Viruses: More Friends Than Foes (Revised Edition). Karin Moelling
people, no more than in a normal seasonal epidemic, so the alarm was a false one. However, this was a real pandemic because of the high number of countries affected. Safety measures had already been taken quickly and a vaccine production initiated, but it came too late for the Western world; the wave of infections was already flattening off. People in the Southern Hemisphere did not even want the vaccine free of charge. Nobody there took the swine flu seriously. I got infected in China, possibly in an internet café in Shanghai. I was rather sick back home and cancelled my flight from Berlin to Zurich out of fear that I could infect someone and thereby make newspaper headlines as a professor of virology who spreads the virus. I indeed had the swine flu, as verified by my own diagnostics department.
The influenza viruses responsible for the bird flu only became dangerous through manipulation in the laboratory by scientists. Researchers produced from a bird-only virus to a virus infectious for humans. The necessary mutations were even introduced into the viral sequence twice, in two independent laboratories in the USA and Holland. Why do scientists perform such risky experiments? This question was only raised when the scientists were naïve enough to publish their studies. Only then did the research funding organizations begin to ring the alarm bells. A mandatory break, a moratorium for 6 months, was imposed on the studies and their publication. This lasted longer than ordained, and the ban on publication was then softened: details had to be omitted, so that not everybody could repeat the experiment and convert a relatively harmless virus into a dangerous one.
A moratorium with self-restrictions had happened once before, with limitations on the use of recombinant DNA technologies — the construction of new genes by combinations of gene fragments — at the Asilomar conference in 1975, as well as restrictions on gene therapy of human diseases using viruses against cancer. Even today, viruses are still not allowed to replicate when applied for therapeutic purposes in order to prevent the possibility that replicating viruses might infect the germ cells of a patient, which in turn would open up the possibility that the virus could then be transmitted to the next generation. This restriction is strictly fulfilled and accepted. As a consequence, gene therapy is safe — but it is also ineffective for exactly the same reason. It would be much more effective if virus replication were allowed. Other approaches are being pursued now.
The prohibition of the influenza viruses studies can be summarized: “no dual use”, which means, that publications are not allowed to serve two potential purposes, scientific ones and also bioterrorist interests or other abuses. The results on the manipulated influenza viruses were published by omitting technical details, and they were not unimportant, because they showed that four mutations out of 13,500 nucleotides were sufficient for the virus to become “humanized”, to be transmitted from people to people. This is always the main threat. Surprisingly, certain influenza strains already carry three of the four mutations — so we are only one mutation away from a dangerous virus in the wild. The danger is real, and therefore a worldwide surveillance system has been installed, the Sentinella survey of local influenza outbreaks. From this study the annual influenza strains are predicted as a basis for vaccine production for the coming winter. Vaccines are still often produced in chicken eggs, one egg per dose, which requires billions of “special pathogen-free” (SPF) eggs. There are essentially only two drugs against influenza, very few compared with HIV: Tamiflu and Relenza. Tamiflu became a blockbuster and was sold to panicking governments around the world. It is now stockpiled in many storerooms and waiting to be aliquoted when needed. There is a rather strange law according to which only the day of aliquoting is the basis for calculating the expiry date of the drug. In Scandinavia resistant viruses have already shown up, and in Japan Tamiflu seems to lead to increased suicide rates among young people. Influenza should not be underestimated. I caught it, not just a cold by some rhinovirus, and was so ill and semi-conscious that I did not even remember that I had Tamiflu in my refrigerator for exactly this possibility. It is only effective if taken early after infection, for simple reasons, because then the virus load is still small. By the way, paper handkerchiefs should not be thrown into a paper basket next to a desk, but into a bin with a lid, and even an irreplaceable secretary should stay home instead of spreading the virus at work.
There is a broad virus-monitoring system, the Global Viral forecasting initiative (globalviral.org). Google also participates in forecasting, in a surprising way: it is assumed that users of the Internet google “influenza” more frequently if it is spreading, “Google Flu Trends” has predicted the arrival of waves of influenza reliably for more than 100 cities in the US, weeks in advance. Very clever!
Ebola viruses had theoretically for a long time been considered a potential danger. However, in 24 outbreaks during 1976 and 2013 it never became epidemic, with about 1500 fatal cases in total. The outbreaks stayed local and small in West Africa. Yet they were frightening enough for people to flee; this sometimes even included health-care workers, who are at greatest risk because almost every second patient dies of hemorrhages, internal bleedings. People were thought to get so terribly sick, that spreading would be impossible. That changed in 2015. Mobility had increased and markets, schools and other crowds contributed more than before. The epidemic spread through three countries — Guinea, Sierra Leone, and Liberia — with 11,000 deaths reported out of almost 30,000 cases. There is a lack of hospitals, and the families are used to care for the patients, thus exposing themselves to the disease. The funeral traditions, with highly infectious corpses and body fluids were always blamed as a major source of contamination, but this may have changed in the meantime by educating people. There is no therapy except supply of fluid by infusions, which however requires sterile needles. During quarantine, which may last up to 30 days for the infection to manifest itself, people were afraid of attracting the disease there. Those who recover are resistant and could help the others. Even their blood was tested for the presence of potentially protective antibodies. Vaccines are now under investigation that were available in research institutions but too expensive to develop — except under new pressure. The virus is spread by bats and bushmeat, whereby the carriers do not have the disease. Carrier animals comprise also dogs, pigs and perhaps rodents, which can be found at many locations worldwide and may be infectious. Endogenization of Ebola sequences has been shown to be a characteristic property of healthy carriers and potential transmitters. Endogenization means the presence of viral sequences in the genome of the animals (see below).
Unexpected was the observation that Ebola viruses can hide in reservoirs like the human brain and caused severe encephalitis several months after recovery of a patient. This was observed for the first time with a nurse who was thought to have survived Ebola but came down 6 months later with viruses in her brain. Viruses can also last for four months in semen of men who have recovered. The newly developed vaccine may become important in the future.
Germany has a certain tradition with Ebola, since it is a close relative of the Marburg disease virus. The Behring company — close to Marburg, Germany — experienced some transmissions of the virus to animal keepers by imported apes in the 1960s. About 30 people became infected and one-third of them died. Then, 40 years later, the television host Gunther Jauch invited survivors and scientific specialists to take part in a talk show. First of all we had to learn to applaud loudly, and long enough, when the host entered the scene. Then there is always the discussion about bioterror-ism with this virus; however, since nobody has a protection or cure yet, this would be dangerous for the terrorists themselves and not attractive for bioterrorism. Based on the tradition of Marburg there is now a safety laboratory at the highest Biosafety Level (BSL4) for Marburg and Giessen Universities. Also, the Robert Koch Institute in Berlin opened a new high-containment laboratory in 2015. There are only about half a dozen such laboratories in the whole of Europe. So Germany has a big chance to contribute to knowledge about newly emerging dangerous pathogens and diseases. It is known that viruses rarely disappear completely, therefore we may have to be aware of viral “come-backs”.
SARS (severe acute respiratory syndrome) is a disease which also requires laboratories working at the highest safety level. In Hong Kong the coronavirus, which causes SARS, has escaped more than once from a research institute. Most surprising was the press release in 2014 that thirty containers with SARS samples had disappeared from the liquid nitrogen tank, the storage place for the samples in the safety laboratory in Paris. They were not declared