were chosen. We recorded patient age, gender, origins of testing, home postcode, tick bite history, relevant travel history, duration of symptoms, timings of testing, antibody results including confirmatory testing and treatment. Results Of the 300 selected patients 241 (80 %) were IgM positive and 83 (30 %) IgG positive using DiaSorin, Liason CLIA. The average age of presentation was 39 years old. There was a predominance of females tested (62%). 32 % of tests originated in primary care. Of the IgM positives only 41 (17 %) were confirmed by C6 peptide or lineblot in the reference laboratory (RIPL, Porton Down). The results highlight the likely low seroprevalence of Lyme disease in Northern Ireland.

Chemical Weapons: History of the Study of Organophosphorus Toxic Agents Abroad

Organophosphorus compounds occupy a unique positon among all chemical warfare agents (CWA's). Since the 1930-s their high toxicity, wide range of physical-chemical properties and complex action attracted close attention of foreign military experts. In 1936 a German chemist, Dr. Gerhard Schrader, synthesized O-ethyl-dimethyl amidocyanophosphate, known as tabun, for the first time. By the beginning of World War II, more than two thousand new organophosphorus and phosphorus containing compounds were synthesized by his laboratory's stuff. Some of these compounds were selected for further study as CW agents and subsequently were adopted as weapons by the German army. In 1938 the same Gerhard Schrader have synthesized the organophosphorus compound, closed to tabun, but more toxic: О-isopropyl methyl fluorophosphate, called sarin. In 1944 the German chemist, the 1938 Nobel laureate in chemistry Richard Kuhn synthesized soman and revealed the damaging effect of organophosphorus CWA's. In 1941 the British chemist Bernard Saunders synthesized diisopropyl fluorophosphate. During World War II the industrial production of organophosphorus CWA's was organized in Germany, Great Britain and in the USA. Germany produced tabun, sarin and soman, the western allies: diisopropyl fluorophosphate. Till the end of World War II the leadership in the sphere of the development of nerve agents belonged to Nazi Germany. After the end of the war the German scientists, many of whom were devoted Nazis, continued their work under the auspices of military departments of the USA and Great Britain. Subsequently phosphorylated thiocholine esters: V-series substances (VG, VM, VR, VX, EA 3148, EA3317 agents etc.) were synthesized with their participation. The wide range of organophosphorus compounds was tested on volunteers in Porton Down (Great Britain) and in the Edgewood arsenal (USA). But after the synthesis of V-series agents the work on organophosphorus CWA's did not stop. In recent years there appeared the tendency of the transformation of real threats connected with the chemical weapons use, to propaganda sphere. The provocation which the «Novichok» agent, arranged primitively by the British intelligence, is the perfect example of such a transformation. But it does not mean that the research in the sphere of new organophosphorus CWA's in the West is stopped