Science in Society Archive

Plant Immune System Spawns New Biopesticides

Monsanto’s Harpin a potential health hazard but natural extract from giant knotweed is best for ‘man and beasties’. Prof. Joe Cummins

Giant knotweed should be used instead of Monsanto’s Harpin

The plant immune system has gained recognition as a major factor in the growth and development of plants and the resistance to disease, predation and environmental stress. Innate immune systems provide immediate defence against infection, and are found in all classes of plants and animals. The innate systems respond in a general way and do not provide the specific long lasting protection of adaptive immunity (antibodies). Plant and animal innate immune systems are similar in design while an adaptive immune system has not been observed in plants.

Innate Immune Systems

Research within the past decade has revealed that plant immunity consists of different layers of defence that have co-evolved with the plants’ pathogens. Particular light has been shed on pathogen-associated molecular pattern-triggered immunity (PTI), mediated by pattern recognition receptors (PPRs) that recognize molecular structures conserved across a broad range of pathogenic species.

Striking similarities between the plant and animal innate immune systems point to a common optimized mechanism that has evolved independently in both kingdoms. PRRs from both kingdoms consist of leucine-rich repeat receptor complexes that recognize invading pathogens at the cell surface or inside the cell. Pathogens can inject effector proteins into the plant cells to suppress the immune responses initiated by PTI by inhibiting or degrading the PPRs. Plants have acquired the ability to recognize the presence of some of these effector proteins, and to mount a quick and hypersensitive response that arrests and terminates pathogen growth.  The similarity between plant and animal immune systems explains why the protein from the pathogen can provoke the immune response to a wide array of pests [1, 2].

Cell death has a central role in innate immune responses in both plants and animals. Besides sharing striking convergences and similarities in the overall evolutionary organization of their innate immune systems, both plants and animals can respond to infection and pathogen recognition with programmed cell death. The hypersensitive response (HR) involving cell death in plants displays morphological features, molecular architectures, and mechanisms reminiscent of different types of inflammatory cell death in animals [3].

Harpin protein activates plant immune systems

Activation of the plants immune response has recently become a target of the biotech industry for fighting plant pests. Harpin is protein that elicits a broad-spectrum immune response in plants. In nature, it is produced by Erwinia amylovora, a bacterium that causes the disease fire blight in apples and pears. A weakened strain of Escherichia coli was modified to produce Harpin on a commercial scale. Commercially produced Harpin protein is claimed to be identical to the protein that occurs in nature. E. coli K-12 is considered to be a non-pathogenic, nutritionally deficient bacterium which is unable to grow in the environment. Harpin is concentrated from the growth medium of the genetically modified (GM) E. coli, and the bacterial cells are killed and removed from the marketed product. Harpin does not act directly on the disease organism, nor does it alter the DNA of treated plants, but instead activates a natural defence mechanism in the host plant, referred to as systemic acquired resistance (SAR). This new active ingredient is currently the only commercially available broad-spectrum, proteinaceous elicitor of SAR. Harpin is effective against certain viral diseases for which there are no other controls or resistant plant varieties. It also protects against soil-borne pathogens and pests, such as certain nematodes and fungal diseases that have few effective controls except methyl bromide, which has adverse human health and environmental impacts [4, 5]. The harpin gene has been used to produce GM rapeseed, cotton, chrysanthemum and rice, but these GM crops are in an early stage of development. Harpin was developed by Eden Bioscience and marketed as “Messenger”. Production was later sold to Plant Health Care which marketed it under the name “Employ” [6]. Plant Health Care licensed Harpin to Monsanto for use in seed treatment [7]. Thus the GM protein can be used to treat both GM and conventional seeds by Monsanto, which owns a large portion of world seed production.

Harpin may be hazardous to humans

Harpin protein encapsulated in poly D,L-lactide-co-glycolide nanoparticles (see Box) was found to have improved bioavailability to the plant leaf, enhancing response of treated plants to the drug [8]. Poly D,L-lactide-co-glycolide nanoparticles have been used elsewhere to deliver drugs to the lung, thus the Harpin protein nanoparticles are a potential hazard to those applying the GM  pesticide. Government regulators and those promoting the GM pesticide maintain that the source of Harpin protein, Erwinia bacteria, is not hazardous to humans because the bacterium infects plants alone but not humans.  However, Erwinia bacteria from fruits and vegetables were resistant to multiple antibiotics when isolated as an infection from a human subject [9] and extracts of Erwinai cells killed human gastrointestinal cells in culture [10].

Poly D,L-lactide-co-glycolide nanoparticles [11]

Poly D,L-lactide-co-glycolide is a biodegradable polymer with the structure [C3H4O2]x[C2H2O2]y, or lactidexglycolidey, where x and y varies according to the ratio in which the monomers are reacted together. It is used for controlled release of biologically active agents encapsulated in it to form nanoparticles.

Harpin GM proteins are being heavily promoted and may now be widely circulated on treated seeds of both GM and conventional crops. The drug is also being used as post-harvest treatment of grain crops and produce. Needless to say, consumers will not be informed about the foods they consume. The Harpin GM drug has not been tested adequately and any detrimental impacts of the drug on human consumers and farm animals will be undetected so long as the use of the drugs on food and feed is hidden from the public scrutiny.

Extract of Reynoutria or Polygonum sachalinensis (Giant Knotweed), a safer alternative

The product Regalia contrasts with the Harpins which are proteins. Regalia is the alcohol extract of giant knotweed. Giant knotweed, Polygonum sachalinensis is a plant that produces many defensive chemicals. These help protect it against insects, diseases, and even other plants. Knotweed defensive chemicals also can have profound effects on other plants and animals, causing beneficial changes in metabolism. Extracts from the giant knotweed, for instance, can protect plants against pathogens that cause powdery mildew, grey mould, insects, and many other diseases. Substantial yield increases are often seen because the treated plants remain free of disease, and their lifetime is extended [12, 13]. Knotweed extracts have low toxicity to mammals and provide protection by boosting the immune system of the plant.  Animal tests have also shown that extracts and pharmaceuticals isolated from giant knotweed or its relative, Japanese knotweed, Polygonum cuspidatum, protect against cancer, are anti-inflammatory, lower blood cholesterol, protect against diabetes, and improve cardiovascular health. The extracts of giant knotweed must be handled with care because they contain allelochemicals (chemicals that inhibit growth of competing plants), and may inhibit the growth of the treated plants. The pigments emodin and physcion were responsible for the growth interference [14]. The interference   pigments have been employed in the treatment of inflammation in humans.

The US Environmental Protection Agency (EPA) has reviewed the acute toxicity and genotoxicity of the extract and has approved its safety noting that the extract is mildly irritating to the eyes. The extract is approved for use with all foods [15]. EPA maintains a fact sheet verifying the safety of the product [16]. Reynoutria sachalinensis (an alternative name for P. sachalinensis), a naturally-occurring plant currently found in 25 US States as an ornamental plant, is an invasive weed, and a grazing crop. In fact giant knotweed and Japanese knotweed are both invasive weeds in Europe and North America. For example giant knotweed threatens to displace native riparian forests in the state of Washington [17]. Harvesting the weed to produce biopesticide useful in both organic and conventional food production might be a project for improving both the forests and healthy food production. The knotweed extracts appear to have a double benefit, guarding the health of the food crops and treating the ills of consumers.

To conclude

The plant immune system is beginning to reveal radical new approaches for producing disease free food and feed crops.  Both genetic engineering and organic agriculture have begun to benefit from the new insights. It is essential that GM crops containing the protein Harpin be thoroughly tested before being released for human consumption. GM Harpin has already been released with inadequate tests and distributed globally in Harpin-treated seeds with no means available to identify long term adverse consequences of the release because the treated crops are not labelled.

The EPA approval of Harpin waived most toxicity tests on grounds that the use of Messenger(Harpin) is not expected to result in any new dietary exposure to this protein [5]: “Harpin and related harpin proteins are common constituents of plant pathogenic bacteria which are often found on fruits and vegetables.” In other words the GM protein was presumed to be safe rather than rigorously tested.

Meanwhile, farmers buying seeds should make sure they have not been treated with Monsanto’s Harpin.

Article first published 19/12/11


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  2. Boller T, Felix G. A renaissance of elicitors: perception of microbe-associated molecular patterns and danger signals by pattern-recognition receptors. Annual Review of Plant Biology 2009, 60, 379-406.
  3. Coll NS, Epple P, Dangl JL. Programmed cell death in the plant immune system. Cell Death Differentiation 2011, 18, 1247-56. doi: 10.1038/cdd.2011.37
  4. US Environmental Protection Agency.  Harpin protein (006477) Fact Sheet  2002
  5. US Environmental Protection Agency. US Environmental Protection Agency Office of Pesticide Programs, Biopesticide Regulatory Action Document Harpin Protein (PC Code 006477), 2002.
  6. EMPLOY® H&T Plant Health Promoter Replaces the discontinued Messenger® Plant Health, 2011 Activator.
  7. Plant Health Care (AIM: PHC), announces that Direct Enterprises, Inc. ("DEI"), a leading provider to the seed treatment industry, has entered into a multiyear agreement with Monsanto Company to become the exclusive distributor of N-Hibit® HX-209 (Harpin aß protein) dry formulated seed treatment to the seed treatment distribution market 2009  detail.html?announcementId=10792969 (This link does not work)
  8. Liang Z, Xu JP, Meng XL, Lu W, Wang J, Xia H. Improve bioavailability of Harpin protein on plant use PLGA based nanoparticle. Journal of Biotechnology 2009, 143, 296-301
  9. O'Hara CM, Steigerwalt AG, Hill BC, Miller JM, Brenner DJ.First report of a human isolate of Erwinia persicinus. Journal of Clinical Microbiology 1998, 36, 248-50.
  10. Duarté X, Anderson CT, Grimson M, Barabote RD, Strauss RE, Gollahon LS, San Francisco MJ. Erwinia chrysanthemi strains cause death of human gastrointestinal cells in culture and express an intimin-like protein. FEMS Microbiological Letters 2000, 190, 81-6.
  11. Poly(D,L-lactide-co-glycolide), Sigma Aldrich, accessed 8 December 2011,
  12. Quarles W. Giant knotweed, plant disease protection and immortality.  The IPM Practitioner  2009, 31, 1-6
  13. “The best offense is a good defense So switch on your crops’ natural defenses to control disease with Regalia” Marrone BioInnovations Regalia, 2011
  14. Nishimura H Mizutani J. Identification of allelochemicals in Eucalyptus citriodora and Polygonum sachalinense  Allelopathy, Editor(s): Inderjit, K. M. M. Dakshini, Frank A. Einhellig ACS symposium Volume 582 Copyright, 1994
  15. US Environmental Protection Agency.  Reynoutria Sachalinensis Extract; Exemption from the Requirement of a Tolerance [Federal Register: September 21, 2005 (Volume 70, Number 182)] [Rules and Regulations][Page 55272-55277]
  16. Environmental Protection Agency, Extract of Reynoutria sachalinensis (Giant Knotweed) (055809) Fact Sheet, US, 2000.
  17. Urgenson L Reichard S Halpern C Community and ecosystem consequences of giant knotweed (Polygonum sachalinense) invasion into riparian forests of western Washington. USA Biological Conservation 2009,142, 1536–1541

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There are 2 comments on this article so far. Add your comment above.

Nancy Oden Comment left 20th December 2011 01:01:59
Japanese Knotweed, which people work very hard to uproot and kill when it invades their property, is excellent food. When it's 2-3 feet high or so, just break off the top couple of feet (hurry because in early spring Knotweed seems to grow a foot a day), break it into manageable pieces, steam lightly over rice or in a steamer by itself, top with a tad of butter, eat. Tastes like lemony asparagus. Really quite good. It's healthy, too. What more could anyone want? Now ISIS tells us it helps our immune systems, too. Excellent news! It grows all over the place. Japanese Knotweed was brought in because it's a beautiful plant with heart-shaped leaves and gorgeous flowers late in the season, one of the last sources of food for bees before winter. I also use it as a 10-foot-high fence between my neighbors' property and mine (crabby neighbor doesn't like the fact that I refuse to mow my lawn, only clip little paths, and have "messy" organic gardens). Thanks, ISIS, for justifying for me my refusal to uproot the Knotweed, although one must pull invading roots every few days or it will take over large sections of your land. Just keep eating it. I also put quite a bit of it up for winter in glass jars so I can put it in soups all winter. Yay for Japanese Knotweed!

joe cummins Comment left 20th December 2011 08:08:18
Yay for Nancy Oden! for a lovely comment.