Microbiology and Immunology

The Institute for Genomic Research (TIGR) WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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TETRACYCLINES•seeANTIBIOTICS

THEINSTITUTE FORGENOMIC

RThe Institute for Genomic Research (TIGR)ESEARCH(TIGR)

The Institute for Genomic Research (TIGR) is a non-profit

research institute located in Rockville, Maryland. The primary

interest of TIGR is the sequencing of the genomes and the sub-

sequent analysis of the sequences in prokaryotic and eukary-

otic organisms. J. Craig Venter founded TIGR in 1992 and

acted as president until 1998. As of 2002, Venter remained as

chairman of the board of trustees for TIGR.

TIGR scientists sequenced the genomes of a number of

viruses, bacteria, archaebacteria, plants, animals, fungi, and

protozoa. The sequences of the bacteria Haemophilus influen-

zaeand Mycoplasma genitalium, published in 1996, were the

first complete bacterial DNAsequences ever accomplished. In

1996, the complete sequence of an archaebacteria

(Methanococcus jannaschii) was published. Since that time,

TIGR has sequenced 19 other bacterial genomes. These

include the genomes of the bacteria that cause cholera, tuber-

culosis, meningitis, syphilis, Lyme disease, and stomach

ulcers. In addition, TIGR sequenced the genome of the proto-

zoan parasite Plasmodium falciparum, the cause of malaria.

The genesis of TIGR was the automation of the DNA

sequencing process. This advance made the idea of large-scale

sequencing efforts tangible. At about the same time, Venter

was the leader of a section at the National Institute of

Neurological Disorders and Stroke. He developed a technique

called shotgun cloning that could efficiently and rapidly

sequence large stretches of DNA. Use of the bacterial artificial

chromosomesin a sequencing strategy that had been devel-

oped by Venter allowed large sections of the human genome to

be inserted into the bacterium Escherichia coliwhere many

copies of the sequences could be produced for sequence analy-

sis. This technique proved to be much faster than the more

conventional sequencing technique that was simultaneously

being done by the United States government. The technique

involved the creation of many overlapping fragments of the

DNA, determination of the sequences, and then, using the

common sequences present in the overlapping regions, piecing

together the fragments to produce the full sequence of a

genome. However, the concept was not readily accepted. At

the time, the conventional sequencing strategy was to begin

sequencing at one end of the genome and progress through to

the other end in a linear manner.

In 1992, Venter left the National Institutes of Health

and, with the receipt of a 10-year, $70 million grant from a pri-

vate company, he founded TIGR in order to utilize the shotgun

cloningphilosophy as applied to the large-scale sequencing of

genetic information.

Acceptance of Venter’s and TIGR’s approach to gene

sequencing came with the 1995 publication of the genome

sequence of the bacterium Haemophilus influenzae. This rep-

resented the first determination of a genome sequence of a liv-

ing organism.

Another major research trust at TIGR has been the

development of software analysis programs that sift through

the vast amounts of sequence information in order to identify

probable gene sequences. Also, programs are being developed

to permit the analysis of these putative genes and the presen-

tation of the structure of the proteins they code for. A technol-

ogy known as micro-arraying is being refined. In this

technique, thousands of genes can be placed onto a support for

simultaneous analysis. This and other initiatives hold the

promise of greatly increasing the speed of DNA sequencing.

TIGR also gained widespread public notoriety for its

involvement in the sequencing of the human genome.

Specifically, TIGR’s establishment thrust the issue of corpo-

rate ownership of genetic information into the forefront of

public awareness. Backed by the financing necessary to begin

operations, TIGR partnered with an organization called

Human Genome Sciences. The latter company had first oppor-

tunity to utilize any sequences emerging from TIGR labs. The

specter of genetic information, especially that associated with

diseases, being controlled by a private interest was, and

remains, extremely controversial.

In 1997, TIGR dissolved the partnership with Human

Genome Services. Since then, the genetic sequencing efforts

have moved more toward the public domain. For example, now

all TIGR gene sequences are posted on the organization’s web

site and the institute spearheads public forums and symposia.

TIGR is now headquartered on a 17-acre facility on the

outskirts of Washington, D.C., and the institute is comprised

of nearly 200 research staff.

See also Biotechnology; DNA (Deoxyribonucleic acid);

Genetic mapping

TTheiler, Max HEILER, MAX(1899-1972)

South African virologist

Max Theiler (pronounced Tyler) was a leading scientist in the

development of the yellow-fever vaccine. His early research

proved that yellow-fever virus could be transmitted to mice.

He later extended this research to show that mice that were

given serum from humans or animals that had been previously

infected with yellow feverdeveloped immunityto this disease.

From this research, he developed two different vaccines in the

1930s, which were used to control this incurable tropical dis-

ease. For his work on the yellow-fever vaccine, Theiler was

awarded the Nobel Prize in medicine or physiology in 1951.

Theiler was born on a farm near Pretoria, South Africa,

on January 30, 1899, the youngest of four children of Emma

(Jegge) and Sir Arnold Theiler, both of whom had emigrated

from Switzerland. His father, director of South Africa’s vet-

erinary services, pushed him toward a career in medicine. In

part to satisfy his father, he enrolled in a two-year premedical

program at the University of Cape Town in 1916. In 1919,

soon after the conclusion of World War I, he sailed for

England, where he pursued further medical training at St.

Thomas’s Hospital Medical School and the London School of

Hygiene and Tropical Medicine, two branches of the

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