© 1993 Nature Publishing Group http://www.nature.com/naturebiotechnology /COMMENTARY• Unsolved Mysteries BERNARD DIXON he hand of the Lord was against fever nine years earlier, and show that most of those the city with a very great destruc­ patients had also developed rising levels of antibodies tion: and he smote the men of the against Legionella pneumophila. city, both small and great, and But what are the prospects of applying PCR to the ' they had emerods in their secret study of pathogens from previous centuries? As with parts" (1 Samuel 5:9). animal cells, the question hinges largely on finding What on earth was going on microbial DNA that has not been denatured and which here? An outbreak of hemor­ therefore still contains meaningful coding sequences. rhoids? Venereal disease? Bibli­ It's a fanciful idea at first, but on reflection the cal citations are not exactly thick on the ground at possibility of retrieving such material seems more scientific meetings, but these were the quotes with plausible than might be imagined. which veteran microbiologist Chris Collins opened Viruses can be maintained indefinitely, like chemi­ part of the Society for Applied Bacteriology's Sum­ cals, on a laboratory shelf. There seems every reason mer Conference in Nottingham last month. Theses­ to suppose, therefore, that some viruses of past times sion ranged over several "old plagues," including may have persisted in, for example, permafrost or several of disputed identity. It also prompted sugges­ desiccated burial vaults. The prospect of viable organ­ tions that the polymerase chain reaction (PCR), now isms being released from such sites was taken very widely famed for the fact and fantasy of amplifying seriously by the World Health Organization during human and other DNA from ancient bones, might also the smallpox eradication campaign of the 1970s, be used to retrieve microbial DNA and thus learn when Peter Razzell of Bedford College, London, something about infections in the mists of history. writing in New Scientist (71 :35, 1976), drew attention After Jurassic Park, the Black Death? to an eighteenth century smallpox outbreak appar­ There are certainly many epidemiological riddles to ently triggered by the disinterring of a smallpox which it would be nice to have answers. Was the victim buried 30 years earlier. bubonic plague of history really what we believe it to Writing in The Lancet (2:1454, 1984), Arie have been-the well-defined condition caused by Zuckerman of the London School of Hygiene and Yersinia pestis? Were Roland Rosquist and colleagues Tropical Medicine argued that the risk of smallpox at the Swedish Defense Research Establishment, reappearing in this way was small, as was the danger Umea, correct in arguing (Nature 334:522, 1988) that for archeologists handling incompletely decomposed single point mutations produced, from less virulent Y. bodies. But the remote possibility remains, while pestis, the hypervirulent strains that triggered the Peter Lewin of the Hospital for Sick Children, Toronto, great epidemics? What of Graham Twigg' s theory, in has drawn attention (JAMA 253:3095, 1985) to the his book The Black Death-A Biological Reappraisal likelihood that viable smallpox virus and other patho­ (Schocken Books, 1985), that the Black Death was a gens have been preserved in the graves of people major epidemic not of plague but of anthrax? buried in the Arctic over the past 150 years. Then there is the puzzle of the Sweating Sickness or Sporing bacteria too are notoriously hardy, as illus­ English Sweat. Affecting the rich rather than the poor, trated by the survival of Bacillus anthracis in the soil this first broke out around the time of the battle of of Gruinard, off the west coast of Scotland, decades Bosworth in the English midlands in 1485, spread after the organism was released there in biological quickly to London, and then caused further epidemics warfare experiments during 1942-43, until the island in 1508, 1517,and 1528beforeinakingitslastappear­ was decontaminated a few years ago. A variety of ance in 1551. After that date, all references to the other organisms, including Mycobacterium tubercu­ disease simply disappeared. Medical historians have losis, with its lipid-rich cell wall, can survive for long suggested that the Sweating Sickness was in fact periods even in nonideal conditions. Finally, there are influenza, but this is hard to accept because while prion and related diseases whose coded information is some symptoms can be recognized in common be­ integrated into human and other animal genomes. tween the two conditions, the Sweating Sickness did Their agents, or fragments of them, may have sur­ not seem to affect the respiratory tract. vived in bones that are already being examined using It has, of course, become successively easier, as the PCR. twentieth century has unfolded, to determine the real Retrieving valuable microbes, or even whole ge­ causes of earlier, hitherto unexplained outbreaks of nomes, preserved over centuries is an undertaking as disease. Thus the investigators of what became known remote as that of cloning Tyrannosaurus rex. But I'll as Legionnaires' disease at the Bellevue-Stratford bet there is sufficient ancient microbial DNA around Hotel, Philadelphia, in July 1976 were later able to test to use to learn some things about the plagues and samples ofblood preserved from the victims of Pontiac pestilences of times past. /// 968 BIO/TECHNOLOGY VOL. 11 SEPTEMBER 1993 .