The first complete genome ever sequenced for a free-living organism, detailed in last Friday's Science, haschalked up its first commercial deal.

Medimmune Inc., of Gaithersburg, Md., and HumanGenome Sciences Inc. (HGS), of Rockville, Md.,announced an alliance to create and market antibacterialvaccines and immunotherapeutics, sparked by totalsequencing of the genes in the bacterium Haemophilusinfluenzae.

HGS (NASDAQ:HGSI) gained 75 cents Friday to closeat $24 per share. Medimmune ended the day at $9.50 pershare, an increase of 63 cents. News of the alliance wasreleased after the market closed on Thursday.

HGS's not-for-profit partner, The Institute for GenomicResearch (TIGR), also in Rockville, describes thatmilestone feat of gene mapping in a Science paper titled"Whole-genome random sequencing and assembly ofHaemophilus influenzae Rd." Heading the roster of 40co-authors from four research centers is Craig Venter,TIGR's founder and president.

HGS in effect serves as TIGR's financial backer andresearch beneficiary. Its first joint program withMedimmune is to construct a vaccine against H.influenzae, a common pathogen that causes middle-earinfections in children, bronchitis and pneumonia,occasionally meningitis, in young and old.

With 700,000 cases a year of otitis media [ear infection],Medimmune's manager of strategic planning and investorrelations, Mark Kaufman, told BioWorld, that H.influenzae accounts for 10 percent of all pediatric officevisits.

He said HGS will provide his company with personneland services, but no cash, in pursuit of their collaboration.This embraces any future bacterial genomes that TIGRmaps, which both partners agree to commercialize.

Kaufman foresees that screening gene libraries andpicking probable vaccine candidates against H. influenzaewill each take "a matter of months," and subsequentclinical trials "a matter of years."

Property rights to TIGR's intellectual output, said HGS'schairman and CEO, William Haseltine, reside with HGSin return for a 10-year, $85-million grant which began in1992.

HGS will contribute TIGR's just-released bacterialgenome data to Medimmune, and use its proteinproduction facility to make experimental products.Medimmune will develop and test these vaccines andantibody molecules, and commercialize products arisingfrom the collaboration.

Venter made public his total genome sequencing of H.influenzae last May at the American Society ofMicrobiology's annual meeting in Washington. (SeeBioWorld Today, May 30, p. 1.)

Germs, People, Have Much In Common

"It has significance for the whole field of biology," hetold BioWorld on Friday. "For the first time, we can seethe whole set of genes associated with the life of acomplex organism." He added, "Understanding life inbacteria is not so far-fetched from understanding life inhumans." [H. influenzae's 38 percent guanine-plus-cytosine base composition is close to that of humans.]

Venter continued, "this new level of information shouldelevate the thinking of not just the biotech andpharmaceutical industries, but also the National InstitutesOf Health [NIH] and other major funding organisms thathave the goal of trying to eradicate some of these majordiseases."

Single-cell bacteria stand more or less midway in size andcomplexity between subcellular viruses and Homosapiens, whose bodies contain 10 trillion cells, eachharboring an estimated 30,000 to 100,000 genes. HIV'scomplement of DNA, Venter observed, is 10,000 basepairs long; Ebola's, even less.

"A few years ago," he recalled, "we sequenced thesmallpox virus genome, which is only 186,000. So H.influenzae, with its 1,830,137 base pairs, numbering1,743 genes, is exactly 10 times as long."

Venter also made the point that "viruses and phages arenot free-living organisms, as bacteria are."

It took TIGR a full year to map the Haemophilus pilot-project genome, with most of that time consumed by thecomputational procedures that mastermind its sequencingshortcut approach. Mapping its second bacterium,Mycoplasma genitalium, took only three months. Thispathogen is closely related to M. tuberculosis, on whichVenter has his sights.

"You know," he said, "TB is one of the top 10 killers inthe world. We're now seeking funds to do its genome."

As for broader medical applications of the TIGRsequencing system, "All you have to do is look at thesituation that exists in antibiotics. At present, they onlyinteract with a few known proteins in microbial cells. Allof a sudden," Venter continued "we have now exposedover 1,700 proteins in a bacterium, which means we nowhave over 1,700 potential targets for antibiotics, and forwhat HGS and Medimmune are trying to do _ developnew vaccines."

His goal "over the next two or three years is to get at leasta dozen microbial genomes, from different parts of thephylogenetic [evolutionary] tree, completely sequenced."By this year's end, TIGR expects to complete work onMethanococcus jannaschii, a bacterium that thrives attemperatures well above boiling point. They hope toreveal the enzymes that make this possible, for use inindustrial high-temperature catalysis.

The total genomic depiction of H. influenzae boils down,Venter said, "to a giant centerfold in Science, showing all1,743 genes in its circular genome, in the order thatthey're in, color-coded by biological function, withpredicted protein structure and biological role."

It has not escaped his notice that TIGR's quicker,cheaper, better genome sequencing technology canbenefit the international effort to map all 3 billion basesin the entire human genome. "Before we did this project,"he observed, "people were thinking that any genomeproject, other than small viruses, were multi-multi-year,multi-multi-dollar undertakings. We completed oursecond genome in only three months. It brings down thecost from $1 to $5 per base pair to somewhere between30 and 50 cents a bp."

The Science paper lays out TIGR's genome-solvingapproach in cook-book detail. Venter compares it to "ajigsaw puzzle in which all pieces are basically the samecolor, and there are no square edges to hint at where tostart. So you have to compare each piece to all the otherson the table to find the one that matches."

In practice, he explained, to do that first bacterial genomerequired 25,000 independent sequences, each 500 basepairs long. "Imagine," Venter said, "that you're holding a500-bp sequence, and looking at 24,999 others on thetable, trying to find a match. That's a lot of calculation.So our TIGR informatics team developed the algorithmand software for doing this." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.