There are still many scientific hurdles to overcome before Dr. Atala’s pioneering work results in the mass use of regenerated organs. Atala estimates that most of what he demonstrated is some years away from being ready for prime time. But in addition to the scientific challenges, the process of getting breakthroughs past the FDA is astonishingly slow. We are likely many years away from seeing approvals for most of these therapies under the current regulatory model.
Standards for clinical trials were designed for the pharmaceutical industry, and those standards pose an extremely steep challenge for regenerative medicine. The FDA has major divisions for medical devices and for “biologics” (covering, for instance, vaccines and transplants). But regenerative medicine falls into both of these categories, Dr. Atala told me, which means that “the regulatory path is one that has to fulfill the requirements from both branches, which is really very complex.” (Of course, as we saw in the case of Abigail Burroughs, it’s hard enough to fulfill the requirements of one branch.)
In the trials the FDA currently demands, a company attempting to bring this technology to market would have to pay these huge costs on its own—and not just the cost of the technology. In addition to the extraordinary costs of growing an organ, clinical trials of regenerative medicine would have to cover surgical costs, X-ray costs, hospital costs, and inpatient costs, which are not common with other types of trials.
Testing regenerative medical technologies is not only expensive, it is fundamentally different from testing a pill. For one thing, the results are basically black and white. A new kidney either works or it doesn’t. This is more definitive than a drug test, in which researchers observe patients for months to look for marginal improvements over other products on the market.
In pharmaceutical trials, every pill is identical. That’s what makes the kind of testing the FDA demands statistically meaningful. But with regenerative medicine, as another doctor reminded me, “you’re using the patient’s own cells, so every time you’re creating a product, you’re really creating a different product because it’s unique to that patient.”
Many in the field agree that the FDA’s unreasonable hurdles are keeping medicine trapped in the past, but the same doctor told me his colleagues are afraid to speak up because the agency holds the keys to everything they do. After all, the FDA has to approve every drug and every medical device a company might want to market, and no one wants to make the prison guards angry. They could draw out the process, demand more expensive trials, set impossibly high evidentiary standards, or even leak rumors to tank a company’s stock price.
“We bring in people from industry, and they’re worried to make the FDA upset, so they’re actually afraid of making any suggestions for change,” the doctor commented. “Everyone is afraid that they’re going to get pounced on because they’re making suggestions for change. They have too much riding on the stuff that they’re doing right now, which is under the current regulatory process.”
To avoid the time and expense involved in testing regenerative medicine products under current FDA regulations, many companies are simply fleeing the United States. “Yes, it is accurate that there are other countries where you can go fairly quickly to the clinic and try these technologies,” Dr. Atala said when asked about this. “What you’re seeing is there are many technologies that are being done abroad that are not yet done in the U.S., and that a lot of these breakthrough technologies are being done clinically first abroad rather than in the U.S.”
How quickly could regenerated organs be widely available in the United States? Dr. Atala predicts that some organs could be available “within five to ten years” under a pathway designed specifically for the new field of regenerative medicine. How long will it take under the current FDA? Data shows that the average regulatory path for a pill—just for a pill—from the time it reaches the first patient of a clinical trial to the time it actually gets distributed to the open market is 15.1 years.
It wasn’t always this way, one doctor tells me. “The process used to be short. It did not take fifteen years before. There was a time when the process only took six years. And there was a time when the process went up to eight years. Then it went up to ten years. In the 1990s, it was twelve years. Now it’s fifteen years.”
Nearly a quarter of all products Americans consume are regulated by the FDA. Every single drug and medical device we rely on must pass the inspection of FDA bureaucrats, not to mention nearly 80 percent of our food supply. That’s an extraordinary amount of power for one federal agency.
Americans deserve an FDA that protects consumer safety but also makes sure lifesaving breakthroughs get from our labs to our pharmacies and hospitals as efficiently as possible. That’s far from what we have today. The agency is still clinging to an obsolete, decades-old regulatory model that will drown the strides in regenerative medicine that could enable us to treat kidney failure, diabetes, many cancers, and other diseases with a brief trip to the hospital. Without a major transformation, the FDA will keep American patients trapped in the medicine of the past, probably for decades.
Think that’s an exaggeration? Consider how long it has taken another lumbering federal bureaucracy, the Federal Aviation Administration, to approve Kindles and iPods for use on commercial airplanes below ten thousand feet. Fifteen years after the introduction of the first MP3 players and nearly a decade after e-book readers became widely available, passengers are still prohibited from reading on Kindles or listening to music for much of their flights. In fact, the entire product life of the iPod has come and gone and e-books have surpassed print books as the dominant format for publishing without the FAA’s noticing. There is no evidence to justify the ban on these items; millions of passengers routinely flout the rules with no effect on safety. The FAA simply hasn’t updated its regulations on in-flight electronics since the 1960s. The agency, moreover, is still mired in the effort to convert the air traffic control system from 1950s-era radar to GPS, which has been commercially available for fifteen years and which virtually all passengers carry onboard the plane in their pockets.
The FDA is as slow and resistant to change as the FAA, but delays and rejections of new medical technologies are a matter of life and death. Congress gave the FDA authority to judge the efficacy of drugs, in addition to its original mission of assessing safety, in 1962. Evidence suggests this new layer of bureaucracy caused a dramatic decline in the number of new drugs introduced. The Wall Street Journal’s Daniel Henninger reports, “A 1974 study by University of Chicago economist Sam Peltzman concluded that since 1962 the new rules had reduced the rate of introduction of effective new drugs significantly—from an average of forty-three annually in the decade before the amendments to just sixteen annually in the ten years afterward.”24 That’s a 63-percent decline in the number of new drugs that reached pharmacies in the decade following the agency’s expansion. Delays continued into the next decade. Henninger cites a study from the Tufts University Center for the Study of Drug Development that concluded that nearly three-quarters of the forty-six drugs approved by the FDA in 1985 and 1986 were available earlier in foreign markets, by an average of five and a half years.25
The FDA’s onerous regulations and strict clinical trial standards come at a price. Avik Roy of the Manhattan Institute reports that development costs rose from $100 million per drug in 1975 (2012 dollars) to $1.3 billion in 2005—a thirteenfold increase.26 The bulk of this increase comes from the exploding cost of the phase III clinical trials, which the FDA scrutinizes heavily. In the six years from 1999 to 2005, Roy reports, “the average length of a clinical trial increased by 70 percent; the average number of routine procedures per trial increased by 65 percent; and the average clinical trial staff work burden increased by 67 percent.”27
No wonder we get the one-pill-fits-all medicine Eric Topol laments! How could any company personalize its drug for you if it had to spend hundreds of millions of dollars on a two-thousand-patient clinical trial for the FDA?
&nbs
p; Needless to say, startup costs in excess of a billion dollars are a colossal barrier to innovation. Only the very largest pharmaceutical companies can afford to bear them, and they can spend such sums on only a handful of major drugs. It is almost unthinkable that an independent business with a technology like Dr. Atala’s could survive such a process.
Even if the exorbitantly expensive and redundant trials the FDA demands inhibit innovation, aren’t they there to keep us safe? Safety may be the goal, but deterring innovation is deadly. Ronald Trowbridge and Steven Walker of the Abigail Alliance for Better Access to Developmental Drugs (named for Abigail Burroughs, whom we met in the introduction to this book) recount one outrageous example:
Beginning in June 2004, we started pushing the FDA to make Nexavar and Sutent, both highly promising drugs for kidney cancer, available. The agency eventually approved Nexavar in December 2005 and Sutent in January 2006. But that was only after evidence of efficacy so compelling emerged for Nexavar that the trial demanded by the FDA—in which dying kidney cancer patients seeking the drug were being given no other choice (except certain death from their cancer) but to agree to a 50/50 chance of being blindly randomized to a sugar pill—was stopped by Bayer for ethical reasons and the placebo patients allowed to get the drug. The sponsor seeking approval for Sutent was given a similar option by FDA if it wanted its drug approved. About 20,000 kidney cancer patients died waiting for both drugs.28
Trowbridge and Walker cite numerous other delays that denied tens of thousands, sometimes hundreds of thousands, of dying patients the breakthrough drugs that might have saved their lives. Yes, the FDA might grant a handful of these patients the “compassionate use” waiver that Abigail sought, but drug companies themselves are understandably reluctant to go along lest they endanger their billion-dollar investments in tightly controlled clinical trials.
If this is how the FDA handles new pharmaceuticals, what will it do to the transformational new technologies of regenerative medicine? The prison guards could set us back decades. Since the FDA is obviously unprepared to adapt to such breakthroughs and speed them to market as efficiently as possible, the American people should demand the right to opt out of this lethal system. Champions of the coming breakthroughs should be able to bypass the FDA with informed consent. Patients whose doctors advise them to accept a lab-grown bladder or a new heart valve should be able to waive the prison guard seal of approval with a written acknowledgment of the risks. The chances are that many of us will want the breakthrough anyway.
It is true that this freedom might pose a challenge to the old model of clinical trials in which half of the patients get placebos and half get the actual drug. After all, it might be harder to get patients to agree to those odds if they can sign a waiver and be sure that they are getting the breakthrough treatment. But with continuous monitoring, as Dr. Topol demonstrated, and decades’ worth of clinical research data under our belts, it is time to look for more humane models of testing, anyway.
Winning this freedom will not be easy. The Blue Diamond nut company got a taste of the prison guards’ insane jealousy when it received an enforcement letter from the FDA. Blue Diamond’s labels had touted the natural health benefits of some of its products. For instance, one stated, “The omega-3 in walnuts can help you get the proper balance of fatty acids your body needs for promoting and maintaining heart health.” The FDA warned Blue Diamond, “We have determined that your walnut products are promoted for conditions that cause them to be drugs because these products are intended for use in the prevention, mitigation, and treatment of disease.” Blue Diamond walnuts were not only drugs, but they were new drugs that had yet to be approved by the FDA and therefore could not legally be sold. Since the “walnut products are offered for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners,” the FDA letter continued, “…adequate directions for use cannot be written so that a layperson can use these drugs [the nuts] safely for their intended purposes.”29 In other words, even if the FDA “approved” the company’s walnuts as a drug, they would require a prescription from a doctor. The company surrendered and changed the labels.
Let anyone who thinks the prison guards will relinquish their power without a fight be instructed.
Americans could soon enjoy longer and healthier lives with personalized medicine and regenerative technology. But the prison guards could delay those benefits by decades. Tens of millions of Americans don’t have that long to wait.
CHAPTER FOUR
BREAKOUT IN AMERICAN ENERGY
After dropping out of high school at the age of sixteen, Andy Turco took work wherever he could find it. Staining decks in the summer and shoveling driveways in the winter, Andy was willing to work hard, but steady employment was difficult to find. He often went months between jobs, and even when working, he earned so little that he was often on the brink of destitution. Surviving was a struggle. Actually improving his life seemed impossible.
That is until he talked to a friend who had recently gotten a great job in a booming industry. For Andy Turco, a personal breakout to a better life was not impossible after all.
It was a pipe dream—an oil and gas pipe dream.
Today Andy makes nearly six figures working ninety hours a week on a drilling rig in the remote town of Williston, North Dakota.1 The story of how Andy and millions like him all across America have achieved a better life thanks to amazing innovations in oil and gas production is a perfect illustration of the great breakout that is possible in America. It begins with a pioneer who ignored conventional wisdom to develop a technological breakthrough nobody else thought possible.
More than thirty years before Williston became a boomtown, President Jimmy Carter held a televised conversation with America, one he warned would be “unpleasant.” Our country, he said, was running out of oil and natural gas. The solution, according to Carter and the conventional wisdom of the time, was for the United States to reduce radically the amount of energy it used.
Laying out a plan to conserve our “rapidly shrinking resources,” the president used the word “sacrifice” ten times. And the energy policy built upon a foundation of pain and sacrifice succeeded in creating just that—gas shortages, high energy prices, and economic stagnation.
All of this suffering was totally unnecessary, but the president and his advisors were prisoners of the past—trapped by a prison guard as dangerous and difficult to defeat as teams of lobbyists or intractable bureaucrats: a false idea accepted as conventional wisdom.
President Carter and most of the energy experts at the time adhered to the “peak oil” idea. The prevailing theory of the time, it stemmed from a 1956 study by M. King Hubbert, who concluded that patterns of production for any finite resource follow a predictable pattern. Hubbert’s model forecast that the United States would reach its peak oil production in 1970 and decline gradually from there.
Many “experts” considered the peak oil theory validated after production indeed reached a plateau in 1970 and began falling steadily after 1985. The problem with the theory of peak oil, however, is the same one that plagues all projections of global disaster and is common to all prison-guard ideas: it fails to account for the breakthroughs by which pioneers solve our toughest problems and create new opportunities.
The peak oil projections did not properly account for the rate of new oil and gas discoveries and improvements in technology for extracting them. The truth was that we still had enormous resources in America—we simply lacked the means to obtain them at a reasonable cost.
In a sense, peak oil and the other theories that put limits on opportunity and growth are pessimistic theories of “peak America.” They can be dangerously self-defeating.
One of the people who understood this was George Mitchell. While the stated policy of the country was to move away from natural gas as a source of energy, this son of Greek immigrants staked his company on a countervailing view—that vast amounts of natural gas wer
e trapped deep underground, just waiting to be safely and economically tapped.
Shale is an extremely dense rock, often between one and two miles below the earth’s surface. At that depth, the rock traps individual molecules of natural gas and oil between its thin layers. Geologists had known this for decades, although they did not appreciate the scale of the resources—and more importantly, nobody had figured out how to extract the oil and gas at a reasonable cost.
Starting in the early 1980s, Mitchell drove his company to develop new technologies for releasing the gas trapped in rock thousands of feet below ground near Fort Worth, Texas, in a geological mass known as the Barnett Formation. Progress was slow and costly. Mitchell’s engineers knew that creating fractures in the shale was the key to extracting the gas. Typically, this involved injecting a fluid into the well at sufficient pressure to push its way into small fissures in the rock below ground, freeing the molecules of oil or gas trapped inside. In fact, developers had been using “fracking” techniques to extract more resources from wells for decades. But nobody had done it on the scale Mitchell had in mind or in such dense rock.
Mitchell’s company spent a decade working to extract gas from the Barnett Shale, but its wells cost much more than traditional ones, and the company ran short on money.2 Then three big breakthroughs changed Mitchell’s fortunes and in the process changed the world.
The first came when an employee at the company suggested adopting a much less expensive fracking technique from a rival company. Instead of pumping a costly gel-based fluid into the rock to create fractures, they used mostly water, combining it with sand to prop open the tiny cracks. The mixture was only about one-fifth the cost of the gel, and it ended up yielding more gas.3
The second breakthrough came soon afterward. A geologist named Kent Bowker suspected that there was much more gas trapped in the Barnett Shale than was thought, but he needed funding for the study. When he brought his proposal to Mitchell Energy, the company president, Bill Stevens, turned him down. Fortunately, Mitchell himself heard about Bowker’s proposal and overrode the decision. The astounding conclusion of Bowker’s study was that there was four times as much gas in the Barnett Shale as previously estimated.4
Breakout: Pioneers of the Future, Prison Guards of the Past, and the Epic Battle That Will Decide America's Fate Page 8
