Stumped

We didn’t know what was causing his death.

When we walked on to the medicine wards of the San Diego VA many years ago, most interns were pretty ignorant. Yet we believed someone else knew what to do.

As in what was causing the large stock of misery before us.

In VA medical wards stuffed with people suffering from chronic obstructive lung disease and heart disease, the causes seemed pretty clear.  First was tobacco; next was alcohol.  Many patients could barely breathe no matter how many steroids or epinephrine-like agents we threw at them.  Still they stole butts from the floors and plugged the burning ends into trache tubes.  Some older folks walked in carrying suitcases.  They quickly told the ER docs they were “100% service connected” and thereby guaranteed admission – for whatever diagnosis their service connection carried.  Not uncommonly they drank – heavily.

Yet many patients were not easily pigeonholed.

One fellow stumped his.  He was 25.  He had come for experimental chemotherapy.  He was dying from squamous cell cancer of the tongue.

We had been taught that “virtually all” such tumors were “caused” by alcohol or smoking.

He did not drink.  He did not smoke.  His life was pretty much that of an Eagle Scout.

He had spent time on a nuclear submarine – was that a possible cause?

But as we ran down what was killing this young, pleasant man,  we did not have a clue as to why he had that tumor.

These days, human papilloma virus, or HPV, is said to be “associated” with throat cancer.  A recent English case control study found an odds ratio over 30 for throat cancer patients with antibodies to a specific HPV protein – compared to controls.

But does association prove “cause”?  Are people with such throat tumors much more likely to have been infected with such viruses as part of an immune defect that makes them prone to cancer?  Do infections take place more readily after the cancer has started its growth– often many years before overt clinical evidence?  Is the antibody just a marker for a separate process?

We still don’t know what caused the young man’s tumor.  Chances are we won’t.

Unknown Unknowns

After 9/11, Secretary of Defense Donald Rumsfeld was pilloried for a speech describing the security threats the nation  faced.

There were “known knowns”, enemies that traditionally had struck at the United States; there were “known unknowns”, groups that were hostile, but might inflict “unpredicted” attacks. Last, there were the unknown unknowns – thoroughly unpredictable foes.

The standard implication was that al Qaeda was in the third category. Who ever expected the Pentagon, the World Trade Center and the Capitol to be successfully attacked by hijacked American civilian aircraft?  The impact of such “unknown unknowns” could only be great – and psychologically shocking – because it was “unthinkable.”

The truth was far more painful. Al Qaeda had attacked the World Trade Center in 1993, and come a lot closer to  toppling it than people realized.  National security staff at the highest level had been told the month before that al Qaeda was “poised” to attack the US. Agents  had so pestered the Attorney General – who was cutting the budget for anti-terrorist activities – that he told them to not even speak to him about possible attacks for six months.

The attack on 9/11 had come from a “known” and watched enemy.  The nature of that force  had been unexpected – though Minnesota FBI agents had been trying to alert their superiors that Saudi students going to pilot school  clearly had no intention of becoming pilots.

Chance favors the prepared mind.  It does not favor the closed mind.

Yet security officials still argue that with so many terrorist groups – so many enemies – how could the Bush administration have  known what would happen?

So instead, let’s consider the human body.

Immunity and Knowledge

Until twenty years ago gut bacteria did not get much respect.  A researcher who proved that one of them, now called helicobacter pylori, caused the common stomach ulcer, was laughed at and ignored – until he won the Nobel prize.

In the last few years people have noticed the 100 trillion bacteria in the gut are doing more than digesting food, creating stool and throwing off  vitamins.  Now the 5000 to 10000 different varieties down there are linked to depression; autism; MS; ulcerative colitis; weight gain – as well as controlling the infections of nastier bacteria and viruses.

How many other major biological systems will we learn about in the next few years?

The “biome” of gut bacteria has been hiding in plain sight for decades.  What have the 100,000 chemicals pumped into the environment done to us?  How is climate change changing the bugs that infest us?  What is reconfiguring rest and sleep – we sleep 90 minutes less each day than 40 years ago – done to our health and work capacity?

We don’t know.   And those are known unknowns.

Fortunately – very fortunately – our biology is brilliant at coping with unknown unknowns.

Our immune system continues to evolve – very rapidly – new ways to cope with trillions of viruses that can all mutate within hours; to deal with thousands of different bacteria that can turn deadly – or cancerous; to knock off thousands of tumors each before we could ever knew they were there.

As Nassim Taleb points out in “Anti-Fragile” biology is very good at surviving the unknown unknowns – and creating an information system that can survive stuff thrown at it  never experienced before.

But to understand that we have recognize something Rumsfeld recognized – that the known unknowns dwarf factors known; and the unknown unknowns are far vaster and often more powerful than factors we think we understand.

What we don’t know is far greater than what we know.

And as we recognize the power chance has in our lives, it pays to recognize something else – that the little we do know can do a lot of good.

Once we can learn to know what we really know.
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