Tech Free Reports
August 11, 2014
The last ten years’ progress in biotechnology and medicine has outpaced the previous ten years significantly. The same thing is true of the ten years prior to that ten years. The next ten years, it’s safe to say, will see greater progress than any other period in history.
Powered by exponential advances in the biological sciences that are outperforming Moore’s Law, we are winning the war on diseases. The war isn’t over, but I’m on record predicting that companies currently in or near human trials will make cancers, antibiotic-resistant bacterial infections, virus-borne diseases, fibrotic diseases, and even Alzheimer’s manageable threats within the next decade.
To one degree or another, most biotechnologists are growing increasingly optimistic about our ability to deal with the old killers. The successes we have already experienced—falling mortality rates for cancers and cardiovascular disease, for example—are working a change in the way the scientific community thinks about medicine.
The most important change is a growing recognition that we need to switch our focus from battling individual diseases to increasing health. This may seem like a minor difference in language, a semantic subtlety, but it’s not.
Internationally, drug regulatory systems are based on the old defensive model. Regulators recognize specific maladies and approve or reject therapies based on very narrow criteria. From the filing of investigational new drug (IND) applications to clinical trial designs, the system is a series of boxes that force innovators into the disease/drug model of medicine.
While many researchers are pursuing methodologies for maximizing health to preclude serious illness, our system is biased against this more systemic approach to healthcare. The consequences of this institutional bias are an increasingly serious problem as the population ages.
This is why I was glad to see a recent commentary, “Medical Research: Treat Ageing,” in the important journal Nature. Written in two parts by different groups, the introduction makes the challenge clear. It states, “By 2050, the number of people over the age of 80 will triple globally. These demographics could come at great cost to individuals and economies. Two groups describe how research in animals and humans should be refocused to find ways to delay the onset of frailty.”
I’m not, incidentally, holding Nature’s commentary out as infallible. There have been numerous instances in the past that I’ve disagreed strongly with Nature commentaries. Nevertheless, the publication has sway, so I’m pleased to note that this article recognizes the need to delay frailty, which is associated with the onset of serious disease. Another way to phrase the goal of delaying frailty and death is “life extension,” though the term has not enjoyed much respect in the past.
The ongoing demographic change referred to in the Nature commentary, which others have called “The Grey Tsunami,” is forcing serious people to finally embrace goals that were once considered slightly weird, at best. In the past, life extension was often considered the domain of the deluded fringe, driven by entirely selfish motives. Today, life extension presents itself as the only real means of solving the biggest challenge facing civilization: our rapidly aging population.
Already, however, we’re experiencing serious problems caused by the inversion of the traditional demographic pyramid. In the past, there were always far more young working people than retired people. When I was born, the ratio was over 15 to one. Today, there are less than three workers for every retired person, but we are still trying to fund programs established when lives were much shorter and birth rates were much higher.
The major component of the deadening debt that afflicts so many nations today is rooted primarily in programs designed to support aged populations. As birthrates, and therefore populations of younger workers, have fallen in proportion to older people with greater healthcare costs, funding for social programs designed when far fewer people lived to old age has fallen behind. Not surprisingly, though, there is little support for reducing benefits to the aged.
Unfortunately, the math is simple. As this University of Michigan study states, “Nearly one-third of lifetime expenditures is incurred during middle age, and nearly half during the senior years.” This means that only one-sixth of lifetime medical expenditures accrue before middle age, which is why policymakers and politicians desperately want these young healthy people paying more into the system.
Experience with the Affordable Care Act (ACA), however, has shown that this is easier said than done. Even if a hundred percent of young healthy people were to buy health insurance, it would only temporarily solve the demographic crisis. In 2050, when aged populations have tripled, there will not be enough young working people to pay older people’s medical bills. Period.
The only solution to this problem is that older people will have to work or invest significantly longer. In fact, they already are. Boomers are delaying retirement longer than ever before, primarily for healthcare-related financial reasons.
We should recognize that current retirement expectations are untenable. The only way for our children and grandchildren to have the same kinds of unburdened opportunities that older people have enjoyed is to increase healthy life spans, health spans, and careers.
Yes, some older people will fight against this change. My sympathies go out to them because they will lose the argument.
The Nature commentary makes a number of proposals about ways we should change our scientific focus to life extension, though that phrase is never explicitly deployed. Extensive evidence that we could accomplish this goal is found in successful efforts to extend health spans in animals.
You should read the entire commentary, though I have some problems with its basic approach. Essentially, the commentary is proposing changes in the way that government regulators and healthcare agencies operate. While I support any effort to reform government, I have little faith that bureaucracies are capable of making meaningful changes. Too often, government is the problem.
If you want evidence, look at the area of diet and nutrition. The ever-changing recommendations put forth by government in this important health-related area have been a complete fiasco. I won’t go into the history of government malfeasance on the dietary roles of carbohydrates and fats here, but most people know how wrong the various pyramids of doom were that we were taught as dietary gospel.
Similarly, government officials seem dead set against recognizing the new and critically important consensus on optimal doses of vitamin D. It’s not surprising, therefore, that the new companies that have identified historically important breakthroughs in life extension are afraid even to cite peer-reviewed, third-party studies on their websites.
Success in the area of life extension depends on liberating scientists and researchers from bureaucratically imposed limitations on their ability to communicate important information. Today, speech regarding drugs and supplements is extremely constrained and even the truth is no defense.
My nutritional biologist wife calls strict federal control over scientific knowledge “information hoarding.” A simple fix might be to mandate that research performed using public funds be made public and that regulators cannot ban or interfere with the publication of any research unless it’s judged fraudulent by unbiased peers. Full disclosure even in controversial areas is always more productive than banning scientific speech.
Then, of course, there is the issue of the extremely expensive drug approval process. According to an estimate by Forbes, “A company hoping to get a single drug to market can expect to have spent $350 million before the medicine is available for sale.” On average, Forbes estimates that the industry spends $5 billion for every approved drug.
Some people, like Susan Desmond-Hellmann, the chancellor at UCSF and former head of development at Genentech, say plainly that this is “crazy” and “unsustainable.” Off the record, most scientists I know will say as much but few will risk offending regulators who make the decisions that determine when and whether drugs come to market.
Former FDA chief Andrew von Eschenbach has proposed the elimination of phase 3 trials due to changes in the way that drugs are developed and prescribed:
These Phase 3 clinical trials served us well in the past. Today, in an era of precision or personalized-drug development, when medicines increasingly work for very specific patient groups, the system may be causing more harm than good for several reasons.
First, because of their restrictive design and the way the FDA interprets their results, Phase 3 trials often fail to recognize the unique benefits that medicines can offer to smaller groups of patients than those required in trials.
Second, information technologies have created improvements in our ability to monitor and improve product performance and safety after medicines are approved for sale. Post-market surveillance can and should reduce dependence on pre-market drug screening in Phase 3 trials.
Third, reducing reliance on Phase 3 trials is unlikely to introduce an offsetting harm induced by more dangerous drugs, since evidence supporting safety is produced in earlier phases. Manufacturers also have powerful incentives to maintain drug safety, since they take enormous financial hits—well beyond the loss of sales—when drugs are withdrawn after approval.
Eschenbach is right and I encourage you to read the entire article, but I don’t want to give you the impression that the only hope for life extension technologies resides in the hands of the same people who oversee the Veterans Administration healthcare system. We live in an era of falling travel costs and expanding options in healthcare tourism.
It’s summer here in South Florida where I live, which means that the hundreds of thousands of Canadians who winter here have gone home. So it’s much easier now to get in to see a doctor. Americans are also increasingly going offshore to get better deals on everything from cosmetic to liver transplant surgeries. If America doesn’t adapt to the increasing demand for life extension technologies, other countries will gladly step up.
The most important example is Japan. Faced with even worse demographics than America’s, Japan has radically streamlined the approval process for regenerative medicine (i.e., stem cell-based therapies). Regenerative medicine, especially stem cell therapies that used our own cells that have been reverted to youthful induced pluripotent status, are particularly well-positioned to benefit from the sort of reforms that Eschenbach lays out.
Essentially, Japan is requiring only that stem cell therapies be safe before they are marketed. This makes sense because many stem cell-based life extension therapies in development now will simply replace aged cells with younger versions of those cells. Anything an aged cell can do, a younger version of the same cell will do better. More importantly, regenerative medicine holds the promise of extending maximum life and health spans far beyond the current theoretical limit of about 120 years.
This essay is getting too long, but I wanted to begin a discussion about this important issue today. Last week, John Mauldin and I went to Minnesota to see a technology that appears on track to providing unlimited bioengineered transplant organs. I’m not, by the way, talking about 3D bioprinting. While there, we spoke a lot about the need to get more involved in the effort to bring reform to the areas of government that are slowing down life extension progress.
In many ways, it’s synergistic with our goals of finding ways to navigate this enormous and unprecedented change in demographics and therefore markets. If this is something that readers are interested in as well, stay tuned. We’ll have much more to say about this in the future.
From the TransTech Digest research team: To learn more about Patrick’s Transformational Technology Alert research advisory at Mauldin Economics, click here.