opioid weaponry

11-13-17  An investigation carried out last year by the Associated Press found 12 businesses in China who said they would readily export the chemical for as little as US$2,750-per-kg.  Months later China’s ministry of public security said it would move to outlaw carfentanil.

  While the investigation into the 42kg that were seized recently in Canada is ongoing, police have said the substance seized could have yielded as many as 420,000 doses of carfentanil with an estimated street value of C$13m.

  Police arrested a 33-year-old man in connection with the Pickering seizure in September, charging him with possession for the purpose of trafficking as well as 337 weapons-related charges.  “Agents like carfentanil could be used in lethal doses that would make them comparable to traditional nerve agents, raising concerns that they could be used as chemical weapons,” a state department official told the Associated Press under the condition of anonymity.

  The remarks came after Canadian police – protected by hazmat suits and oxygen containers – seized one kilogram of carfentanil hidden inside cartridges labelled as printer ink and which had been shipped to Vancouver from China.

Given the purity of the substance seized, police estimated that the package could contain as many as 50m lethal doses – enough to wipe out the entire population of the country.  Allan Lai of the Royal Canadian Mounted Police told reporters “With respect to carfentanil, we don’t know why a substance of that potency is coming into our country.”

https://www.theguardian.com/world/2017/nov/12/carfentanil-bust-canada-fentanyl-opioid-crisis-dangers

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  The biological weapons program of the former Soviet Union reportedly included a special program for developing bioregulator-based weapons.8 Moreover, several countries now appear to be pursuing incapacitating biochemical weapons based on analogues of bioregulators. Indeed, three years before its report on globalization and biosecurity, the National Research Council released a report from a different committee which strongly recom- mended that the U.S. military pursue a ‘‘non-lethal’’ biochemical weapons capability.9 

Opioid compounds, including fentanyl, were investigated by U.S. and U.K. military researchers as potential biochemical incapacitants during the early Cold War programs but were discarded because their lethal doses were at most 10􏰀20-fold greater than their incapacitating doses.61 Indeed, in addition to causing sedation and unconsciousness, the opioids can cause vomiting, hypotension, bradychardia (reduced heart rate), muscle rigidity (including of the chest wall muscles), and severe, life-threatening respiratory depression.62 

During the 1970s, a series of compounds related to fentanyl were discovered that were both more potent and said to have a much higher safety margin.63 One such compound, sufentanil, is 5􏰀10 times more potent than fentanyl and is the most potent opioid currently in routine clinical use.  A second compound, carfentanil, is perhaps the most potent analgesic currently known with roughly 10,000 times the potency of morphine.64 It is currently used as a veterinary drug to sedate large animals but is not approved for use in people. Like fentanyl, both of these opioids are fast acting and have a relatively short duration of effect. 

These and other new fentanyls were the focus of extensive U.S. military research, including inhalation studies in nonhuman primates, to develop new incapacitating biochemical weapons during the 1980s and early 1990s.65 According to a recently released 1994 Army research proposal, at least some of the new fentanyls had ‘‘shown promise in previous studies’’ and were ‘‘excellent candidates for situations where a quick knock-down agent is needed.’’  However, they also had drawbacks. Specifically, ‘‘earlier materials showed high safety ratios in rodents, but much lower ratios in primates because of respiratory depression.’’66 

Delivery of fentanyl as an aerosol is as effective as delivery intravenously.71  If sufentanil and carfentanil act similarly, they may thus be as, or even more, toxic than the nerve agent VX, which has an LD50 of approximately 15 m/kg, when delivered via inhalation.72 As already noted, aerosol delivery of carfentanil was tested by U.S. researchers, although the results are not publicly known.73 

Yet, more than a decade later there is still no publicly available evidence that the United States has developed and fielded biochemical incapacitating weapons for either military or police use, other than scattered reports that U.S. special forces are equipped with ‘‘knock-out’’ agents.82 

In the case of the fentanyls, since 1992, advances have included the discovery of the new ultra-fast (30-second onset time) and ultra-short-acting (5 􏰀 10 minutes duration after exposure terminated) opioid remifentanil, which was of particular interest to Army researchers in 1994; the cloning of all four human opioid receptor genes; the characterization of the anatomical locations at which each receptor is expressed; and the generation of strains of mice in which each opioid receptor has been eliminated.88 As a result, it is now known that one opioid receptor, the mu opioid receptor (MOR), is responsible for mediating both the analgesia/ anesthesia and the respiratory depression caused by morphine, such that ‘‘any agent acting at the MOR will invariably cause [potent] analgesia in combination with [variable] respiratory depression.’’89 

Clearly, the Naval Science Board was correct when it concluded in late 2002 that biochemical incapacitants were once again ‘‘under study . . . after [a] lull in R&D for 10 years.’’99 

The North Atlantic Treaty Organization has listed ‘‘chemical technologies [that] could act on the central nervous system by calmatives, dissociative agents, [and] equilibrium agents,’’ and ‘‘by convulsives’’ as two of its 17 anti-personnel non-lethal ‘‘technologies of interest.’’103 And there are indications that China may be interested as well. An article written by two Chinese analysts that appeared in the U.S. Army journal Military Review in July 2005 argued that the ‘‘times call for new kinds of weapons, and modern biotechnology can contribute such weapons.’’ ‘‘War through the command of biotechnology,’’ they said, will ultimately ‘‘lead to success through ultramicro, non-lethal, and reversible effects. . . . Modern biotechnology offers an enormous potential military advantage.’’104 

Meanwhile, militaries and police forces would very likely not be the only users.137 It is likely that criminals, terrorists, despotic regimes, paramilitary organizations, and armed factions in failing and failed states could all find utility in incapacitating biochemical weapons and that many would not feel as constrained by international law and concerns about lethality as nominally more legitimate users will.138  As Mark Wheelis has pointed out, the ideal targets for attacks with biochemical incapacitants are people who cannot protect themselves*that is, ordinary civilians.139 Criminals could thus find them useful for aiding in burglary, kidnapping, incapacitation of security guards, and other activities. 

Another danger arises from what is perhaps the most serious problem of all: the likelihood that the momentum associated with the growth of incapacitating biochemical weapons programs and the institutional interests that surround them will, over time, lead to an ever-broader and more powerful array of biological and chemical weapons. 

8 Christopher J. Davis, ‘‘Nuclear Blindness: An Overview of the Biological Weapons Programs of the Former Soviet Union and Iraq,’’ Emerging Infectious Diseases 5 (July􏰀 Aug. 1999), pp. 509􏰀512. 

9 Committee for an Assessment of Non-Lethal Weapons Science and Technology, Naval Studies Board, National Research Council, An Assessment of Non-Lethal Weapons Science and Technology Wsshington, DC: National Academies Press, 2003), p. 4 

Taylor Pharmaceuticals, ‘‘Sufenta (Sufentanil Citrate) Injection,’’ package insert, B/www.akorn.com/documents/catalog/package_inserts/11098-050-01.pdf􏰓/. The package insert states, ‘‘As with all potent opioids, profound analgesia is accompanied by respiratory depression . . . which may persist into or recur in the postoperative period.’’ See also note 69. 

W.F. Van Bever, C.J. Niemegeers, K.H. Schellekens, and P.A. Janssen, ‘‘N-4-Substituted 1-(2-arylethyl)-4-piperidinyl-N-phenylpropanamides, a novel series of extremely potent analgesics with unusually high safety margin,’’ Arzneimittel-forshung 26 (1976), pp. 1548 􏰀 1551. 

65 Thomas Stanley, ‘‘Human immobilization: Is the experience in Moscow just the beginning?’’ European Journal of Anaesthesiology 20 (June 2003), pp. 427􏰀428. 

66 ERDEC, ‘‘Synthetic Opioids’’; see also Brian D. Anderson and Patrick M. Grant, ‘‘Dose Safety Margin Enhancement for Chemical Incapacitation and Less-Than-Lethal Target- ing,’’ NIJ (National Institute of Justice) Final Report (Livermore, CA: Lawrence Livermore National Laboratory, Jan. 1997); Lois Pilant, ‘‘Less-than-Lethal Weapons: New Solutions for Law Enforcement,’’ Science and Technology, publication of the International Association of Chiefs of Police (Dec. 1993), p. 3, reporting a safety ratio of 4 for alfentanil in the operating room. The source for this figure is unknown.

72. Franz, ‘‘Defense Against Toxin Weapons,’’ p. 607. 

73 Stanley, ‘‘Human immobilization.’’ 

82 Mark Wheelis, ‘‘‘Nonlethal’ Chemical Weapons: A Faustian Bargain’’, Issues in Science and Technology (Spring 2003), B/www.issues.org/19.3/wheelis.htm􏰓/, citing statement by retired Rear Admiral Stephen Baker that U.S. special forces were equipped with ‘‘knockout gases.’’ 

89. R. Romberg, E. Sarton, L. Teppema, H.W. Matthes, B.L. Kieffer, and A. Dahan, ‘‘Comparison of morphine-6-glucuronid and morphine on respiratory depressant and antinociceptive responses in wild type and mu-opioid receptor deficient mice,’’ British Journal of Anaesthesia 91 (Dec. 2003), pp. 862􏰀870). 

99.  Applied Research Laboratory, Pennsylvania State University, Independent Technology Assessment Report of Findings: The Objective Individual Combat Weapon Non-Lethal Munition (Oct. 10, 2002), pp. 10, 15,B/www.sunshine-project.org/incapacitants/jnlwdpdf/oicwairburst.pdf􏰓/.    p.125

103. NATO Research and Technology Organization, Non-Lethal Weapons and Future Peace Enforcement Operations, RTO-TR-SAS-040, Dec. 2004, pp. 3􏰀10, B/www.rta.nato.int/Main. asp?topic 􏰁/sas.htm#􏰓/. 

104  Guo Ji-wei and Xue-sen Yang, ‘‘Ultramicro, Nonlethal, and Reversible: Looking Ahead to Military Biotechnology,’’ Military Review 85 (July 􏰀 Aug. 2005), pp. 75 􏰀 78, B/http:// usacac.army.mil/CAC/milreview/download/English/JulAug05/yang.pdf􏰓/. Like much of the work by non-lethal weapons enthusiasts and technology boosters, this article, which talks about a wide range of biotechnology-enabled weapons, is more science fiction than science fact. But it reveals a clear interest in the future of biotechnology for military purposes. It also includes such statements as ‘‘such devastating, non-lethal effects will require us to pacify the enemy through postwar reconstruction efforts and hatred control,’’ p. 76; and ‘‘[w]e can control the degree of injuries and damage produced and even provide an antidote or a cure . . . Providing such an anodyne to our enemies would represent real ‘mercy,’’’ p. 77 

137 Not considered here are private military contractors (or PMCs), who are increasingly prominent, but largely unregulated, purveyors of security services and armed force at the local, national, and global levels. It seems likely that PMCs could find great utility in any incapacitating biochemical weapons that might come on the market. For more information on PMCs, see for example Peter W. Singer, Corporate Warriors: The Rise of the Privatized Military Industry (Ithaca, NY: Cornell University Press, 2003).

138 Wheelis, ‘‘Faustian Bargain.’’ 

139 Ibid.  https://fas.org/biosecurity/resource/documents/132pearson.pdf