Jurassic Park for real?
Mohammad A Zaman, MD writes form North Carolina
As their lungs filled ... the patients became short of breath and increasingly cyanotic. After gasping for several hours they became delirious and incontinent, and many died struggling to clear their airways of a blood-tinged froth that sometimes gushed from their nose and mouth. It was a dreadful business. --Isaac Starr, 3rd year medical student, University of Pennsylvania, 1918.That was a sobering observation by a medical student as the great Spanish Flu pandemic of 1918 swept through the United States killing about 675,000 lives during a short span of a little more than a year. Worldwide toll was estimated to be about 30 to 40 million. With a tripling of the world-population by now, a similar pandemic is poised to take at least100 million lives. According to experts, another pandemic of 1918-proportion is certain to occur. It is only a matter of when and not if. As Robert Webster (chairman of the Department of Virology and Molecular Biology at Saint Jude Children's Research Hospital in Memphis, Tennessee) maintains: "All the genes of all influenza viruses in the world are being maintained in aquatic birds, and periodically they transmit to other species ... The 1918 viruses are still being maintained in the bird reservoir. So even though these viruses are very ancient, they still have the capacity to evolve, to acquire new genes, new hosts. The potential is still there for the catastrophe of 1918 to happen again." Well, by 1918 virus was already discovered, but the flu virus remained elusive until 1933 when it was isolated by three British scientists (Smith, Andrews, and Laidlaw). Since then it remained a latent desire of researcher to see what exactly made that 1918-virus so deadly. Hultin was a microbiology doctorate student at University of Iowa. In 1950, he was captivated by a casual reference from a professor, that intact samples of 1918-strain can still be preserved in the bodies buried in Alaskan permafrost. Hungry for a dissertation project, off he traveled to Alaska. In June of 1951, he, two Iowa professors, and a paleontologist dug three feet of Alaskan permafrost and sampled four Inuit (Eskimo) bodies, all with the evidence of pulmonary hemorrhage (bleeding in the lungs), the hallmark of rapid death from influenza alone. Back in Iowa, high hope turned into ashes -- no live virus. And he could not garner further information from the dead virus for lack of right technology. Anyway, Hultin eventually got into medical school and became a pathologist. It is yet one more pathologist, armed with the cool new technologies of molecular biology, is needed to do the undone. Armed Forces Institute of Pathology (AFIP) in Rockville, Maryland boasts a staggering three million pieces of preserved human tissue -- dating back to 1862. In 1995 Jeffery Taubenberger, a pathologist at AFIP, driven by the same desire as Hultin, decided to try a rather biblical approach -- "scooping the life out of dead." After reviewing lung slides of seventy-eight cases of 1918-pandemic-death they looked for biologic remnant of Influenza A virus (a broad family of virus that includes the pandemic 1918-virus) in left-over lung tissues of ten cases. Out of ten only two came back positive for traces of Influenza A virus. One was a 21-year-old private who died in South Carolina. The other was a 30-year-old private who died in Upstate New York. And such was the kismet that they both died on the same day -- September 26, 1918. By adopting painstakingly detailed PCR (polymerase chain reaction) procedures involving many primers (from human, animal, and bird viruses) Taubenberger's laboratory triumphed in sequencing some genes. When Hultin, now retired and in his 80s, read the published description of the first identified gene segment -- the scientist in Hultin could retire no more. He teamed up with Taubengerger and again went back to Alaska to get a little more frozen tissue. On August 20, 1997 he dissected out lung tissues from a female victim of 1918 pandemic -- and this provided the total material to sequence all the eight genes of the deadly virus. Next chapter unfolded in New York City. With the sequenced genome information at hand, the researchers at Mount Sinai Medical School, by using a technique -- reverse genetics, bestowed life to Taubengergre's information in the form of "plasmid" (a small ring of DNA independent of the chromosome, but that can replicate). The Plasmids are then sent to the Centers for Disease Control and Prevention (CDC) in Atlanta, where Tumpey and his team inserted the plasmids in human kidney cells. Plasmids, once inside the cells, assembled themselves in live complete viral particles. So far, about 10 vials are created, each containing about 10 million infectious particles. This tremendous feat. Like the PCR technique of Kary Mullis, this is a defining event for life sciences and by inflection, for the entire human kind. It is sort of like playing God. It is Jurassic Park for real ...
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