| I researched this story, of how it all came about, while preparing for a talk. Most of it is taken from the book Flu: The Story Of The Great Influenza Pandemic by Gina Kolata.
After the 1918 pandemic, scientists were worried that it would happen again. But they had little clue to work on, and no idea what organism was causing the disease. They were not able to isolate viruses till the 1930s.
Anyway, the story centers around 2 characters, Johan Hultin and Jeffery Taubenberger.
First, Johann Hultin. Who is he? He is a pathologist, originally from Sweden. The story started in 1940s, when Hultin was a medical student. His university had a program that allowed students to take time out to pursue other interests, and he decided to see America. He enrolled in a program in the University of Iowa to study influenza, but before that he and his wife spent the summer traveling, on a shoestring budget. They managed to visit every single state, finishing with Alaska. There they met a famous paleontologist Otto Geist who was doing research, who needed someone to help him with the digs, in return for a dorm room. They spent weeks traveling up and down Alaska, to remote places, seeing the wilderness, meeting Eskimos, digging and learning.
When the summer was over, Hultin went on to his program at the University of Iowa, which was only supposed to last a few months. As part of his studies, he had to work in a lab. They were using Bunsen burners, and often times they would need to time the experiment, to turn off the flame at the right time. The students were using alarm clocks, but as you can imagine, it's a bit annoying when so many alarm clocks keep going off, and it's easy to make mistakes. Finally, Hultin made a contraption, by somehow rigging the clock to the Bunsen burner, so that it would turn off at the right time.
One day, a famous virologist came to visit. He was taken around the lab, and someone showed him Hultin's alarm clock/Bunsen burner. The visitor was impressed. Afterwards, he was invited to join the visitor for lunch at the faculty dining room.
So here he was, among the dignitaries. They were talking about how so many mysteries have been solved in science. At the end of that conversation, the guest speaker said, well, there's just one more thing to do. If only someone can go to Alaska, to find that 1918 virus, we may be able to discover why the pandemic was so severe.
It was just one sentence, but it stuck with Hultin. He realized he was in a unique position to do precisely what was suggested, because of his time spent with Geist in Alaska. He obsessed about it for a long time. He wrote to Geist, who put him in contact with missionaries, who told him where he might be able to find mass graves in the permafrost. Eventually, he obtained a grant to go to Alaska to find the remains of victims, to try and recover the virus.
Come 1951, Hultin set off with a couple of friends. There were various adventures which I won't go into, including close-shave plane crashes. Plus a couple of digs that didn't lead to anything. Finally, they got to the Brevig mission (check out this map to see how remote it is, it's at the Bering Straits! http://www.mapquest.co.uk/mq/m... ) They found a mass grave, dug and found some bodies, and got some tissue samples.
Now, it was actually quite dangerous, cos by then the virus had been buried for 30+ years, and there's no telling what would have happened if they had released this in the world. There were certainly no BSL-whatever labs!! All they had was a thermos to put specimens in, and dry ice from fire extinguishers. Flights in those days required many stops, and at each stop they would go behind the airport building, get out the fire extinguisher, and add more dry ice to the thermos!!
But by the time they got to the lab, they were unable to recover any virus. Hultin was disappointed, but he never forgot the idea. He went on to become an MD and then a pathologist, but over the decades he was following the science, hoping one day someone would be able to do this again.
Enter Taubenberger.
JKT had known from a very young age that he wanted to be a scientist. He got a taste of high end science as a teenager when he got a summer job helping out at the NIH. He never forgot that and always wanted to go back to work there.
As I said, he was totally a genius. School was too easy. He started college around 15 or 16, got his first degree, went to med school, got his MD, PhD, decided to train as a pathologist etc.. Some time after that he started a job with the Armed Forces Institute of Pathology (AFIP).
This was an institution set up by the US military from Civil war days, when it was decreed that all soldiers that died would be autopsied and records kept, so that they would learn better how to protect their soldiers (cos even in those days, it was well known that more soldiers died of disease than of combat). Over time, the AFIP became a place where other scientists and clinicians would send tissue samples for diagnosis, when they had strange, unusual or difficult cases. The AFIP would deal with these consultations under 2 conditions: all referrals must have all clinical records, and the AFIP get to keep the tissue samples. As a result, they collected millions of tissue samples with accompanying clinical data, that became a treasure trove.
All this became very useful later.
So how did it start, this quest for the 1918 pandemic virus? In this lab where JKT was heading a small team, they used to hold journal clubs, where every 2 weeks someone from the group would present an interesting published journal article for discussion. This time it was JKT's turn, and he picked an article newly published in Science The chemistry of John Dalton's color blindness.
John Dalton was a scientist who lived in the 18th century. He discovered he was color blind, and wondered whether it was something in his eyes that was causing the problem, or something else. He instructed his students to remove his eyeballs and examine them when he died. They duly did that. They took his eyeballs, cut a small slit at the back of one of them, looked through it, and saw that the world was normal, thus proving the problem was not in the eyes. They also cut open one of the eyeballs, and proved that the vitreous was clear. After that, they put the other eyeball in formaldehyde. Luckily the science of preserving tissue had not changed much over centuries, so come 1990s as PCR techniques were invented, some scientists took the tissue from this preserved eyeball, and proved that John Dalton did indeed have the gene for color blindness.
Taubenberger thought this was an intriguing experiment, and presented that at the journal club.
After that, they got all excited, and started to wonder whether they could also do something as exciting. They realized they were sitting on a huge archive of tissue samples, and it was a great opportunity to do something useful with it.
Around the same time, their lab had been asked to identify the virus that was killing a lot of dolphins. They were sent these really horrid putrid samples of dolphin, and their lab, (especially Ann Reid, one of the technicians) were able to identify a new virus, the mobillivirus, that was killing dolphins. It was difficult forensic work, and they were getting better and better at it.
So, after the John Dalton discussion they went round and round wondering what would be a worthwhile project. They didn't want to just prove anything historical, rather to discover something that would be useful for the modern world.
Which was when they hit upon the idea of trying to reconstruct the 1918 pandemic virus.
So they sent off to the AFIP for records of soldiers that died in the pandemic. To cut a long story short, they basically looked for soldiers that had died within a very short time from symptom onset, cos there was more chance of recovering RNA fragments. They got several cases, worked on them for months and months, before they found the first piece of RNA that was from the 1918 virus for sure.
Anyhow, the long and short of that was, over time, they put together some of the segments. Their first paper was published in Science in 1997 Initial genetic characterization of the 1918 "Spanish" influenza virus.
This was ground breaking work. It was also being published at around the same time as the 1997 H5n1 outbreak in Hong Kong. For the first time, scientists realized that an avian virus may not need reassortment to cause a pandemic!! Imagine the horror and consternation!!
But, even so, their work was far from complete. They needed more samples to work on, as well as more work on existing samples. More importantly, all their samples were from the military, and it would be better if they could get verification from a totally different source, just so to verify that it was indeed the virus that caused the pandemic.
At this time, there were other scientists, including Robert Webster and John Oxford, who were planning on the same thing. They had a lot of funds, lots of publicity, and they were going to dig in the permafrost in Noway, but after years of planning, a big expedition and a lot of publicity, they didn't find what they wanted.
In the meantime, Hultin has been following all this with interest.
Some time after their first paper was published, JKT took a long vacation cos his wife was having a baby. When he got back, among the big pile of mail, was a letter written by someone called Johann Hultin, who very carefully laid out what he had done in 1951, and said he was sure he knew where they could find bodies in good conditions that would likely have the virus.
So they arranged to meet. By this time Hultin was 72 years old. But it seemed to Jeff that this guy had it all worked out, how he was going to go back and find the virus. Hultin said, he knew how difficult, how much red tape they would need to go through, if they went the official route. So he said, all it needed was $3000, which he could afford, and he offered to go on his own. If he succeeded, he would give Jeff the samples. If he failed, there wouldn't be any repercussions. Jeff of course was totally tickled, and asked him when he could do that. He was thinking maybe this guy could do it within the next few months or so.
Guess what? Hultin said, well, I can't go this week, cos I've got some prior engagements (he was finishing hand-building his own cabin!!) but I can go next week! ;-D
So this whole 'expedition' consisted of one 72 year old, with his own money, going alone on this quest. All that JKT contributed, was like a $5 bottle of preservative, cos he decided they weren't going to risk releasing the virus in the world. All they wanted was to get the RNA, and not the live virus.
Hultin duly went off, to the same old mission, found the elders, paid his respects, got their permission, and basically got some of the younger native Inuits to do the digging for him. After a few days, they found some bodies. Underneath the top pile, he found a rather fat woman whose tissues looked very fresh. He figured that the layers of fat would have provided extra insulation through the decades, so he took samples from her, plus a few others. But it was this female victim's tissues that yielded the most segments for analysis.
After he got all done, he re-buried the victims, built a couple of new wooden crosses to mark the grave, went home, and sent the samples to JKT. The rest, as they say, is history.
So, that is the story. I've told this in various forms to different people, but every time, I still stand in awe of both the many 'coincidences', and the vision and sheer will, of these 2 people, Johann Hultin and Jeffery Taubenberger. it is no exaggeration to say, the work of these 2 great men will benefit many generations to come. |
