Jeffery Taubenberger
Encyclopedia
Jeffery K. Taubenberger is a US-virologist
. Together with Ann Reid he was the first to sequence the genome of the influenza virus, which caused the 1918 pandemic of “Spanish flu
”.
with his parents after his father was posted at the Pentagon. He completed a combined M.D. (1986) and Ph.D. (1987) at the Medical College of Virginia in Richmond
in a course designed for students who wanted to follow a career in medical research. For his thesis he studied how stem cells of the bone marrow differentiate into the mature cells of the white blood cell system. In 1988 he began a training to become a pathologist
at the National Cancer Institute
of the National Institutes of Health
. In 1993 he was recruited to start a new lab at the Armed Forces Institute of Pathology
(AFIP) in order to apply the then current molecular techniques to the Institute's pathology work. After a year he was promoted to chief of the Division of Molecular Pathology. This included a research lab, where he was free to pursue questions of basic science.
The AFIP is one of more than a dozen tenant facilities located on the campus of the Walter Reed Army Medical Center
in the north-east of Washington, so it's director reports to the Surgeon General of the Army and not to the commander at Walter Reed. It had originally been established by a Civil War general as the Army Medical Museum in 1862 to combat “diseases of the battlefield”. Today, the pathology division acts most of its time as a consultant, giving second opinions
free of charge to the military and for a fee to civilian physicians. It handles tens of thousands of cases yearly on the understanding that it may keep a representative sample from any case. In this way it has collected tissue samples of some 2,600,000 people from surgical and autopsy material. They mostly take the form of dice-sized pieces of tissue fixed in formalin and embedded in wax blocks of paraffin
.
from dolphins who fell victim to a similar disease in the Mediterranean, but the samples from the first die-off were considered to be too degraded to isolate any viruses. Nevertheless, Taubenberger was asked to give it a try.
In the late 1980s Kary Mullis
had found a way to duplicate DNA
strands by a technique called Polymerase Chain Reaction
(PCR). Using this method molecular biologist Amy Krafft eventually managed to isolate fragments of morbillivirus RNA
. Here, the team perfected the techniques to extract RNA by PCR from highly degraded tissue (If you set out with an anti-sense RNA strand – as is the case with influenza or morbilliviruses – you first have to copy it back into a sense DNA strand).
The genome of the flu virus includes about 13,000 base pairs, which had decayed into pieces as small as 100 base pairs. In order to make PCR work, primers
have to be constructed, i.e. a short bit of DNA with mirror sequences of the sequence at the two end points of the fragment. They bind to the fragment, and with the help of a polymerase
bases are added between the primers to make a copy. The millions of copies of the gene segment are labelled with a radioactive probe as they are being made. They can then be separated on a thin gel by running an electric current across the gel. The radioactive labels create a black mark on a X-ray film which is put over the gel.
From serum tests of people who had witnessed the “Spanish” flu it was known that the virus had to belong to the H1N1 subtype. The team looked at all available sequences of influenza genes of this subtype to find out whether there were any parts of a given gene which were virtually identical. These were turned into primers. The first aim was to clarify whether any fragments of the flu virus were left in the tissue samples at all. The laboratory work was mostly done by Ann Reid and for more than a year she didn't find anything. On 23 July 1996 Amy Krafft, whom she had turned to for help, got a positive result on a case from the 1957 influenza pandemic. That success led Ann to test more cases from 1918, with an eventual positive signal from tissue belonging to an army private named Roscoe Vaughn, who had died on 26 September 1918 at Camp Jackson, South Carolina from a pneumonia of the left lung. His right lung seems to have been a few days behind in the progression of the disease, so that the virus was still present on this side when he died.
The sequence of a matrix gene didn't match any known sequence exactly, so that a contaminant could be ruled out. In all, Taubenberger's team isolated nine fragments of viral RNA from five different genes. They decided to send their first publication to Nature
, but the editors rejected the paper without even mailing it to experts for peer review. Science
was sceptical too at first, but eventually published what amounted to about 15 percent of the haemagglutinin gene as well as small fragments of the four other genes on 21 March 1997. By the summer of 1997 the team had the full sequence of the haemagglutinin. At this point the problem arose that they had used up half the tissue available from Private Roscoe Vaughn for this one gene. It seemed most probable that all ten genes of the 1918 virus couldn't be sequenced from the available material. (In September 1997 tissue from a private called James Downs, who succumbed to influenza at Camp Upton, New York, turned out positive as well.)
. In 1951 the pathologist had already tried to isolate the 1918 influenza virus from victims, who had been buried in the Alaskan permafrost. At what was called Teller Mission
at the time, he had unearthed bodies but had failed to find any live viruses. He never finished his thesis. Now, with PCR available, he realized the time had come to try again.
In July 1997 he offered Jeffery Taubenberger to return to what is now Brevig, Alaska. Again he received permission to dig for victims of the 1918 “Spanish flu”, and this time he unearthed the remains of an obese woman, maybe thirty years old, whom he christened “Lucy”. The fat had protected her lungs from decay, and he took both of them. It turned out that in Lucy's case the fragments were even smaller – around 100 base pairs as compared to 150 in the case of Vaughn and Downs – but now there was enough material to sequence the complete 1918 virus many times over. Taubenberger and Reid managed to generate a complete haemagglutinin sequence to confirm the one they had got from Vaughn. In all three cases – Vaughn, Downs, and “Lucy” – the 1,800 base pairs differed only in a few places. This was the best confirmation that the sequence of the 1918 haemagglutinin had actually been found.
In a series of papers the team published the complete genome
of the 1918 influenza virus. The work was funded by the Veteran's Administration and the Department of Defense
. The completion of the genome in 2005 was numbered among the “breakthroughs of the year” by Science and was elected as "paper of the year" by Lancet
.
To Carter's surprise Taubenberger agreed to read the hefty manuscript despite his workload. But it was not the scientific aspects of the story that Taubenberger responded to most strongly, it was the naval scenes set in the Pacific. Taubenberger thought that there were unresolved plot lines involving the naval carrier task force that played a central role in the escalating international conflicts in the book, later published as Ninth Day Of Creation. Carter relented and added a new section to the book involving a battle scene between a U.S. naval aircraft carrier and an advanced Chinese nuclear attack submarine.
Taubenberger then agreed to be interviewed by Carter about his ongoing work with the sequencing of the 1918 strain. Where was the research likely to lead, would the 1918 strain ultimately be reconstructed, and did Taubenberger have any reservations about publishing the gene sequences for a killer strain of flu? The interview was conducted and placed online in March 1998 as An Interview With Dr. Jeffery Taubenberger.
In his free time Taubenberger is a woodwind player – oboe, English horn, clarinet; but his main interest has mainly been composition. In 1981 he created his first opus, the operetta The Wayward Prince, lyrics with Andrew Russo. The overture was performed by the George Mason University Orchestra in July 1982 with Taubenberger as conductor. In 1984 he wrote a "Symphony in D minor", from which he performed two movements with the Richmond Community Orchestra in the same year with Taubenberger conducting. Further work includes two lieder for tenor and piano on poems by Goethe (1985-6), two woodwind quintets (1987& 1988), and a string quartet in G major (1990), which was performed the same year by Columbia String Ensemble and in 1995 again by the Gallery Quartet. Next came eight two-part inventions for solo piano (1994), a string quartet in E minor (1997), and "Daydreams", a symphonic tone poem for large orchestra (2000). He is currently working on a symphony in C major (since 2005) and a string quartet in B minor (2007). With work and family obligations extremely little time is left for composing, though.
Jeffery Taubenberger is married and has two children. He is currently working for the National Institutes of Health
.
Dr. Taubenberger is a second cousin to former Philadelphia Mayoral candidate Al Taubenberger
.
Virology
Virology is the study of viruses and virus-like agents: their structure, classification and evolution, their ways to infect and exploit cells for virus reproduction, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy...
. Together with Ann Reid he was the first to sequence the genome of the influenza virus, which caused the 1918 pandemic of “Spanish flu
Spanish flu
The 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...
”.
Training
Taubenberger was born in Germany, the third son of an Army officer. When he was nine he moved to a suburb of Washington, D.C.Washington, D.C.
Washington, D.C., formally the District of Columbia and commonly referred to as Washington, "the District", or simply D.C., is the capital of the United States. On July 16, 1790, the United States Congress approved the creation of a permanent national capital as permitted by the U.S. Constitution....
with his parents after his father was posted at the Pentagon. He completed a combined M.D. (1986) and Ph.D. (1987) at the Medical College of Virginia in Richmond
Richmond, Virginia
Richmond is the capital of the Commonwealth of Virginia, in the United States. It is an independent city and not part of any county. Richmond is the center of the Richmond Metropolitan Statistical Area and the Greater Richmond area...
in a course designed for students who wanted to follow a career in medical research. For his thesis he studied how stem cells of the bone marrow differentiate into the mature cells of the white blood cell system. In 1988 he began a training to become a pathologist
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
at the National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
of the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
. In 1993 he was recruited to start a new lab at the Armed Forces Institute of Pathology
Armed Forces Institute of Pathology
The Armed Forces Institute of Pathology was a US government institution concerned with diagnostic consultation, education, and research in the medical specialty of pathology. It was founded in 1862 as the Army Medical Museum and was located in Washington, DC on the grounds of the Walter Reed Army...
(AFIP) in order to apply the then current molecular techniques to the Institute's pathology work. After a year he was promoted to chief of the Division of Molecular Pathology. This included a research lab, where he was free to pursue questions of basic science.
The AFIP is one of more than a dozen tenant facilities located on the campus of the Walter Reed Army Medical Center
Walter Reed Army Medical Center
The Walter Reed Army Medical Center was the United States Army's flagship medical center until 2011. Located on 113 acres in Washington, D.C., it served more than 150,000 active and retired personnel from all branches of the military...
in the north-east of Washington, so it's director reports to the Surgeon General of the Army and not to the commander at Walter Reed. It had originally been established by a Civil War general as the Army Medical Museum in 1862 to combat “diseases of the battlefield”. Today, the pathology division acts most of its time as a consultant, giving second opinions
Second opinion (medicine)
A second opinion is a visit to a physician other than the one a patient has previously been seeing in order to get a differing point-of-view. Second opinions may be sought by a patient under the following circumstances:*Physician recommends surgery....
free of charge to the military and for a fee to civilian physicians. It handles tens of thousands of cases yearly on the understanding that it may keep a representative sample from any case. In this way it has collected tissue samples of some 2,600,000 people from surgical and autopsy material. They mostly take the form of dice-sized pieces of tissue fixed in formalin and embedded in wax blocks of paraffin
Paraffin
In chemistry, paraffin is a term that can be used synonymously with "alkane", indicating hydrocarbons with the general formula CnH2n+2. Paraffin wax refers to a mixture of alkanes that falls within the 20 ≤ n ≤ 40 range; they are found in the solid state at room temperature and begin to enter the...
.
A dolphin disease
The AFIP also works on veterinary diseases. In the winter of 1987 half the population of bottlenosed dolphins along the Atlantic seaboard of the United States died of a mysterious disease. From samples taken from washed up dolphins a veterinary pathologist at the AFIP suspected a viral infection. In 1991 Albert Osterhaus managed to isolate a morbillivirusMorbillivirus
Morbillivirus is a genus belonging to the Paramyxoviridae family of viruses in the order Mononegavirales. Many members of the genus cause diseases, such as rinderpest and measles, and are highly infectious.- External links :* *...
from dolphins who fell victim to a similar disease in the Mediterranean, but the samples from the first die-off were considered to be too degraded to isolate any viruses. Nevertheless, Taubenberger was asked to give it a try.
In the late 1980s Kary Mullis
Kary Mullis
Kary Banks Mullis is a Nobel Prize winning American biochemist, author, and lecturer. In recognition of his improvement of the polymerase chain reaction technique, he shared the 1993 Nobel Prize in Chemistry with Michael Smith and earned the Japan Prize in the same year. The process was first...
had found a way to duplicate DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
strands by a technique called Polymerase Chain Reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
(PCR). Using this method molecular biologist Amy Krafft eventually managed to isolate fragments of morbillivirus RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
. Here, the team perfected the techniques to extract RNA by PCR from highly degraded tissue (If you set out with an anti-sense RNA strand – as is the case with influenza or morbilliviruses – you first have to copy it back into a sense DNA strand).
In search of the 1918 “Spanish” influenza virus
Fearing government cutbacks Taubenberger looked for an application of PCR to the immense warehouse of tissue samples at the AFIP. He eventually settled on finding remains of the flu virus, which caused the 1918 “Spanish flu”. The warehouse stored wax blocks from seventy-seven soldiers, who had died in the pandemic. Taubenberger's team searched for samples of victims who had succumbed to the initial viral infection and not the subsequent bacterial pneumonia. Seven samples seemed promising.The genome of the flu virus includes about 13,000 base pairs, which had decayed into pieces as small as 100 base pairs. In order to make PCR work, primers
Primer (molecular biology)
A primer is a strand of nucleic acid that serves as a starting point for DNA synthesis. They are required for DNA replication because the enzymes that catalyze this process, DNA polymerases, can only add new nucleotides to an existing strand of DNA...
have to be constructed, i.e. a short bit of DNA with mirror sequences of the sequence at the two end points of the fragment. They bind to the fragment, and with the help of a polymerase
Polymerase
A polymerase is an enzyme whose central function is associated with polymers of nucleic acids such as RNA and DNA.The primary function of a polymerase is the polymerization of new DNA or RNA against an existing DNA or RNA template in the processes of replication and transcription...
bases are added between the primers to make a copy. The millions of copies of the gene segment are labelled with a radioactive probe as they are being made. They can then be separated on a thin gel by running an electric current across the gel. The radioactive labels create a black mark on a X-ray film which is put over the gel.
From serum tests of people who had witnessed the “Spanish” flu it was known that the virus had to belong to the H1N1 subtype. The team looked at all available sequences of influenza genes of this subtype to find out whether there were any parts of a given gene which were virtually identical. These were turned into primers. The first aim was to clarify whether any fragments of the flu virus were left in the tissue samples at all. The laboratory work was mostly done by Ann Reid and for more than a year she didn't find anything. On 23 July 1996 Amy Krafft, whom she had turned to for help, got a positive result on a case from the 1957 influenza pandemic. That success led Ann to test more cases from 1918, with an eventual positive signal from tissue belonging to an army private named Roscoe Vaughn, who had died on 26 September 1918 at Camp Jackson, South Carolina from a pneumonia of the left lung. His right lung seems to have been a few days behind in the progression of the disease, so that the virus was still present on this side when he died.
The sequence of a matrix gene didn't match any known sequence exactly, so that a contaminant could be ruled out. In all, Taubenberger's team isolated nine fragments of viral RNA from five different genes. They decided to send their first publication to Nature
Nature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...
, but the editors rejected the paper without even mailing it to experts for peer review. Science
Science (journal)
Science is the academic journal of the American Association for the Advancement of Science and is one of the world's top scientific journals....
was sceptical too at first, but eventually published what amounted to about 15 percent of the haemagglutinin gene as well as small fragments of the four other genes on 21 March 1997. By the summer of 1997 the team had the full sequence of the haemagglutinin. At this point the problem arose that they had used up half the tissue available from Private Roscoe Vaughn for this one gene. It seemed most probable that all ten genes of the 1918 virus couldn't be sequenced from the available material. (In September 1997 tissue from a private called James Downs, who succumbed to influenza at Camp Upton, New York, turned out positive as well.)
Johan Hultin comes in
The March paper in Science was also read by Johan HultinJohan Hultin
Johan Hultin is a retired pathologist known for discovering tissues containing traces of the 1918 influenza virus that killed millions worldwide, and for this he has been described as the "Indiana Jones of the scientific set."-Biography:...
. In 1951 the pathologist had already tried to isolate the 1918 influenza virus from victims, who had been buried in the Alaskan permafrost. At what was called Teller Mission
Brevig Mission, Alaska
Brevig Mission is a city in Nome Census Area, Alaska. The population was 276 at the 2000 census.-Geography:Brevig Mission is located at ....
at the time, he had unearthed bodies but had failed to find any live viruses. He never finished his thesis. Now, with PCR available, he realized the time had come to try again.
In July 1997 he offered Jeffery Taubenberger to return to what is now Brevig, Alaska. Again he received permission to dig for victims of the 1918 “Spanish flu”, and this time he unearthed the remains of an obese woman, maybe thirty years old, whom he christened “Lucy”. The fat had protected her lungs from decay, and he took both of them. It turned out that in Lucy's case the fragments were even smaller – around 100 base pairs as compared to 150 in the case of Vaughn and Downs – but now there was enough material to sequence the complete 1918 virus many times over. Taubenberger and Reid managed to generate a complete haemagglutinin sequence to confirm the one they had got from Vaughn. In all three cases – Vaughn, Downs, and “Lucy” – the 1,800 base pairs differed only in a few places. This was the best confirmation that the sequence of the 1918 haemagglutinin had actually been found.
In a series of papers the team published the complete genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
of the 1918 influenza virus. The work was funded by the Veteran's Administration and the Department of Defense
United States Department of Defense
The United States Department of Defense is the U.S...
. The completion of the genome in 2005 was numbered among the “breakthroughs of the year” by Science and was elected as "paper of the year" by Lancet
The Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...
.
Stranger Than Fiction
Sometime in early 1998 Taubenberger received a manuscript from a novelist who had recently contacted him. Dr. Stephen Carter had discovered Taubenberger's work through the paper in Science, and he wanted to know whether Taubenberger would be interested in reading the first draft of a novel in which an ambitious vaccine biotechnology company known as Immunological Technologies resurrects the 1918 Spanish Flu virus in secrecy in its state-of-the-art facility in San Diego, California. The book had taken almost three years to research and write, and Carter was looking for someone to critique the scientific elements. Jeffery Taubenberger seemed the perfect candidate.To Carter's surprise Taubenberger agreed to read the hefty manuscript despite his workload. But it was not the scientific aspects of the story that Taubenberger responded to most strongly, it was the naval scenes set in the Pacific. Taubenberger thought that there were unresolved plot lines involving the naval carrier task force that played a central role in the escalating international conflicts in the book, later published as Ninth Day Of Creation. Carter relented and added a new section to the book involving a battle scene between a U.S. naval aircraft carrier and an advanced Chinese nuclear attack submarine.
Taubenberger then agreed to be interviewed by Carter about his ongoing work with the sequencing of the 1918 strain. Where was the research likely to lead, would the 1918 strain ultimately be reconstructed, and did Taubenberger have any reservations about publishing the gene sequences for a killer strain of flu? The interview was conducted and placed online in March 1998 as An Interview With Dr. Jeffery Taubenberger.
Personal interests
Jeffery Karl Taubenberger was born in the US Army hospital in Landstuhl but to a German father and US-born mother. His father Heinz Karl Taubenberger was a well-known figure skater in his youth, and was Germany‘s junior champion several times both in pair-skating and men's singles in the late 1940s and early 1950s.In his free time Taubenberger is a woodwind player – oboe, English horn, clarinet; but his main interest has mainly been composition. In 1981 he created his first opus, the operetta The Wayward Prince, lyrics with Andrew Russo. The overture was performed by the George Mason University Orchestra in July 1982 with Taubenberger as conductor. In 1984 he wrote a "Symphony in D minor", from which he performed two movements with the Richmond Community Orchestra in the same year with Taubenberger conducting. Further work includes two lieder for tenor and piano on poems by Goethe (1985-6), two woodwind quintets (1987& 1988), and a string quartet in G major (1990), which was performed the same year by Columbia String Ensemble and in 1995 again by the Gallery Quartet. Next came eight two-part inventions for solo piano (1994), a string quartet in E minor (1997), and "Daydreams", a symphonic tone poem for large orchestra (2000). He is currently working on a symphony in C major (since 2005) and a string quartet in B minor (2007). With work and family obligations extremely little time is left for composing, though.
Jeffery Taubenberger is married and has two children. He is currently working for the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
.
Dr. Taubenberger is a second cousin to former Philadelphia Mayoral candidate Al Taubenberger
Al Taubenberger
Alfred Wilhelm "Al" Taubenberger is the president of the Greater Northeast Philadelphia Chamber of Commerce and president of the Burholme Civic Association and Town Watch. He is also a Republican politician from Northeast Philadelphia. He has run for office three times, losing each time...
.