As gifts go, this one鈥檚 certainly different. Inside the neat presentation box stand five test tubes, each containing a smear of brownish-yellow goo dotted with small dark patches. At first glance you might think it a most unpleasant present. But for a microbiologist, it鈥檚 the perfect choice. That unappealing goo contains the remains of cultures of the tubercle bacillus prepared by Robert Koch, the great German bacteriologist. Any microbes that survive in it are the direct descendants of those on which Koch was working when he identified them as the cause of TB in 1882.
This TB gift box started out as the centrepiece of an exhibition at the British Congress on Tuberculosis in 1901. Since then, it has passed from one microbiologist to another, ending up in the Hunterian Museum at the Royal College of Surgeons in London. Today the tubes are temporarily in a London lab, where some of Koch鈥檚 successors are hoping to learn more about their contents than Koch could ever have imagined.
FOR ONE week in July 1901, Robert Koch鈥檚 little case of cultures was the star attraction. There wasn鈥檛 one microbiologist who could resist taking a look. There, among the photographs, the microscope slides, and the bits and pieces chopped out of the bodies of some of TB鈥檚 luckless victims was the genuine article. 鈥淚solated from a case of Miliary Tuberculosis on August 15th, 1881. By Professor Robert Koch MD. Institut f眉r Infectionskrankheiten, Berlin. Five culture tubes containing pure cultures of the Tubercle bacillus inoculated on the 20th June, 1901. This culture was originally obtained on the 15th August, 1881 . . . since that date it has undergone 435 sub-cultures without again being passed through the body of an animal.鈥�
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The practice of displaying live specimens at microbiological meetings has died out. Maybe tighter health and safety regulations have ruled it out-or maybe the improvement in audio-visual aids has rendered it pointless. In truth, it was also a bit pointless a hundred years ago. Koch was not expecting anyone at the London conference to scoop up morsels of his gel to take back to their own labs. What counted was simply the thrill of seeing the real thing-much as people who鈥檝e been looking at images of the Mona Lisa all their lives are still keen to visit the Louvre and gaze on Leonardo鈥檚 original painting.
By 1901, Koch was already revered as the father of modern microbiology. He鈥檇 devised a way of growing bacteria on jelly-like agar in the flat circular dishes made by his colleague Julius Petri. He鈥檇 invented new methods of staining bacteria to make them easier to recognise under the microscope. But it was TB that gave him real scientific status. The white death, or consumption as the Victorians called it, was the scourge of early industrial society. Victims suffered fevers and night sweats, and coughed up blood. Among the urban poor TB killed as many as one person in four.
Koch, unlike some of his contemporaries, thought the illness was infectious. So he removed diseased tissue from Heinrich Gunther, a young labourer who had died of TB, and injected it into guinea pigs and rabbits. It was from these animals that he was able to extract the rod-shaped tubercle bacillus, Mycobacterium tuberculosis. His standards of proof-鈥淜och鈥檚 postulates鈥�, as they鈥檙e now known-were high. The organisms had to be found in every victim; it had to be possible to grow them outside the body; and these cultured microbes must in their turn be capable of causing the disease.
After the London meeting, Koch decided to present his goo-filled tubes to someone who might appreciate them-Walter Jobson Horne. Jobson Horne was an English laryngologist who was interested in TB of the larynx. His name may be unfamiliar, but anyone who has ever been examined by an ear, nose and throat surgeon will have encountered one of his inventions, the Jobson Horne head mirror. What Jobson Horne did with his unexpected gift is uncertain. Perhaps he displayed the cultures in his consulting room. Maybe they stood on the drawing room mantlepiece alongside the candlesticks and family photos.
When Jobson Horne died in 1953, he bequeathed the famous tubes to the Royal College of Surgeons, where pathologist John Turk tucked them away in a safe place. When Turk retired in the early 1990s, he passed the tuberculous test tubes to the college鈥檚 Hunterian Museum in London. There Koch鈥檚 cultures languished in a storeroom, not through any neglect but to protect them from light, which might have destroyed any surviving bacteria. And there they stayed until a visiting microbiologist suggested that they really should be investigated.
TB microbes show a lot of variation in their genetic make-up. But are these adaptations to circumstances? Do the strains that thrive in poverty and overcrowding do less well in affluent conditions, and vice-versa? With genome sequencing it鈥檚 possible to identify even minor genetic differences in strains from different places. Historical samples, like the Koch cultures, provide an opportunity to find out how the microbes have changed over time. And so the samples were off again, this time to the Department of Infectious Diseases at St Mary鈥檚 Hospital in west London.
The tubercle bacillus is a hardy creature. It can survive for many months if it is dried, and can withstand disinfection. The goo in one of the test tubes has obviously dried up. Rubber bungs have kept the gel in the other four moist. The team at St Mary鈥檚 has removed a tiny scoop of material from each of the tubes and tried to grow whatever they contain on several different culture media, so far without any luck.
To microbiologists who are working at the molecular level, death is nowadays more of a technical hurdle than an insurmountable barrier. The bacteria may be beyond resuscitation, but the information in their DNA lives on. The team at St Mary鈥檚 has extracted DNA from the cultures and confirmed that the tubes really do contain M. tuberculosis. The next step is to investigate a gene called plcD. This carries the recipe for making an enzyme which some microbes-perhaps including the tubercle bacillus-use to penetrate the membranes of cells they鈥檙e colonising. The plcD gene occurs in at least three different states, and the variant carried by any particular bug might affect its virulence.
Even if its DNA turns out to be well-preserved, one population of organisms-never mind that Koch himself cultured them-can鈥檛 reveal a great deal. But there are other sources of ancient microbial DNA, including the bones of people who鈥檝e died of TB and even the occasional well-preserved corpse. If enough historical material could be collected and studied, it might be possible to explain changes in TB鈥檚 pattern of virulence.
Koch would be delighted to know that his gift, a century on, is still keeping scientists busy.