Antonie van Leeuwenhoek 71: 15±20, 1997. 15 c 1997 Kluwer Academic Publishers. Printed in the Netherlands. The birth of virology Marian C. Horzinek Head, Virology Unit, Dept. Inf. Dis.& Immunol. Director, Institute of Veterinary Research, Veterinary Faculty, Utrecht University, Yalelaan 1, de Uithof, 3584 CL Utrecht, The Netherlands Si quis sit ea immanitatae naturae ut congressus haminum fugit atque oderit, tamen id pati non poterit ut non anquirat aliquem apud quem evomat virus acerbitatis suae Introduction Consequently, virology should occupy quite a prominent position in microbiological thinking, and This quote is from Cicero's `De Amicitia' (23, 87) it does world-wide. However, in paraphrasing the bib- Ð I happen to remember it from my days at school, lical `A prophet is not without honour, save in his own and it comes in conveniently to start a talk on the country' (New Testament; St. Matthew Chapter 13, birth of virology, my occupation since three decades. Verse 57) - concerning the hero we celebrate today it In Cicero's quote it is said of an intransigent person should read: `..., not even in his own country'. Beijer- that she `...still cannot be without somebody where to inck's importance for virology was barely mentioned spit out the venom of one's own bitterness' (Horzinek by the `NRC Handelsblad', a leading Dutch newspaper 1 1995). Throughout antiquity `virus' was a common, which ran a 1 /2 page article on him (November 30, general term to designate anything unpleasant and dan- 1995) at the occasion of this Centennial. Our Calvinist gerous, from snake and scorpion poison to disease heritage still shows. I have the privilege of compensat- agents, viscous ¯uids from plants and animals, semen, ing for this omission. the salty taste of sea water, even bad odour or stench Any centenary is welcomed as an opportunity to (Klotz 1857). The word probably originated in Sanskrit look back and celebrate. With respect to virology, and is related to German `Wiesel', English `weasel', the ambiguity of this approach becomes obvious when French `vison', all names for an animal that Ð as reviewing recent and not-so-recent commemorations: mustellids do Ð sprays a strong smelling ¯uid from its ± in 1982 a two-day symposium `100 Years of Virol- peri-anal glands when threatened. ogy in Wageningen' was organized in honour of In this Centennial's programme it will be my task Adolf Mayer's ®rst publication on the transmissi- to illustrate the role Martinus Willem Beijerinck has bility of tobacco mosaic disease; played in de®ning the nature of a group of novel dis- ease agents, of `contagia', as he used to call them. He ± in 1992 a meeting in St.Petersburg celebrated 100 thereby indeed gave birth to a new discipline. Virolo- years after Dmitri Ivanovsky had published his gy keeps attracting young scientists, with World Con- results of the ®lterability of the agent causing tobac- gresses of some 2000 participants every 3 years and co mosaic; an estimated tenfold number working in academia, in ± the present Beijerinck Centennial highlights 100 hospitals, diagnostic laboratories, in industry. Virolo- years of the Delft School of Microbiology and its gy has played a pivotal role in addressing public health lasting in¯uence on the study of microbial bio- issues, in solving animal and plant production prob- chemistry, biodiversity and biotechnology; lems and in the biological sciences in general. Of ± for 1998 plans are being developed to honour the Nobel Prizes between 1950 and 1980 in physi- Friedrich Lof¯erÈ and Paul Frosch with a sympo- ology/medicine, 13 were awarded to virologists, and sium on the Baltic Sea island Riems for their work several more to scientists that used viruses as tools on the etiology of foot-and-mouth disease, and (Table 1). ®nally MENNEN/Pre/cor: Pipsnr.: 105715; Ordernr.:233850-ag; sp-code: anto872-bei BIO2KAP anto872.tex; 28/11/1996; 15:02; v.5; p.1 16 Table 1. Nobel Prizes in Physiology or Medicine connected with virology 1951 Theiler yellow fever discoveries 1954 Enders, Weller, Robbins growth of poliovirus in cell culture 1966 Huggins/Rous virus as a cause of sarcoma 1969 Delbruck,È Hershey, Luria viruses & viral diseases 1975 Dulbecco, Temin, Baltimore tumour viruses, reverse transcription 1976 Blumberg, Gajdusek hepatitis, kuru 1978 Nathans, Smith, Arber restriction endonucleases (bacteriophages) 1993 Roberts, Sharp gene splicing (adenovirus) the Virology Division of the International Union petals is caused by a virus infection. Using advanced of Microbiological Societies is considering a similar techniques in phytopathology, the infection has been event in the same year. controlled, and presently available tulip bulbs are virus- free Ð the ¯ame patterns today having a genetic rather than an infectious origin. The detailed grafting instruc- However, as Dmitri K. Lvov proclaimed in his opening tions published in 1675 by Blagrave are probably the statement to the St. Petersburg meeting (Lvov 1993), ®rst publication of an infection experiment in virology. `...the birth of virology occurred neither in a day nor We ®nd more elements of estheticism in early in a year...'. In the following account therefore I shall microbiology, and it may be more than chance that rather try to capture the atmosphere around the turn its cradle stands in this country. The visual arts have of the century, to emphasize the relative merits of the culminated in the Netherlands of the Golden Age, with personalities involved, but also to look at the period of painters reaching global fame that none of our com- pregnancy preceding the happy parturition, the birth of posers, architects or poets has ever matched. Microbi- virology. ology owes much to this Dutch passion for the visible, I think, of which the invisible is just the coin's oth- er face. A monumental ®gure in the exploration of Prehistory of virology the microcosmos is Antoni van Leeuwenhoek, born in 1632 in the same city of Delft that domiciled Beijerinck Let us therefore start some 300 years earlier. In 1576, some 200 years later. Antoni had no university educa- Carolus Clusius (Charles de l'Ecluse, born in Arras tion and still became a Fellow of the Royal Society 1526, died in Leiden 1606), Professor of Botany at in London (1680), a peer to contemporary scientists Leiden University, the Netherlands, published a book- and famous already during life. Using his self-made let entitled Rariorum aliquot stirpium per Hispanias microscopes, he examined microorganisms and tissue observatorium Historia (The history of strange stripes samples and gave the ®rst descriptions of bacteria, pro- observed in Spain). He described conspicuous colour tozoa and spermatozoa. His burial monument can be changes on the petals of tulips - white streaks and ¯ame found in Delft's Old Church, and its custodian assured patterns Ð which immensely increased their appeal to me that it is visited almost weekly by some scientist. buyers. The popularity of these varieties is not only Beijerinck was a great admirer of his countryman and re¯ected by the punctilious plant portraits in still lives found out about his priority in cultivating and observ- of Flemish and Dutch painters from the beginning of ing anaerobic bacteria - on October 9, 1676 (Beijerinck the 17th century, but also by commercial documents: 1913). for one bulb of the `Viceroy' tulip a price equivalent While Leeuwenhoek has become a household to US$ 30.000 was payed in Holland. The `bulb mad- name, so to speak, in microbiology, another ®gure ness' had reached its climax around 1635 when the in the virology, immunology, vaccinology triangle has trade ®nally collapsed. As early as 1637, Dutch tulip been almost completely forgotten. Only three months growers knew that the desired stripe pattern could be ago, however, during his veterinary immunology inau- transferred to the petals of monochrometulips by graft- gural lecture in Utrecht, Prof.Willem van Eden drew ing bulbs to those of the streaked variety. Some 250 the audience's attention to another self-taught Dutch- years later it was shown that the `breaking' of tulip man, a miller and farmer, whose observations and anto872.tex; 28/11/1996; 15:02; v.5; p.2 17 relentless vaccination efforts were focused on a high- disease symptoms were described in terms emphasiz- ly lethal disease of cattle, rinderpest. His name was ing their visual appeal Ð break, ¯ame, streak, mosa- Geert Reinders (1737±1815). After the 1768 epidemic ic. Euphemisms are only left when man himself falls he concluded victim to an infectious disease Ð its sinister quali- ± that cattle which had experienced the natural illness ty is then also re¯ected verbally. But the use of the were protected from disease after another infection, term `virus' for agents of killer diseases in animals ± that the same was true for animals with only light and man certainly does not suf®ce to identify the ®rst symptoms e.g. after vaccination, and scientists that had a conception of its uniqueness. The ± that the mode of inoculation and supportive therapy microbiologists at the turn of the century seem to have had no in¯uence on the outcome of infection. He been largely unaware of the fact that these uncultivable also discovered what we today would call `maternal agents might be very different from the bacteria caus- immunity', transferred from an immune cow to its ing anthrax, tuberculosis and diphtheria, although Pas- calf through colostral antibodies. teur, working in the 1880's on rabies, did conceive of Geert Reinders published his observations in 1776 Ð the agent as being an `micro-organism in®nitesimally Edward Jenner's variola-vaccinia protection experi- small' (Pasteur et al. 1884). As so often in the history of ments appeared 22 years later.