Fritz Haber was an academic chemist who contributed enormously to industrial chemistry. As the prime mover in the fixation of atmospheric nitrogen, he was responsible for myriad chemicals, from fertilisers to pharmaceuticals, and thus for alleviating hunger and prolonging life. Yet he was also the father of modern chemical weaponry and thus responsible for bringing death to many.
Alfred Nobel represents ambiguity of another kind. He, too, was responsible for a variety of developments, the invention of dynamite being the most famous, and his fertile, commercial mind is to some extent a summary of what is best in chemical industry, when applied to quarrying and construction, for example. Yet his invention can also be applied to killing. His conscience, however, led him to encourage the peaceful deployment of chemistry and other disciplines by the foundation of his Nobel prizes. The clash of these two symbols of ambiguity was witnessed by the fury directed at the award of the 1918 chemistry prize to Haber, which he collected in 1920. In 1918, Haber had been included in the list of war criminals; his name did not appear in the list compiled in 1920, but outrage lingered on.
Chemical versus physical weapons
In a lecture entitled ‘Chemistry in war’, at the German Ministry of Defence on 11 November 1920, Haber raised an important ethical point. He said that ‘gas weapons are definitely no more inhumane than flying bits of metal’.
So why is chemical warfare regarded these days, if not by Haber, as more inhumane than physical warfare, the use of knives, spears, bullets, and bombs? Why is chemical warfare linked in repulsiveness with biological warfare, warfare conducted by propagating disease? Put another way, why is there an effective Organization for the Prohibition of Chemical Weapons (OPCW), but not an Organization for the Prohibition of Physical Weapons (OPPW)?
All weapons, physical and chemical, maim, so this is not the reason why chemical weapons induce such horror. Chemical weapons inflict injury that persists for a lifetime, but physical weapons often remove limbs, which also lasts for a lifetime. Chemical weapons are said to induce a singularly painful and lingering form of death, but a bullet in the stomach can be equally painful and lingering. Chemical weapons are regarded as being indiscriminate, killing and maiming blindly, but bombs do not dismember only those in uniform. Indeed, although chemical weapons are regarded as a particularly nasty way of bringing death to an enemy, it is conceivable that one could be developed that brought that death in a kinder way: what would be our reaction to a compound that smelled of lily-of-the-valley, induced unconsciousness, and killed the insensate victim gently and peaceably?
There are, however, differences between the effects of physical and chemical weapons. One is the persistence of the effects of some chemical weapons, which denies access to certain terrains for months. Then there is the psychological impact of such weapons, not only the fear that death might creep up on one unseen but a visceral discomfort at the thought of being poisoned and subjected to a slow, agonising death.
And, like nuclear and biological weapons, chemical weapons are regarded as weapons of mass destruction. But I think there is a difference in the nature of the underlying fear. For nuclear weapons, it comes down to mankind’s ability to annihilate itself on a global scale; for chemical and biological weapons, it is more the prospect of debilitation and pain locally rather than globally; the fear is more personal than geopolitical.
There are, I think, fundamentally two reasons why there are institutions like OPCW and not OPPW. The first is that, unlike a physical weapon that can be used benignly, a chemical weapon is perceived as a weapon to kill and only kill; it has no compensating use. In contrast, conventional explosives have been used to quarry, mine, and build canals. Even guns can be regarded as providing protection and guarding sensitive installations. Nuclear weapons have engendered nuclear power.
The second reason is pragmatic: physical weapons have been with us since the first shaped flint was used to slay an opponent. Chemical weapons have been with us, in the current meaning of the term, only since the invention of industrialised war in the early 20th century, and as such can be scotched at birth.
Going back to Haber’s remark about those ‘flying bits of metal’, the bullets and shells are impelled by explosives that chemistry has striven to perfect.
About 1000 years ago came gunpowder. A crude mixture of charcoal, sulfur, and potassium nitrate, gunpowder was used until the middle of the 19th century. This low explosive explodes in a rather lazy way, propelling a projectile smoothly along a barrel rather than exploding violently in the breech. One social consequence of the development and long-lasting deployment of gunpowder for use in firearms was the emergence of standing armies. When bows and arrows, swords and spears were the weapons of choice, a rabble could easily be raised by a baron with little notice and less training. When firearms became the norm, the technicalities of their use were such that a professional force had to be sustained. The immensely technical arena of modern armies is a direct consequence of the invention and slow improvement of gunpowder.
A thousand years on, to Haber again, and the use of potassium nitrate as an oxidising agent had further significant consequences for war and peace. Potassium nitrate was in short supply for war on an industrial scale and other sources of nitrates had to be found. That search famously led to the arid uplands of Chile and the caliche found there. There are two problems with Chilean caliche, or Chile saltpetre. One is that it is largely sodium nitrate, not potassium nitrate. The sodium salt is moisture absorbing, and so cannot be used in gunpowder, which would become damp. Therefore, it had to be converted to the potassium salt. That could be done only on a small scale as long as the only sources of potassium salts were wood ash and seaweed, but the conversion became commercially viable once the large deposits of potassium chloride, as carnallite, were discovered in Stassfurt, Germany. The resulting gunpowder was used in the Crimea. The second problem with Chilean saltpetre was more substantial: the shortage of supply and the vulnerability of the sea routes from far-away Chile.
These problems were responsible for Haber’s development, together with Carl Bosch, of the catalytic synthesis of ammonia and the so-called fixation, but better the chemical liberation, of abundant and freely available atmospheric nitrogen. Once ammonia was available, it could be oxidised to nitric acid and thus used to generate nitrates galore.
The drawback with gunpowder, the root of its low-explosive character, is that the oxidising agent and the fuel are present as a simple granular mixture. High-explosive character, which imparts a short, sharp shock, and so destroys rather than impels could be achieved by increasing the intimacy of the oxidising agent and the fuel. The ultimate intimacy is achieved when the oxygen atoms are neighbours of the fuel atoms within the same molecule, and that is a characteristic of all modern high explosives.
The grandfather of these high explosives is nitroglycerin, the first of several compounds to replace gunpowder. Enter onto the scene Alfred Nobel and his series of inventions that include the taming of this ferocious liquid by absorbing it on kieselgur, a diatomaceous earth, to form dynamite. Modern high explosives include Semtex, built around pentaerythritoltetranitrate (PETN) and now rendered more readily detectable by various volatile additives.
A feature of the high explosives is the presence of nitrogen. The presence of oxygen is easy to understand insofar as it is an oxidising agent, but why nitrogen? The answer lies in two aspects of the generation of nitrogen gas as a fragmentation product. First, nitrogen atoms form the very stable diatomic nitrogen molecule, N2, whereas carbon forms, among other molecules, the triatomic CO2 molecule. That means that the presence of nitrogen gives a lot of gas molecules per explosive molecule, and hence a strong, shattering blow. Technically, the presence of nitrogen enhances the brisance, the shattering power, of the explosion. Secondly, the formation of triply bonded N2 molecules from individual nitrogen atoms is highly exothermic, and that release of energy adds power to the explosion.
From a positive perspective, explosives have many peaceful uses, ranging from quarrying and mining up to some of the greatest earth-moving enterprises on the planet, as in the construction of the Corinth Canal and the Panama Canal. Rocket engines are essentially shells that have embedded motors, and use what could be regarded as low-explosives. The booster rockets of the NASA Space Shuttles, for instance, were fuelled by aluminium and oxidised by ammonium perchlorate with iron oxide as a catalyst. Nobel himself experienced the ambiguity of nitroglycerin as a killer and a life prolonger, for he was given it to alleviate his heart condition shortly before his death in 1896. Nitroglycerin is a vasodilator, which widens blood vessels and permits a better flow of blood to the heart.
Modern chemical weapons
Chemistry has also contributed to Haber’s ‘gas weapons’ and to modern chemical weapons, which are typically viscous, clinging liquids. If we disregard the use of poisoned arrows in the Amazon, then chlorine, came first, and, under Haber’s direction, was simply pumped across the battlefield in the general direction of the enemy. That primitive procedure was subject to the vagaries of the weather and the local nuisance of an errant wind that might turn the scorpion on its tail.
More sophisticated were the mustards, the infamous sulfur mustards, known as ‘mustard gas’, and their cousins, the less familiar nitrogen mustards. They are so called because they smell like various mustard plants, such as garlic and horseradish.
Sulfur mustard is an especially vindictive weapon, for it operates at two levels and is lipophilic. The latter property means that it penetrates clothes and dissolves on contact with the skin, so avoiding breathing it by wearing a respirator is dangerously and misleadingly ineffective, and symptoms might start to appear many hours after exposure. The first level of attack is chemical burning, leading to the formation of blisters. Any inhaled vapour attacks the respiratory system, causing similar blistering and damaging mucous membranes. The second level of attack might lie undetected, for the mustards attack the DNA of the victim and can initiate cancers.
Where is the possible good news buried in this account? For a hint of this, we need to turn to the nitrogen mustards, where an NH group takes the place of the sulfur atom. The glimmer of good in them is that, in principle, they can be used as cytotoxic therapeutic agents to stop the uncontrolled replication of runaway cancer cells. Thus, the loss of one chlorine atom and the attack on a guanine base forms one link, just like the action of sulfur mustard. However, this attack may be followed by a similar attack by the other end of the molecule on a guanine base of the second strand of a DNA double helix, so binding them together and preventing their unwanted replication.
One advantage of the nitrogen mustards over the sulfur mustards is that the H atom on nitrogen is open to modification, which can result in a variety of types of control over the potency and possible side effects of the drug. Thus, the first nitrogen mustard to be used was mustine, in which the H atom is replaced by a CH3 group. Chemists can tinker much more elaborately though, and bendamustine is one of their modifications, and is sometimes given to treat chronic lymphocytic leukaemia and non-Hodgkin lymphoma.
Chemical warfare moved on from the mustards, which attack the body, and turned its attention to the destruction of the nervous system.
Nerve agents include a variety of phosphorus-containing compounds that fall broadly into two classes, the non-persistent G-series and the persistent V-series. The G series include tabun (GA), first synthesised in 1936, and sarin (GB), which came along in around 1938 and is 10 times more effective. The V series emerged from research at ICI on organophosphate pesticides, and include VX, one of the most potent, developed at Porton Down in Wiltshire, UK.
The military advantage of the V series is that they are persistent, their slow degradation, once dispersed over a battlefield, renders certain terrains inaccessible so the motion of the enemy can be controlled. The symptoms of both series include the usual list of horrors, descending from a runny nose, through vomiting, urination, and defecation, and ending with asphyxiation, which is brought about not by the paralysis of muscles but by the excessive activity of the neuromuscular junction of the diaphragm. The agents kill by stimulating over exertion.
Can there be an angel buried amid all this devilry? To answer this question, it is helpful to understand the molecular mechanism of the action of nerve agents.
We need first to understand how a signal along a nerve is translated into muscular action. When an electrical impulse arrives at a synapse the neurotransmitter acetylcholine is released, travels across the synaptic gap, and stimulates action of the muscle. Its job done, the enzyme acetylcholinesterase hydrolyses the acetylcholine and the muscle stops firing and relaxes. A nerve agent inhibits the action of the enzyme so that the acetylcholine is not removed, the muscle does not relax, and its contractions do not stop. It is not only muscles that don’t stop contracting: glands too continue to release their contents and the victim effectively dies by drooling. At a molecular level, the nerve agent plugs a little hole that leads into the active site of the enzyme, and the acetylcholine cannot get into it and undergo hydrolysis.
There are three principal soft points for attack: the release of acetylcholine; its attachment to the postsynaptic membrane; and the processes that occur in the postsynaptic cleft itself. All the military nerve agents focus on the role of the enzyme acetylcholinesterase. However, the two other options also provide opportunities for chemical attack on the release and attachment of acetylcholine itself.
In fact, what could be regarded as the first agent of chemical warfare, pre-dating Haber’s initiative by centuries, is the use of curare by the South and Central American Indians. Curare is extracted from the plant Strychnos toxifera and the active component blocks the acetylcholine receptors on the muscle membrane of the postsynaptic cleft. As a result, the muscle does not respond to signals along the nerve, breathing ceases, and the victim suffocates. One antidote is to increase the concentration of acetylcholine by inhibiting the action of acetylcholinesterase, just like its action when used as a nerve agent, but now aimed at seeking to achieve a higher concentration of acetylcholine in the hope that some will stick; so here we see how one form of chemical warfare can mitigate the effect of another. Once again, there are ambiguities afoot, for curare, by preventing muscles to respond to orders, is an effective muscle relaxant, and consequently has applications in surgery, for relaxation is decoupled from sedation.
Control and elimination
Amid all the aggression that has marked history, and currently geography, I think we can all discern a glint of hope for the future of mankind. The development of weapons of mass destruction, be they chemical, biological, or nuclear, and the recognition that they represent a threat to all civilisation, has led, for the first time in history, to the prospect of their elimination or at least their outlawing.
International agreement on the limitation of use of chemical weapons of various kinds goes back to 1675, when Germany and France agreed not to use poison bullets. Modern treaties really stem from an agreement two centuries later, with the Brussels Convention on the Law and Customs of War, in 1874, which prohibited the use both of poison or poisoned weapons, and arms, projectiles, or materiel to cause unnecessary suffering. This, however, had little impact, for together with its successors in 1899 and 1907, which purported to prohibit chemical weapons, in fact oversaw their deployment on an industrial scale in World War 1. No doubt as a result of experiencing the horrors that chemical warfare engenders in practice in gas-filled trenches rather than by abstract considerations in smoke-filled rooms, matters moved on with the Geneva Protocol in 1925, which prohibited the use of chemical (and biological) weapons in warfare, but did not ban their possession. Moreover, it left loopholes for their deployment should a non-signatory launch an attack.
In due course, there emerged the Chemical Weapons Convention, 1993, which came into force in 1997. The convention imposes a legally-binding, world-wide ban on the production, stockpiling, and use of chemical weapons and their precursors. Notwithstanding, there remain large stockpiles, the usual justification being that they are a precaution against possible use by an aggressor or, like whale-hunting in Japan, are needed for scientific research.
The elimination of chemical weapons presents a variety of challenges. Even the elimination of them at source, through their prohibition, is not entirely clear cut, because although some are single-use killers, like the mustards and VX, others can be made from chemicals that are reasonably readily available. Indeed, some nerve agents are made while the shell delivering them is actually in flight; that is, there is a distinction between ‘unitary’ and ‘binary’ weapons. The former consist of the nerve agent itself; the second of its precursors.
It is for reasons like this that OPCW has devised three Schedules for identifying actual and potential lethal compounds. Thus, Schedule 1 materials have no other use except in killing, and include nerve agents like sarin, VX, and related materials. Schedule 2 includes materials that are immediate precursors of lethal chemicals. They include a variety of phosphorus compounds, but others too. Schedule 3 includes materials that are important in the production of the Schedule 1 and 2 materials and might be produced in commercial quantities for legitimate applications. This Schedule includes a variety of phosphorus compounds, such as phosphorus trichloride.
Naturally, evasion occurs and stockpiles are discovered either voluntarily or on inspection, as recently with Syria. The question then arises as to how the stocks may be destroyed. Schedule 3 materials might well find a legitimate home as they include materials that are already used commercially. Schedule 1 and 2 are typically incinerated or hydrolysed, such as by heating with concentrated sodium hydroxide. These procedures are infinitely superior to the previous practice of dumping shells and other active weapons at sea and hoping for the best. Such, for example, was operation CHASE, an acronym of Cut Holes and Sink ‘Em, that consisted of filling a ship with old munitions and scuttling them in deep water. The US alone seems to have dumped about 300,000t of munitions in locations that it seems to have largely forgotten.
The current, incomplete effort to eradicate Syria’s stockpile is centred on the American cargo ship Cape Ray: land-based procedures were considered but no country was willing to offer hospitality. The cargo holds of the vessel are fitted out with two titanium-lined hydrolysis units that use sodium hydroxide, sodium hypochlorite, and heat to convert chemical agents into conventionally hazardous waste. The procedure, which is designed to deal with about 50t/day, will be carried out in international waters. The effluent, about 500t, will not be discharged at sea but treated as ordinary hazardous commercial waste.
While the role of chemistry in war and peace can often be ambiguous, there can be no doubt of the positive contributions of chemistry to the modern world, through the liaison of academe and industry and catalysed by the invigorating spice of entrepreneurship.
Every branch of human knowledge and endeavour has lurking evil, as Pandora discovered, but the light generally overwhelms the dark. If we stand back from the dark corner of our subject and keep our vision of chemistry in proportion, then there is brilliant radiance, the unquestionable radiance of improved and lengthened life, and the joy of ever increasing understanding.
Peter Atkins retired as a professor of physical chemistry at the University of Oxford and fellow of Lincoln College in 2007 and now spends his time as an author.