J. R. Sharma*, R. K. Lal, H. O. Misra, A. A. Naqvi and D. D. Patra

Successful development of a non-narcotic (opiumless and alkaloid-free) var. Sujata of opium poppy for the first time in the world has heralded a new era of opium poppy cultivation which need not be licensed. This novel variety offers a cheap and permanent natural means of combating opium-linked social abuses across the world. It is also a high calorie and protein-rich (>23%) seed (food) crop. Its seeds possess higher oil content (50–>52%) with greater proportion of hypocholesterolemic unsaturated fatty acids, than the major oilseed crops, viz. rapeseed and mustard in India. Hence, the var. Sujata is a potential supplement to the production of healthful vegetable oil, referred to as ‘Sonola’, for a good dietary control for coronary heart disease. Besides, it forms a sound parental base for development of hyper-alkaloid true CPS chemotypes/varieties for pharmaceutical purposes.

 

PERHAPS no medicinal plant hitherto on record possesses a rich food value together with an excellent pharmaceutical property as does the opium poppy (Papaver somniferum) ¹. Moreover, its historic and contemporary importance coupled with the notoriety and mystique can be attributed to very few plants². The ‘sleep-inducing’ property of its byproduct, i.e. opium (dried latex) obtained by lancing the ripe fruits (capsules) of plants has been known and exploited throughout the course of human history^3,4. Even today, its pharmaceutical significance in modern medicine is unparalleled, chiefly because of the three morphinane alkaloids, namely morphine, codeine, and thebaine and the three phthalideisoquoline alkaloids, viz. papaverine, narcotine and narcine that it contains. In addition to opium, the poppy-straw (capsule hull + 1/3 peduncle) is also the site of accumulation, though in much lower concentration, of alkaloids, which can be solvent-extracted and concentrated chemically for diverse pharmaceutical uses⁵. Besides, poppy seeds (Posta or Khas-Khas) and seed oil are also the important economic byproducts of opium poppy^3,6. The delicious protein-rich seeds are used in certain food items while the seed-oil (fatty acid – technically called lipoprotein) is a very healthful cooking medium^7,8, it contains a large propor-

 

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The authors are in the Central Institute of Medicinal and Aromatic Plants, Lucknow 226 015, India

*For correspondence. (e-mail: jrsharma@satyam.net.in)

tion of unsaturated fatty acids, viz. oleic and linoleic acids (high level of HDL, i.e. high density lipoprotein –
a ‘good cholesterol’), which offer a very good dietary control for the coronary heart disease (CHD).

Among the opium alkaloids, morphine is a strong analgesic, while codeine is antitussive and papaverine antispasmodic. Besides being a potent pain-killer, morphine, the largest component of opium, exhibits a combination of depression and stimulation in the central nervous system (CNS) and the gut⁹. Thus, opium causes sedation and euphoria simultaneously. The user feels relieved of pain and anxiety and tends to ever remain in the heavenly bliss, which obviously leads to opium-addiction. Therefore, opium and morphine both are addictively strong narcotic products.

Owing to its intoxicating property and rendering a blissful ‘kick’, illicit cultivation of opium poppy and illegal use of opium have perpetuated as a social evil for centuries. With easy chemical conversion of morphine into the still stronger narcotic compound – the notorious heroin, opium-linked abuses have now assumed a menacing proportion across the world. Today, around 17 million people are reported to be opium-addicts and nearly half as much addicted to heroin throughout the world. About two million people are opium-addicts in India. The cases of seizures of opium and heroin are whoppingly increasing – from 5299 cases of heroin seizure registered in 1991 to 14,596 in 1994 and much more lately. The ‘Golden Triangle’ (comprising Thailand, Myanmar and Laos) and ‘Golden Crescent’ (Iran, Afganistan and Pakistan) are the two hot-spots engaged in such nefarious activities of production of opium and heroin and drug trafficking via Balkan route (Turkey, Bulgaria and Hungary) through Pakistan and India and recently Taiwan. The trend is dangerously upbeat unless an effective control over the production of opium and morphine is exercised. A couple of years ago, Sharma¹⁰ had raised the vital ‘opium question’ of how to combat the problem of opium-linked global abuses by natural means.

One approach is crop-substitution, i.e. replacement of poppy cultivation by equally remunerative crops like German chamomile (Matricaria recutita), isabgol (Plantago ovata) or Chrysanthemum morifolium¹⁰. Another is growing Papaver bracteatum which synthesizes neither morphine nor codeine but only thebaine, as is practiced in some Mediterranean countries^11–13. But it is not successful in subtropical conditions in India. Still another viable approach widely in vogue under the aegis of the International Narcotic Control Board (INCB), Vienna, is shifting the emphasis from opium-collection (gum-gathering) to extraction of alkaloids from the straw. This involves growing concentrated poppy-straw (CPS) cultivars rich in straw-morphine/codeine¹⁴. All the poppy-growing countries (covering an area of about 300,000 ha) except India are now following this practice. Development of alkaloid-rich CPS varieties is, therefore, a common practice in the world and several CPS varieties, viz. Cosmos (Hungary), Lazur and Modry (Poland), etc. have been developed in various countries^15–20. In India also, we are aware of the international state-of-the-art²¹ and therefore, have developed a CPS var. Sanchita with >1.0% morphine in straw (better than 0.7% in Tasmania, Australia). Alternatively, Liersch and Krzymanski²² suggested breeding CPS varieties with negligible or no amount of narcotic alkaloids (morphine, codeine) in their straw. Therefore, screening of some CPS varieties and lines e.g. Swedish var. Soma, Polish var. Przenko and German var. Riesenmohn for detecting low morphine (»  0.01%) plants was carried out by Nothnagel et al.¹⁶ in Germany. In India also, an accession with 0.05% straw-morphine was identified earlier²³. However, such efforts are not permanent solutions of the problem of opium abuse because such CPS varieties are not free from opium/latex, hence can be incised/lanced to collect opium by unscrupulous growers. Then, could it be possible to inactivate or arrest the function of the genes/enzymes controlling the biosynthesis of opium and opium-alkaloids in the opium poppy plant? More than a decade ago, this was articulated by Sharma and Singh²⁴ as one of the future prospects in opium poppy.

A cheap and permanent natural solution

Physiologically/metabolically disturbed plants of opium poppy bearing no opium do occur in nature. Long ago, such plants, referred to as Bunjha, were reported to occur in Indian land races²⁵. At the Central Institute of Medicinal and Aromatic Plants (CIMAP) also, as early as in 1981–82, we collected 35 Bunjha plants in our breeder’s nursery of germplasm collections. But all their progenies reverted to normal²⁶. During 1994, we commenced a systematic and concerted programme for conversion of the narcotic opium poppy into a non-narcotic crop by inactivating the opium gene through mutation breeding. We have now developed and stabilized (>99% homozygosity) an opiumless and alkaloid-free var. Sujata of opium poppy¹. It does not exude latex (opium) on ‘ray-plucking’ or lancing (Figure 1). The capsule hulls (straw) have no opium alkaloid either.

This var. Sujata might offer a cheap and permanent natural solution to the problem of opium-linked social abuses across the world. It gives a perfect non-narcotic crop – no opium and no opium-alkaloids, hence no abuse. Thus the social ills related with opium can be put to an end. Indeed, the var. Sujata might prove to be the harbinger of global peace by eradicating opium abuses during the 21st century.

The var. Sujata may also be marshalled to derive other multiple uses as described here.

Var. Sujata: A potential seed (food) crop

Of nearly 300,000 plant species occurring on earth, only 40 species provide most of the calories and proteins to human beings, with 50% being contributed by nine species of cereals²⁷. There has hardly been any addition to this list for more than a century²⁸, though man has always been looking for a new plant species to be used as a food crop. Opium poppy seeds have undoubtedly been used as food since prehistoric times. Ancient Sumerians (now in Iraq) and Southern Europeans used its seed as food as early as 4000 BC (refs 4, 6). Even in India, poppy seeds have been used for culinary purposes since 16th century BC (ref. 3). But it was not included in the above list because as a narcotic crop its cultivation has never been safe and unrestricted, like other food crops such as cereals or oilseed crops. This was obviously a great barrier to its being exploited as a food crop with high production of seeds.

Var. Sujata has successfully broken this barrier and made a breakthrough by converting the ‘opium poppy’ into ‘seed poppy’. Being non-narcotic (no risk of opium or opium-alkaloids), it can be grown as a seed crop safely and extensively for augmenting the world food production in general and of India in particular.

The comparison of seed producing ability and seed quality (protein content) of var. Sujata against the best check var. Sanchita revealed that it was the moderate seed yielder at par with var. Sanchita (Table 1). But with 23.9% seed protein, it was better than the check

 

Figure 1.  Latex (opium) oozing out in capsules of a normal plant (left) and no latex flowing in var. Sujata (right) of opium poppy. a, ‘Ray-pluck’ test; b, Lancing test; c, Normal and Sujata plants after lancing.

 

 

var. Sanchita which manifested 20.8% protein. Indian opium poppy has been found to have 22.3 to 24.4% seed protein⁷, while European poppies have 25–35% protein⁸. However, the white seeds of var. Sujata score over the black seeds of European poppy varieties with respect to preference in confectionery, culinary and bakery industries, especially in India. Thus, var. Sujata of opium poppy is a potential food crop with high nutritive value.

Var. Sujata: A viable supplement to edible
oilseed crops

There has undoubtedly been a significant improvement in oilseed production in the last decade in India^29,30. But the total production of oilseeds remained inadequate to

 

Table 1.  Seed yield and seed protein of var. Sujata compared to sister strains and standard check var. Sanchita and parent Sampada
of opium poppy

Table 2.  Oil content in seeds of var. Sujata and sister strains/var. of
opium poppy compared to that in rapeseed and mustard

 

meet the national demand for edible oils: the deficit was made up by importing 0.8 m tonnes of vegetable oil during 1994–95 and 0.15 m tonnes in 1995–96 (ref. 31). Export of vegetable oil is a distant dream. Among all the nine major oilseed crops, more than 60% oilseed production is accounted for by groundnut and rapeseed and mustard³². While the former is grown as both kharif (monsoon) and rabi (winter) crops, the latter is raised as a rabi crop which can be supplemented with the opium poppy var. Sujata during the same season for oilseed production. Var. Sujata giving 10–12 q/ha seed yield is nearly at par with mustard crops giving 8–15 q seeds per hectare³³. But it is superior in seed oil content
which ranges from 50.5 to 52.6% in comparison to maximum 48% oil in rapeseed and mustard (Table 2). In Brassica juncea (mustard), which now occupies a much greater area than B. campestris (rapeseeds), the oil content is even less – around 43% only, though it gives better seed yield per unit area. Therefore, the total production of seed oil per unit area of var. Sujata would axiomatically be equal to or more than rapeseed and mustard in India.

Table 3.  Unsaturated fatty acid composition of the oil of var. Sujata
and sister strains of opium poppy versus mustard

 

In addition, the oils of rapeseed and mustard have high proportion of long chain fatty acids which are less digestible in test animals³⁴. High concentration of erucic acid (5–45%) and low concentration of unsaturated fatty acids, viz. oleic acid (8.9–38.1%), linoleic acid (14.6–36.1%) and linolenic acid (10.5–22.3%) in 800 samples of mustard oils analysed at Kanpur³³ are also their negative scores over var. Sujata of opium poppy which contains no erucic acid but 19% oleic acid, 56% linoleic acid and 3% linolenic acid (Table 3). Whereas the saturated fatty acids and to some extent erucic acid tend to cause loss of body weight and increase in blood cholesterol and size of adrenal gland³⁴, unsaturated fatty acids reduce the low density lipoprotein (LDL) by increasing the high density lipoprotein (HDL) in human blood. Thus, the non-narcotic var. Sujata of opium poppy makes a most viable oilseed crop which can successfully supplement the production of healthful vegetable oil for human consumption. Like ‘Conola’ (the rapeseed oil) or ‘Linola’ (the linseed oil), we may call this high value edible oil ‘Sonola’ (opium poppy var. Sujata oil) for commercial consumption.

Var. Sujata: A parental base for developing
hyper-alkaloid CPS variety

The pharmaceutical/medicinal value of opium poppy is attributed to its opium containing the potent analgesic morphine, respiratory depressant codeine and antispasmodic papaverine alkaloids⁹. In CPS varieties, while opium is not gathered, major opium alkaloids (morphine, codeine and papaverine) are chemically extracted from the poppy straw as stated earlier. But the non-narcotic var. Sujata of opium poppy is devoid of both opium and opium alkaloids. Therefore, it attracted and rightly so, a searching remark ‘Beer without alcohol’. An excellent medicinal plant, opium poppy, has been converted into a non-medicinal plant (seed poppy).

However, let us not become oblivious of the fact that on one hand, we intend to get rid of the opium-linked global evils and on the other, we wish to retain the pharmaceutical attributes of opium poppy. The novel var. Sujata might accomplish the first job neatly though not the second. But it can definitely serve as a base (parental) material for developing CPS chemotypes with specific alkaloids in straw, e.g. morphine⁺, codeine⁺, and papavarine⁺ CPS varieties. Such varieties would be the true CPS varieties as they would lack opium but have specific opium alkaloids accumulated in the capsule hulls (straw). They will thus meet both the above-mentioned requirements of opium poppy – being non-narcotic and pharmaceutically viable simultaneously. And if they also combine high yields of protein-rich seeds and unsaturated fatty acid-rich edible seed oil, it would be an unique example of ‘killing four birds (not only two) with one stone’.

Now the question before us is – can we induce alkaloid biosynthesis and their accumulation in capsule hulls and keep the natural biosynthesis of opium (latex) restricted? A major bottleneck is the contention that latex carries enzymes required for the biosynthesis of alkaloids³, i.e. without opium there cannot be alkaloid biosynthesis. Nevertheless there appears to be a silver lining.

Empirically we have observed that nature has evolved many Papaver species bearing latex but no alkaloids, such as P. rhoes, P. orientale, P. argemone, etc. on one hand, and P. somniferum with latex and alkaloids both, on the other. This offers a clue about the dichotomy of latex and alkaloid biosynthesis in opium poppy. Some reports are also available which reinforce our observation^2,35–37. Thus, enzyme-systems operating for biosynthesis of latex and alkaloids perhaps independently, might help develop opium-less CPS chemotypes/varieties enriched with specific alkaloids in capsule hulls to meet pharmaceutical needs. The biogenetic pathway of phenanthrene isoquinoline alkaloids, mainly the narcotic morphine, codeine and thebaine has already been established³ (Figure 2). Therefore, activating or inactivating/blocking of the enzyme activity at a specific site of the chain by appropriate mutagenesis may be a distinct possibility. We have already initiated a breeding programme following the double-faceted mutational and recombinational approaches to achieve the above goal²⁶.

Concluding remarks

The opium-less and alkaloid-free non-narcotic var.
Sujata of opium poppy developed for the first time by us

 

Figure 2.  Biosynthetic pathway of phenanthrene alkaloids in opium poppy (A, B and C are the genes/enzymes involved in the process of bioconversion of opium alkaloids from thebaine ®  morphine).

(US patent application No. 09/276,720 dated 26 March 1999) is a breakthrough. It offers a cheap and permanent natural means of combating the global menace of opium abuse. Being a fine example of genetic conversion of narcotic ‘opium poppy’ into non-narcotic ‘seed poppy’, it is a potential seed crop and a viable supplement to oilseed crops. The oil being largely apportioned by unsaturated fatty acids provides a natural dietary control for CHD. Besides, seeds are not only rich in fatty acids but also in proteins, and hence are a good source of high calorie nutritive food, extensively used in culinary, confectionery and bakery industries. In contrast, seeds of mustard, the major oilseed crop of India, are not edible as food item, though their whole grains do have protein.

The current level of seed and oil yields of the opium poppy var. Sujata can be further improved by evolving more superior non-narcotic varieties – var. Sujata is only the forerunner. It can also be tailored into a ‘designer crop’ with specific unsaturated fatty acids (oleic/linoleic) and/or with specific straw-alkaloids (especially thebaine, morphine or codeine) as in case of rapeseed and mustard^38,39. As far as the utility of seeds and seed oil is concerned, there is no problem with seeds as such in India. But, the problem is with poppy oil because our dietary habit is not yet tuned to its taste and flavour, unlike in Russia and other European countries. The oil and seeds might become good export commodity – a potential foreign exchange earner. Extensive cultivation and seed production should now be no bar with the non-narcotic var. Sujata of opium poppy.

 

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ACKNOWLEDGEMENTS.  We thank Mr Ram Chandra and
Mr Mohd. Rashid for help in field operations. Oil content was determined using NMR technique at NRL, IARI, New Delhi.

Received 4 August 1999; accepted 5 October 1999