1

At the 86th meeting of the British Association for the Advancement of Science (BAAS), held in

Newcastle upon Tyne in September 1916, the President of Section K read a paper prepared by Mr

Edward Morrell Holmes FLS, 'Lecturer in Materia Medica’ at the Pharmaceutical Society.1 To meet

the nation’s urgent need to avoid shortages of vital plant-derived drugs, Holmes proposed, ‘the

collection of herbs by instructed children, the establishment of public drying-houses, and the

cultivation of certain plants, Belladonna, Henbane, and Digitalis’. The President was Professor HG

Greenish of the Pharmaceutical Society and the session he chaired was a ‘Discussion on the

Collection and Cultivation of Medicinal Plants’. The scientists joining the discussion identified three

goals: improvement of the alkaloidal value of the plants; improvement in the yield of essential oils;

and the definition of the most favourable conditions of cultivation for each particular species. Such

practical matters were however not addressed by scientists during World War I (WWI), or in the

peacetime years that followed. Although Sir Robert Robinson was making advances on the

chemistry of alkaloids (including drugs) during the 1930s and 40s2, links between academia and

growers of medicinal plants in Britain were few, as they had always been.3 The problems outlined in

1916 at the BAAS meeting had to wait until WWII to be addressed, when they were tackled through

the Oxford Medicinal Plants Scheme (OMPS).

Exactly why they were not tackled earlier remains a question for speculation, but one reason must

have been the shortage in 1916 of scientists with the appropriate skills in either universities or

industry, and even those few with the skills were probably cautious about becoming involved in this

particular field of research for, as admitted in 1916 by Ada Teetgen4 one of the strongest

contemporary advocates of plant-based medicines,

Some people think that herbalism is a quack or empirical system of medicine unworthy of

support or perpetuation. They believe it to be a tissue of mere 'old wives lore' and

superstition.

2

Even in 1941, the founder of the OMPS, WO James, admitted,

The use of plants in medicine once went to lengths that had no justification in anything but

fantasy and riotous imagination....As a result the term 'herb' is still highly suspect: indeed, to

admit to an interest in medicinal herbs would be to endanger one's scientific reputation – or

so I have been warned.5

The context for the BAAS discussion was that before the outbreak of World War I Britain had relied

heavily upon German pharmaceutical companies for supplies of both synthetic and plant-derived

drugs, supplies of which were cut off in wartime. (In the latter case, difficulties were compounded

because the raw materials were commonly grown in Germany itself or in the lands of its allies, the

Austro-Hungarians.)6 During the post-unification, Wilhelmine, years (1871-1918) in Germany there

had been close collaboration between its universities and its chemical and pharmaceutical

companies, collaboration that was encouraged by its government. Thus, several large companies

developed in Germany. The largest, Merck, had annual revenues of 26.2 million marks (Mm) in

1913 while the biggest British company, Allen & Hanbury, had revenues of 10.4 Mm in 1914.7

Britain succeeded in maintaining stocks of plant-derived drugs during World War I (WWI). Small

pharmaceutical companies adapted to make new products, some companies such as Boots added

manufacturing to their well-established marketing activities, the public collected medicinal plants

growing wild, and ‘materia medica’ farms increased their acreages, while some market gardeners

turned from growing vegetables to growing foxgloves and deadly nightshade.

In peacetime, however, Britain relapsed into depending on Germany. Companies remained smaller

than their German rivals as the British pharmaceutical industry generally failed to invest in either

research staff or in constructing the means of drug manufacture. Even in the last years of WWI, the

industry had assumed that in the post-war world German industries would dominate once again.8,9

3

Government had given modest support to the industry in war time but through the years of the

Great Depression it decided investment was needed more urgently in other areas. As opined on 27

March 1941 by the government’s advisor on vegetable drugs, M Ashby10 of the Imperial Institute and

Ministry of Supply, acreages of medicinal plants declined because,

At the end of the last war, when a measure of self sufficiency had been achieved by the

Allies, the bottom dropped out of the market because the pharmaceutical manufacturers

found it paid them better to buy supplies of plants collected by cheap foreign labour, even

though these plants contained less active principles than plants grown by their own

nationals.11

The Vegetable Drugs Committee

When, in January 1940, only six months after the outbreak of World War II, the Whitechapel Hospital

contacted the Royal Botanic Gardens, Kew (RBG), about a rapidly developing shortage of drugs from

medicinal plants12, history may, however, have been about to repeat itself. Britain was again faced

with the major problem of a cessation of imports of drugs from Germany. However, this time, Britain

was a little better prepared. Recognising the deteriorating political situation in Europe in 1938, a year

before WWII began, the Medical Research Council (MRC) compiled a list of drugs that would be

essential in the event of war.13

In March 1941, the Ministry of Health, in collaboration with Sir Arthur Hill, Director of the RBG,

established the Vegetable Drugs Committee (VDC) to deal the supply of plant-derived drugs. Sitting

on the VDC were representatives of the Ministry, the Pharmaceutical industry, the Wholesale Drug

Trade Association, the Colonial Office, and the Imperial Institute (the last two bodies focussing on

exotic plants and drugs, such as opium and quinine). Among various botanists on the VDC were Dr

Ronald Melville (an economic botanist and pharmacist14), representing RBG, Kew, and Dr William Owen

James (Department of Botany, University of Oxford). Also from Oxford, there was Leslie Witts, MD,

4

FRCP, Nuffield Professor of Clinical Medicine, the Radcliffe Infirmary15, and Chair of the MRC's

Therapeutic Requirements Committee.

A report by Witts‘ committee16 helped the VDC decide that, among native plants, those given the

rank "essential", i.e. prioritised for attention, were: Deadly Nightshade, Atropa belladonna (called

‘belladonna‘, for which the country had an estimated annual requirement of 104 tons dry weight; the

amount then grown in Britain was 10.25 tons), Henbane, Hyoscyamus niger, called ‘hyoscyamus‘ (30;

1.25), Thorn Apple, Datura stramonium, called ‘stramonium‘ (20; 0.25), Meadow Saffron, Colchicum

autumnale (12; 0.25), Purple Foxglove, Digitalis purpurea, called ‘digitalis‘ (16; 2.7), and Common

Valerian, Valeriana officinalis, called ‘valerian‘ (amounts not stated). The 'Normal countries of origin'

of those plants included Yugoslavia, Hungary, Italy - all enemy territories - and Germany itself. While

the first three species provided atropine, hyoscyamine and hyoscine in differening proportions,

Colchicum provided colchicine (an alkaloid), foxglove provided digitoxin (a cardiac glycoside), and

valerian gave a cocktail of active ingredients, collectively called valerian.

What triggered Will James‘ interest in medicinal plants is unclear. Although he was a highly

competent all-round botanist, who had written with his colleague AR Clapham a general text, The

Biology of Flowers17, and who had helped his Head of Department, AG Tansley, produce a revised

edition of Elements of Plant Biology18, his main interest was in the physiology of photosynthesis and

respiration. As an undergraduate at University College, Reading, he had been taught by Walter Stiles

– at that time the leading authority on respiratory metabolism, and when James moved to

Cambridge to complete a Ph. D. under the supervision of FF Blackman (and, later, his brother VH

Blackman at Imperial College, London), it was Stiles who proposed the subject of James‘ study,

photosynthesis in water plants.19 Appointed in Oxford in 1927, James‘ research concentrated on the

biochemistry of respiration and a stream of publications emerged which culminated in him being

made a Fellow of the Royal Society in 1952.

What is clear from documents held in the National Archives, Kew, is that through the growing

5

season of 1940 he was already conducting preliminary experiments on medicinal plants, and he was

building a network of collaborators who would supply him with seeds.

The Oxford Medicinal Plants Scheme (OMPS)20

The proposal from James to the Ministry of Health for an initial grant of £200 is undated but letters

in reply show it must have been written sometime before 28 August 1940. In the application, he

wrote,

...in response to the appeal by the Ministry of Health for the home production of some

important medicinal herbs, usually obtained from Germany and the Balkans. The Minister of

Health has given his official approval to the scheme of production outlined below. Besides

production on a limited commercial scale, research on the growing and utilisation of these

plants is being undertaken since the direct growing of relatively large quantities affords a

specially favourable opportunity for such investigation

He continued,

Professor J.H. Burn and Professor T.G.B. Osborn have agreed to meet the incidental expenses

of the laboratory research from the funds of the University Pharmacology and Botany

Departments [respectively], where it will be carried out.

The proposal had two aspects. On what was called "The Production Side" the Scheme would grow,

dry and market belladonna, stramonium, henbane, and digitalis, the drug plants asked for by the

Ministry of Health. Growing would be carried out by volunteer gardeners21, on experimental plots at

the Botanic Gardens - where the Botany Department was located -, and at the village of Islip, near

Oxford, using paid labour and rented land adjoining James' garden. The initial proposal was to dry

plants with a modified grain-dryer put a James’s disposal by Magdalen College (located across the

6

London Road from the Oxford Botanic Garden). However, James soon designed a cheap and easily

built drying apparatus, an example of which was installed in the stables of his house in Islip.22 Given

the widely held belief that it was necessary to dry plants quickly after harvesting in order to

maximise drug yield, which, as will be seen, was not always correct, it must be presumed that the

‘volunteer gardeners‘ used their own local facilities.

On what was called "The Research Side", it was noted that,

With the cooperation of field botanists, about 90 seed samples have already been collected

from plants growing wild all over the country. It is proposed to grow these...in search for

high yielding strains and for an investigation of cultural conditions. Results already obtained

suggest, for example, that a marked increase of alkaloid would be brought about in

stramonium leaf by liming. Wild foxgloves have also been found to vary considerably in their

digitalis [sic] potency. Various methods of assay are at present being worked out and

applied...; together with experiments on the extraction and utilisation of some of the active

substances.

The Ministry of Health approved James' proposal, as did the Ministry of Agriculture and Fisheries to

whom it was shown. Progress was slow as the proposal got caught up in government bureaucracy,

first becoming the concern of the Development Committee of the Ministry of Health and then

awaiting Treasury approval – for the commitment of £200. However, James pressed his case, arguing

the urgency of knowing that funding was in place before a programme of spring planting could be

undertaken. His pressure was successful for, on 20 February 1941, The Treasury gave its approval.23

Annual accounts for the OMPS are available for the years 1941-4624 . They show that external

funding increased year-on-year, though each year income from sales of harvested plants was keenly

scrutinised by the Agricultural Research Council (ARC), as was expenditure on salaries. The accounts

show how efficiently the Scheme was managed by James for income and expenditure were almost

exactly balanced. Income rose from £191 in 1941 (of which a Treasury Grant accounted for £150, and

7

sales for £18), to £549 in 1942 (£316; £164), £773 in 1943 (£356; £246), £1113 in 1944 (£500; £419),

£990 in 1945 (£480; £215) to £2436 in 1946 (£2300, £59).

In 1941 the Scheme employed two 'field workers' and one person responsible for drying plants. In

1942 the first scientific worker, an 'analyst', was added. By 1945 the Scheme had expanded to

include three scientific assistants (a botanist, a chemist, and a pharmacologist), as well as one field

worker, and one analyst. In 1946, the first year after the war, when, as will be seen, the emphasis

had switched from growing medicinal plants to understanding their physiology and biochemistry, the

Scheme employed five scientific staff, including two post doctoral assistants. In administering the

Scheme, James was helped initially by his colleague in the Botany Department, Roy Clapham. In later

years - certainly from 1946 - this role of Secretary was taken over by Edgar Crandle, a retired

administrator from the Sudan Government Customs service, who happened to live next door to

James in Islip. Crandle also acted as Treasurer for the Scheme.

The ‘Research‘ conducted by OMPS during the war years was essentially applied research – much

of it agronomic - aimed at maximising ‘Production‘. The starting point was to collect, with the help of

collaborators, strains of the chosen plants from around Britain in order to select the most productive

from what might be expected to be a genetically diverse gathering. Wild plants were to be compared

with each other and with strains already cultivated by commercial growers, such as Stafford Allen,

and Ransoms. The effects of fertilizer on yield would be explored since this had seldom been

investigated and it was possible that the order of productiveness of different strains might be altered

by the conditions under which plants grew. But if these these very practical problems were to be

addressed, it was necessary (at least to begin) to resolve some age-old dilemmas. Where exactly do

the chemicals of interest occur in the plant? And what is the most effective way of preserving those

chemicals during harvest?

Assaying Alkaloids. Little was known about where alkaloids accumulated in plants, and when.

Were they distributed equally in all tissues or found only, say, in leaves? And if in leaves, was it in

8

young, mature, or senescent leaves? And was the generally held belief that plants should be dried

very soon after they were collected, in order to preserve yield, a correct belief? The answers to such

fundamental questions would help improve the efficiency of both growers and collectors.

James decided to concentrate on the tropane alkaloids - bicyclic compounds with a nitrogen atom

as part of a tropane ring – produced by belladonna, hyoscyamus, and datura25, all members of the

family Solanaceae.26 There was however an immediate impediment to progress. Methods for

quantifying the critical alkaloids were unsatisfactory. A histological method, by which the alkaloids

were precipitated as red spots after tissue sections were treated with Bouchardet’s reagent (1%

iodine in 1% potassium iodide), had limitations27 although it was used by James to demonstrate that

within the stem of belladonna alkaloids were most abundant in the young regions – especially their

epidermal cells - and that, with advancing age and the approach of winter, alkaloids were

progressively undetectable. However, it could not used used where cells contained significant

amounts of protein. In meristematic tisues, for example, the reagent combined with proteins to

produce a bown flocculent deposit which masked any evidence of alkaloids. Such histological

approaches were, at best, semi-quantitative, time consuming, and – because of the small number of

plants that could be examined - subject to huge sampling errors.

A theme of OMPS‘ work, which continued throughout and even after the war years, was to develop

a reliable, fully quantitative method which utilised small tissue samples – so allowing many plants to

be sampled and, thus, statistical accuracy to be maximised. Rejecting a complicated bioassay which

involved measuring the dilatation of the pupil of the eye in mice, James and his collaborators from

the Pharmacology Department concentrated on a chemical assay, based on the Vital-Morin (V-M)

reaction, which involved a colorimetric determination of the alkaloids using a “Spekker” photo-

electric absorptiometer [sic].28 However, realising that the results from the V-M reaction obtained by

earler workers were sometimes contradictory, that the colours it produces are evanescent, and that

substances other than solanaceous alkaloids may also give these evanescent colours, they set about

testing and improving the method. Using standardised conditions, in particular employing acetone

9

to enhance and stabilise the blue products29 characteristic of dinitrobenzene derivatives, such as

those from solanaceous alkaloids, the OMPS team was able to show the V-M reaction was affected

by very few complicating chemicals.30 It was was used to show that alkaloid concentrations peak in

fully expanded leaves, just below the crown, of young shoots. When the alkaloid content of leaves

and stems of belladonna were compared, it was found that a significant fraction was present as

hyoscyamine (in a racemic mixture with atropine), especially in the stem, but with the right

extraction technique all could be extracted as atropine, the drug in greatest demand.

By 1947 the assay had been improved further to the point where it required only one gram dry

weight of belladonna leaf or similar material.31 It was now, comparatively, rapid because it avoided

“the use of partitions between more or less immiscible solutes, with all the tedious purifications this

involves.”

Drying. While it was generally believed that tissues of medicinal plants should be dried as soon as

harvested, OMPS‘ research showed belladonna needed different treatment. While OMPS confirmed

foxglove leaves should be quickly dried after cutting, and such advice was passed via Dr RW Butcher

(the VDC’s Coordinator of Collections) to all County Herb Committees32, which by the end of 1942

had installed three dozen of the recommended drying sheds. Treatment of belladonna leaves was

another matter. As noted in the Annual Report for 1943, drying immediately after harvest was

probably less critical since laboratory experiments had shown their atropine content could increase

by up to 30% (this was not just a concentration effect which occurred as the tissues become

dehydrated), before declining.

Belladonna. The Atropa/Datura/Hyoscamus complex, as it was called, was a major focus for the

attention of OMPS, though H. niger (Henbane) was soon omitted from plans because not enough of

the plant could be gathered and it was difficult to cultivate. As the first samples of belladonna leaves

and seed were collected and analysed, the most significant practical finding was that strains collected

from the nearby Chiltern Hills had the highest alkaloid content. Members of the local Women's

10

Institute were encouraged to make wider, more systematic collections from that area for James to

cultivate. Thus, by 1942 forty strains of belladonna were cultivated at Islip, with further strains being

tested at the Botanic Garden and at Guildford in Surrey, and Headington, on the outskirts of Oxford.

Although yields of hyoscyamine - the alkaloid normally assayed - varied from year to year, the order

of strains, from highest to lowest in alkaloid production, changed little indicating that alkaloid

production was genetically determined. In collaborative work with Dr R Melville (RBG, Kew and VDC)

a detailed study was made of the taxonomic characteristics of A. belladonna. One strain of

belladonna was found to be widespread throughout the country and, with two exceptions, all strains

in cultivation belonged to that type.

Recognising that belladonna is naturally nitrophilous, often found growing with elders and nettles,

the effect of nitrogen on growth and alkaloid yield was one of OMPS' targets for investigation. In

1942, fertilizer grade ammonium sulphate was applied to field plots in May. Two strains were grown.

The plants were cut down to ground level in June, just before flowering (as is normal commercial

practice). They sprouted rapidly and were cut again on 10th September. Fertiliser had no effect on

the first crop but gave increased plant dry weight and alkaloid concentration per unit dry weight in

the second. The total gain in atropine formation was 92% with one strain and 71% with the other.

Experiments with pot plants showed nitrogen fertilisation gave even greater increases in atropine

production. The conclusion drawn was that it was hardly possible for growers to overmanure on

such soils with any nitrogenous fertilizer. And, under such circumstances, growers might reduce their

planting densities while maintaining productivity.

Early in his researches, James had noticed that the literature concerning the effects of nitrogenous

fertilizers on plants such as belladonna contained some contradictions; not all promoted growth and

alkaloid formation equally well. He decided to investigate possible interactions between added

nitrogen and other mineral elements, particularly calcium and potassium. The literature on

potassium was not always consistent, but commonly reported that increasing potassium levels in

soils depressed alkaloid formation. OMPS embarked on a series of experiments in which precise

11

amounts of mineral nutrients were supplied to belladonna growing in sand culture. From

measurements of growth and alkaloid formation in experiments which extended into the post-war

years, James was able to "arrive at a conception of a competitive formation of protein and alkaloids

during the growth period with calcium favouring the diversion of nitrogen towards alkaloids, and

potassium in the direction of proteins". His "conception" had practical lessons emphasising the

need for each grower to adjust fertilizer regimes to take account of local soil conditions.33

Digitalis. Foxglove proved something of a problem for the Oxford team. Although 48 strains had

been collected from throughout Britain they did not grow well, "on account of the high lime-content

of our soils". Ten strains were grown by James but a further 16 were grown at the University College

of North Wales, Bangor, under the supervision of a geneticist, Professor David Thoday. Levels of

digitoxin were satisfactory in most strains but the highest were in those collected and grown in North

Wales. Such information was passed to Dr Butcher, who built it into the published programme for

collectors in 1942. The information was subsequently updated each year.

Stramonium and Valerian. Noting that Stramonium rarely establishes itself wild in England, James

relied upon collections made from semi-natural sites and gardens. The plants grew well in cultivation

at Islip and one strain in particular (Datura stramonium var inermis) proved high yielding, its seeds

being collected and passed to the commercial grower, Stafford Allen. In contrast, when collections of

wild Valerian were made from across the country and grown in the Oxford Botanic Garden, it was a

strain already-cultivated by Stafford Allen which proved to be the highest yielding, a result probably

related to that strain’s habit of producing more rootstock (the drug yielding part) and fewer

flowering heads than the wild plants.

The “Production“ side

Lessons from experiments carried out by OMPS continually informed the production side, but there

12

were a number of ancilliary activities undertaken by OMPS. Drs. James and Melville arranged for a

panel of lecturers chosen from the chemical industry and from pharmacy colleges across England,

Scotland, and Wales to meet with their local County Herb Committees to give expert instruction.34 In

Oxford, James‘ wife, Gladys (herself an academic botanist of distinction35), gave lectures which

attracted an audience from well beyond the county's boundaries. Collectors were given the names

and addresses of companies willing to purchase dried, or fresh, plant material; companies such as

Stafford Allen of Long Melford, Ransom & Son, Brook Parker of Bradford, and Brome & Schimmer of

London. On 4 September 1943, Will James broadcast a short talk on herb gathering on the BBC

Home Service. In the same year, OMPS produced a silent 16mm film, ‘Foxglove‘, showing the

collection, drying, and medicinal uses of foxglove, which the Ministry of Supply made available to

interested bodies nationwide.

The outcome of such efforts may be illustrated by reference to two groups of collectors.

The Annual Report for the Oxfordshire Federation of Women’s Institutes for 1941 tells how, in its first

year of operation, the Islip centre processed enough foxgloves to produce 350,000 doses of

digitoxin.36 In 1944, Monks Risborough WI in Buckinghamshire sent nine sacks of belladonna stalks

to the Islip Herb Centre.37 (In addition to plants collected from the wild, significant quantities of leaf

and seed material were produced at OMPS' own growing sites. At Islip 38lbs of foxglove seeds and

13cwt dry weight of belladonna leaves were harvested in 1943.38 In West Sussex, the Felbridge Herb

Gatherers were similarly productive. One member of the Felbridge WI, Dora Wheeler, mobilised

local schoolchildren to gather the required plants from hedgerows, waste ground, and the

commons.39 Herbs were hung from strings above the classrooms to commence drying before being

sold to Brome & Schimmer. This obviously proved to a very satisfactory method, as evidenced by a

hand written comment on the bottom of one of Brome & Schimmer‘s receipts which states: ‘A

remarkably useful collection and all very well done’. Another receipt reveals the Felbridge group had

collected 3lbs of foxglove seeds.

13

Commercial growers. Britain again turned to its experienced professional growers. Two such,

Stafford Allen and Ransom & Son, reached an agreement with the Ministry of Health as early as

August 1940 to supply 63 tons of belladonna (leaf) and all the henbane they could manage to grow,

in return for which they would receive a grant to cover 62.5% of the total cost (£3,800) of installing

new drying apparatus.40 By 1946, 35 acres were planted with henbane at Ransom‘s farms, and 70

acres with belladonna. Ransoms also collected foxgloves growing wild within woodlands on their

various farms in and around Hitchin.

Royal Botanic Gardens, Kew. Some of OMPS‘ activities were not so quick to bear fruit but

neverthless made fundamental advances of longer term importance. Thus, as early as 1941 it was

realised that Valerian collections were coming from either of two contrasting habitats, xerophytic

(dry) sites on chalk or limestone hills, or rich and swampy sites. Microscopic examination of the cell

nuclei in root tips, made by Dr M Skalinska (RBG, Kew), showed that those from rich sites contained

56 chromosomes per cell nucleus (they were octaploid) whereas those from drier sites contained

only 28 (they were tetraploid), a level of polyploidy being previously unrecognised in British

Valerians. Along with the knowledge that the basic diploid form (n= 14) occurred only on the

continent, such results not only told researchers about both the history of the species, but

potentially helped them breed more productive strains for the future. At that time a general

understanding was emerging that polyploidy endows a species with greater physiological tolerance,

enabling it to extend its geographic range.

OMPS from 1945 onwards: work upon a wider scientific basis

Late in 1944, with an eye to post-war opportunities, and cutting-edge work being carried out in

America which used tissue cultures to investigate alkaloid production, James began to lobby MAF for

a grant that would allow Gladys to make a fact finding tour of key laboratories in the USA. He wrote

to MAF41,

14

For a variety of reasons I cannot go over there myself; but we are hoping to send Mrs GM

James who, as you know has taken an active part in the research side of our work since its

beginning. The Massachusetts College of Pharmacy in Boston, a leading college in this branch

over there, is offering Mrs James "a visiting lectureship in pharmacognosy" for the duration

of her visit to the States, which will involve giving lectures and exchanging research

experience at the College itself; and also travelling to other centres for similar purposes

while retaining the College as headquarters.

A grant was approved, the British Embassy arranged introductions, and by late-Spring of 1945 Mrs

James was in the USA. On July 1945 she reported back to the VDC42,

All the work in America is undertaken by commercial firms who promoted large scale

growing by farmers and supported research work. During the first year (1942) double the

estimated requirement was grown of most of the drug plants cultivated; the policy now is to

grow only the current requirement but to cultivate seed.

On 28 May 1945, WO James, TGB Osborne, and JH Burn applied to the Development Commissioners

for a grant of £2500 for the year 1946, which would enable them, "...to carry on the work of the

Oxford Medicinal Plants Scheme upon a wider scientific basis..." 43. Citing their accumulated

experience and success, they argued that OMPS would be uniquely well placed to undertake:

The organised exploration of important and little known fields in plant biology (such as

alkaloid metabolism) ... As botanists and plant biochemists we could tackle such problems

not merely from any specialised angle (pharmaceutical, chemical etc.) but in their general

biological setting.

15

The case was considered by MAF, the MRC, the Ministry of Supply's Directorate of Medical Supplies,

and the ARC. Particularly telling may have been the Ministry of Supply's comments,

The Ministry is advised that there is likely to be a world shortage of many vegetable drugs,

particularly alkaloids, which are important and cannot be sythesised and this shortage will be

accentuated by currency difficulties. It is essential therefore that the home plant drug

industry should be encouraged to produce as much material as possible, and in this

connection it would seem advisable, in the national interest, to extend the scope of the

present research work... Large supplies of belladonna, henbane and digitalis in particular will

be required. A big field of investigation is open in connection with these three crops, mainly

concerned with nitrogen metabolism and improved strains of high alkaloid content ....44

Finally, after many letters were exchanged concerning remuneration of staff, the Treasury agreed

funding and the Commissioners wrote to WO James on 19 December 1945 approving a grant, "...for,

say, another three years". Thereafter, the Agricultural Research Council should consider taking over

any further funding.45

In these post-war years more emphasis was put on pure research as OMPS examined biochemical

pathways of alkaloid biosynthesis, in particular trying to identify the amino acid(s) at their origins.

The biosynthesis of hordenine in barley – a non-medicinal plant – was chosen as the model system.

Modest advances were made in understanding the synthesis of hordenine, which was found to occur

naturally in the radicles of young seedlings. Conventional wisdom held that the amino acid tyrosine

was first decarboxylated to form tyramine, which then underwent two methylations, the first giving

N-methyltyramine, the second giving hordenine. The methylations steps were confirmed by the

OMPS laboratory, which fed various amino acids to excised barley embryos - deprived of their

endosperm in order to remove any external source of amino acids - but attempts to identify a

16

tyrosine decarboxylase gave consistently negative results. A vigorous glutamic decarboxylase was

isolated46, however, suggesting that glutamic acid, rather then tyrosine, might be the precursor of

hordenine.

Although it was widely accepted that alkaloids can move upwards in the xylem, along with the

transpiration stream of the plant, possible movement in the phloem was what James called, "a

prettier problem" .47 Alkaloids could be demonstrated in phloem parenchyma and bundle sheaths

but not in seive tubes. James speculated that the latter was because movement kept concentrations

in seive tubes too low to be detected. Consistent with this idea was the observation that whereas

mature belladonna leaves lose alkaloids while attached to the plant, detached leaves of a

comparable age do not.

An answer to the translocation question was provided by Pamela Warren Wilson (née Grant) who

skilfully modified normal stock/scion grafting methods so that the scion developed its own roots; she

managed this by cutting a flap from one side of the scion's stem, which soon gave rise to

adventitious roots. Using a belladonna scion on a tomato stock, she showed that after 2 to 3 months

she could measure belladonna alkaloids in the tomato roots. This was clear evidence of downward

transport in phloem - through the stock/scion graft.48

There are numerous alkaloid-forming species in the Solanaceae and members of this family readily

form interspecific grafts. In the Southern USA it was commercial practice to grow tomatoes on

Datura stocks. This was done because tomato roots suffered heavy infections to which Datura roots

were immune. Wilson’s research reassured growers because it showed that only minute and

harmless traces of Datura alkaloids could be found in tomato fruits49, i.e the stock/scion graft

interrupted the upward transpiration stream. And, while it was known that the alkaloids which

accumulate in both stock and scion are characteristic of the stock, Gladys James and Thewlis

showed50 showed that the proportions of the different alkaloids produced by the stock was

unchanged after grafting, e.g. the ratio of hysocine/hyoscyamine in grafts between Atropa

belladonna and Datura innoxia.

17

The demise of OMPS

Throughout the post-war years progress slowed. The subject of alkaloid biochemistry was inherently

difficult because of "...the extreme sluggishness of the reactions"51, a fundamental problem which

could not be overcome using the equipment and techniques available at the time52. Radiocarbon-

labelling was in its infancy and 15N was not yet available. Paper chromatography was the standard

separation technique. Laboratories in Britain had little or no money to spend on equipment, which

probably was not readily available in this country. A young American post-doctoral student

employed by OMPS, Harry Beevers, recalled,

...unique in England at the time, was the first Waring blendor, brought over from the United

States by Mrs James. I lived in fear that I would break this treasured item. In retrospect, since

we used it to grind belladonna leaves in pure acetone, and the solvent frequently

overflowed, the wonder is that we were not incinerated.53

OMPS was active for approximately eleven years. Its first paper appeared in 1941 and its last in

1952. Only papers reporting original research bore the OMPS address. Throughout that period

James had continued to publish on the subject of plant respiration, but all such papers bore the

simple address, “Department of Botany, University of Oxford“, as did various reviews he wrote about

alkaloids or medicinal plants. In 1952, he returned to his 'first love', respiratory metabolism. In

1953, Cyril D Darlington succeeded Osborne as the Sherardian Professor of Botany. He was not

universally liked by his staff. 5455 In 1959, after 32 years in Oxford, James left to take a chair at

Imperial College, London.

Through government grants, and the assiduous use of Rhodes Scholars, James had built the first

research group in Oxford’s Botany Department.56 OMPS was able to attract post-doctoral students of

18

the highest calibre, such as Harry Beevers, Arwyn Charles, Basil Thewlis, and Vernon Butt, setting

them on long and successful careers. It had brought the alkaloids, previously thought of as having

little interest, ‘lying in a by-way, if not a blind-alley, of nitrogen metabolism‘57, into the mainstream of

plant biochemistry58. But most importantly of all, OMPS had in positive, practical ways contributed

to the war effort by helping the British people to grow more and collect more of a group of

‘essential‘ medicinal plants.

The help of Alison Foster, Associate Director of the Oxford Botanic Garden, and of Anne-Marie

Catterall, Sherardian Librarian, Department of Plant Sciences, University of Oxford, is gratefully

acknowledged. I thank Simon Bailey, Keeper of the Archives, University of Oxford, for allowing for

me to listen to the Burnett tape recording.

1Anonymous. Report of the British Association for the Advancement of Science 1916, p.507. London:

John Murray.

2Oxford University's Waynefleet Professor of Chemistry from 1930-1955, Robinson was awarded the

Nobel Prize for Chemistry in 1947 for his work on plant products, especially the alkaloids.

3Francis Ransom (1859-1935), head of the his family’s herb growing company in Hitchin, Herts, was a

rarity. He worked in the laboratories of the Pharmaceutical Conference on improving methods for the

extraction and estimation of the alkaloids from belladonna, research which produced a series of

papers in scientific journals from 1885 onwards. Respected by the scientific community, he was

President of the British Pharmaceutical Conference in 1910.

4Ada B Teetgen. Profitable Herb Growing and Collecting. London: George Newnes. 1916, p.11.

5 Will O James. British Drug Plants Biology: A Journal for Schools and Teachers (1941) 7, 6-11

6 House of Commons, Parliamentary Command Papers, Cmd 183. 1919. Memorandum of the special

measures taken by the National Health Insurance Commission (England) in relation to the supply of

drugs and other medical stores during war. Para. 9 and 51.

19

7Tobias Cramer. Building “The World’s Pharmacy”. A co-evolutionary approach to the rise of the

German pharmaceutical industry 1871-1914. Cologne Economic History Paper No.3, ed. Carsten

Burhop. www.wigesch.uni-koeln.de. 2012. pp.9-10.

8Jonathan M Liebenau. The rise of the British pharmaceutical industry. British Medical Journal

(1990) 301, 724-728.

9Michael Robson. The British pharmaceutical industry and the First World War’, pp.83-105, in JM

Liebenau (ed), The Challenge of New Technology: Innovation in British Business since 1850. 1988.

Gower: Aldershot. p.99.

10Ashby M. Report to the VDC, Ministry of Supply. 27 March 1941. Archives of RBG, Kew : 1/MUS/28.

11Archives of the RBG, Kew: Kew 1/MUS/28

12Laura Hastings. The botanic gardens at Kew and the wartime need for medicines. The

Pharmaceutical Journal (1996) 257, 923-927.

13TAB Corley. The British Pharmaceutical Industry Since 1851. pp.14-32 in Lesley Richmond, Julie

Stevenson, and Alison Turton eds., Pharmaceutical Industry: A Guide to Historical Records. (2003)

Aldershot: Ashgate. p.22

14Archives of the RBG, Kew: 1/MUS.

15M Ashby. Note: Medicinal herbs in war time. Bulletin of the Imperial Institute (1941) 39, 125-128.

16Report to the VDC, Ministry of Supply, 27 March, 1941. Archives of the RBG, Kew: 1/MUS/28.

17A Roy Clapham and Will O James. The Biology of Flowers. Oxford: Clarendon Press. 1935.

18Arthur G Tansley and Will O James. Elements of Plant Biology. London: George Allen & Unwin.

1935.

19A Roy Clapham and John L Harley. William Owen James (1900-1978). Biographical Memoirs of

Fellows of the Royal Society (1979) 25, 336-364.

20Annual Reports for the OMPS were prepared for each of the years 1941 to 1945 (see Manske 1950,

below), but only those for the first three years have been traced. These are held in the National

Archives, at Kew (MAF 33/279); possibly, the last two were lost during transfer to Kew from the

20

Agricultural Research Council, which had the task of reviewing them. Nevertheless, the work of the

OMPS can be pieced together from letters in the National Archives (MAF 200/1), from

OMPS‘ publications, and from aspects of OMPS‘ work described by Will O James in Alkaloids in

plants, pp.16-90, in Manske RHF and Holmes HL , eds, The Alkaloids. New York: Academic Press.

1950.

21By 1942, volunteer gardeners included ‘Robin’ Snow FRS, an Oxford colleague, growing plants at

Headington, CT Prime, Head of Biology at Whitgift School, growing plants at Croydon, and Dr. E

Shawyer, growing plants at Guildford.

22Peter Ayres. Britain’s Green Allies. Medicinal Plans in Wartime. 2015. Leicester: Matador Books.

2015.

23Approval is referred to in a letter, dated 28 February 1941, from WR Black of MAF to EHE Havelock

of the Development Committee. National Archives, Kew: T161/1132 Materials: Medical

24National Archives, Kew: MAF 33/279 Oxford Medicinal Plants Scheme

25 These closely related plants all produce hyoscyamine and hyoscine (aka scopolamine). During

extraction of the naturally occurring form of hyoscyamine, some is converted to a much less active

optical isomer, the mixture of isomers being known as atropine.

26Colchicine, too is an alkaloid, but it has a very different chemistry

27Will O James. Demonstration of alkaloids in solanaceous meristems. Nature (1946) 158, 377-378.

28GM Watson, CRC Heard, and Will O James. A comparison of the biological and chemical assays of

Belladonna and Stramonium. Quarterly Journal of Pharmacy and Pharmacology (1941) 14, 253-258.

29Atropine, hyoscine and hyoscyamine showed absorption peaks in the 550 to 610nm waveband.

30Will O James and M Roberts. The nature and specificity of the Vitali-Morin reaction for

solanaceous alkaloids. Quarterly Journal of Pharmacy and Pharmacology (1945) 18, 29-35.

31M Roberts and Will O James. A method for the estimation of total alkaloids in Belladonna and

Stramonium. Quarterly Journal of Pharmacy and Pharmacology (1947) 20, 1-16.

21

32 The Vegetable Drugs Committee worked through the Women’s Institute, and Scottish Women’s

Rural Institute, to establish County Herb Committees. In each county members were organised to

collect medicinal plants from fields and woodlands, dry, and sell them to the wholesale trade.

33Will O James. Alkaloids in plants. pp. 16-90 in The Alkaloids, ed RHF Manske and HL Holmes. New

York: Academic Press. 1950. p.76.

34See letter of 5 May 1941, from Elizabeth Hess, Agricultural Organiser of the National Federation of

WI to Sir Arthur Hill, Director RBG, Kew, acknowledging she has recently received such a list.

Archives of the RBG, Kew: 1/MUS/28

35A fellow-student of Will James at Reading, Gladys James (née Redfern) was an active researcher,

occasional lecturer in the Department of Botany in the 1930s when her husband suffered one of the

recurrent bouts of tuberculosis which plagued his adult life. From Trinity term 1942 until at least

1952, “Mrs James” is listed in her own right in the Oxford University Gazette, timetabled to give

lectures and practical classes in plant physiology.

36Annual Report of the Oxfordshire Federation of Women’s Institutes, 1941, Tackley, Oxon

37Ibid. 1944

38Ibid 1943

39www.felbridge.org.uk/index.php/publications/felbridge-herb-gatherers

40National Archives, Kew: 1/MUS/28 VDC Min of Supply. Agenda and Minutes.

41 National Achives,Kew. MAF 33/279 Oxford Medicinal Plants Scheme.

42Archives of the RBG, Kew. 1/MUS/28 Vegetable Drugs Committee Ministry of Supply Agenda and

Minutes.

43National Archives, Kew: MAF/33/279 Oxford Medicinal Plants Scheme.

44National Archives, Kew: T 161/1132 Materials Medical.

45Op.cit. 38

46Harry Beevers. An l-glutamic acid decarboxylase from barley. Biochemical Journal (1951) 48, 132-7.

22

47 Will James. Alkaloid formation in plants. Journal of Pharmacy and Pharmacology (1953) 5, 809-

822. p.815.

48 Pamela M Warren Wilson. Formation and transport of alkaloids in Solanaceous grafts. New

Phytologist (1952) 51, 301-316. Will James. Alkaloid formation in plants. Journal of Pharmacy and

Pharmacology (1953) 5, 809-822, explains that Wilson‘s research was carried out in Oxford, as part

of the OMPS, although it bears the address of her next post, the University of Reading.

49Ibid.48

50Gladys James and Basil Thewlis. The separation and identification of solanaceous alkaloids from

normal and grafted plants. New Phytologist (1952) 51, 250-255.

51Op.cit.47, p.818.

52Harry Beevers. Forty years in the New World. Annual Review of Plant Physiology and Plant

Molecular Biology (1993) 44, 1-12.

53Ibid.52. At Purdue University, Indiana, Beevers subsequently became the world’s leading authority

on plant respiration, thus making a connection with Walter Stiles by way of Will James.

54www.st-hildas.ox.ac.uk/sites/default/files/pdfs/oxfordsumitratalukdar.pdf

55 Tape-recorded seminar given by Sir John Burnett on 8 May 1990 at Linacre College, The plant

sciences in twentieth-century Oxford. Available at the Bodleian Library, Oxford. Burnett was a

contemporary of James and, later, Sibthorpian Professor of Rural Economy.

56Ibid55.

57Op.cit.33, p.16.

58 The Alkaloids, to volume 1 of which Will James contributed a leading chapter, see 33, reached

volume 75 in 2015.