While writing my monthly AIDS column for A & U Magazine for many years, I've wondered at the 20+ years and millions of dollars already spent on vaccine research. From the U.S. alone, NIH/NIAID has funded study of around 50 vaccine candidates around the world, and approved some 30 clinical trials so far. Other countries have their own vaccine initiatives going. But as yet, there is no FDA approval. And the word is, that "many years" will pass yet before a vaccine reaches the market. AIDS-industry leaders make excuses that "vaccine research is very challenging." They cite the difficulty of designing a vaccine that can deal with HIV's astonishing ability to mutate new strains.
But economic imperatives are clearly skewing their decisions as well.
The term "disruptive technology" was coined in 1995 by economist Clayton Christensen, and has become business-speak for somebody's new discovery that gets in the way of somebody else's accustomed profits. Big industry has perfected a strategy for effectively sidetracking "disruptive technologies" that threaten its established profits. And big government supports this strategy when it, too, can benefit financially from doing so.
World War II Secret
A classic example comes from the automobile. By the end of World War I, new technology for getting higher mileage on gasoline was already stirring. The typical engine (like the popular Ford Model T) was getting only 13-21 miles per gallon. That new tech aimed to redesign the engine's carburetor so it burned gas more efficiently.
In 1935-7, Canadian engineer Charles Nelson Pogue patented a device that reportedly tested at an astonishing 200 mpg. But when the Pogue carburetor hit the headlines, it set off stock-market panics and crashes of oil stocks. Big Government and Big Oil promptly joined forces to blockade Pogue's carburetor from the Canadian and U.S. markets. Pogue was harassed, and his factory was vandalized. Eventually he was forced to stop production. The oil industry started putting additives in gas to make it harder for a redesigned engine to increase the mpg.
Those 200-mpg test figures were later questioned. Yet the carburetor apparently worked well enough that, during World War II, the U.S. government secretly installed it on American military vehicles, including tanks in the North African desert campaign. So the unwelcome invention helped our troops to outrun Nazi Germany, whose gasoline supply was limited.
After the war, even as America grew more dependent on car and truck transportation, the high-mileage carburetor was quietly put on the shelf. Yet our government allowed other wartime tech advances -- like nylon and radar -- to go into wide civilian use.
When the environmental movement exploded in the 1960s, and the public started crying out for "clean air," and other inventors worked on other high-mileage approaches, government/industry policy kept on fiercely resisting these innovations. Their actions ensured that the world would go on gulping gasoline, and the oil industry would go on gulping huge profits. The innovative Fish carburetor, for instance, never got further than limited use in stock-car racing. Its American inventor/manufacturer, John Fish, was driven into bankruptcy by government harassment.
Automotive policymakers apparently lost no sleep over the medical downside of air pollution. Health problems were caused by (among other things) toxic emissions from millions of low-mileage carburetors that burned gasoline so inefficiently. In 2000, Medscape reported on an alarming study that estimated 3% of all deaths in the U.S. could be attributed directly to dangerous particles from vehicle exhaust, not to seasonal flus and bronchial problems. The World Health Organization (WHO) has sounded similar alarms, estimating that millions die prematurely every year in smog-smothered regions of the globe.
Today the U.S. sends out sophisticated space probes that explore the farthest reaches of our solar system. Behind the scenes, automakers know they can equal these space feats. By 2013 Volkswagen might release a concept 2-seater, the L1, that hits 170 mpg. In the U.S., car designer Ron Mathis has reportedly tweaked the mpg up to 100 on an experimental sports car, the Edison2. Yet the handful of "fuel efficient" cars that have actually been allowed to trickle onto the market still can't do much better than 40 mpg. Not surprisingly, the only car that edges over 50 mpg is expensive -- the Toyota Prius, starting at $22,800. So we won't be seeing millions of Priuses on the road.
The key strategy is to drag out that tech transition as long as possible. Retool the engines by tiny increments, thus saving on costs. Give consumers just a few mpg at a time, and make them pay through the nose for it as a feature of a new model.
Alternative-energy vehicles, like electric cars, still take only 2.8% of the U.S. market share. So Big Oil still has things pretty well locked down.
Today, it's fashionable to blast Republicans for their coziness with Big Oil. But both Democrat and Republican administrations must shoulder blame for the gas-mileage boondoggle. Government and industry both continue to protect their cash flow from gasoline. In 2004, according to the Tax Foundation, combined oil-industry profits went to $40 billion, while the grand total of state and federal taxes from gas soared to $60 billion. Profits and tax revenues have slumped since 2008, because of the recession. But this is all the more reason to fight tooth and nail to protect what's left of profit.
As I write this, the Obama administration appears to okay the next stage of strategic delaying by the auto and oil industries. By the year 2025, the feds want the upper end of mileage per gallon to inch up another 10 or so...to a measly 62.
Meanwhile, for over two decades now, the AIDS industry keeps promising us that a vaccine will happen. If not today, then tomorrow or the next day. NIAID declares May 18 to be Vaccine Awareness Day. In July 2010, as the XVIII International AIDS Conference convened in Vienna, the buzz was all about launching a "new era" of research on vaccines that employ antibodies to neutralize HIV viruses. More recently, this month, 1000 scientists flocked to Atlanta for the AIDS Vaccine 2010 conference. There, the atmosphere was equally bullish about "new research" -- in spite of growing economic problems and waning funds.
For us LGBT people, AIDS looms large on our history time-line. But in our world, a vaccine breakthrough has historically been over-shadowed by issues of PWA and community empowerment, as well as personal access to the latest anti-retroviral drugs. Yet many of us do hope for a vaccine. Gay men do participate in vaccine trials, as Father Tony's recent post is pointing out. Well-to-do LGBT people have invested in vaccine-research ventures.
And the vaccine is vital to those of us who are at risk, because it is literally the only hope of curtailing the AIDS pandemic. Drug-based anti-retroviral treatments offer no such hope -- they deal with infection after the fact. While ARVs may lengthen a person's life, they prompt the strains of HIV to mutate resistance to these drugs. Often, ARVs have toxic side effects that are debilitating, even fatal. "Prevention" is important, but it can't end global infections. Only vaccines can do that -- the way they did for smallpox and polio.
Now and then, the AIDS-industry generals send out their PR troops to trumpet the announcement that some current study may finally hold the key to a vaccine that works. Earlier research focused on trying to use DNA and cellular immunity as an approach. For instance, in 2001, trumpets blared for the DNA-based VaxGen vaccine, and for the Merck STEP vaccine in 2007. But both DNA vaccine studies were disappointments when it came to performance in clinical trials. HIV's propensity for mutating continued to foil success in those earlier DNA vaccine studies.
At the Vienna AIDS conference this summer, major media were bugling the latest allegations once again. Under the headline "Advance in Quest for HIV Vaccine," Mark Schoofs wrote in the Wall Street Journal: "In the latest development, U.S. government scientists say they have discovered three powerful antibodies, the strongest of which neutralizes 91% of HIV strains, more than any AIDS antibody yet discovered. ... The trick for scientists now is to develop a vaccine or other methods to make anyone's body produce them."
NIAID head Anthony Fauci, MD, greeted this news with a typical comment. He talked about these "exciting advances." Indeed, since 2005, Fauci has openly sent the message that neutralizing antibodies are the way to go.
A scientist himself, Fauci is named "inventor" on some AIDS-related patents. Though the government owns any patents on medical inventions by its employees, the employees are acknowledged as inventors so they can share profits from licensing deals with corporations.
Follow the Money
Now and then, some independent-minded academics scratch their heads and wonder why HIV vaccine research is going so slowly.
In 2006, for example, Christopher M. Snyder of Dartmouth College and Michael Kremer, senior fellow at The Brookings Institution, asked the question as they published a paper that posited a possible corporate bias against producing vaccines. Their conclusion: "Simulations based on the distribution of infection risk and income in the U.S. population suggest that revenue from a HIV/AIDS drug may be twice that from a vaccine."
What Snyder and Kremer are saying is -- follow the money, and you find out that AIDS vaccine is a disruptive technology.
The blunt figures reveal what these two scholars are talking about. The pharma industry makes around $10 billion a year from ARV sales. It all started in 1987 when AZT debuted at $10,000 a year per individual treatment -- the most expensive drug in history, at that time. AZT's price tag touched off widespread outrage. Yet corporate profits have spiked dizzyingly upwards from there. An American PWA's treatment with a combination of meds (including those for opportunistic infections) can now reach $100,000 a year. Multiply that by the many years that a person with HIV/AIDS might be treated before he or she finally dies. And multiply THAT by global marketing, and the grand total is expected to soar to $15 billion a year by 2015. This is when the AIDS industry plans to achieve its goal for "universal access" to ARV treatment in every country where the epidemic is found.
Along the way, the top pharma firms (mostly located in Europe and the U.S.) are fighting desperately to limit the movement of cheaper generics into the distribution pipeline -- even though AIDS generics are what developing countries can best afford.
True, $15 billion in ARV profits would be dwarfed by the oil industry's vaster haul in profits. But $15 billion is reason enough to fight a "disruptive technology."
Why would the AIDS industry give up these billions in favor of one or two skin pops of HIV vaccine that would make all those years of ARV treatment obsolete? Even if the first AIDS vaccine enters the marketplace with a bigger price tag than the HPV vaccine (currently the most expensive @ $360), that high price for life-time protection against HIV is a drop in the bucket, compared to hundreds of thousands of dollars for years of ARV treatment.
The U.S. government is anxious to protect its own vested interest in ARV cash flow. The FDA collects millions in user fees from pharmaceutical companies. The Dept. of Treasury collects additional taxes on pharmaceuticals. Plus there are royalties from medical inventions created by government scientists.
In short -- the dragged-out AIDS-vaccine history suggests an eerie repeat of the high-mileage carburetor boondoggle.
A Closer Look at Clone 3
For some time, I've been looking into the story of that discovery by Joseph Cotropia, MD. Why? Because Dr. Cotropia found what the conference-goers in Vienna were buzzing about -- the first antibody that had real potential to neutralize HIV across a broad spectrum of mutations. But he did it 21 years ago, right in the first decade of the epidemic.
Put simply, the discovery was a human cell line producing a specific human antibody that targets a genetic sequence designated KLIC on the surface of the HIV virus's outer envelope. Dr. Cotropia named it Clone 3. This antibody can lock onto the KLIC epitope (the epitope is a key spot on the envelope where the virus is vulnerable to antibody action) in such a way that the virus is unable to reproduce, and ultimately cannot infect a human cell.
Dr. Cotropia started his immunology career as a protege of polio-vaccine discoverer Jonas Salk. Veteran inventor Salk had already taken a pioneering shot at an AIDS vaccine, and experienced his own difficulties with the research industry, so he warned Joseph about what he might be up against.
After Dr. Cotropia patented his discovery in 1989, the NIH did fund some initial study of his approach at the University of South Florida. Through the '90s, several other independent studies took positive looks at the work. Further support came from Polymun, a distinguished research institute in Vienna that also did innovative work with neutralizing antibodies. With his brother Charles Cotropia, a noted patent attorney with Sidley Austin, LLP, Dr. Cotropia founded a privately held biotech firm, BioClonetics Immunotherapeutics, Inc. and hoped to develop Clone 3 towards market. Salk wrote a letter supporting Dr. Cotropia's work.
But then further progress seemed to be blockaded. In 2004, when Dr. Cotropia and BioClonetics applied to NIH for another grant, aiming to take the next step, namely a Phase I clinical trial, his application was reviewed by two members of NIH's Center for Scientific Review Committee. The committee members (who didn't identify themselves by name on the paperwork) were careful to concede that a product like Clone 3 "would be of benefit to society, and should be subject to commercialization." But they viewed the trial proposal itself with dismissiveness.
"Lack of innovation," they sniffed, implying that the proposal had no scientific merit.
Without NIH support for clinical trials, Clone 3's development had to halt.
Yet in August 2010, the U.S. government's own Los Alamos HIV Clinical Database published a review of Clone 3 Antibody's capacity to bind directly with the 2,229 known strains of HIV around the world. By searching the surface (amino acid) composition of these 2,229 HIV isolates, Los Alamos found that 98% of them have an exact match -- or conservative amino-acid substitution -- for the minimal essential "core" epitope KLIC to which the CLONE 3 antibody binds. In other words, Clone 3 epitope KLIC has the potential to elicit in active vaccination, a protective antibody ("CLONE 3") that broadly neutralizes 98% of all known HIV strains -- which is more than any other vaccine candidate whose study results have been published.
Clearly this government data should put the Clone 3 KLIC epitope at the front of the pack of leading candidates -- those few that are screaming to be further scrutinized in a series of clinical trials, to see which one can actually be developed into an effective vaccine. So the government's ongoing refusal to support trials for Clone 3 KLIC is baffling.
Clone 3 KLIC has also been ignored by the major media, who mostly content themselves with regurgitating industry press releases, and seldom do any real scrutiny of biomedical research. (This is not surprising, given the amount of advertising leverage that Big Pharma has with the media.)
Now based in Texas, BioClonetics is still looking to do its planned broad development of its technologies into two distinct products. In addition to the active vaccination possibilities made possible by the Clone 3 KLIC epitope, the CLONE 3 antibody also has potential as a passive immunotherapy, that will make it possible to treat those infected with HIV/AIDS without the toxicity dangers presented by ARV drugs. Moreover, Dr. Cotropia tells me that the 1989 discovery has possible applications for diseases caused by other retroviruses as well, in both human and animal medicine.
At its website, BioClonetics makes some points of its own about the state of HIV vaccine research. Among them:
"Experts in the field see human monoclonal antibodies as being the likely way to control HIV/AIDS. At the 2004 Proceedings of the National Academy of Sciences (USA), vaccinologist Maurice Hilleman wrote that any vaccine based upon cellular immunity was unlikely to be effective....In 2005, Anthony Fauci, MD, Director of NIAID, stated that a successful vaccine against HIV/AIDS will require inducing the production of a neutralizing antibody. Significantly, the pharmaceutical industry has disregarded this scientific truth that a neutralizing antibody will be necessary to produce a successful vaccine, and has instead focused primarily on DNA-based cellular immunity vaccines, none of which have succeeded in any clinical study."
As I talked with the Cotropia brothers and their CFO, Paul Fellegy, I learned another intriguing fact:
In 1999, the U.S. government made a patent application that overlapped an area covered by Dr. Cotropia's 1989 patents. The government listed Anthony Fauci and others as the "inventors." In the affidavit required by the filing process, Fauci et al declared under oath that the neutralizing technology in question had "utility" and "commercial value." But the U.S. Patent Examiner threw out the government's bid to own the key area covering Clone 3. He pointed out that Dr. Cotropia and BioClonetics had a prior claim.
This attempt was made five years before BioClonetics was turned down for that 2004 NIH grant. If Fauci's bid for the patent had succeeded, and it was he standing before that NIH committee asking for trial approval, instead of an outsider like Dr. Cotropia, I wonder what the committee would have decided.
BioClonetics also mentioned to me that they've foiled several attempts to steal their patented cell line. Espionage is as big a problem in biomedical research as it is in other industries. Anybody who successfully steals a patented product can proceed to patent it under their own name.
Some Burning Questions
Today BioClonetics continues its battle to find funding and move its technology onwards. And today, for me, the questions are piling up. Some of them are:
1. Why is the Wall Street Journal burbling about an antibody that "neutralizes 91% of HIV strains, more than any AIDS antibody yet discovered," when the government's own Los Alamos HIV data shows that an antibody discovered in 1989 can neutralize 98% of the strains?
2. Why does the International AIDS Vaccine Initiative (IAVI) make the following statement: "An AIDS vaccine with 50% efficacy given to 30% of the population would avert 5.6 million new infections in low and middle income countries between 2015 and 2030." Surely IAVI knows that a vaccine candidate of 98% potential has been sitting on the government's shelf since 2004?
3. And what's up with the Bill & Melinda Gates Foundation, which is supposedly committed to an AIDS vaccine? According to a recent report in the L.A. Times, the Gates Foundation's multi-billion dollar portfolio is heavily invested into pharmacorps that manufacture anti-retroviral AIDS drugs.
4. If AIDS vaccine itself is a "disruptive technology," perhaps Dr. Cotropia's discovery is the most potentially disruptive of all? It has been around a long time, and logged the most impressive stats in studies so far. If it goes through clinical trials and proves that it can deliver that 98% in an actual vaccine, AIDS activists will put heat on the FDA to approve it for market ASAP -- as they did with AZT's approval in the 1980s. But might that global pressure come too soon for powers that protect their profits from ARV drugs?
5. Have the government and AIDS industry been patching together that old energy-industry strategy? One that will let them have their cake and eat it too? I.e., spend some money on vaccine research, which makes them look good on the humanitarian front and provides jobs for cronies? But delay on bringing a vaccine to market till the last dollar of profit has been squeezed out of the drugs?
6. Will the "bigs" push this old high-mileage strategy until growing resistance to ARVs everywhere in the world is stirring a tidal wave of righteous outrage? Meanwhile, will the "bigs" lose any sleep over millions of lives lost to AIDS while the delaying game is being played out?
A shorter version of this article
was published in A & U Magazine,
Los Alamos HIV Clinical Database figures showing the long list of HIV strains neutralized by KLIC. The neutralized strains show up in red.
For a stark close-up on AIDS-industry politics, interested readers can go to Bruce Nussbaum's book Good Intentions: How Big Business and the Medical Establishment are Corrupting the Fight Against AIDS.
The book was first published in 1990, but the ugly behind-the-scenes politics that the author spotlights are still running the AIDS industry today. Nussbaum noted the "not invented here" attitude in the research world, and described the process by which a close-linked insider group of big corporations, scientists and government officials control the gateway to FDA approval. This process was what moved an "insider" drug, namely AZT, into position as the first drug released for market, and ensured that several other promising AIDS drugs got sidelined because their inventors were outsiders.
Then as now, Nussbaum was an editor of Business Week. -- and one of the few in the major media who paid attention to the skulduggery that infests much of the biomedical-research industry.
The "not invented here" problem is another factor in AIDS vaccine research. But that's a subject for another article.