Sunday, November 3, 2013

Of Pindar and the Politics of Longevity: Larry Page, Meet the Hayflick Limit, Henrietta Lacks and the Ironic Secret of Cancer 

Google co-founder and CEO Larry Page is super-smart and super-rich.  Now, he wants to end aging as we know it.  And all of us who are aging should naturally wish him well.   But as Lt. Columbo would say on the 70s TV show, “There’s just one more thing.”

That “one thing” is context.   Specifically, political context.   In the abstract, putting an end to aging may be a scientific mission.  But in the real world—and even megabillionaire tech titans inhabit the real world—a massive new medical-scientific effort will end up being political.  That’s why it’s so important for Page’s effort to be anchored in public support.  

Without a new doubt, Page’s new venture, Calico—an ironically understated  acrostic of “California Life Company"—is aiming big.  As Page said in a September 18 Google press release,

“Illness and aging affect all our families. With some longer term, moonshot thinking around healthcare and biotechnology, I believe we can improve millions of lives.” 

We certainly admire moonshot-type thinking.   Nobody rallied the nation to a great goal better than John F. Kennedy.  Thanks to the firm support of the American people, the space program reached its goal.   So here we are reminded that the Apollo mission was, in fact, a public program.   It endures today as one of the great triumphs of the United States—all Americans can take pride in its success.  

Back to the here and now, Calico has enlisted Arthur D. Levinson, Chairman and former CEO of Genentech, to be an investor-CEO of the new venture.  Genentech under Levinson developed landmark drugs to attack certain kinds of breast, colon, and lung cancers. The Google press release included poignant words from Apple CEO Tim Cook:

“For too many of our friends and family, life has been cut short or the quality of their life is too often lacking. [Levinson] is one of the crazy ones who thinks it doesn’t have to be this way.  There is no one better suited to lead this mission and I am excited to see the results.”

Cooks’s predecessor at Apple, of course, was Steve Jobs, who died of cancer at 56.  So there’s every reason to hope that Calico succeeds.  Indeed, if it does succeed, one can imagine a new longevity business that would make even mighty Google look small.  

Given Levinson’s background, and the lingering presence of Jobs’ example -- life cut short -- you’d think cancer would be a big concern of a life-extending effort.  According to the American Cancer Society, nearly 1.7 million Americans will be diagnosed with cancer in 2013, and more than 580,000 will die of it.  

Yet curiously, in a recent Time interview—the magazine’s cover story asked, “Can Google Solve Death?”—Page seemed to downplay cancer’s importance.  Cancer, Page seemed to muse, as bad as it is, was a sideshow on the road to longevity:

“If you solve cancer, you’d add about three years to people’s average life expectancy.  We think of solving cancer as this huge thing that’ll totally change the world, but when you really take a step back ...  in the aggregate, it’s not as big an advance as you might think.”

Page is looking beyond cancer, or any other single disease.  He is reaching, instead, for immortality.  If so, then surely he is going to seek to tackle the Hayflick Limit, named after the scientist Leonard Hayflick.  The Hayflick Limit describes the number of times a normal cell can divide.  Writ large, it appears to put a time-limit on all of our lives.  

In Greek mythology, the three Moirai, or Fates, first spun the the thread of life, then measured it, and then snipped it.  As the ancient poet Pindar wrote, they were “fine-armed daughters of Night…all-terrible goddesses of sky and earth.”   Through the eons, the sorrow of death has a way of eliciting the greatest eloquence, haunting our imagination.  In this more scientific era, the Hayflick Limit is the scientific expression of that doomed inexorability.  

Page is right that we should focus on big medical breakthroughs that might overcome the Hayflick Limit.  

Yet perhaps he is overlooking a key point when he speaks “in the aggregate” and minimizes the value of curing cancer.  

Why?  Because, politically speaking, most people understand that cancer -- even with advances like Genentech medicines -- remains a seemingly random and fearsome prospect; and scientifically, in its own terrible way, cancer is immortality. 

We can see how these political and scientific strands interweave in the life of Henrietta Lacks, an African-American woman who labored in a Baltimore steel mill during World War II, raising five children.  Lacks died some 62 years ago, in 1951, aged 31, the victim of a fast-growing cervical cancer.  

Her poignant story is also instructive.  Though dead some 62 years, Lacks’s cancer lives on.  Her tumor was rare, and, in the right cell culture, immortal.  That’s the scientific value of her example, the connection between cancer and longevity.  However, as described in the 2010 book, The Immortal Life of Henrietta Lacks, there is a political dimension as well.  Lacks’ cancer cells were extracted without her consent and farmed out to cancer researchers worldwide for decades.  Decades later, with genetic screening, some of her descendants’ genetic data was published without their consent.  That’s the kind of personal exploitation that breakthrough medical research must avoid at all costs.  Great science benefits everyone, but it begins by respecting everyone as well.  In Lacks’ case, NIH Director Francis Collins tried to right past wrongs this year, setting new rules with Lacks’ descendants governing how her cells can be used and genetic information can be released.

Once ethical concerns about individuals’ participation in research are reconciled—and those concerns aren’t small, but they are solvable —then we can see that cancer does, in fact, offer us a window of hope on immortality.  If regular cells, in becoming cancerous, can reprogram themselves to be immortal then why can’t other kinds of cells live forever, too?  Like a human body?  

Scientists are making great strides in coaxing regular cells back to their primeval states, to a time before their genetic programs told them to be skin cells or liver cells, or any other cell.  However, once reset, these cells remain subject to aging --  decay, degeneration, and death.  By contrast, cancer causes resilient, hyper-growth tumors.  It may be possible to fuse that which kills us and that which gives us life.  The problem is we just don’t understand it well enough.  Getting to that understanding will require great science, and leadership by scientists and politicians to build widespread support for work that may transform our lives. 

Cancer research holds a second lesson for anti-aging therapies. People with the same cancer treated the same way often have different outcomes.  Some live, some don’t.  Cancer therapies have to be tailored to tumor types and individuals.  Like cancer, anti-aging will need to build on hundreds of millions of data points, each data point representing a person who choses to share their information.  

In law, hard cases make bad law.  Not so in medicine.  Unique cases shed new light on old mysteries.  You never know when another Henrietta Lacks, a rare individual with a uniquely informative situation, may come along.

As an aside, that’s why it was so disappointing to see an October 14 op-ed in The New York Times, entitled, "In Cancer Care, Cost Matters," which denounced new cancer drugs for being too expensive for the health value they offered.  The three co-authors, all MD's, declare that they will boycott these new drugs.  Indeed, they make it plain that they see their boycott as part of a larger effort to curb healthcare costs.  As the trio asserts, "The current level of spending on health care, estimated to be $2.8 trillion this year, is already too high. The growth rate in health spending is unsustainable." Their boycott, they add, "Is a step in the right direction—one of many we need to take."

That Times op-ed was followed by a cover story in New York magazine headlined, “The Cost of Living: New drugs could extend cancer patients’ lives—by days. At a cost of thousands and thousands of dollars. Prompting some doctors to refuse to use them.”  

We can say of both of these pieces, and the many others that followed: In the battle against cancer or aging, we need as many people involved as possible, even long before they get sick or retire.  The cost of cancer drugs is a function of the high upfront cost to determine which drugs might work against which tumors in which people.  Every data point, every person, we involve can lower that cost.   

If some doctors believe that treating cancer on an incremental basis isn’t worth the cost, well, they should be reminded that the history of treating any disease—or, for that matter, the history of any technological advance—is replete with high upfront costs, followed by declining costs, and greater efficacy, as science progresses.  To short circuit that process is a supreme instance of being penny-wise and pound-foolish.  It allows the judgement of comparatively few skeptical researchers to be placed ahead of the collective benefit of great research.  What gives some doctors the right to place their narrow perspective of the possible ahead of the public’s broader right to live longer, healthier lives?

The prototype of anything, we might observe, is ridiculously expensive.  By definition, the new thing has no economic value--it's just a cost-center, someone's obsession.  Yet if the concept proves out, and as production ramps up, prices naturally start to come down, as the product slides down the experience curve.  That's how things that were unattainable at any cost--because they simply didn't exist--go from being, first, expensive luxuries, to second, inexpensive commodities, to third, unrecognizable, because some new innovation has come along to obsolesce the old thing.   That's been the story of the Scientific and Industrial Revolutions over the last four centuries, and it's lifted up not only our standard of living, but also our lifespan.

So if we were to take seriously, as a society, the challenge of curing cancer, then we might consider new financing mechanisms, aimed at rewarding discoverers, innovators, and producers, and yet also making sure that the cancer drugs are widely available.   But that's a topic for another post.  

So we come back to the lessons of Henrietta Lacks.  Her case reminds us that scientific research does not always have an immediate "business model."  Of course it doesn't: It's science. 

The Lacks case also shows the that the gathering and sharing of human information simply must occur within an acceptable ethical framework.  Most obviously, that ethical framework begins with the sine qua non of informed consent, which is so important that we find a lengthy discussion of informed consent on the American Cancer Society website. 

Yes, it’s easy to imagine human information-gathering outside of an acceptable ethical framework.  But it’s impossible to imagine such research staying secret for very long.  And then there would be hell to pay.  This is a world of social media, Twitter, and Instagram; information wants to be free.  Indeed, even the government’s efforts to monitor all that information seems to quickly become public. 

So the only politically sustainable way to conduct breakthrough research is to explain to each individual the benefits and risks of participating, to create incentives for them to do so, and protections that information derived will not be held against them.     

Perhaps in our big data age computers and algorithms will do most of the work.  That is, ones and zeros will be the new white mice.  That’s great, and will help reduce costs drastically, but sooner or later, any treatment will need human testing.  The pool of human test-subjects could be drawn from desperate patients, or perhaps even compensated volunteers.  But individuals and societies will have to to go in to the exercise with their eyes wide open. 

Who better than companies like Google to get people to share data and crunch it?  No one, except giving tech companies your search history is very different than giving them your genetic data - the essence of who you are.  Refining medicines, too, is much dicier than optimizing software.  Web browsers have “back” arrows; bad code can be undone.  Not humans.  There’s no “Command Z,” or undo, when treatments go wrong.

So even if computers become powerful enough to design drugs without lab work, researchers will need patients’ trust.  Otherwise many who might benefit from trying a drug in a trial will say, “thanks, but no thanks.”  A treatment that might have worked well in some will be written off as a failure, or dismissed by insurers and governments as having little value for the cost.  That’s happening already, as we see in the New York magazine article cited above.

Calico—and other similar efforts that are no doubt already ongoing—need to operate with the support of millions and maybe billions of people, sick and well.  

For big data and big science to work their wonders, each participant must feel personally connected to the research’s goal.  After all, there’s much data that a healthy person could offer between now and when they fall ill that might help scientists detect their condition earlier and treat it better.  

That’s why politics matter.  Every major gain in lifespan has followed a political and cultural shift in support of better science.  This was true for vaccinations, safer childbirth, antibiotics, Franklin D. Roosevelt’s work on polio—the March of Dimes was a spectacularly successful public-private partnership—and recent efforts to cure HIV and eradicate malaria.  Political support will matter even more in fighting age-related disease since effective treatment may have to start long before a condition is outwardly clear. 

Investments in real science, such as Page’s, are a welcome contrast to Washington DC’s belief that health issues can be solved solely by manipulating finance and insurance coverage.  But for billionaire-funded “big science” to have lasting impact, funders must realign their interests with the public interest.  Durable political coalitions rely on shared belief and coordinated action, not top-down brilliance.  Once you earn people’s trust, you can ask them to lend their data, their voice, and eventually their lives; but trust comes first. That’s the enduring lesson of Henrietta Lacks. 

Indeed, we must never lose sight of the real glory that is humanity and human expression.  As Pindar wrote 2500 years ago: 

“Creatures for a day! What is a man?
What is he not? A dream of a shadow
Is our mortal being. But when there comes to men
A gleam of splendor given of heaven,
Then rests on them a light of glory
And blessed are their days.”

Yes, we all are lit by the splendor given of heaven.  And we should all have the right to participate in its glories.  

Today, we know longer fear The Fates, except as a metaphor.    

Yet the common humanity that Pindar described is still with us.  The shared radiance of collective purpose should shine down on all of us.   If it does, we will all live longer, and better.  

Editor's note: This piece was co-authored by Jeremy Shane and James P. Pinkerton.

1 comment:

  1. Interesting article; good points made especially relating to perspectives.