HG51

Feature

From Rudbeckia to Echinacea

The Emergence of the Purple Coneflower in Modern Therapeutics

by Michael A. Flannery

 

Perhaps no other herb can match echinacea for sustained popularity among the general public. For the past two years echinacea has ranked number one in herbal supplement sales in the natural food market. In the mass market, echinacea has also earned impressive figures, with $33 million dollars posted in sales over a 52-week period ending in July of 1998, representing a 151% growth in the mass merchandising market.¹

Given its tremendous popularity, echinacea is an interesting and timely medicinal plant to examine historically. Three main species have primarily been used medicinally: Echinacea purpurea (L.) Moench, E. angustifolia DC., and E. pallida (Nutt.) Nutt., Asteraceae. All are generally known today as the purple coneflower. This colorful member of the daisy family grows in dry open woods and prairies in the south from Georgia to Louisiana, north to Virginia and into the Ohio Valley, Michigan, Illinois and Iowa. Some species, like E. angustifolia, are more predominant in westerly regions, from the dry prairies and tundra of Saskatchewan eastward to Minnesota, and south to Oklahoma and Texas.² While this is the general range of echinacea, the American heartland really plays host to all three species in varying degrees of abundance. One can find E. pallida in the Mississippian plateau of Kentucky, for example, with E. angustifolia also found in the Mississippian plateau and Pennyroyal regions and E. purpurea extending from the Western coal fields to the Mississippian and Cumberland plateaus.³ [Note: the taxonomy and distribution of the genus Echinacea has been discussed previously in this journal. See Hobbs C. Echinacea: A Literature Review. HerbalGram 1994;30:33-48.]

Spread across the North American continent, all three primary species of echinacea have been used by Native Americans. E. angustifolia, for example, was used by the Blackfoot and Lakota as a toothache remedy (a reasonable application given the relatively high content of isobutylamides in the root, a constituent that produces a characteristic tingling or numbing sensation in the mouth). Many other tribes used E. angustifolia for everything from snakebite to rheumatism. E. purpurea likewise had many medicinal uses among Native Americans: the Choctaw used it as a cough medicine and as a gastrointestinal aid, the Delaware used it for venereal disease, the Comanche for sore throats and toothache. E. pallida too was used by many western tribes: the Cheyenne used it as an antirheumatic, cold remedy, and dermatological aid; the Dakota took a decoction of the root as a vermifuge and eye medicine; and the Sioux used the species as an analgesic and an antidote for snakebite.⁴

In Euro-American medical botany, John Clayton (1686-1773) mentioned the use of E. purpurea for saddle sores on horses in the second edition of his Flora Virginica compiled and edited by Laurens Theodore Gronovius (1690-1760) in 1762.⁵ His use was carried forward by the Prussian army surgeon Johann David Schšpf (1752-1800), who cited Clayton in his Materia Medica Americana of 1787.⁶ The study of echinacea continued in Europe with Johann Heinrich Dierbach (1788-1845) who examined and commented on the volatile oils of the plant in 1831.⁷ After this brief mention in the literature, echinacea sinks into therapeutic obscurity.

Taxonomically the plant had been described by Linnaeus under the genus Rudbeckia. In 1794, however, Conrad Moench (1744-1805) revised this to Echinacea in his Methodus plantas.⁸ Nonetheless, this taxonomic change was slow to be incorporated into botanical scholarship. Well into the nineteenth century most botanical texts continued to use the Rudbeckia designation, as shown in a plate from William P.C. Barton's (1786-1856) Flora of North America (1821). Rafinesque complicated matters by referring to the genus Echinacea as Helichroa (his own invention) in his 1830 Medical Flora.⁹ It seems that the generally recognized name remained Rudbeckia until Asa Gray (1810-1888) adopted Moench's change in his Manual of Botany of the Northern States published in 1848.¹⁰ Dr. Asahel Clapp appears to be the first medical botanist to prefer Echinacea over the older Rudbeckia, which he included in his American Medical Association "Report of the Committee on Indigenous Medical Botany and Materia Medica for 1850-51."¹¹ Further clouding the waters was an attempt to establish the genus Brauneria, Necker ex TC Porter et NL Britton, at the turn of the 20th century. Today the genus Echinacea is universally preferred over Rudbeckia or Brauneria,¹² but historians looking at the therapeutic history of this plant would do well to remember to look under all three genus headings, especially in reference sources prior to the Civil War or at or before the early 1900s.

Issues of nomenclature aside, it seems clear that Echinacea purpurea was the specific plant first noted by physicians and medical botanists for its therapeutic properties. Dr. John Riddell, the author of "the first regional flora west of the Allegheny Mountains,"¹³ listed this plant as "aromatic and carminative" in his 1834 "Western Flora."¹⁴ Dr. Clapp, just mentioned, recognized the use of echinacea in folk medicine under the common name "black Samson."¹⁵ About that same time, E. purpurea appeared in the 1852 dispensatory of Eclectic physicians John King (1813-1893) and Robert S. Newton (1818-1881) under the common name "red sunflower," and was recommended for use "with benefit in syphilis; the root is the part employed, and which, when fresh is acrid and burning."¹⁶

Indeed it was the Eclectics who first recognized the therapeutic potential of echinacea; not with E. purpurea as one might expect, however, but with E. angustifolia. The plant was first brought to the attention of John Uri Lloyd (1849-1936) of Cincinnati and Dr. John King in the fall of 1885 by a self-styled "physician" from Pawnee City, Nebraska, named H.C.F. Meyer.¹⁷ Meyer sent Lloyd a sample of root and claimed he used it in making his "Meyer's Blood Purifier." Meyer made wild and unsubstantiated claims for the plant, and Lloyd was inclined to dismiss this unidentified piece of root as the product of a self-promoting quack. But more samples arrived. In June of 1886 Lloyd received a large box of echinacea root and in September the whole plant arrived, which was subsequently identified as E. angustifolia. By now Dr. King's interest was sufficiently aroused to pursue some preliminary investigations of the plant, and he directed Lloyd to pursue some pharmaceutical tests. Those systematic inquiries proved favorable, and by 1887 King announced in The Eclectic Medical Journal that "... he [Dr. Meyer] entertains a very exalted idea of his discovery, which certainly merits a careful investigation by our practitioners; and should it be found to contain only one-half the virtues he attributes to it, it will form an important addition to our materia medica."¹⁸

King's prediction was fulfilled. Soon after King's initial announcement of the therapeutic potential of E. angustifolia other Eclectic physicians began using it. Dr. Goss of Atlanta spoke highly of the plant, as did H.T. Webster. Finley Ellingwood (1852-1920) included an extensive entry on it in his 1898 Systematic Treatise on Materia Medica and Therapeutics.¹⁹ It was recommended for numerous conditions, but the most commonly repeated therapeutic applications included its use in typhoid, puerperal (during the period after childbirth) and septic fevers, sore and ulcerated throat and mouth, and topically for wound healing and other inflammatory skin conditions.

It was John King who ultimately persuaded the Lloyd Brothers pharmaceutical firm to start manufacturing an echinacea product. Lloyd himself admitted his own reluctance to commit to the purple coneflower. "The introduction of Echinacea to the medical world," he wrote, "must be credited wholly to Dr. King's confidence in the remedy."²⁰ He went on to praise empirical experience in drug discovery by insisting, "I am now more pronouncedly of the opinion, as experiences multiply, that a person who is restricted to laboratory experiments, especially if he be more or less adversely prejudiced (as was I against Echinacea), is not in a position to judge with discretion."²¹

Therapeutic considerations aside, Lloyd's decision to begin manufacture of echinacea on a large scale proved economically wise. Starting in the 1880s Lloyd first made an echinacea tincture and later developed Specific Echinacea, a hydro-alcoholic concentrate. Another purified, assayed form of echinacea called Echafolta was manufactured, which Lloyd described as the "trade name of a pharmaceutical preparation of Echinacea ... . From this the coloring matters, and the sweet principle of the drug, are excluded, as explained on the label. It is not a mixture or a drug compound." Lloyd explained in a question and answer session at the National Eclectic Medical Association's annual meeting of 1908 that echinacea contained what he called "a sweet principle" (perhaps a glycoside or carbohydrate) which was prone to ferment when applied externally to an open wound. To avoid this, Lloyd applied a "neutral solvent" that dissolved this molasses-like substance. The resulting preparation he called Echafolta, insisting that it contained all the useful therapeutic properties of the whole plant but without the tendency to fermentation, thus making it better suited for topical application.²²

Echinacea in all forms became a rousing success. The Eclectics' devotion to this remedy was eventually felt in mainstream pharmacy. E. angustifolia and E. pallida entered the 4th edition of The National Formulary in 1916, and would remain in this compendium through the 8th edition of 1947.²³ Soon the plant was also listed in The United States Dispensatory, a position it would hold from 1926 through 1943.²⁴ In an interesting article by Lloyd on "Vegetable Drugs Employed by American Physicians," both Eclectic and Regular physicians were surveyed as to their use and preference for various phytopharmaceutics.²⁵ Topping the Regular physicians' list was echinacea.²⁶ Curiously, although echinacea ranked high among Eclectics, it was fifth on their list of preferred remedies. When the list of several hundred phytopharmaceutical items was combined to include all
physicians surveyed (over 6,000 responding), echinacea ranked a notable eleventh. Suffice it to say, Lloyd's echinacea was a resounding success.

But 1912 was the beginning of the end for whole plant drugs in the United States. In 1910 three events occurred that signaled a dramatic new era for modern pharmacy. First, Abraham Flexner published his watershed study of medical education in the United States.²⁷ Using the clinical research model that had developed in Europe and adopting Johns Hopkins' new and innovative medical school as its benchmark, the Flexner report represented a significant nail in the coffin of a faltering botanico-medical education system. Second, Paul Ehrlich achieved pathbreaking success in a clinical trial with his 606th compound, arsphenamine, in treating syphilis. While the optimism accompanying Salvarsan eventually succumbed to more restrained expectations, it did set researchers upon the path of exploring the possibilities of chemotherapeutic agents in earnest. Another major indication that botanicals were in trouble in the United States appeared in the 1910 USP; for the first time in the history of the American pharmacopeia, botanicals no longer predominated the materia medica. At 47% of 773 different substances, the reduced number of medicinal plant drugs in the ninth decennial revision of the USP was a clear portent of things to come.²⁸

In a symposium sponsored by AIHP in March of 1995 titled "Milestones of Pharmaceutical Botany," Varro Tyler Ph.D., professor emeritus of pharmacognosy at Purdue University, pointed out that the history of echinacea is reasonably typical of the fate of 300 or more classic plant drugs during the years 1900-1962. As early as 1915 studies began to demonstrate that the beneficial effects of echinacea were not directly antimicrobial but rather that its actions resulted from a nonspecific stimulation of the human immune system. In that year, Dr. Victor von Unruh, a medical practitioner in New York City observed: "Echinacea increases the phagocytic power of the leukocytes."²⁹

Indeed, von Unruh conducted extensive studies into the therapeutic actions of echinacea for over three years and determined that the plant "antagonizes all septic processes, facilitates the elimination of toxins from the organism, and lastly, it has a destructive effect upon the streptococci, staphylococci and other pyogenic organisms."³⁰ Even earlier, in 1907, Dr. Terpening of Fulton, New York, sang the praises of echinacea. "It is not a cure-all," he declared, "but ... it is indicated in a wide range of diseases, most of them acute, caused by some form of sepsis which may come from within or without. It is nonpoisonous and can be given in any size dose, usually in doses of from one to thirty drops every one to three hours as required.³¹

But the American Medical Association, associating the drug with Eclectics, disparaged echinacea. This professional hostility, plus the rise of patentable antibiotics on the cutting edge of research and development, spelled the demise of echinacea as a widely accepted therapeutic agent. "The direct antimicrobial effects of these new drugs," concluded Dr. Tyler, "were easily demonstrated; such was not the case with echinacea, which functioned by an entirely different mechanism. By 1962, echinacea was as obsolete as a drug could be in the United States even though research data supporting its utility as an immunostimulant was beginning to herald its renascence in Europe."³²

If the story of echinacea was left to its history here in America, little would probably be known about the plant today. Fortunately, however, homeopaths began experimenting with the purple coneflower in the 1920s and brought it to Europe. There echinacea caught the attention of Gerhard Madaus, a German pharmaceutical manufacturer, who went to America for seeds. Thinking he had brought back E. angustifolia (the most studied species to date), he began growing it only to find out that he had planted E. purpurea. The mistake proved fortuitous because E. angustifolia does not grow in Germany nearly as well as its purpurea cousin.³³ From this point forward research shifted in the 1930s to Germany, where today it remains the center for echinacea study. Just as echinacea is representative of the decline of medicinal plant use here in the United States, so too is its resurgence in Europe typical of much phytopharmaceutical research. As German investigators began subjecting the plant to serious and sustained laboratory analysis and later clinical study, America's interest in--and more importantly its knowledge of--echinacea declined, proving both Thomas Kuhn's and Arthur Koestler's points that scientific progress is neither straight nor linear.³⁴

So where does echinacea stand today? The statistics that opened this paper indicate echinacea's tremendous popularity in terms of sales, so in some senses it is one of those herbs that have truly come full circle: from classic acceptance, to eventual decline, and back to a resurgence of the whole plant's therapeutic use, this time as a "dietary supplement" in the United States.

It would be wrong to leave the story at that, however. Echinacea represents much more than a popular symbol of America's faddish fascination with herbs. One of the most popular herbal products today, most people take echinacea in one of several dosage forms (e.g., capsule, tablet, tincture, or fluid extract) during the cold and flu season to ward off, shorten, or attenuate the familiar symptoms of one of our most commonly encountered communicable diseases; but more significantly such use rests upon an ever increasing body of research. Since the mid-1980s researchers in Germany such as R. Bauer, M.L. Lohmann-Mathes, H. Wagner, and others have performed what have been described as "elegant experiments" on the pharmacological properties of echinacea.³⁵ Up through 1991 the journal Economic Medicinal Plant Research observed that echinacea had been the subject of over 350 scientific studies analyzing the chemistry, pharmacology, and clinical applications of the purple cone flower.³⁶ [Editor's note: an update on the components of echinacea appeared in HerbalGram 1994;30:33-48.] Supporting Dr. von Unruh's 1915 assessment, a review of this article concluded that:

high-molecular weight heterocyclan polysaccharide components of Echinacea have profound immunostimulatory effects. The majority of these effects appear to be mediated by the binding of active Echinacea polysaccharides to carbohydrate receptors on the cell surface of macrophages and T-lymphocytes. Echinacea promotes nonspecific T-cell activation. ... The resultant effect is enhanced T-cell mitogenesis, macrophage phagocytosis, antibody binding, and natural killer cell activity.³⁷

In a 1994 study led by D. Melchart and others published in Phytomedicine, researchers reviewed the data on echinacea and concluded that "Existing controlled clinical trials indicate that preparations containing extracts of Echinacea can be efficacious immunomodulators." But they went on to observe that "evidence is still insufficient for clear therapeutic recommendations as to which preparation to use and which dose to employ for a specific indication. Further methodologically sound, randomized clinical trials should be conducted."³⁸ Of interest here is the shift in emphasis. No longer is the ability of echinacea to affect the human immune response in question, but rather the specific nature of the extracts to be used and the dosages to be adopted in practical therapeutic applications.

Arguments of dosage and extract reliability aside, research on echinacea continues with promising results. Especially encouraging are clinical results of echinacea's use against the gram-positive Listeria bacillus and Candida yeast infections. Immunosuppressed and immunocompetent mice have withstood and survived lethal doses of these pathogens when treated with the polysaccharides of echinacea.³⁹ "Similar results have been obtained in humans," write Peter B. Kaufman, Leland Cseke, Sara Warber, James Duke, and Harry Brielmann. "Although the polysaccarides stimulate the immune system, much as an invading organism would, they are completely nontoxic. Another group has done preliminary work using E. purpurea extracts in combination with cyclophosphamide and thymostimulin to stimulate the immune system of patients with hepatocellular and advanced colorectal cancer. Their results are encouraging. These experiments," conclude Kaufman and his colleagues, "give new credence to the herbalists' claims of the immune-enhancing effects of Echinacea spp. Soon it may be an integral part of accepted therapy for withstanding cancer and other infectious diseases."⁴⁰

Thus modern research substantiates much of the Eclectics' adulation of echinacea in the treatment of "septic" conditions. But can the same be said of the Eclectics' use of the drug in wound healing, as indicated in their use of Lloyd's Echafolta? An exact correlation between Lloyd's Echafolta and modern topical echinacea preparations cannot be made, but German research in the last 50 years would seem to substantiate many of the Eclectics' claims for the topical use of the purple coneflower. As early as 1952 research suggested that the topical application of echinacea enhanced the production of hyaluronic acid, a substance that helps bind cells together.⁴¹ One year later further studies indicated that echinacea activated the non-specific immune system through direct contact with tissue.⁴² In 1956 echinacea appeared to accelerate healing in skin grafts on both human and animal subjects.⁴³ By the late 1970s research supporting the beneficial effects of topical echinacea were mounting. In a five-month study of 4,598 individuals conducted in 1978, physicians documented favorable results in 85.5% of patients using Echinacin^¨ ointment in the treatment of a variety of inflammatory skin conditions such as wounds, eczema, burns, and Herpes simplex.⁴⁴ Again, in another German report published in 1984, a study of skin wound healing rates in guinea pigs showed a significant wound reduction in those treated with Echinacin^¨ ointment over the control group.⁴⁵

It seems fair to conclude that if an important benchmark for the validation of nineteenth-century physicians' claims for their remedies is our ability to replicate their empirical observations under more scientifically controlled conditions, then echinacea's standing remains strong. While every ethnobotanical application and every therapeutic claim ever reported or published for the use of echinacea cannot be supported, it must be concluded that in the main, where practitioners and indigenous peoples have used the purple coneflower historically for conditions attenuated and ultimately cured through the stimulation of the immune system (either externally or internally), such use has been substantiated in numerous scientific studies.

One further comment needs to be made regarding echinacea. Because of the extensive research that has already supported echinacea's immunomodulating properties, most of the argument over echinacea rests not on the value of the genus itself but upon the respective species and the plant parts used. The recent English translation of German Commission E Monographs by the American Botanical Council, for example, indicates that E. pallida root and E. purpurea leaf were approved by the Commission while E. purpurea root and E. angustifolia root were unapproved. Steven Foster has observed that purpurea root was assessed negatively because of adulteration concerns and the historical confusion of the plant with Parthenium integrifolium.⁴⁶ This, plus issues regarding "the availability of the research on the respective species," led to differences in approvals. Noting that additional studies have been favorable for the species in question, the publication of E. purpurea root among unapproved herbs was not unanimously supported by members of the Commission. Also based in part on Commission E, the PDR for Herbal Medicines lists specific indications for the approved echinaceas, which include its use in treating the common cold, bronchitis, fevers, urinary tract infections, inflammation of the mouth and pharynx, tendency to infections, and wounds and burns.⁴⁷

So present indications substantiate much of the historical use of the purple coneflower. It is beyond the scope of this paper to exhaustively review recent clinical analyses of echinacea, but I will leave you with this: The popularity of hundreds of echinacea products and other multi-ingredient preparations now marketed worldwide and the growing body of scientific research on the plant suggest that the therapeutic use of the purple coneflower is more than a passing fad. The evaluation of plants like echinacea rich in historical use is of increasing interest, but in an age of growing concerns over what seems to be a mounting list of antibiotic-resistant pathogens, echinacea perhaps offers itself as a unique agent, which can support our own human immune systems in the battle against illness. If so, we will be hearing and reading much more about this plant.

Michael Flannery is the Associate Director for Historical Collections at the Lister Hill Library of the Health Sciences, University of Alabama at Birmingham. This paper was originally presented at the American Institute of the History of Pharmacy Annual Meeting, March 1999, and subsequently published in Pharmacy of History 1999;41(2):52-9. Reprinted, with slight modifications by the author, with permission from the American Institute of the History of Pharmacy.

 

Notes and References

1.         Brevoort P. The Booming U.S. Botanical Market: A New Overview. HerbalGram 1998; 44:33-46.

2.         Fernald ML. Gray's Manual of Botany, 8th ed. New York: American Book Co.; 1950, pp. 1485-6.

3.         Browne ET Jr, Athey R. Vascular Plants of Kentucky: An Annotated Checklist. Lexington: University Press of Kentucky; 1991, p. 123.

4.         Moerman DE. Native American Ethnobotany. Portland, OR: Timber Press; 1998, pp. 205-206.

5.         Clayton J. Flora virginica exhibens plantas. Lugduni: n.p., 1762, p. 130.

6.         Schšpf JD. Materia Medica Americana. Bulletin of the Lloyd Library, 1787; 6, reprint, 1903; Cincinnati: Lloyd Library, p. 127.

7.         Dierbach JH. Abhandlung Ÿber die ArzneikrŠfte der Pflanzen. Lemgo: Meyersche Hof-Buchhandlung; 1831, p. 200.

8.         Moench C. Methodus plantas. Marburgi Cattorum: Libraria acadeniae; 1794, p. 591.

9.         Rafinesque C. Medical Flora, or, Manual of Medical Botany of the United States of North America, 2 vols. Philadelphia: Atkinson & Alexander; 1828-1830, 2:227.

10.       Gray A. Manual of the Botany of the Northern United States. Boston: J. Munroe; 1848, p. 223.

11.       Clapp A. Report of the Committee on Indigenous Medical Botany and Materia Medica for 1850-51, Transactions of the American Medical Association 5; 1852:689-906.

12.       Greuter W, et al. Names in Current Use for Extant Plant Genera. Regnum Vegetabile, 129. Kšnigstein: International Association for Plant Taxonomy; 1993, p. 383. The author is grateful to Michael McGuffin for pointing out the Brauneria side-track in the curious and somewhat tortured taxonomic history of echinacea.

13.       An interesting discussion of Riddell's activities is available in Stuckey RL. Medical Botany in the Ohio Valley 1800-1850. Transactions & Studies of the College of Physicians of Philadelphia July 1978; 45:262-79.

14.       Riddell JL. A Synopsis of the Flora of the Western States. Western Journal of Medical & Physical Sciences 1834; 2:500.

15.       Clapp. Report of the Committee on Indigenous Medical Botany (n. 11), p. 798.

16.       King J, Newton RS. The Eclectic Dispensatory of the United States. Cincinnati: Derby; 1852, p. 351.

17.       The complete story of echinacea's "discovery" is told in Lloyd JU. A Treatise on Echinacea, Drug Treatise, no. XXX. Cincinnati: Lloyd Brothers; 1917.

18.       Quoted in Lloyd, A Treatise on Echinacea (n. 17), p. 5.

19.       Ellingwood F. A Systematic Treatise on Materia Medica and Therapeutics. Chicago: Chicago Medical Press; 1898, p. 444-451.

20.       Lloyd, A Treatise on Echinacea (n. 17), p. 13

21.       Lloyd, A Treatise on Echinacea (n. 17), p. 14.

22.       Transactions of the National Eclectic Medical Association 36; 1908:64-5.

23.       See The National Formulary, 4th ed. Washington, DC: AphA; 1916, p. 294; and The National Formulary, 8th ed. Washington, DC: AphA; 1946, p. 185.

24.       See Wood HC, et al. The Dispensatory of the United States of America, 21st ed. Philadelphia: JB Lippincott; 1926, pp. 418-419; and, Wood HC, Osol A. The Dispensatory of the United States of America, 23rd ed. Philadelphia: JB Lippincott; 1943, pp. 377-8.

25.       Lloyd JU. Vegetable Drugs Employed by American Physicians. Journal of the American Pharmaceutical Association Nov 1912; 1:1228-41.

26.       Lloyd, "Vegetable Drugs" (n. 25), p. 1229.

27.       Flexner A. Medical Education in the United States and Canada: A Report to the Carnegie Foundation for the Advancement of Teaching. New York: Carnegie Foundation, 1910. The Flexner Report has been the subject of considerable controversy among historians. For a review of that debate see Flannery MA. Medicine's Remarkable Brothers: Simon and Abraham Flexner of Louisville, Kentucky. Journal of the Kentucky Academy of Science Fall 1998;59:158-67.

28.       For a detailed historical listing of botanicals in the USP see Boyle W. Official Herbs: Botanical Substances in the United States Pharmacopoeias, 1820-1990. East Palestine, OH: Buckeye Naturopathic Press; 1991.

29.       Tyler VE. Pharmaceutical Botany in the U.S. -- 1900-1962. Pharmacy in History 1996; 38:21.

30.       vonUnruh V. Echinacea Angustifolia and Inula Helenium in the Treatment of Tuberculosis. The National Eclectic Medicine Quarterly 1916; 7:64.

31.       Terpening HJ. Echinacea. Transactions of the Eclectic Medical Association 1907; 35:43.

32.       Tyler, Pharmaceutical Botany in the U. S. (n. 29), p. 21.

33.       Hobbs C. Echinacea: The Immune Herb. Santa Cruz, CA: Botanica Press; 1997, p. 51.

34.       See Kuhn TS. The Structure of Scientific Revolutions, 2nd ed., enlarged. Chicago: University of Chicago; 1970; and Koestler A. The Sleepwalkers: A History of Man's Changing Vision of the Universe. 1959; reprinted, London: Arkana, 1989.

35.       Kaufman PB, et al. Natural Products from Plants. Boca Raton, FL: CRC Press; 1999, p. 171.

36.       Bauer R, Wagner H. Echinacea species as potential immunistimulatory drugs. Econ Med Plant Res 1991, 5:253-321. Cited in Werback MR, Murray MT. Botanical Influences on Illness: A sourcebook of clinical research. 2nd ed. Tarzana, Calif: Third Line Press; 2000, p 381.

37.                   Werback MR, Murray MT. Botanical Influences on Illness: A sourcebook of clinical research. 2nd ed. Tarzana, Calif: Third Line Press; 2000, p. 381.

38.                   Melchart D, et al. Immunomodu-lation with Echinacea--A Systematic Review of Controlled Clinical Trials. Phytomedicine 1994; 1(3):245-54. The call for further research in this area has at least partly been answered in specific product studies such as the one recently comparing Echinaforce¨, a 6.78 mg E. purpurea extract made from 95% herb and 5% root, with a 48.27 mg concentrate of the same extract and a special E. purpurea root extract. The research team concluded the "Echinacea concentrate as well as Echinaforce^¨ represent a low-risk and effective alternative to the standard symptomatic medicines in the acute treatment of common cold." See  Brinkeborn RM, Shah DV, and Degenring FH. Echinaforce^¨ and

Other Echinacea Fresh Plant Preparations in the Treatment of the Common Cold: A Randomized, Placebo Controlled, Double-Blind Clinical Trial," Phytomedicine 1999;6(1):1-5.

39.       Kaufman, et al. Natural Products from Plants (n. 35), p. 172.

40.       Kaufman, et al. Natural Products from Plants (n. 35), p. 172.

41.       Busing KH. [Inhibition of hyaluronidase by Echinacin.] Arzneimittelforsch 1952; 2:467-72 (in German). Cited in Werback MR, Murray MT. Botanical Influences on Illness: A sourcebook of clinical research. 2^nd ed. Tarzana, Calif: Third Line Press; 2000, p. 381.

42.       Hobbs, Echinacea: (n. 33), p. 57.

43.       Tunnerhoff FK, Schwabe HK. [Studies in human beings and animals on the influence of Echinacea extracts on the formation of connective tissue following the implantation of fibrin.] Arzneimittelforsch 1956; 6:330-4 (in German). Cited in Werback MR, Murray MT. Botanical Influences on Illness: A sourcebook of clinical research. 2nd ed. Tarzana, Calif: Third Line Press; 2000, pp. 601-603.

44.       Hobbs, Echinacea: (n. 33), p. 58.

45.       Kinkel HJ, Plate M. Tlllner U. [Effect of Echinacin ointment in healing of wound]. MedKlin 1984; 79(21):580-3 (in German). Cited in Werback MR, Murray MT. Botanical Influences on Illness: A sourcebook of clinical research. 2nd ed. Tarzana, Calif: Third Line Press; 2000, p. 602.

46.       Blumenthal, et al. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin: American Botanical Council; 1998, p. 61.

47.       PDR for Herbal Medicines, 1st ed. Montvale, NJ: Medical Economics; 1998, p. 816-823.