Resurrecting the zombie killer flu virus

The steady advances in the new science of synthetic biology have been brought to the attention of media and the public through the revelation of the whole gene complement of the extinct killer influenza strain that caused the 1918 influenza pandemic.

This marks another milestone in design of life, by man through the use of molecular tools developed over the last three decades, and is a first tentative step on the way to fulfil the prophecies of the resurrection of extinct species depicted in so many science fiction novel and movies. It is a truly groundbreaking scientific achievement but it also raises questions about the wisdom of resurrecting what has been labelled “potentially the most effective bioweapon now known to mankind”.

The 1918 virus - which only contains eight genes absolutely required for its replication and its lethal interactions with its host - killed 20 million people in a matter of months and then vanished off the surface of this planet, until 1995, when two independent sources of preserved lung tissues from flu victims were tracked down. Intriguingly fragments of the virus nucleic acid were found to have survived in deep frozen bodies of victims of the flu entombed in the permafrost of the high Arctic and also in preserved lung specimens for more than 80 years.

For Johan Hultin, the retired Swedish born US pathologist who retrieved the preserved lung tissue from the body of an Inuit woman, it also meant the successful culmination of a lifelong quest for the identification of this killer disease. Dr Hultin’s quest began more than 40 years earlier when, as a young researcher in 1951, he tracked down the preserved bodies of the victims of the 1918 flu at Brevig Lutheran Mission in Alaska. Dr Hultin was looking for the best potential source of live virus.

However, the virus was already extinct in 1951, and the mapping and resurrection of the virus had to await the discovery of the central role played by nucleic acids in life, and in death, made by Watson and Crick in 1953. Their finding gave rise to the study of molecular biology in the 1970s which in turn led to the new era of synthetic biology in the mid-1990s.

It was in 1997, 10 years after Dr Hultin had retired, that he learned of the work of a new breed of molecular pathologist working for the US Armed Forces Institute of Pathology. They were using all the latest molecular biology technologies in an effort to map the 1918 virus. However they faced a shortage of reliable sources for virus fragments. They had run out of the minute specimens of 80-year-old wax-embedded lung biopsies collected from diseased US soldiers.

Dr Hultin returned to the Inuit mass grave at Brevig, Alaska, and collected some preserved lung tissue containing the fragments of viral nucleic acid required for the continuation of the painstaking molecular detective work of identifying, multiplying and assembling together the thousands of overlapping genetic jigsaw pieces into an intact infective virus genome.

The importance of this quest to increase the knowledge of this ancient killer strain of influenza has only begun to be understood, and it will take some time to follow up the information that is present in the genes of the 1918 killer virus. The most pressing issue being how it compares with the H5N1 avian flu virus: the bird flu that is causing so much concern among scientists and policy-makers all over the world today.

However, the initial analysis of the 1918 flu virus genes reveals it is a very different beast to the more recent 1957 and 1968 human flu sequences which were assembled from largely human flu virus strains with a few defined segments of avian influenza sequences included by recombination between human and avian flu strains.

The 1918 virus is the most bird-like of all mammalian flu viruses and most critically shares some, but not all, of the critical changes with the H5N1 strain of bird flu that since 1997 has affected mainly poultry in many parts of Asia but occasionally has infected humans.

How virulent is the resurrected 1918 flu compared to a “normal” human contemporary flu strain?

In lung tissue of mice the resurrected killer flu produced 39,000 times more virus particles four days after controlled infection than the human flu strain. The resurrected virus showed 100 per cent lethality within six days after infection while none of the mice infected with the human flu strain died. The lethality of the synthetic virus surprised the researchers that performed the experiment, and is spurning them on to create more combinations of the synthetic virus with and without certain mutations in all combinations, to see which are the most important for virulence in mice and in cultured human lung cells.

But will the public and the politicians allow further tinkering with nature in the present climate of fear and distrust of new technologies?

To alleviate public fears about scientists playing God and the risks associated with resurrecting a killer flu, the US national body that oversees biosecurity policy asked the authors of the analysis of the 1918 flu virus to insert a statement that explained the importance of the work to public health and that it was conducted safely.

The scientists continuing the work readily admit there can be no 100 per cent guarantee of safety. However the work is directed at understanding what happened in nature and how to prevent another pandemic. They argue that in this case the bio-terrorist is nature not the intelligent designer.