The code war

November 17, 1998 San Jose Mercury News

THE CODE WAR BIOTECH FIRMS ENGAGE IN HIGH-STAKES FIGHT OVER RIGHTS TO THE HUMAN BLUEPRINT

by Usha Lee McFarling Mercury News Washington Bureau

IN a modern-day gold rush complete with disputes over claims, burgeoning biotechnology companies are racing to patent snippets of genes in the hopes of gaining what could be an extraordinarily profitable monopoly on the human blueprint.

Earlier this month, Palo Alto-based Incyte Pharmaceuticals Inc. quietly announced it had received the nation's first patent of a gene fragment called an expressed sequence tag -- an award many scientists see as a distortion of the patent system, because the subunits are simple structures that can be decoded by computers and arguably do not involve invention.

The debate over the patenting of sequence tags has become the latest flash point in the competition between the government and industry to spell out the entire human genome, the tangled molecular code book of 3 billion chemical keys whose mysteries define us as humans.

Incyte Chief Executive Officer Roy Whitfield rejects the criticism that his company's patent doesn't involve a valid discovery. The 44 tags that fall under the new Incyte patent, he said, have been shown by company scientists to be related to a specific human function -- in this case cellular responses to drugs -- much like a gene, a structure that has been patented for two decades. Roughly 200 sequence tags make up one gene.

"We're not filing random applications,' he said. "We're patenting things with biological relevance.'

In the past year, the race between public and private interests has intensified. Three companies have claimed that they would beat the government's goal of sequencing the genome by 2003. And in an energetic counterattack, government-funded scientists are running a marathon effort to decode and dump as much genetic information as they can onto the Internet, where it is free to all.

A single patent for a portion of the genome could represent billions of dollars to a company: If that fragment is linked to a disease, the patent-holder could claim a share of the profits made from new drugs that exploit that discovery.

Patents of sequence tags are known as "submarine patents' because they can lie in wait, shrouded in proprietary secrecy, until someone does research showing there is money to be made in that region of the genome, said Rebecca Eisenberg, a biotechnology lawyer and professor at the University of Michigan.

"Patent rights could spring up unawares on someone who's made an investment,' Eisenberg said.

With millions of patents on tags, getting permission to use even one gene could be a legal nightmare for university researchers and drug companies, because one gene might be covered by dozens of patents held by dozens of drug companies.

Incyte has patents pending on 1.2 million DNA fragments. Another company, Human Genome Sciences Inc. of Rockville, Md., has patents pending on millions more -- enough to grant ownership rights for most human genes. A handful of other companies have filed for smaller numbers of the new patents.

Though Washington University in St. Louis is the largest government DNA decoding center, much of the public research is also being done in the Bay Area. At Stanford University, for example, 50 people armed with robots, lasers and roomfuls of code-breaking computers work nearly around the clock only a few miles from Incyte. Other research is being done at Lawrence Berkeley National Laboratory.

Government and academic researchers warn that allowing companies to patent -- and keep secret -- DNA codes already may be slowing critical research.

"Our concern is that patents are being used in ways that create obstacles to conquering human diseases,' Bruce Alberts, president of the National Academy of Sciences, said in a letter to the U.S. Patent and Trademark Office. Those fears have been echoed by Dr. Harold Varmus, director of the National Institutes of Health.

Leroy Hood, who heads the department of molecular biotechnology at the University of Washington and first developed the automatic DNA sequencers central to these patent claims, said he stopped work on a possible colon cancer screening test after he learned it involved a gene that included a sequence tag for which Incyte has a patent pending.

"The attempt to obtain patent protection of tags violates the intent of patent law, violates the spirit of patent law and uses the patent system exactly opposite its true intent,' said Jonathan King, a professor of molecular biology at the Massachusetts Institute of Technology who sits on the board of the Council for Responsible Genetics, a group of research scientists opposed to private ownership of genetic material.

"It is the suppression of invention and the constraining of discovery.'

Human Genome Sciences Chief Executive Officer William Haseltine, known for his combative nature, argues that government attempts to keep genes as a free-for-all are "inimical to medicine and human health. They are being irresponsible.' Incyte's Whitfield points out that the entire biotechnology industry, which so far has led to dozens of new treatments for disease, was born because companies were allowed to patent genes.

The argument over whether sequence tags should be patented is almost certainly headed to the courts, said the University of Michigan's Eisenberg. The legal debate might spark a wider examination of where property rights should end and human rights begin.

"There's going to be a lot of work for patent lawyers,' she said.

The nation's top health and science officials are alarmed at the prospect of any chunks of our genetic code being claimed by private interests. They say the information should remain unfettered and free to all medical researchers.

The Supreme Court has ruled that genetically engineered biological organisms -- bacteria that devour oil or mice that contain human cancer genes -- can be patented as inventions. And lower courts have ruled that pieces of human DNA can be patented because they are useful and because they are considered chemicals rather than human parts.

Patent office officials say there is no legal reason not to grant patent rights for sequence tags, which in theory could provide an economic spur to genetic research.

Applications for expressed sequence tags historically have been among the most controversial of all genetic patents. In 1991, the National Institutes of Health caused a furor when it attempted to patent more than 350 gene fragments decoded by Craig Venter, the flamboyant former NIH scientist who now heads Maryland-based Celera Genomics, one of the companies racing against the government to sequence the human genome.

The NIH had contended that by claiming the tags, it should receive a patent for an entire gene. Many prominent scientists argued the effort would spur a rush to lay claim to bits of genetic code that are meaningless and that stifle research -- and the application was eventually rescinded.

Company executives say the patent applications filed recently are very different from the one filed by NIH. Incyte officials take strong exception to the characterization of sequence tags as worthless bits of information that can be generated by computers. Fragments of large numbers of genes, they predict based on new research, will be the key to curing genetic diseases.

Regardless, academics contend the whole issue of patenting has introduced new veils of secrecy that already might be having a chilling effect on genetic research. Columns in scientific journals offering patent advice to scientists tell them, "Don't submit abstracts. Don't give talks to colleagues. Don't show them your notebooks,' said MIT's King. "This is absolutely contrary to the cooperative culture in science that gave birth to the biotechnology revolution.'

"It's ludicrous on its face to think anyone owns DNA, that they had anything to do with it and did anything but find it,' said George Annas, a bioethicist and professor of health law at the Boston University School of Public Health. "DNA is the common heritage of humankind.'

----------------------------------------------------------- ------------- Mercury News Staff Writer Ariana Eunjung Cha contributed to this report. ©1997 - 1998 Mercury Center.