August 13, 2003 | A maverick scientist and founder of a biotech finds himself at the center of an intensifying storm in the world of DNA patenting — and no, his name is not J. Craig Venter.

Receiving scant attention when they were first filed, two key patents awarded in the 1990s to immunologist Malcolm Simons have granted a small Australian biotech firm broad mapping and diagnostic rights to as much as 95 percent of the human genome, often slighted as "junk DNA." As Genetic Technologies Ltd. (GTG), a Melbourne company co-founded by Simons and Mervyn Jacobson in 1989, starts to enforce these patents, some biotechnologists are warning that the community's oversight could rank as one of molecular biology's biggest mistakes.

During the 1980s, Simons worked in research groups at Cetus and the University of Utah, sites of breakthroughs in gene amplification and human gene mapping. At the time, attention was focused on identifying genes. But if junk DNA — the morass of repetitive and seemingly functionless DNA that makes up the majority of the genome — really has no purpose, he reasoned, why would humans have collected so much of it? Simons recalls: "The reaction was smiling disbelief at best: 'You're off your [freakin'] head. And if you're any good at squash, stick to your day job!'" (He happens to be a former international squash player.)


Genius of Junk 
Simons was undeterred. In the early 1990s — while Venter was embarking on the systematic search for expressed gene sequences and igniting a firestorm over the ethics of gene patenting in the process — Simons filed several patent applications, which were eventually granted by the U.S. Patent and Trademark Office (PTO).

Two patents (#5,612,179 and #5,851,762) cover the use of amplifying intron DNA (the noncoding sequences that interrupt genes) to map genes and determine individual haplotypes, either by DNA sequencing or allele- specific oligonucleotides (the staple of many microarray methods). Granted in more than 20 countries, they apply to the genomes of all organisms, not just humans. Simons licensed these patents to GTG but departed the company after it went public in 2000, leaving Jacobson in charge. Simons now owns neither the intellectual property nor shares in GTG.

GTG has since signed licensing agreements with a handful of biotechs, including Nanogen, Sequenom, Perlegen Sciences, and Myriad Genetics. Worth between $250,000 and $1 million each, Jacobson says, the deals have netted GTG several million dollars to date. One senior executive said his company felt it had little choice but to sign, not so much because of the apparent strength of GTG's legal position but out of a desire to avoid litigation. GTG, it should be noted, has obtained insurance on its patents.

An Australian television documentary that aired last month, Catalyst, profiling Simons and his inventions, showed GTG staffers compiling a comprehensive database of users in potential violation of its patents, edging toward 2,000 entries. Jacobson says three biotech companies could be sued shortly unless licensing agreements are reached (see "Playing by Aussie Rules").


Academic Freedom? 
But what has geneticists up in arms is GTG's recent decision to seek research licenses from academic institutions. In May, the University of Utah signed the first academic license for 15 years and $1,000 (commercial uses were covered under a separate license).

Jacobson considers this a trivial sum to ask. He insists his company is acting "in a socially responsible way — we want the technology to get out." He also points out that after the patents expire, GTG's invention will pass into the public domain. The company's position is strengthened by recent U.S. court rulings, such as Duke v. Madey, that make it more difficult for academic researchers to claim exemptions from patented technologies.

Last month, Francis Collins told delegates at the International Congress of Genetics (ICG) in Melbourne that Simons' patents are of "questionable appropriateness." This prompted Simons to fire back: "He was having a smack at my inventiveness, and I don't appreciate that."

The usefulness of noncoding DNA for mapping human disease genes has been known for at least 25 years. In 1978, Y. W. Kan and Andres Dozy published a paper in The Lancet in which they used a variation in the flanking DNA of the beta-globin gene in the first successful prenatal genetic diagnosis of sickle cell anemia. Of course, the GTG patents do not claim ownership of the junk DNA itself, but rather processes for detecting changes in those noncoding sequences for mapping, diagnosis, and haplotype analysis.

The revelation that the PTO has in effect ceded (intellectual) property rights covering a large portion of the human genome to a single biotech company should not come as a complete surprise. The PTO has come under intense pressure in recent years to raise the bar for individual gene patents. Now researchers have further grounds to admonish the PTO's largesse.

Regardless of GTG's patent position, many scientists believe that the company has crossed the line. Besides surely damaging GTG's reputation, the decision to charge universities could impede progress in many areas of research.

Simons, meanwhile, is saying little about the controversy. Seriously ill with multiple myeloma, he appeared at a Melbourne press conference in July frail from the effects of chemotherapy, but determined to unveil his new company, Haplomics, which will license patented technology for gene discovery for a token $1. Mindful of his legacy, Simons says: "The discoveries we make today using Haplomics will be with us in 500 years, 5,000 years, and forever."

Kevin Davies, Ph.D.
Editor-in-Chief
Bio·IT World