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Making viruses in the lab deadlier and more able to spread: an accident waiting to happen
投稿者 手紙 日時 2020 年 5 月 15 日 22:58:09: ycTIENrc3gkSo juiOhg

Making viruses in the lab deadlier and more able to spread: an accident waiting to happen


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Good morning pal,
Questo ti interesserà, e’ dal The Bulletin of the Atomic Scientists, also available at: http://thebulletin.org/making-viruses-lab-deadlier-and-more-able-spread-accident-waiting-happen7374 , FYI,

The Spanish flu patients.

Analysis08/13/2014 - 21:42Making viruses in the lab deadlier and more able to spread: an accident waiting to happenTatyana Novossiolova | Malcolm Dando

All rights come with limits and responsibilities. For example, US Supreme Court Justice Oliver Wendell Holmes famously noted that the right to free speech does not mean that one can falsely shout "fire" in a crowded theatre.

The same constraints and obligations apply to the right of scientific inquiry, a topic that has been in the news recently after researcher Yoshihiro Kawaoka of the University of Wisconsin-Madison published an article in the journal Cell Host and Microbe in June describing the construction of a new flu virus from wild-avian-flu strain genes that coded for proteins similar to those in the 1918 pandemic virus; the new virus was not only able to spread between ferrets—the best current model for human flu transmission—but was also more virulent that the original avian strains. (The 1918 Spanish Flu killed an estimated 50 million people; the molecular structure of the new strain is only three percent different than the 1918 version.)

Asked for comment by The Guardian newspaper, Robert, Lord May of Oxford, the former chief scientific advisor to the British Prime Minister and former president of the British Royal Society—one of the oldest and most prestigious scientific organizations in the world—condemned the work as "absolutely crazy," calling "labs of grossly ambitious people" a real source of danger.

As if that research were not enough to cause worry, in July a newspaper investigation asserted that Kawaoka was also conducting another controversial—but so far unpublished—study in which he genetically altered the 2009 strain of flu to enable it to evade immune responses, "effectively making the human population defenseless against re-emergence."

If true, it may be that Kawaoka has engineered a novel strain of influenza with the capability of generating a human pandemic, if it ever escaped from a laboratory. (“Pandemic” means that it occurs over a wide geographic area and affects an exceptionally high proportion of the population. In comparison, the Centers for Disease Control define an “epidemic” as merely “the occurrence of more cases of disease than expected in a given area or among a specific group of people over a particular period of time.”)

An independent risk-benefit assessment of this work conducted at the request of the journal Nature demonstrated that Kawaoka’s work did indeed meet four of the seven criteria outlined in the US Policy for Oversight on Dual Use Research of Concern (DURC) of March 29, 2012, meaning that the institution found that the research could be misused to threaten public health and would therefore require additional high-level safety measures, including a formal risk-mitigation plan.

But even with these measures in place, this research still seems like an unnecessary risk, given the danger that the bio-engineered viruses could turn into a pandemic threat, and that some experts think that there are far better and safer ways to unlock the mysteries of flu transmissibility. Claims that this work would help in the manufacture of a preventive vaccine have been strongly contradicted by Stanley Plotkin of the Center for HIV-AIDS Vaccine Immunology, among other critics.

Part of the justification behind conducting these experiments, apparently, was to develop a better understanding of the pandemic potential of influenza viruses by enhancing their properties, such as altering their host range, for example. Since the newly engineered viruses possess characteristics that their naturally found, or "wild," counterparts do not, this type of study is commonly referred to as "gain-of-function" research in virologists’ parlance.

But considering the likelihood of accidental or deliberate release of the virus created by gain-of-function experiments, the following issues should be considered before approving any such studies—and preferably they would have been taken into consideration by those attending the Biological and Toxin Weapons Convention earlier this month.

In a nutshell: The convention’s attendees should have agreed on a common understanding requiring that all gain-of-function experiments be stopped until an independent risk-benefit assessment is carried out; the scientific community should exhaust all alternative ways of obtaining the necessary information before approving gain-of-function experiments; biosecurity education and awareness-raising should be given a priority as tools for fostering a culture of responsibility in the life sciences; and there should be a modern version of the “Asilomar process” to identify the best approaches to achieving the global public health goals of defeating pandemic disease and assuring the highest level of safety. (At Asilomar, California, in the early 1970s, researchers studying recombinant DNA met to discuss whether there were risks from their research, what the negative social implications could be, and how to contain the dangers.)

There will be another meeting of the Biological and Toxin Weapons Convention in December; one can only hope that it will consider these proposals then.

What, me worry? Sometimes, the potential for accidents is inherent in a system, making their occurrence not only able to be anticipated but inevitable, even "normal." For example,Charles Perrow’s famous account of the Three Mile Island nuclear accident contends that the very structure and organization of nuclear power plants make them accident-prone. As a result, even in the presence of sophisticated safety designs and technical fixes, multiple and unexpected interactions of failures are still bound to occur, as illustrated more recently in the Fukushima disaster.

Gain-of-function research in the life sciences is another example of the inevitable failure of overly complex, human-designed systems with multiple variables. Some of the most dangerous biological agents—anthrax, smallpox, and bird flu—have been mishandled in laboratories. As noted by the newly formed Cambridge Working Group, of which one of us —Malcolm Dando—is a member, these are far from exceptional cases; in the U.S. alone, biosafety incidents involving regulated pathogens "have been occurring on average over twice a week."

Such situations are not confined to the United States; China’s poor track record for laboratory containment means that it was "appallingly irresponsible" (in Lord May’s words) for a team of Chinese scientists to create a hybrid viral strain between the H5N1 avian influenza virus and the H1N1 human flu virus that triggered a pandemic in 2009 and claimed several thousand lives. In a July 14, 2014 statement about the creation of such pathogens, the Cambridge Working Group noted:

An accidental infection with any pathogen is concerning. But accident risks with newly created “potential pandemic pathogens” raise grave new concerns. Laboratory creation of highly transmissible, novel strains of dangerous viruses, especially but not limited to influenza, poses substantially increased risks. An accidental infection in such a setting could trigger outbreaks that would be difficult or impossible to control.

Against this backdrop, the growing use of gain-of-function approaches for research requires more careful examination. And the potential consequences keep getting more catastrophic.

High-profile examples. In April, 2014, the Daniel Perez Lab at the University of Maryland engineered an ostrich virus known as H7N1 to become “droplet transmissible”—meaning that the tiny amounts of virus contained in the minuscule airborne water droplets of a sneeze or a cough would be enough to make someone catch the illness. Hence, it could be easily transmitted from one subject to another.

So far, there has not been one laboratory-confirmed case of human infection by H7N1. It is apparently not a threat to man, unlike H5N1 and H7N9.

However, while the chance of airborne transmission of H7N1 in humans by droplet is apparently low, the test animals that it did manage to infect became very ill indeed—60 percent of ferrets infected through the airborne route died. This is a phenomenal rate of lethality; in contrast, only about two percent of humans who contracted the illness died from it during the Spanish Flu pandemic of 1918.

So it was with concern that the scientific world noted Kawaoka’s study describing the construction of a brand-new flu virus from wild-avian-flu strain genes that coded for proteins similar to those in the 1918 pandemic virus. The resulting new pathogen was not only able to spread between ferrets—the best current animal model for human flu transmission—but it was also more severe in its effects than the original avian strain. But the story does not finish here. As an article in Nature revealed, the “controversial influenza study was run in accordance with new US biosecurity rules only after the US National Institute of Allergy and Infectious Diseases (NAID) disagreed with the university’s assessments,” thus showing the real need for reform of the current system.

Avoiding a ‘normal’ accident. While biotechnology promises tremendous public health benefits, it also holds a considerable potential for catastrophe, as these gain-of-function experiments illustrate. As scientific capabilities and work involving dangerous pathogens proliferate globally, so too do the risks and the prospects for failure—whether coming from technology or arising from human error. Indeed, in assessing the rapidly evolving life-science landscape, Jose-Luis Sagripanti of the US Army Edgewood Chemical Biological Center—the nation’s principal research and development resource for chemical and biological defenses—has argued that “current genetic engineering technology and the practices of the community that sustains it have definitively displaced the potential threat of biological warfare beyond the risks posed by naturally occurring epidemics.”

Laboratories, however well equipped, do not exist in isolation but are an integral part of a larger ecological system. As such, they are merely a buffer zone between the activities carried out inside and the greater environment beyond the laboratory door. Despite being technologically advanced and designed to ensure safety, this buffer zone is far from infallible. Indeed, as researchers from Harvard and Yale demonstrated earlier this year, there is almost a 20 percent chance of a laboratory-acquired infection occurring during gain-of-function work, even when performed under conditions of the highest and more rigorous levels of containment. Addressing the rapid expansion of gain-of-function studies is therefore both urgent and mandatory.

In December 2013, the Foundation for Vaccine Research sent a letter to the European Commission calling for a “rigorous, comprehensive risk-benefit assessment of gain-of-function research” which “could help determine whether the unique risks to human life posed by these sorts of experiments are balanced by unique public health benefits which could not be achieved by alternative, safe scientific approaches.” Given the recent developments with influenza viruses, there is a need for an independent assessment of the costs and benefits of gain-of-function research. Such independent review would allow for adopting newer and better regulations and conventions, as well as help to identify policy gaps. As David Relman of the Stanford School of Medicine recently pointed out in the Journal of Infectious Diseases, the time has come for a balanced and dispassionate discussion that “must include difficult questions, such as whether there are experiments that should not be undertaken because of disproportionately high risk.”

Correction: Due to an editing error, the second paragraph of this article initially contained an erroneous description of research published in June in the journal Cell Host and Microbe. The Bulletin regrets the error.

# # # Malcolm Dando

Malcolm Dando is a biologist researching international security at the University of Bradford’s Department of Peace Studies with a focus on chemical and biological weapons, arms control, and biosecurity. Author and contributor to numerous books on bioweapons and biotechnology, including Deadly Cultures: Biological Weapons Since 1945, Dando’s recent research includes how the revolution in the life sciences might open up possibilities for new biological weapons. Dando previously held a Ministry of Defence-funded fellowship in operational research at the University of Sussex.

Recent work:

"The Impact of Scientific and Technological Change"

Bioterrorism: Confronting a Complex Threat (Lynne Rienner Publishers, 2007)
"Preventing the Future Military Misuse of Neuroscience"

Technology and Security (Palgrave Macmillan, 2007)
"Scientific Outlook for the Development of Incapacitants"

Incapacitating Biochemical Weapons: Promise or Peril? (Rowan and Littlefield, 2007)
"A Scientific Advisory Panel for the Biological and Toxin Weapons Convention as an Element in the Web of Prevention"

The Web of Prevention: Biological Weapons, Life Sciences, and the Governance of Research (Earthscan Publications Limited, 2007)
"A Hippocratic Oath for Life Scientists"

EMBO Reports (July 2006)

# # #
Tatyana Novossiolova

Tatyana Novossiolova is a Wellcome Trust Doctoral Researcher at the Bradford Disarmament Research Centre at the University of Bradford, UK. She is currently working on a project about the governance of biotechnology in post-communist Russia. Her research focuses on the development of academic and specialized training courses for biosecurity and international arms control. Past collaborations include work with the Public Health Agency of Canada, the UK Global Partnership Program, and the Landau Network-Centro Volta, Italy.

# # #
David Vincenzetti

Hacking Team
Milan Singapore Washington DC

email: d.vincenzetti@hackingteam.com
mobile: +39 3494403823
phone: +39 0229060603


*Yoshihiro Kawaoka

*新型コロナウイルス感染症に関する専門家有志の会 - 河岡が参加する有志の会の公式ウェブサイト

*Why the Scientific Debate Over a UW Bird Flu Study Isn’t Going Away - 16 Mar 2019, 6:58 pm

*在米の中国人研究者が銃で殺害 新型コロナで「非常に重要な発見をする寸前」- May 06, 2020 22:08

*The Strange Case of Dr. Jekyll and Mr. Hyde



1. 手紙[385] juiOhg 2020年5月17日 02:10:25 : fmj3GeWwE6 :TOR NGcwWVFhR0d4bEE=[4] 報告


石田雅彦 | ライター、編集者 2019/10/5(土) 9:00






 例えば、急性好酸球性肺炎(Acute Eosinophilic Pneumonia)という病気がある。日本から加熱式タバコ(アイコス=IQOS)を吸ったことで急性好酸球性肺炎になったという症例報告があるが(※2)、電子タバコでもこの病気になる危険性はありそうだ。







 電子タバコによるグリセリンはリポイド肺炎(Lipoid Pneumonia)という、これも珍しい呼吸器疾患との関連が示唆され、例えば呼吸困難とひどい咳、発熱で入院した42歳の女性の事例では、約7ヶ月前から電子タバコを吸い始めてから症状がひどくなり始めたという(※10)。














※2019/10/06:15:12:英国の医学雑誌「BMJ(the British Medical Journal)」に2019年9月30日に出た論文(※18)によれば、電子タバコを吸うことによる長期的な悪影響は研究されていないが、呼吸器疾患の症例が増加している現状をみれば、電子タバコが肺に何らかの悪影響を及ぼすことは十分考えられるという。その理由として、電子タバコを吸うことで、肺に脂肪蓄積マクロファージ(lipid-laden macrophage)による泡沫細胞(Foam Cell)ができることが関与しているのかもしれないとする。マクロファージは白血球の一種で、死んだ細胞など生体廃棄物のスカベンジャー(腐肉あさり)の役割をする。脂質をあさって泡だった状態になったのが脂肪蓄積マクロファージだ。脂肪蓄積マクロファージはアテローム性動脈硬化症の原因になることが知られている。また、この論文では電子タバコの成分が免疫機能を抑制するかもしれないとも述べている。

※1-1:Irfan Rahman, William MacNee, "Lung glutathione and oxidative stress: implications in cigarette smoke-induced airway disease." Lung Cellular and Molecular Physiology, Vol.277, Issue6, L1067-L1088, 1999

※1-2:Anupam Kumar, et al., "Current Concepts in Pathogenesis, Diagnosis, and Management of Smoking-Related Interstitial Lung Diseases." CHEST, Vol.154, Issue2, 394-408, 2018

※2-1:Takahiro Kamada, et al., "Acute eosinophilic pneumonia following heat‐not‐burn cigarette smoking." Respirology Case Reports, Vol.4, Issue6, 2016

※2-2:Toshiyuki Aokage, et al., "Heat-not-burn cigarettes induce fulminant acute eosinophilic pneumonia requiring extracorporeal membrane oxygenation." Respiratory Medicine Case Reports, Vol.26, 87-90, 2019

※3-1:Hiroshi Uchiyama, et al., "Alterations in Smoking Habits Are Associated with Acute Eosinophilic Pneumonia." CHEST, Vol.133, Issue5, 1174-1180, 2008

※3-2:Federica De Giacomi, et al., "Acute Eosinophilic Pneumonia. Cause, Diagnosis, and Management." American Journal of Respiratory and Critical Medicine, Vol.197, No.6, 2018

※3-3:Beenish Fayyaz, "Acute eosinophilic pneumonia associated with smoking: a case report." Journal of Community Hospital Internal Medicine Perspectives, Vol.8, Issue3, 2018

※4:Federica De Giacomi, et al., "Acute Eosinophilic Pneumonia: Correlation of Clinical Characteristics With Underlying Cause." Chest, Vol.152, Issue2, 379-385, 2017

※5:David R. Janz, et al., "Acute eosinophilic pneumonia: A case report and review of the literature." Critical Care Medicine, Vol.37, No.4, 1470-1474, 2009

※6:Darshan Thota, Emi Latham, "Case Report of Electronic Cigarettes Possibly Associated with Eosinophilic Pneumonitis in a Previously Healthy Active-duty Sailor." The Journal of Emergency Medicine, Vol.47, Issue1, 15-17, 2014

※7:Zhaohui I. Arter, et al., "Acute eosinophilic pneumonia following electronic cigarette use." Respiratory Medicine Case Reports, Vol.27, 2019

※8:Yasmeen M. Butt, et al., "Pathology of Vaping-Associated Lung Injury." New England Journal of Medicine, DOI: 10.1056/NEJMc1913069, 2019

※9:Dominic L. Palazzolo, "Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review." frontiers in Public Health, doi.org/10.3389/fpubh.2013.00056, 2013

※10:Lindsay Mccauley, et al., "An Unexpected Consequence of Electronic Cigarette Use." CHEST, DOI: 10.1378/chest.11-1334, 2012

※11:Kevin Davidson, et al., "Outbreak of Electronic-Cigarette-Associated Acute Lipoid Pneumonia-North Carolina, July-August 2019." Morbidity and Mortality Weekly Report, Vol.68(36), 784-786, 2019

※12:I Weinberg, Z G. Fridlender, "Exogenous lipoid pneumonia caused by paraffin in an amateur fire breather." Occupational Medicine, Vol.60, Issue3, 2010

※13:My Hua, Prue Talbot, "Potential health effects of electronic cigarettes: A systematic review of case reports." Preventive Medicine Reports, Vol.4, 169-178, 2016

※14:Sonia L. Betancourt, et al. "Lipoid pneumonia : spectrum of clinical and radiologic manifestations." American Journal of Roentgenology, Vol.194, Issue1, 103-109, 2010

※15:C G. Perrine, et al., "Characteristics of a Multistate Outbreak of Lung Injury Associated with E-cigarette Use, or Vaping- United States, 2019." Morbidity and Mortality Weekly Report, Vol.68(39), 860-864, 2019

※16:I Ghana, et al., "E-cigarette Product Use, or Vaping, Among Persons with Associated Lung Injury- Illinois and Wisconsin, April-September 2019." Morbidity and Mortality Weekly Report, Vol.68(39), 865-869, 2019

※17:Christian Giroud, et al., "E-Cigarettes: A Review of New Trends in Cannabis Use." International Journal of Environmental Research and Public Health, Vol.12, Issue8, 2015

※18:Jeffery E. Gotts, et al., "What are the respiratory effects of e-cigarettes?" the BMJ, Vol.366, doi.org/10.1136/bmj.l5275, 2019

※筆者は喫煙者を批難しない。喫煙者は、日本では国によって推進されてきたタバコ政策とタバコ会社のビジネスの犠牲者だからだ。禁煙外来などで処方されるニコチンパッチやニコチンガム、ニコチン代替薬には免疫系への悪影響がないことがわかっている(1)。ある物質は毒にも薬にもなる。医師の適切な指示に従って処方されるなら、ニコチンは禁煙にとって重要な薬物となる。1)Kate Cahill, et al., "Nicotine receptor partial agonists for smoking cessation." Cochran Database of Systematic Reviews, 2008

2. 手紙[386] juiOhg 2020年5月17日 02:13:39 : fmj3GeWwE6 :TOR NGcwWVFhR0d4bEE=[5] 報告





 電子タバコまたはベイピング関連肺損傷(lung injury associated with e-cigarettes or vaping:EVALI)は、重度の肺損傷や、全身および消化器症状と関連する新たな疾患であり、重症度は多岐にわたること、多くが抗菌薬やステロイドで治療されているが、臨床的に改善しても異常が残存する患者が多いことが、多施設共同前向き観察コホート研究で示された。米国・Intermountain HealthcareのDenitza P. Blagev氏らが報告した。米国では2019年3月からEVALIの発生が急増し現在も報告が相次いでいるが、本疾患の原因、診断、治療および経過は明らかになっていなかった。著者は、「EVALIの臨床診断は、感染症や他の肺疾患とオーバーラップしているままで、原因、適切な治療および長期的アウトカムを理解するには本疾患を疑う高度な指標が必要である」と述べている。Lancet誌オンライン版2019年11月8日号掲載の報告。

 研究グループは2019年6月27日〜10月4日の期間で、米国ユタ州の総合医療システムIntermountain Healthcareにおいて確認されたEVALI患者全例のデータを収集した。

 中央管理組織としてソルトレークシティーに拠点を置くTeleCritical Careに肺疾患専門医および救命救急医からなる委員会を設け、症例の検証と分析を行った。また、カルテの再評価とユタ州保健局が実施した患者面接から、患者の症状、治療および退院後2週間のデータを抽出し、短期追跡結果をまとめた。

 Intermountain Healthcareの13施設において確認されたEVALI患者は60例であった。






 なお、TeleCritical Careの委員会は今回の調査結果を基に、EVALIの診断と治療のガイドライン案を作成し公表もしている。

(医学ライター 吉尾 幸恵)

3. 手紙[387] juiOhg 2020年5月17日 03:00:39 : Yu2et2k4VY :TOR NExUTjdNVGpDUmc=[41] 報告

Published on Aug 29, 2019 / FCI (Fujisankei Communications International, Inc.)

【電子たばこで初の死者か 呼吸器系疾患の原因に?】
4. 2020年5月17日 19:56:53 : IF2RS2Wphc : bnRrV3E0SXdsNGM=[12] 報告

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