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Pacific Biosciences

Pacific Biosciences and Harvard Scientists Decode Genome of Haitian Cholera Pathogen

Thursday, December 9, 2010

Rapid Whole Genome Sequencing and Analysis of Five V. Cholerae

Strains Supports South Asian Lineage; Sets Groundwork for Potential New

Preventative or Therapeutic Strategies


Scientists from Pacific Biosciences of California, Inc. (NASDAQ:PACB)

and Harvard Medical School have successfully employed single molecule,

real-time (SMRT™) DNA sequencing technology to rapidly characterize the

pathogen responsible for the recent deadly cholera epidemic in Haiti.

Published online Thursday in the New England Journal of Medicine, the

results provide the first whole genome sequence analysis and most

detailed genetic profile to date of the Haitian Vibrio cholerae

outbreak strain.

The multi-strain sequencing and bioinformatic analysis confirm that the

cholera pathogen now present in Haiti is closely related to the “El Tor

O1” variant from South Asia. Given that the existence of this strain has

never been documented in the Caribbean region or throughout Latin

America, the evidence suggests that the Haitian epidemic began as a

result of the introduction of a new strain from a distant geographic

source. While the sequence analysis confirms a South Asian lineage, it

does not identify the specific source of the Haitian strain or suggest

how it may have arrived in the country.

In this collaboration, DNA prepared from five V. cholerae strains

at Harvard Medical School was received at Pacific Biosciences on

Wednesday, November 10, 2010. “Through the truly remarkable and

dedicated efforts of Dr. Schadt and his colleagues at PacBio, we had a

good understanding of the genome of the Haitian V. cholerae

isolates and their likely origin by Friday evening, November 12,” said

John Mekalanos, Ph.D., Chair of the Department of Microbiology and

Molecular Genetics at Harvard Medical School, a senior author on the

study. “This understanding has important public health policy

implications for preventing cholera outbreaks in the future.”

Members of a team led by Stephen Calderwood, M.D., Chief of the Division

of Infectious Diseases at Massachusetts General Hospital and Morton N.

Swartz M.D. Academy Professor of Medicine (Microbiology and Molecular

Genetics) at Harvard Medical School, recently returned from working

alongside public health experts in Haiti where they collected samples

for the study in cooperation with Haitian collaborators.

“Witnessing the scale of human suffering caused by the rapidly

progressing cholera outbreak, our team was compelled to deploy a

technology that could immediately provide comprehensive genomic

information about this virulent strain and quickly get it into the hands

of the global health and research community,” said Jason Harris, M.D.,

Physician, Pediatric Infectious Disease Unit at Massachusetts General

Hospital and Assistant Professor of Pediatrics at Harvard Medical

School. “In the initial stages of a major epidemic, real time is the

speed we need to be working in order to have the greatest impact on

saving lives.”

Whole genome sequencing involves decoding the precise order of

nucleotide bases that make up an organism’s complete set of DNA and

provides more comprehensive information than other analysis methods such

as DNA fingerprinting or arrays. With advances in technology and

decreasing cost, whole genome sequencing is emerging as the gold

standard method for identifying and classifying infectious agents. SMRT

technology is the latest advance in DNA sequencing, capable of

generating long sequence reads to resolve structural variations and

complex genomes at ultra-fast speeds by ‘eavesdropping’ on DNA

replicating in real time.

“Now armed with a more complete characterization of this pathogen, the

scientific community is empowered with information that can be used to

inform public health policy decisions such as the appropriate use of

vaccines to quell this epidemic,” said Eric Schadt, Ph.D., Chief

Scientific Officer of Pacific Biosciences and co-author of the paper.

“The ability to quickly and easily perform real-time monitoring of

pathogens also opens the door to using this technology as a routine

surveillance method, for public health protection in addition to

pandemic prevention and response.”

To obtain a comprehensive genomic characterization of the origin of the

Haitian cholera pathogen, the PacBio/Harvard team sequenced two samples

from the current Haiti outbreak, two samples from South Asia

(Bangladeshi isolates from 1971 and 2008), and one sample from Latin

America (a 1991 Peruvian isolate). The team then compared this high

resolution whole genome sequence information to DNA sequence information

available in public databases for 23 diverse strains of V. cholerae.

Matthew Waldor, M.D., Ph.D., Professor of Medicine at Harvard Medical

School, and Howard Hughes Medical Institute Investigator, is the lead

author on the paper entitled “The Origin of the Haitian Cholera Outbreak

Strain.” A copy of the paper is available at www.nejm.com.

Real-time infectious disease monitoring is featured in a new documentary

film that was produced by Pacific Biosciences called “The New Biology.”

The film profiles how new technologies are leading to advances in

cancer, infectious diseases, and agriculture. To view the infectious

disease segment, visit https://www.pacificbiosciences.com/newbio.

More information about SMRT technology is available at www.pacificbiosciences.com.

About Pacific Biosciences

Pacific Biosciences’ mission is to transform the way humankind acquires,

processes and interprets data from living systems through the design,

development and commercialization of innovative tools for biological

research. The company has developed a novel approach to studying the

synthesis and regulation of DNA, RNA and proteins. Combining recent

advances in nanofabrication, biochemistry, molecular biology, surface

chemistry and optics, Pacific Biosciences has created a powerful

technology platform called single molecule, real-time, or SMRT™,

technology. SMRT technology enables real-time analysis of biomolecules

with single molecule resolution, which has the potential to transform

the understanding of biological systems by providing a window into these

systems that has not previously been open for scientific study.

This press release contains forward-looking statements, including

statements regarding our belief that our SMRT technology could be used

as a routine surveillance method for public health protection in

addition to pandemic prevention or response, and our expectation that

the ability to rapidly access complete sequence information for

bacterial or viral pathogens will greatly improve the identification and

surveillance of infectious diseases, as well as provide a more complete

characterization of medically relevant molecular targets for potential

new vaccines or therapeutics. Forward-looking statements may contain

words such as “believe,” “will,” “may,” “estimate,” “anticipate,”

“continue,” “intend,” “expect,” “plan,” the negative of these terms, or

other similar expressions, and include the assumptions that underlie

such statements. These statements are subject to known and unknown risks

and uncertainties that could cause actual results to differ materially

from those expressed or implied by such statements, including but not

limited to risks discussed from time to time in documents we have filed

with the Securities and Exchange Commission, including the risks

identified under the section captioned “Risk Factors” in our final

prospectus relating to our initial public offering filed pursuant to

Rule 424(b) under the Securities Act of 1933, as amended, on October 27,

2010. All forward-looking statements are based on management’s

estimates, projections and assumptions as of the date hereof. We

undertake no obligation to update any forward-looking statements.

For Pacific BiosciencesNicole

Litchfield, 415-793-6468

Medical SchoolDavid Cameron, 617-432-0441

BiosciencesBen Gong, 650-521-8203

Source: Pacific Biosciences of California, Inc.

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