Jeffery Taubenberger

Jeffery Karl Taubenberger (* 1961 in Landstuhl , Germany ) is an American virologist . Together with Ann Reid , he was the first to sequence the genome of the influenza virus that triggered the “ Spanish flu ” of 1918. The publication of the genome was named one of the most important breakthroughs of the year by the journal Science in late 2005 and was voted study of the year by the medical journal The Lancet ("2005 Paper of the Year").

education

Jeffery Taubenberger was born in Germany as the third son of an officer in the US Army. He and his parents moved to the suburbs of Washington, DC when he was nine after his father was transferred to the United States Department of Defense . Taubenberger completed a combined training as a doctor ( MD , 1986) and natural scientist ( Ph. D. , 1987) at the Medical College of Virginia in Richmond in a course for students who wanted to go into basic medical research. In his doctoral thesis, he examined how the stem cells of the bone marrow differentiate into mature, white blood cells . In 1988 he began training as a pathologist at the National Cancer Institute of the National Institutes of Health . In 1993 he received his first job at the Pathology Institute of the US Armed Forces ( Armed Forces Institute of Pathology, AFIP ). There he was supposed to set up a new laboratory in order to introduce the then common molecular methods into the pathological work of the institute. After a year he was appointed head of the Department of Molecular Pathology. This included a research laboratory in which he could pursue basic research questions .

The AFIP is part of the Walter Reed Army Medical Center in northeast Washington. It was originally created by Abraham Lincoln in 1862 to combat "diseases of the battlefield". Today the pathology department serves primarily as a consultation service, where a second opinion can be obtained free of charge from military doctors and for a fee from civilian doctors. Tens of thousands of inquiries are processed annually, with the assumption that a representative sample of each case may be retained. Over time, the AFIP has collected tissue samples from around 2,600,000 people from surgical and autopsy material. Mostly it is FFPE , i.e. pieces of tissue the size of a cube that have been fixed with formalin and embedded in blocks of paraffin .

A dolphin sickness

The institute is also active in veterinary medicine . In the winter of 1987, about half of the bottlenose dolphins on the Atlantic coast of the United States died of a puzzling disease. An AFIP veterinary pathologist concluded that there was a viral infection from samples from driven animals. In 1991 Albert Osterhaus succeeded in isolating a morbillivirus from dolphins that had fallen victim to a similar disease in the Mediterranean. The samples from the first epidemic were considered too bad to be able to find viruses; Taubenberger was asked anyway to try it.

In the late 1980s, Kary Mullis had found a way to amplify DNA using a technique called the polymerase chain reaction (PCR). With this method, the molecular biologist Amy Krafft finally succeeded in isolating fragments of morbillivirus RNA . On that occasion, the team perfected the techniques to extract RNA from highly decomposed tissue using PCR. (If you start with an opposite strand of RNA, as is the case with influenza or morbilliviruses, you must first copy them into a strand of DNA in the same direction).

In search of the causative agent of the "Spanish flu" of 1918

Since Taubenberger feared funding cuts, he looked in 1995 for an application of PCR at his workplace, the immense storage of tissue samples in the "Armed Forces Institute of Pathology (AFIP)" in Washington, where millions of tissue samples are stored, many of which are not yet examined, let alone evaluated. He finally decided to look for the remains of the influenza virus that caused the 1918 Spanish flu. The camp contained paraffin blocks from a total of 77 soldiers who had died in the pandemic. Taubenberger's team looked for samples from the dead who had fallen victim to the original viral infection rather than the subsequent bacterial pneumonia. Seven samples looked promising.

The genome of the influenza virus comprises around 13,000 base pairs, which had broken up into pieces of around 100 base pairs in length in the tissue samples. In order to be able to use PCR, primers first had to be constructed, i.e. short pieces of DNA with the sequence in mirror image to the two ends of the fragment. They bind to the fragment and a polymerase is used to replenish the bases between the primers to make a copy. The resulting millions of gene copies are radioactively marked in the process. They can then be separated on a thin gel by flowing an electric current through the gel. The radioactive labeled fragments ultimately leave a blackening on an X-ray film that is placed over the gel.

It was known from serum tests of people who had lived at the time of the "Spanish flu" that the virus must belong to the H1N1 subtype . The team first looked at all of the available sequences of influenza viruses of this subtype to see if any sections of a particular gene matched at virtually all bases. These sections were converted into primers. The first goal was to determine whether fragments of influenza viruses were actually present in the tissue samples. Most of the lab work was done by Ann Reid , and for over a year she found nothing at all. On July 23, 1996, Amy Krafft, whom she had turned to for help, succeeded in providing initial evidence. The tissue belonged to a corporal named Roscoe Vaugh, who died on September 26, 1918 in Camp Jackson, South Carolina , of inflammation of the left lung. The right wing appears to have lagged a few days behind as the disease progressed, so the virus was still present when he died.

The sequence - it was a matrix gene - did not exactly match any known sequence, so that contamination could be ruled out. Taubenberger's team isolated a total of nine fragments of viral RNA from five different genes. They offered the first publication to Nature , but the editors returned it without ever having given it to reviewers. Science was also skeptical at first, but finally published the nucleotide sequences on March 21, 1997, which together corresponded to 15 percent of the hemagglutinin gene and a few small fragments from four other genes. By the summer of 1997, the team had worked out the full sequence of the hemagglutinin. At this point the problem arose that half of the available material from Roscoe Vaughn for that one gene had been used up. It was foreseeable that all ten genes of the 1918 virus could not be sequenced from the available material. (In September 1997, tissue from a private named James Downs, who died of influenza in Camp Upton, New York, in 1918, was also found positive.)

Johan Hultin gets in

The March article in Science had also been read by Johan Hultin . As early as 1951, the pathologist tried to recover the "Spanish flu" virus from victims buried in the permafrost on the Seward Peninsula, Alaska . In a place called Teller Mission at the time , he had dug up bodies, from which he took samples from the lungs to his laboratory in Iowa. He had used all the research methods known at the time, but found no active viruses. He submitted his work together with Albert P. McKee in 1951 to the University of Iowa. Well, in the age of PCR, he realized he could try again.

In July 1997 he offered Jeffery Taubenberger to return to Brevig - as the place was now called - in Alaska. He was again given permission to dig for victims of the "Spanish flu" and this time he came across the remains of an overweight woman, around 30 years old, whom he named "Lucy". The body fat had kept the lungs from rotting , and Hultin removed both lungs, which he sent to Taubenberger in Washington.

It turned out that in the case of "Lucy" the virus fragments were even smaller - about 100 base pairs compared to 150 in the case of Vaugh and Downs - but now there was enough material to completely sequence the virus multiple times. Taubenberger and Reid succeeded in creating a complete hemagglutinin sequence and thus confirming the results obtained at Vaughn. In all three cases - Vaughn, Downs and "Lucy" - the 1,800 base pairs differed only in a few places. This was the best possible confirmation that the 1918 hemagglutinin sequence had actually been found.

In a series of articles, the team published the entire genome of the influenza virus of 1918. The work was supported by Department of Veterans Affairs ( Veteran's Administration ) and the Ministry of Defense funded the United States. The publication of the genome was named one of the most important breakthroughs of the year by the journal Science in late 2005 and was voted study of the year by the medical journal The Lancet ("2005 Paper of the Year").

After almost ten years of work, Taubenberger and his colleagues succeeded in isolating gene fragments of the pathogen and then putting them together like a puzzle to form a virus genome. This is now protected in the high-security laboratories of the US Disease Protection Agency.

Personal

Jeffery Taubenberger was born in the US Army Hospital in Landstuhl as the son of his American mother and his German father. His father, Heinz Karl Taubenberger, was already a computer expert and a successful roller skater at that time, who in the late 1940s and early 1950s repeatedly won the title of German junior roller skate champion in both individual and pair skating.

In his spare Jeffery Taubenberger various plays woodwind instruments , especially the oboe , English horn and clarinet . His main interest, however, is composing . In 1981 he wrote his first work, the operetta The Wayward Prince ("The Moody Prince"), the text together with Andrew Russo, whose overture Taubenberger premiered in July 1982 as conductor of the George Mason University Orchestra . In 1984 he wrote the Symphony in D minor , which he performed as conductor of the Richmond Community Orchestra that year. Other works were u. a. Songs for tenor and piano based on poems by Goethe (1985/86), two quintets for woodwinds (1987/88) and a string quartet in G minor (1990) performed by the Columbia String Ensemble in the same year and again by the Gallery Quartet in 1995 has been. Various fantasies for solo piano (1994), a string quartet in E minor (1997) and “Daydreams”, a symphonic poem for large orchestra (2000) followed. The symphony in C major and a string quartet in B minor have been in progress since 2005 and 2007, respectively, but their completion suffers from increased professional and family obligations.

Jeffery Taubenberger is married and has two children. Today he works for the National Institutes of Health .

literature

• Pete Davies: Catching Cold. Penguin, 1999, pp. 194-259. ISBN 0-718-14349-3
• Gina Kolata: Flu. Macmillan, 2000, pp. 187-218. ISBN 0-333-75105-1

Individual evidence

1. ↑ Jeffery K. Taubenberger, Ann H. Reid, Amy E. Krafft, Karen E. Bijwaard, Thomas G. Fanning: Initial Genetic Characterization of the 1918 'Spanish' Influenza Virus. In: Science , Vol. 275, 1997, pp. 1793-1796
2. ↑ Johan v. Hultin and Albert P. McKee: Fixation of "Neutralized" Influenza Virus by Susceptoble Cells. In: Journal of Bacteriology. Volume 63, No. 4, 1952, pp. 437-447, PMC 169294 (free full text).
3. ↑ Photo Hultin in: Bird Flu - A Virus of our own hatching
4. ↑ UI alum honored at spring commencement for helping decipher 'Spanish flu' causes. ( October 9, 2009 memento on the Internet Archive ) University of Iowa Carver College of Medicine, May 2009
5. ↑ Ann H. Reid et al .: Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene. In: PNAS . Volume 96, No. 4, 1999, pp. 1651-1656, doi: 10.1073 / pnas.96.4.1651
   Ann H. Reid et al .: Characterization of the 1918 “Spanish” influenza virus neuraminidase gene. In: PNAS. Volume 97, No. 12, 2000, pp. 6785-6790, doi: 10.1073 / pnas.100140097
   Christopher F. Basler et al .: Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS recover. In: PNAS. Volume 98, No. 5, 2001, pp. 2746-2751, doi: 10.1073 / pnas.031575198
   Ann H. Reid et al .: Characterization of the 1918 'Spanish' influenza virus matrix gene segment. In: Journal of Virology. Volume 76, No. 21, 2002, pp. 10717-10723, doi: 10.1128 / JVI.76.21.10717-10723
   Ann H. Reid et al .: Novel origin of the 1918 pandemic influenza virus nucleoprotein gene. In: Journal of Virology. Volume 78, No. 22, 2004, pp. 12462-12470, doi: 10.1128 / JVI.78.22.12462-12470
   Jeffery K. Taubenberger el al .: Characterization of the 1918 influenza polymerase gene. In: Nature . Volume 437, 2005, pp. 889-893, doi: 10.1038 / nature04230