A tale of two poppies
James Wearn, leading a project called ‘Kew Gardens at War’, describes how one poppy helped to keep pain away during wartime while another poppy lets us remember and reflect on the pain and sorrow of war.
Of the c. 70 species of poppy within the genus Papaver (Papaveraceae), two have been responsible for two very different, but equally influential, tasks during the past century.
They are P. rhoeas L. (common poppy, corn poppy, field poppy) and P. somniferum L. (opium poppy, or literally ‘sleep-inducing’ poppy) and they have a rich history of economic, medical and scientific importance, peppered with sad irony.
A long history of medicinal value
The flowers of the field poppy have long been used as a painkiller for soothing mild aches and pains (e.g. toothache, earache and sore throat), a mild sedative/relaxant, an expectorant for treating catarrh and coughs, as a digestive, and even for reducing the appearance of wrinkles and in lipstick.
Traditionally, two methods of preparation have been employed: fresh petals used to prepare a syrup, and dried petals added to water to make an infusion.
Moreover, chemical extracts from the petals of P. rhoeas have recently been tested for potential in the prevention of skin cancer.
Whilst equally pleasing to the eye, “the opium poppy’s power does not reside in its beauty”. The white latex of the opium poppy contains far greater quantities of potent narcotics than that of the field poppy, which has led to its importance in medicine but also to its exploitation through illicit trade.
Indeed it became “a drug hailed as the most important remedy in the pharmacologist’s entire materia medica, yet one judged capable of creating more misery by its abuse ‘than any other drug employed by mankind’”.
‘Milk of the poppy’ was prescribed liberally for centuries for virtually any ill. Although evidence has been found to suggest its use since prehistory, the ancient Greeks gave rise to the more familiar name for the poppy’s sap (Gr. opion).
The East India Company (EIC) produced most of the opium in India during the 18th Century, the poppies officially being grown for medicinal use.
However, an illicit opium trade, primarily with China, was conducted privately and so the opium reaching China had come, albeit indirectly, from EIC plantations.
China banned the sale (1729) and import (1796) of opium in an attempt to be rid of its corrupting influence, so complex networks were developed to continue its trade.
Growth of the trade and related disputes came to a head in two ‘Opium Wars’ between Britain and China during the 19th Century.
Of particular note, the EIC Herbarium, assembled by botanist and EIC surgeon Nathaniel Wallich, now resides in a wall of mahogany cupboards within the Herbarium at Kew.
Amongst the sheets are three collections of P. somniferum, appropriately followed by three of P. rhoeas, all collected in India during the early 1800s.
From 1914, morphine ampoules were needed en masse to aid millions of soldiers injured in the bloody battles of the First World War.
In fact this sudden and important demand temporarily halted advances made in preceding years concerning the regulation of opiates (e.g. The Hague International Opium Convention of 1912).
Opium generally contains about 10-14% morphine, which is an important chemical in the management of severe pain, acting directly on the central nervous system.
However, a pharmaceutical cultivar called ‘elite’ has been selected to contain 91% morphine, codeine, and thebaine.
The effects of morphine on other tissues are now being explored because studies have shown that “morphine may either promote or inhibit the tumor growth”.
Kew’s scientific collections
The genus Papaver is well-represented among Kew’s vast scientific collections. Kew’s collection of 7 million herbarium specimens contains multiple examples of both species described here, while the DNA of Papaver rhoeas is stored in Kew’s DNA Bank, available for use in studies on the evolutionary relationships of plants.
Poppy seeds are also stored for research and conservation in the Millennium Seed Bank, which currently holds 50 accessions of Papaver seeds along with a wealth of information on seed parameters and germination. Papaver species have ‘orthodox’ seeds, which can be dried, without damage, to low moisture contents.
Kew’s Economic Botany Collection houses 94 accessions of Papaver material, the two focal species comprising the majority of these collections. They include ‘tools for scooping poppy juice’ as well as donations from the Pharmaceutical Society of Great Britain and samples in the the Harrod Materia Medica Collection, “one of the finest collections of its kind in the world” (see Related Links below), which was recently moved to Kew from King’s College London, and is available for study.
The spark for the endowment of the field poppy with the heavy burden of becoming the international symbol of remembrance came from the opening lines of a poem entitled ‘In Flanders Fields’, written by Lieutenant Colonel John McCrae in 1915, though he did not live to see the powerful and far-reaching influence his heart-felt words were to induce.
In Flanders fields the poppies blow.
Between the crosses, row on row.
Scientifically, the heavily churned soil, tossed around by so many explosions, had provided the stimulation required for the seeds within the seed bank (which can often remain dormant for up to 80 years) to germinate.
Emotionally, the ‘sea of blood’ they represented became an overwhelming sight, and continues to evoke compassion, empathy, sorrow and hope, a century on.
Kew’s own Director, Sir Arthur Hill commented on the Somme: “Nowhere, I imagine, can the magnitude of the struggle be better appreciated than in this peaceful poppy-covered battlefield hallowed by its many scattered crosses”.
It became a huge task to prepare this heavily battle-scarred land for formal landscaping of war cemeteries.
Selection of planting for Commonwealth War Graves was led by serving Kew staff during and after the First World War, and this will be the subject of an upcoming article.
But not all scars are visible.
Some were more insidious than the physical destruction of the land and the men and women who served upon it.
New categories of distress such as ‘shell-shock’ (a trauma that was poorly defined) dictated a need for new treatments – including time spent in botanic gardens.
Emotional trauma was long-lasting, and one ex-Kew gardener who had been in action in Gallipoli and elsewhere sadly never recovered, apparently taking his own life a year after the fighting was over.
Thus, we wear our poppies for those who were crushed by the conflict both outwardly and inwardly.
Many millions died in wars before the field poppy became the symbol of remembrance; many more will do so.
The opium poppy has become a source of significant painkilling drugs still used in modern medicine; yet its legacy continues to be clouded by a multi-billion pound international drug trafficking network.
In a recent treatise on the history of the poppy, Saunders (2013) reflected on the “opium fields of Afghanistan” – a sad twist on the ‘sea of blood’ metaphor.
This is an ongoing tale of two common plants with a past and future no less colourful than their flowers. They are undoubtedly “the poppies of war”.
Bimonte, S., Barbieri, A., Palma, G. & Arra, C. (2013). The role of morphine in animal models of human cancer: Does morphine promote or inhibit the tumor growth? BioMed Research International2013: Article ID 258141.
Ennamany, R. Leconte, N., Leclerc, J., Jabès, A., Rezvani, H-R., Rambert, J. Ezzedine, K. & Djavad Mossalay, M. (2013). Sublethal UVB induces DNA lesions and pro-apoptotic gene transcription in human keratinocytes: Attenuation by a mixture of plant extracts. Journal of Preventive Medicine 1: 4-10.
Hill, A. W. (1917). The flora of the Somme battlefield. Bulletin of Miscellaneous Information, Kew 1917: 297-300.
Potter, J. (2013). Seven flowers and how they shaped our world. Atlantic Books, London.
Saunders, N. J. (2013). The poppy. A cultural history from Ancient Egypt to Flanders Fields to Afghanistan. Oneworld Publications, London.
A tale of two poppies James Wearn, leading a project called ‘Kew Gardens at War’, describes how one poppy helped to keep pain away during wartime while another poppy lets us remember and reflect
Why Harvest Opiates When You Can Get Yeast to Produce Them?
To revist this article, visit My Profile, then View saved stories.
To revist this article, visit My Profile, then View saved stories.
Every opiate painkiller—say, Percocet, Vicodin, or good old-fashioned morphine—is born from the bulbous green fruit of the opium poppy plant. Sown in spring, the poppy blooms by early summer in vibrant reds, pinks, whites, and purples. After pollination, these flowers shed their petals and make way for the fruit that contains the moneymaker: raw opium, which takes the form of dribbly, milky latex when you cut the unripe seed pod. In Tasmania, where much of world’s legal opium poppy crop grows, these fruits dry before machines harvest them for refining. The fruit seeds go to your muffins, and what’s left goes to the extraction of opiates: morphine, codeine, and thebaine.
But the pastoral beginnings of painkillers may soon be migrating from the Tasmanian poppy fields into vats of genetically modified yeast in the laboratory. Scientists and pharmaceutical companies have been concocting more cost-effective ways to produce opiates—by attempting to genetically engineer yeast to make them. To this end, scientists have been trying to deduce the multi-step process that opium poppies use to produce opiates. They’ve been able to alter yeast to perform specific steps in this complicated process, but a single strain of yeast has never undergone all the steps sequentially—because they haven’t understood what happens in each individual step. But at long last, a research team from the University of York, collaborating with British pharmaceutical company GlaxoSmithKline, has figured out the last step in how poppies produce opium, in a paper published today in Science.
Specifically, the team identified a gene—fused together from multiple genes—that code for enzymes that catalyze the key two-pronged chemical reaction. “It’s such an unusual combination of genes,” says Ian Graham, a biochemical geneticist at the University of York who led the research. The genes are found separately, unfused, in the genomes of a variety of other plants and animals, and “for some reason, the poppy has evolved to allow this hybrid reaction to happen,” says Graham. “And that now makes up the pathway that we rely on to produce the most important painkillers known to humankind.”
Over millions of years, opium poppies evolved to produce opiates to protect their seeds from nature’s threats, such as bacteria and fungi. The plants go through fifteen steps catalyzed by some twenty enzymes in the process. “It’s like a production line in a factory making a complicated machine,” says Graham. The enzymes are the workers in the line that assemble the opiates, step by step.
To understand this key two-pronged step in this production line, the team made mutant poppies by soaking regular seeds in a chemical, creating random changes in its DNA. The team then selected the poppies that were bad at making opiates—and found that the impaired poppies got stuck at one specific point in the process.
“It’s like having some workers in the middle of the production line gone on strike,” Graham says. The process can’t complete itself, and instead you get a buildup of a half-finished product. By studying the genes of these mutants, Graham’s team was able to identify the one responsible for the buildup.
And with the identification of this gene, scientists now know all the genes needed to engineer a single strain of yeast to produce opiates like morphine.
Christina Smolke, a bioengineering professor at Stanford University, points out that while we now know the genes that enable the entire opiate production process in poppies, it doesn’t mean that making yeast mimic that process will be easy. “If you have to engineer yeast to make about twenty enzymes it doesn’t normally make, it’s really complex,” she says. “This work is certainly a piece of the puzzle, but we still need a lot more pieces.”
Smolke’s lab has recently replicated some of the opiate-producing steps in yeast and has been aiming to not only to have the yeast produce the opiates, but also further refine the chemicals into purer forms like hydrocodone that pharmaceutical companies need—essentially making the fermentation vat into a pharmaceutical factory. But scientists like Smolke and Graham can’t forge ahead blindly in their laboratory goals: When they finally manage to make yeast produce opiates, this may open new legal questions regarding the risk of people procuring the genetically modified yeast and homebrewing the opiates themselves.
Graham predicts that within the next year, someone will be able to engineer yeast to undergo the entire process, but echoes Smolke that it will be a while before opiate production in yeast will be commercially viable. “We’re still some way away from producing it cheaply,” he says. For now, let the poppies keep blooming.
Scientists have figured out the final piece of the puzzle in how to genetically modify yeast to produce opiates.