by Matthew Albright
Revolutions follow a predictable pattern. After the smoke clears and the excited rhetoric of a utopian future is exhausted, sleeves are rolled up and the real work begins. The heroes of the revolution are exiled, if not executed, and bureaucrats and businessmen take their place. The heady days of rebelling against the old regimes become quiet days of building new structures and organizations with which to carry out the revolution’s promises. People resume their lives and then, later, often question whether the revolution really changed anything.
And so it goes with the genomic revolution. Quiet days of economic and scientific reflection have replaced the rhetoric of a future where suffering and hunger are defeated. Genetic determinism, the march anthem of the revolution, has been quieted (but not yet silenced) with the genome project’s revelation that humans have only a few genes more than a fruit fly or worm. Heroes of the revolution like Craig Venter – that proud mixture of rogue scientist and American entrepreneur who gave voice to the hopes of every budding scientist millionaire as well as to the dreams of a medicated society – have been told to get off the battlefield and make way for business designs that will actually make money from their discoveries. Recent business magazine articles, reports from government agencies, and analyses from industry consultants have all reported that the fun is over and the future is questionable for the budding biotech industry.
Even the foot soldiers of the revolution, the researchers themselves, talk of the death of genomics and are looking for the next sexy science. “In terms of research, genomics is passé and proteomics is the new buzz work,” the faculty dean of Harvard Medical School told The Boston Globe. The genomic slogan – a world with no disease – has been borrowed, unchanged, for proteomics. “Knowing the structure of the protein gives you a big clue in how to build drugs,” says John Novell, head of the NIH’s proteomics effort.
In “Unraveling the DNA Myth,” an article in the February 2002 Harper’s, Barry Commoner writes that “the biotechnology industry is based on science that is forty years old and conveniently void of more recent results.” Chakrabarty’s oil-eating bacteria that never actually ate oil should have been a sign of things to come. The products of the genetic research so far have been questionable at best; at times they have been downright fatal. Gene therapy killed more patients then it helped. Genetically modified crops did not give the hunger-eradicating yields that they promised and now, in fact, threaten to destroy the planet’s food supply. Genetic tests gave questionable risk statistics for non-curable diseases which informed patients of the risk factors they knew they had before they took the tests.
If biotechnology companies are to survive the post-revolution purges, they must make the jump from an era of inventiveness to an era of industry, producing real products that yield real profits. Standing in the way of real products is a minefield of life patents created by the biotech industry itself. Life patents have become destructive tools ––exploiting indigenous cultures and endangering the world’s seed and food supply–– but their final victim may be the biotech industry itself.
As in any good minefield, no one is quite sure how many life patents there are. Two years ago, Todd Dickinson, the former director of the US patent office, told Congress that his office had awarded 6,000 patents on “full length genes from human, animal, plant, bacterial, and viral sources.” Last summer, John J. Doll, the head of the patent office’s biotech department, said 20,000 gene patents had been awarded, with another 25,000 waiting in the wings. Exactly what these patents cover is also in question. One estimate is that life patents cover 500,000 different molecular structures.
Historically, the United States has excelled at taking enthusiastic inventiveness and turning it into competitive, lucrative industries. In the case of both the airplane and the automobile, freedom from patent constraints was an essential part of the birth of formidable industries. The aeronautic industry followed the automobile’s lead and pooled its patents, including the Wright brothers’ original patent that covered all airplanes. By freeing the basic research from patents, the tinkering of gentlemen hobbyists was turned into an industry that could be largely credited for establishing the United States’ military and economic might in the 20th century. The same needs to happen with life patents and the biotech industry.
The blockbuster years are over for the drug companies. There are no drugs in development that will give Big Pharma the success they have come to expect in the past. They are coming off two decades where they increased sales from $22 billion to $149 billion, giving back an average annual return of 25% to their investors. But experts suggest that the pharmaceutical industry must completely overhaul its way of doing business in order to survive. They are being told to create some real products – like drugs that work – - or they will go the way of the dot-coms.
The hope of building an actual industry from the genomic revolution lies in attacking a much wider range of ailments with much smaller target audiences. It means a “shift from a relative handful of blockbusters to a medical armamentarium consisting of thousands of sharpshooter drugs aimed at small disease populations,” according to Fortune magazine. In the entire history of the drug industry, only 500 basic targets – disease-causing functions in cells – have been researched. There will now be 10,000 potential new targets because of the discoveries in genomics. In other words, the blockbuster model for developing drugs must be replaced with the “sharpshooter model:” lots of products, each intended for few people.
This is where biotechnology companies, university facilities, and governmental research institutes come in. Where once biotech companies were the golden boys of venture capitalists and day traders, they have now become the “farm system” of the pharmaceuticals or, like Amgen and Venter’s Celera, they have consolidated and developed into pharmaceutical companies themselves. Experts claim that in order to turn these new drug hopes into actual products, pharmaceutical companies must increase their R & D money as well as broaden their partnerships with smaller, more efficient research groups like biotechs and universities.
But the pharmaceutical companies, and the biotech and research institutes they employ, will not be able to develop thousands of new drugs with any efficiency if the basic descriptions of molecular materials are caught up in patents. It is analogous to the threat the early aerospace industry was under with the Wright brothers’ patent infringement suits. In order for efficient and useful products to be developed from the Wright brothers’ invention, a broad number of technologies needed to be developed on top of the basic Wright design. In order to develop the 10,000 drug targets, freedom must be given for biotech to explore the basic upstream knowledge. Paralyzing upstream knowledge with patents will be like giving the Wright Brothers a twenty-year monopoly on the airplane.
When and if the new drugs promised by the genomic revolution reach the market, they will be covered not by life patents ––patents that describe molecular structures, transgenic animals, or plants–– but by patents that describe laboratory-produced chemical compounds that affect molecular structures. The only company to ever make real money on a product directly from a life patent was Amgen with their EPO patents–– and Amgen killed many a good compatriot in the biotech revolution to keep its EPO monopoly.
The justification for life patents as a counter to the financial risk inherent in developing drugs has become moot as well. Technological improvements in genetic research, called pharmacogenomics, have made drug development much less expensive. The efficiencies in cost lie in the amazing progress that genetic research has made by using computers, robotics, and free public genetic databases in drug development. Pharmacogenomics will make drug development cheaper by $300 million and take two years off the entire process, according to the Boston Consulting Group. Before beginning human trials, researchers may be able to model how the drugs work in the human body, what side effects the drugs might have on patients, and how the drugs interact with other drugs. This will save thousands of hours of research by eliminating hopeless drugs in the beginning stages of research instead of during costly trials.
The importance of patents in reaping a return on investments remains questionable. The famous Office of Technology Assessment report of 1993 which found that development costs nearly $400 million a drug, also reported that sales of drug products declined very little after their patents expired. “Three years after patent expiration, the mean annual dollar sales of the original compound were 83% of mean sales revenue in the year of patent expiration.” Big Pharma is well aware that the financial success of a product depends much more on marketing and advertising than on patent protection – as any glance at a drug company’s budget will prove.
The biotech and pharmaceutical companies have a lot of work to do to produce products that work from the genetic discoveries of the past ten years. Unless they do something to unravel the mass of life patents that currently restrict upstream knowledge, that work will never get done. The genomic revolution may prove to be one of those revolutions that claim many victims but very few real victories.
Matthew Albright is a Harvard Divinity School Student and a second year intern at CRG. He is the author of Profits Pending, a book on life patents to be published this fall by Common Courage Press.