THE JOURNAL OF INFECTIOUS DISEASES. VOL. 136, NO.3. SEPTEMBER 1977 © 1977 by the University of Chicago. All righls reserved.
EDll"'ORIALS The Origins of Vaccinia Virus The 20th century. Speculation about the origin of vaccinia continues. The isolation and characterization of various poxviruses has increased the confusion because current vaccine strains are different not only from cowpox virus [5, 6] but also from all other poxviruses [7]. In addition, vaccinia virus has no natural host. Accidental infection with vaccinia virus is usually traced to a recently vaccinated individual [7, 8]. This phenomenon has led to the generally accepted view that vaccinia virus is an artificially propagated virus, derived in some way from poxviruses naturally occuring in the 18th and 19th centuries. Derivation from smallpox. Many early claims were made that vaccinia virus was derived from smallpox virus by adaptation to animals. However, much ,of this work was done in vaccine laboratories, and there were many opportunities for contamination with vaccinia to occur. All recent, carefully controlled experiments have failed to provide any evidence of such a transformation [9, 10], and this hypothesis is now given little credit. It has been suggested that smallpox may have been transformed into vaccinia by arm-to-arm passage during vaccination in the early 19th century [11]. Although such a transformation is possible, one would expect the transformed virus to retain the limited host range of smallpox virus rather than to develop the wide host range of vaccinia virus [12]. Derivation from cowpox virus. Some authorities suggest that vaccinia has been derived from cowpox virus [12, 13]. However, Dekking considers the differences between cowpox and vaccinia viruses to be too great to make such an origin probable [8]. This hypothesis also assumes that the vaccine virus used by the early workers was the same as the present-day cowpox, an assumption discussed below. Vaccinia as a hybrid virus. The idea that vaccinia virus is a hybrid of smallpox and cowpox viruses [14] is one which I favored in the past [7] and to which there is no obvious objection. Such a hybrid could have been genetically selected after the use of contaminated vaccine. Small-
Received for publication December 29, 1976, and in revised form March 28, 1977. I thank Mr. D. M. Crook for allowing me to examine historical material owned by the Liverpool Medical Institution (Liverpool, England). Please address requests for reprints to Dr. Derrick Baxby, Department of Medical Microbiology, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, England.
453
Downloaded from http://jid.oxfordjournals.org/ at duke university medical ctr on December 28, 2012
One of the factors contributing to the success of the World Health Organization Smallpox Eradication Campaign has been the existence of a safe, effective vaccine. Unlike most vaccine viruses very little is known of the origins of vaccinia virus, and there has been much speculation on the subject. Smallpox vaccination was established long before the nature of viruses was known, and therefore very little is known about the number of poxviruses that were circulating in the 18th and 19th centuries. After the introduction of vaccination in 1796 by Edward Jenner, there was controversy concerning the origin of his "variolae vaccinae." The alternatives considered were that, as the name suggests, it was smallpox of the cow or that cowpox was a separate disease. A considerable debate followed that compared the new vaccination with smallpox inoculation, and a number of problems emerged. Some vaccines produced generalized lesions and severe symptoms; these were usually due to smallpox infection caused by the use of contaminated vaccine or by vaccinees contracting smallpox in the hospitals where the early vaccines were given [1, 2]. In other instances the vaccine did not "take," or an apparently successful vaccination did not protect against smallpox. Jenner suggested that these problems were caused by inexperienced vaccinators who selected material from other bovine infections (spurious cowpox) or from old lesions or who allowed the vaccine to undergo putrefaction during storage [3, 4]. Further confusion was caused by jenner's belief that his vaccine originated from an infection of the heels of horses ("grease") and became more suitable for human use after passage through the cow [3].
454
ly acquired "cowpox" show relatively severe lesions and could, from the recorded descriptions, have been caused by present-day cowpox virus [21-23]. Other lesions, however, do not seem particularly severe. Not all deliberately inoculated vaccines produced the same effect. They were not of equal potency, and some were possibly contaminated with other viruses or bacteria. Some vaccines were withdrawn, and constant attempts were made to maintain material which gave an attenuated "take" [24]. However the relevant literature indicates that illustrations of the earliest vaccinations are remarkably similar to those of today. The earliest illustrations were reviewed by McVail [25] who said in 1896 of jenner's illustrations, "... The appearances shown ... were those of vaccinia as we still know it." Of Kirtland's paintings of 1802, which McVail thought superior to all others, he said, "... The same appearances can be seen at the present time ... the vaccination of 1802 is identical with the vaccination of 1896." The very close similarity between early and present-day vaccination can be appreciated by a comparison of the early engravings [4, 25] with more recent engravings or photographs [1, 26, 27]. In addition, early written descriptions might equally apply to present-day vaccine [4, 28]It would seem, therefore, that there is no clincal reason to postulate a specific recent origin of vaccinia virus. Where did vaccinia go? If one accepts the above reasoning, then poxviruses other than smallpox and cowpox were available to the early 19th century vaccinators, and it is possible that what we now call vaccinia virus was one of them. No laboratory studies have been made of horsepox ("grease") since techniques for identification of poxvirus were developed. The disease appears to be extinct, and the identity of the causative agent remains a mystery (horsepox is now sometimes used to describe an equine herpesvirus infection). It is possible that 19th century horsepox is identical to present-day vaccinia. Alternatively, since there is some evidence that human horsepox was more severe than human cowpox [17, 23, 29], it is perhaps more likely that 19th century cowpox is identical to present-day vaccinia and that it was eliminated from its natural environment, an occurrence that left horsepox
Downloaded from http://jid.oxfordjournals.org/ at duke university medical ctr on December 28, 2012
pox and cowpox viruses will hybridize readily under experimental conditions [14], and apparently unique poxviruses have been isolated from nature that may be hybrids of other poxviruses [15]. Vaccinia as the prototype poxvirus. It has been suggested that vaccinia is the parental poxvirus from which all others have been derived [9]. Although I do not agree with this suggestion, I find the related suggestion that vaccinia virus was actually used by the early vaccinators attractive. Vaccinia now has no natural host, and the host in which it may have been maintained has not been identified [12]. Nevertheless, although nothing can be proved, a search of the literature as discussed below provides evidence that is consistent with such a hypothesis. Were viruses other than cowpox and smallpox used by the early vaccinators? In considering this question, we can be guided only by the early records. In 1789 Jenner assisted Hickes in experiments which showed that "pigpox" in humans would induce immunity to smallpox [16]. There was also the confusion concerning "grease"; Loy [17] showed in 1801 that horses were naturally susceptible to a poxvirus that would confer im· munity to smallpox in humans, and in 1813 Jenner himself was "equinating constantly" [18]. It is possible that early pigpox, horsepox, and cowpox were all caused by the same virus, but the possibility that they were not should receive equal attention. If viruses other than cowpox and smallpox were available, it is possible that one or more of them could have been used as a source of vaccine. Comparison of lesions produced by vaccination. The only information we now have on the possible identity of the viruses used by the early vaccinators comes from their written descriptions and the engravings accompanying them. . The pathogenesis of vaccinia in humans is similar to that of human cowpox, but the latter usually runs a more severe course [19, 20]. Cowpox in humans is characterized by lesions that tend to be hemorrhagic, more edematous, and take longer (six to 10 weeks) to heal than those of vaccinia. There is often adenitis and pyrexia, and patients are often admitted to a hospital. A provisional diagnosis of anthrax is not uncommon [20]. Some of the earliest descriptions of accidental-
Baxby
455
Editorial
10.
11. 12.
13.
14.
15. 16. 17.
18.
19. 20. 21.
DERRICK BAXBY
Department of Medical Microbiology University of Liverpool Liverpool) England References 1. Dixon, C. W. Smallpox. Churchill, London, 1962.512 p. 2. Jenner. E. Correspondence. Med. Phys. J. 3:101-102. 1800. 3. Jenner, E. The origin of the vaccine inoculation. Shury, London, 1801. 12 p. 4. Jenner, E. An inquiry into the causes and effects of the variolae vaccine. Low, London, 1798.75 p. 5. Downie, A. W. A study of the lesions produced experimentally by cowpox virus. J. Pathol Bacteriol. 48:361-379, 1939. 6. Downie, A. W. The immunological relationship of the virus of spontaneous cowpox to vaccinia virus. Br. J. Exp. Pathol. 20:158-176,1939. 7. Baxby, D. The identification and interrelationships of the variola/vaccinia subgroup of poxviruses. Prog. Med. Virol. 19:215-246, 1975. 8. Dekking, F. Cowpox and vaccinia. In J. van der Hoeden, [ed]. Zoonoses. Elsevier, London, 1964, p. 411-418. 9. Herrlich, A., Mayr, A., Mahnel, H., Munz, E. Experimental studies on transformation of the vario-
22.
23.
24. 25.
26.
27. 28.
29.
30.
la virus into the vaccinia virus. Arch. Gesamte Virusforsch. 12:579-599, 1963. Dumbell, K. R., Bedson, H. S. Adaptation of variola virus to growth in the rabbit. J. Pathol. Bacteriol. 91:459-465,1966. RazzeH, P. E. Edward Jenner: the history of a medical myth. Med. Hist. 9:216-229, 1965. Downie, A. W. Smallpox. In S. Mudd [ed.]. Infectious agents and host reactions. Saunders, Philadelphia, 1970, p. 487-518. Fenner, F., Burnet, F. M. A short description of the poxvirus group (vaccinia and related viruses). Virology 4:305-314, 1957. Bedson, H. 5., Dumbell, K. R. Hybrids derived from the viruses of variola major and cowpox. J. Hyg. (Camb.) 62:147-158, 1964. Bourke, A. T. C., DumbeH, K. R. An unusual poxvirus from Nigeria. Bull. W.H.O. 46:621-623,1972. Anonymous. Records of an old medical society. Br. Med. J. 1: 1296-1298, 1896. Loy, J. An account of some experiments on the origin of the cowpox. Webster, Whitby, London, 1801. 29 p. Jenner, E. Letter to J. Moore (1813). In J. Baron. The life of Edward Jenner. Vol. 2. Colborn, London, 1838, p. 388. Downie, A. W. Jenner's cowpox inoculation. Br. Med. J. 2: 251-256. 1951. Baxby, D. Is cowpox misnamed? A review of ten hu· man cases. Br. Med. J. 1:1379-1381, 1977. Ceeley, R. Further observations of the variolae vaccinae. In E. M. Crookshank [ed.]. History and path· ology of vaccination. Vol. 2. Lewis, London, 1889. p.469-511. Bousquet, M. On cowpox discovered at Passay (near Paris). In E. M. Crookshank [ed.]. History and pathology of vaccination. Lewis, London, 1889, p. 311-322. Crookshank, E. M. Outbreak of cowpox near Crick· lade (Wiltshire). In E. M. Crookshank [ed.]. History and pathology of vaccination. Vol. 2. Lewis. London, 1889, p. 591-610. Crookshank, E. M. History and pathology of vaccination. Vol. 1. Lewis, London, 1889.466 p. McVail, J. C. Cowpox and smallpox: Jenner, Wood· ville, and Pearson. Br. Med. J. 1:1271-1276, 1896. Smadel, J. E. Smallpox and vaccinia. In T. M. Rivers [ed.]. Viral and rickettsial infections of man. 2nd ed. Lipincott, Philadelphia, 1952, p. 414-439. Emond, R. T. D. A colour atlas of infectious diseases. Wolf, London, 1974. 384 p. Anonymous. Directions for the practice of the vaccine inoculation. Med. Chirurg. Rev. 9:393-394, 1802. de Carro, J. Letter to E. Jenner (1803). In J. Baron. The life of Edward Jenner. Vol. 1. Colborn, London, 1838, p. 432. Jenner, E. Letter to J. Moore (1816). In J. Baron. The life of Edward Jenner. Vol. 2. Colborn, Lon· don, 1838, p. 399.
Downloaded from http://jid.oxfordjournals.org/ at duke university medical ctr on December 28, 2012
(now called cowpox) to establish its present pattern of sporadic outbreaks in humans and animals from an unknown reservoir [20]. Poxvirus infections of horses and cattle were not very common in the 18th and 19th centuries. This is shown, for exampIe, by the difficulties the early vaccinators sometimes had in obtaining material. It is also clear that the farmers were concerned about reducing the incidence of disease in their herds. This concern is demonstrated by jenner's fears that his current vaccine might fail. "... I know not what we should do, for the precautions of the farmers ... have driven the cowpox from their herds" [30]. It is quite possible that these precautions and also improved methods of breeding might lead to certain infections becoming extinct, as in the case of "grease." Conclusions. "The origin of vaccinia virus ... poses a question for which there is no certain answer" [12]. While agreeing with this statement, I hope that the present paper will encourage people to consider the possibilities that a recent specific origin for vaccinia virus is not necessary and that the vaccines used by the early pioneers are essentially the same as those used in the eradication of smallpox.
EDll"'ORIALS The Origins of Vaccinia Virus The 20th century. Speculation about the origin of vaccinia continues. The isolation and characterization of various poxviruses has increased the confusion because current vaccine strains are different not only from cowpox virus [5, 6] but also from all other poxviruses [7]. In addition, vaccinia virus has no natural host. Accidental infection with vaccinia virus is usually traced to a recently vaccinated individual [7, 8]. This phenomenon has led to the generally accepted view that vaccinia virus is an artificially propagated virus, derived in some way from poxviruses naturally occuring in the 18th and 19th centuries. Derivation from smallpox. Many early claims were made that vaccinia virus was derived from smallpox virus by adaptation to animals. However, much ,of this work was done in vaccine laboratories, and there were many opportunities for contamination with vaccinia to occur. All recent, carefully controlled experiments have failed to provide any evidence of such a transformation [9, 10], and this hypothesis is now given little credit. It has been suggested that smallpox may have been transformed into vaccinia by arm-to-arm passage during vaccination in the early 19th century [11]. Although such a transformation is possible, one would expect the transformed virus to retain the limited host range of smallpox virus rather than to develop the wide host range of vaccinia virus [12]. Derivation from cowpox virus. Some authorities suggest that vaccinia has been derived from cowpox virus [12, 13]. However, Dekking considers the differences between cowpox and vaccinia viruses to be too great to make such an origin probable [8]. This hypothesis also assumes that the vaccine virus used by the early workers was the same as the present-day cowpox, an assumption discussed below. Vaccinia as a hybrid virus. The idea that vaccinia virus is a hybrid of smallpox and cowpox viruses [14] is one which I favored in the past [7] and to which there is no obvious objection. Such a hybrid could have been genetically selected after the use of contaminated vaccine. Small-
Received for publication December 29, 1976, and in revised form March 28, 1977. I thank Mr. D. M. Crook for allowing me to examine historical material owned by the Liverpool Medical Institution (Liverpool, England). Please address requests for reprints to Dr. Derrick Baxby, Department of Medical Microbiology, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, England.
453
Downloaded from http://jid.oxfordjournals.org/ at duke university medical ctr on December 28, 2012
One of the factors contributing to the success of the World Health Organization Smallpox Eradication Campaign has been the existence of a safe, effective vaccine. Unlike most vaccine viruses very little is known of the origins of vaccinia virus, and there has been much speculation on the subject. Smallpox vaccination was established long before the nature of viruses was known, and therefore very little is known about the number of poxviruses that were circulating in the 18th and 19th centuries. After the introduction of vaccination in 1796 by Edward Jenner, there was controversy concerning the origin of his "variolae vaccinae." The alternatives considered were that, as the name suggests, it was smallpox of the cow or that cowpox was a separate disease. A considerable debate followed that compared the new vaccination with smallpox inoculation, and a number of problems emerged. Some vaccines produced generalized lesions and severe symptoms; these were usually due to smallpox infection caused by the use of contaminated vaccine or by vaccinees contracting smallpox in the hospitals where the early vaccines were given [1, 2]. In other instances the vaccine did not "take," or an apparently successful vaccination did not protect against smallpox. Jenner suggested that these problems were caused by inexperienced vaccinators who selected material from other bovine infections (spurious cowpox) or from old lesions or who allowed the vaccine to undergo putrefaction during storage [3, 4]. Further confusion was caused by jenner's belief that his vaccine originated from an infection of the heels of horses ("grease") and became more suitable for human use after passage through the cow [3].
454
ly acquired "cowpox" show relatively severe lesions and could, from the recorded descriptions, have been caused by present-day cowpox virus [21-23]. Other lesions, however, do not seem particularly severe. Not all deliberately inoculated vaccines produced the same effect. They were not of equal potency, and some were possibly contaminated with other viruses or bacteria. Some vaccines were withdrawn, and constant attempts were made to maintain material which gave an attenuated "take" [24]. However the relevant literature indicates that illustrations of the earliest vaccinations are remarkably similar to those of today. The earliest illustrations were reviewed by McVail [25] who said in 1896 of jenner's illustrations, "... The appearances shown ... were those of vaccinia as we still know it." Of Kirtland's paintings of 1802, which McVail thought superior to all others, he said, "... The same appearances can be seen at the present time ... the vaccination of 1802 is identical with the vaccination of 1896." The very close similarity between early and present-day vaccination can be appreciated by a comparison of the early engravings [4, 25] with more recent engravings or photographs [1, 26, 27]. In addition, early written descriptions might equally apply to present-day vaccine [4, 28]It would seem, therefore, that there is no clincal reason to postulate a specific recent origin of vaccinia virus. Where did vaccinia go? If one accepts the above reasoning, then poxviruses other than smallpox and cowpox were available to the early 19th century vaccinators, and it is possible that what we now call vaccinia virus was one of them. No laboratory studies have been made of horsepox ("grease") since techniques for identification of poxvirus were developed. The disease appears to be extinct, and the identity of the causative agent remains a mystery (horsepox is now sometimes used to describe an equine herpesvirus infection). It is possible that 19th century horsepox is identical to present-day vaccinia. Alternatively, since there is some evidence that human horsepox was more severe than human cowpox [17, 23, 29], it is perhaps more likely that 19th century cowpox is identical to present-day vaccinia and that it was eliminated from its natural environment, an occurrence that left horsepox
Downloaded from http://jid.oxfordjournals.org/ at duke university medical ctr on December 28, 2012
pox and cowpox viruses will hybridize readily under experimental conditions [14], and apparently unique poxviruses have been isolated from nature that may be hybrids of other poxviruses [15]. Vaccinia as the prototype poxvirus. It has been suggested that vaccinia is the parental poxvirus from which all others have been derived [9]. Although I do not agree with this suggestion, I find the related suggestion that vaccinia virus was actually used by the early vaccinators attractive. Vaccinia now has no natural host, and the host in which it may have been maintained has not been identified [12]. Nevertheless, although nothing can be proved, a search of the literature as discussed below provides evidence that is consistent with such a hypothesis. Were viruses other than cowpox and smallpox used by the early vaccinators? In considering this question, we can be guided only by the early records. In 1789 Jenner assisted Hickes in experiments which showed that "pigpox" in humans would induce immunity to smallpox [16]. There was also the confusion concerning "grease"; Loy [17] showed in 1801 that horses were naturally susceptible to a poxvirus that would confer im· munity to smallpox in humans, and in 1813 Jenner himself was "equinating constantly" [18]. It is possible that early pigpox, horsepox, and cowpox were all caused by the same virus, but the possibility that they were not should receive equal attention. If viruses other than cowpox and smallpox were available, it is possible that one or more of them could have been used as a source of vaccine. Comparison of lesions produced by vaccination. The only information we now have on the possible identity of the viruses used by the early vaccinators comes from their written descriptions and the engravings accompanying them. . The pathogenesis of vaccinia in humans is similar to that of human cowpox, but the latter usually runs a more severe course [19, 20]. Cowpox in humans is characterized by lesions that tend to be hemorrhagic, more edematous, and take longer (six to 10 weeks) to heal than those of vaccinia. There is often adenitis and pyrexia, and patients are often admitted to a hospital. A provisional diagnosis of anthrax is not uncommon [20]. Some of the earliest descriptions of accidental-
Baxby
455
Editorial
10.
11. 12.
13.
14.
15. 16. 17.
18.
19. 20. 21.
DERRICK BAXBY
Department of Medical Microbiology University of Liverpool Liverpool) England References 1. Dixon, C. W. Smallpox. Churchill, London, 1962.512 p. 2. Jenner. E. Correspondence. Med. Phys. J. 3:101-102. 1800. 3. Jenner, E. The origin of the vaccine inoculation. Shury, London, 1801. 12 p. 4. Jenner, E. An inquiry into the causes and effects of the variolae vaccine. Low, London, 1798.75 p. 5. Downie, A. W. A study of the lesions produced experimentally by cowpox virus. J. Pathol Bacteriol. 48:361-379, 1939. 6. Downie, A. W. The immunological relationship of the virus of spontaneous cowpox to vaccinia virus. Br. J. Exp. Pathol. 20:158-176,1939. 7. Baxby, D. The identification and interrelationships of the variola/vaccinia subgroup of poxviruses. Prog. Med. Virol. 19:215-246, 1975. 8. Dekking, F. Cowpox and vaccinia. In J. van der Hoeden, [ed]. Zoonoses. Elsevier, London, 1964, p. 411-418. 9. Herrlich, A., Mayr, A., Mahnel, H., Munz, E. Experimental studies on transformation of the vario-
22.
23.
24. 25.
26.
27. 28.
29.
30.
la virus into the vaccinia virus. Arch. Gesamte Virusforsch. 12:579-599, 1963. Dumbell, K. R., Bedson, H. S. Adaptation of variola virus to growth in the rabbit. J. Pathol. Bacteriol. 91:459-465,1966. RazzeH, P. E. Edward Jenner: the history of a medical myth. Med. Hist. 9:216-229, 1965. Downie, A. W. Smallpox. In S. Mudd [ed.]. Infectious agents and host reactions. Saunders, Philadelphia, 1970, p. 487-518. Fenner, F., Burnet, F. M. A short description of the poxvirus group (vaccinia and related viruses). Virology 4:305-314, 1957. Bedson, H. 5., Dumbell, K. R. Hybrids derived from the viruses of variola major and cowpox. J. Hyg. (Camb.) 62:147-158, 1964. Bourke, A. T. C., DumbeH, K. R. An unusual poxvirus from Nigeria. Bull. W.H.O. 46:621-623,1972. Anonymous. Records of an old medical society. Br. Med. J. 1: 1296-1298, 1896. Loy, J. An account of some experiments on the origin of the cowpox. Webster, Whitby, London, 1801. 29 p. Jenner, E. Letter to J. Moore (1813). In J. Baron. The life of Edward Jenner. Vol. 2. Colborn, London, 1838, p. 388. Downie, A. W. Jenner's cowpox inoculation. Br. Med. J. 2: 251-256. 1951. Baxby, D. Is cowpox misnamed? A review of ten hu· man cases. Br. Med. J. 1:1379-1381, 1977. Ceeley, R. Further observations of the variolae vaccinae. In E. M. Crookshank [ed.]. History and path· ology of vaccination. Vol. 2. Lewis, London, 1889. p.469-511. Bousquet, M. On cowpox discovered at Passay (near Paris). In E. M. Crookshank [ed.]. History and pathology of vaccination. Lewis, London, 1889, p. 311-322. Crookshank, E. M. Outbreak of cowpox near Crick· lade (Wiltshire). In E. M. Crookshank [ed.]. History and pathology of vaccination. Vol. 2. Lewis. London, 1889, p. 591-610. Crookshank, E. M. History and pathology of vaccination. Vol. 1. Lewis, London, 1889.466 p. McVail, J. C. Cowpox and smallpox: Jenner, Wood· ville, and Pearson. Br. Med. J. 1:1271-1276, 1896. Smadel, J. E. Smallpox and vaccinia. In T. M. Rivers [ed.]. Viral and rickettsial infections of man. 2nd ed. Lipincott, Philadelphia, 1952, p. 414-439. Emond, R. T. D. A colour atlas of infectious diseases. Wolf, London, 1974. 384 p. Anonymous. Directions for the practice of the vaccine inoculation. Med. Chirurg. Rev. 9:393-394, 1802. de Carro, J. Letter to E. Jenner (1803). In J. Baron. The life of Edward Jenner. Vol. 1. Colborn, London, 1838, p. 432. Jenner, E. Letter to J. Moore (1816). In J. Baron. The life of Edward Jenner. Vol. 2. Colborn, Lon· don, 1838, p. 399.
Downloaded from http://jid.oxfordjournals.org/ at duke university medical ctr on December 28, 2012
(now called cowpox) to establish its present pattern of sporadic outbreaks in humans and animals from an unknown reservoir [20]. Poxvirus infections of horses and cattle were not very common in the 18th and 19th centuries. This is shown, for exampIe, by the difficulties the early vaccinators sometimes had in obtaining material. It is also clear that the farmers were concerned about reducing the incidence of disease in their herds. This concern is demonstrated by jenner's fears that his current vaccine might fail. "... I know not what we should do, for the precautions of the farmers ... have driven the cowpox from their herds" [30]. It is quite possible that these precautions and also improved methods of breeding might lead to certain infections becoming extinct, as in the case of "grease." Conclusions. "The origin of vaccinia virus ... poses a question for which there is no certain answer" [12]. While agreeing with this statement, I hope that the present paper will encourage people to consider the possibilities that a recent specific origin for vaccinia virus is not necessary and that the vaccines used by the early pioneers are essentially the same as those used in the eradication of smallpox.
