Jeffery Taubenberger - Transcript Summary

Jeffery TaubenbergerSenior Investigator in the Laboratory of Infectious Diseases at the US National Institute for Allergy and Infectious Diseases

Interview location: His office at the NIH campus in Bethesda, Maryland
Interview date: 27th November 2007

Key Themes: Attributes of a Pathologist, Life, death and the hereafterNew Technologies, Research versus Clinical Work

 

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Section 1

  • Growing up in a military family in the US.  Father was a German immigrant, specialising in computer science.  Jeffery inherited his father’s interest in “figuring out how things work”.
  • As a teenager started working in a lab of the National Cancer Institute in his school holidays:  “the systems that control biology are just fascinating to me.”
  • Got involved in the earliest stages of the molecular biology revolution.
  • Mentored by virologist William Drohan who was working on endogenous retroviruses – those that can “incorporate themselves into the genome of cells and become resident, become part of your DNA”.
  • Continued working at the lab throughout his first degree in science.  Encouraged by Drohan, he then did a medical degree: “medicine as a discipline was enormously interesting, intellectually interesting, and rewarding. ”Makes the point that rewards in medicine are more instant than in basic science: “science moves at a much slower pace generally.”
  • He feels that one of the advantages of being a pathologist is being “able to do both patient care-oriented work as well as basic science”.
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Section 2

  • Had another important mentor for his PhD, Jack Haar, whose interest was developmental immunology. “I ended up doing my training, doing immunology work but in an anatomy department from a person (Haar) who taught histology.”
  • This was a “good grounding” for pathology, although at the time he knew little of the profession. “It's this sort of magic thing that happens behind the scenes.”
  • Believes pathologists do themselves a disservice by remaining in the background, thus reinforcing the public perception that “pathologists are either doing autopsies or are forensic pathologists”.
  • Toyed with the idea of paediatrics, but realised “I wanted to have a very lab-centric career”.
  • Found a residency at the National Institutes of Health in Washington DC.
  • Worked at the NIH Clinical Center where all patients are involved in clinical research studies: “there was a much higher concentration of ‘interesting cases’… we saw every kind of sarcoma imaginable…”
  • Describes some of these ‘unusual’ cases.
  • Built on his PhD work with research into T cell development.
  • Another powerful mentor enters his life: Timothy O’Leary. “He showed me that my dream was possible – that you could still keep a hand in pathology, a hand in clinical medicine, but also do basic science.”
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Section 3

  • Tells of the importance and history of the Armed Forces Institute of Pathology and its world famous archive begun in the 1860s [and which since this interview has been closed down].
  • Recruited to AFIP by O’Leary in 1993 to lead a new molecular biology diagnostic unit. “He was looking to recruit people who had dual interests in anatomic pathology and molecular biology…it ended up being a fabulous niche.”
  • Describes technical challenge of extracting nucleic acids from fixed tissues, which most people didn’t believe was possible.
  • Having succeeded, they decided to apply the technology to breast cancer genetics to unpick the complexity of tumour progression. “Most molecular biologists who are not pathologists don’t see those complexities.”
  • Describes another unusual project that took advantage of the technology: research into dolphin viruses.
  • How an article describing an experiment with the preserved eyes of John Dalton, father of the modern atomic theory of matter, who died in the mid-1840s, gave him ideas about the potential riches in the AFIP archive. “It made me think, I’m sitting on a collection of millions of cases going back over 100 years – there must be something I can do that’s exciting like that.”
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Section 4

  • The “something” was the 1918 flu virus that killed millions of people worldwide.  Could he find samples of this in the AFIP archive? “This started literally as a hobby project…an idea that I thought was really interesting, but the chances of success seemed extremely remote.”
  • In 1918 no one knew influenza was a virus; they thought it was a bacterial infection.
  • Describes the extraordinary epidemiology of the 1918 flu outbreak. The speed and the scale of spread were phenomenal, but the real mystery was who it killed: “It had this enormous impact on the healthiest, most robust segment of the population.”
  • This was precisely the age of those fighting in World War I, and he discovered that at the AFIP they had autopsy tissue samples from 100 cases.
  • But he and his colleague Ann Reid had to develop new techniques to search for viral DNA in these ancient tissues. Describes the mixture of intense frustration and fascination that kept them going.
  • But “the amount of material we had was vanishingly tiny”. So they put a moratorium on using this tissue for anything else while they searched for other positive cases.
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Section 5

  • Relates the story of Swedish pathologist Johan Hultin’s discovery of 1918 flu victims preserved in Alaskan permafrost.
  • How Hultin returned to Alaska to exhume more bodies for AFIP project. “It became obvious within about a week of receiving the material that it was going to be positive.”
  • This enabled real progress:  “Using the frozen material it became possible to sequence the entire genome of the virus.”
  • Coincidentally, as they published their first paper in 1997, a three-year-old in Hong Kong died from bird flu. “This was the first time that there was evidence that a bird virus could actually infect a human and cause disease.” 
  • Since then the stories of the two influenzas have been “intertwined”.
  • All this had to be fitted in around his main service work, until “flu just kind of took over my life!”
  • Managed finally in 2005 to sequence the entire 1918 virus genome.  The search was then on to answer some vital questions: what made that virus so exceptionally lethal?  And “what mutations have to occur for a bird virus… to become transmissible in humans?”
  • Describes process of ‘reverse genetics’ by which the 1918 virus has been recreated.
  • Explores also the question of why 1918 virus killed young adults, and discusses various hypotheses, all of which remain unproven. “I don’t want to admit defeat – but it is certainly possible that...we might never be able to explain this.”
  • The search for clues to unanswered questions takes them back in time as well as to archives overseas. They also investigate ancient tissue samples from birds. “This kind of ‘viral archaeology’ is extraordinarily painful!  And very slow.” 
  • His work constantly challenges received wisdom about flu and its course: “It’s just an unbelievably complicated and dynamic system.”
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Section 6

  • Returns to discussion about the advantages of having a pathology training in pure science research.
  • Relates amusing anecdote about a child’s perspicacious definition of a pathologist.
  • Describes the extraordinary magnification powers of modern electron microscopes. “At 100,000 x magnification [you can see] viruses around a bacterium.”
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Section 7

  • His life outside the laboratory: “Music has been [my] other key passion…[but] it seemed more practical to have music as a hobby and science as a profession.”
  • A self-taught composer, he cites Alexander Borodin as his hero: “Borodin was a physician who did organic chemistry research and composed on the side.”
  • Science has had a profound influence on his view of life: “I fully believe there is a molecular basis for everything we see... So I have…faith that eventually science will be able to explain a lot of things.”

 

 

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