Monday, January 01, 2018

Remembering 2017's Losses

A new year beckons and with it a burst of enthusiasm for writing.  Which also means combing through post ideas from last year that never quite were completed -- some as stubs or at least headlines.  But before tackling the new, I feel I need to tackle some personal losses in 2017.
Humans are mortal creatures.  Some companies and individuals may promise that immortality is just around the corner, but I do not believe it.  I cling to the idealistic notion that the biopharma industry exists in large part to keep pushing against the swing of the lethal scythe, but know that is a tough task. 

On every New Year's Day, news sites have lists and galleries of notables who exited during the previous annum. I won't review these in depth, but will note that NASA lost four retired astronauts who were all familiar to me for their actions, though I never had the luck to meet any in person.  Bruce McCandless looked over me through four years of college, sitting in the most glorious armchair ever invented.  Paul Weitz lived in orbit both on Skylab and the Shuttle.  Ron Evans was command module pilot on the second lunar landing mission, an exquisitely alone role.  And Gene Cernan was the last man standing on the moon and a frequent commentator on space launches.  Farewell to all.

Loss of someone is always difficult, but proximity and expectations can modulate that effect.  I learned through social media that someone I knew as a child was gone, but I had not thought of him in decades.  Others are lost who have traveled long lives, and the mourning is tempered by knowledge that they had a full chance.  But to lose people I had interacted with relatively recently and who were not at the extreme edge of the actuarial tables, that often hits hard.  Writing this is partly for closure, and partly to try to extract some useful insight on the state of biopharma.

My Best Friend's Best Friend

B lived up the street from us and was just a bit younger than Amanda.  There are four basic walking routes from our driveway, and on afternoons in the warmer seasons she would steer me in one direction and then turn into B's driveway.  Because she knew that B's human companion would almost always invite us to their fenced backyard, where the two pups would run around together. They were closely matched in both size and age.  He had a jaunty look, due to one ear being perpetually erect and the other flopped over.

Early last year, B's human detected an oddity in his gait.  Testing revealed a pituitary tumor which was pressing on his brain, leading to the symptoms.  A course of radiation therapy was initiated which seemed to make a dent, but the prednisone to control the immune response had the same effects as in humans: ravenous overeating.  He did better and we enjoyed a few more romps, but over the Christmas break I got the awful news that the tumor had beaten him.

I know someone else who is treating their dog for cancer -- a lymphoma in a older dog.  She commented that the balance of goals for canine patients is often different.  Chemotherapy is more likely to be dosed for palliative rather than curative effect.  Society accepts that lingering deaths are acceptable to short-circuit.  

The Scoutmaster

In early March the ground was beautifully snow-covered.  Our town has a lovely landscaped cemetery, a gift from the Victorians for time perpetual. The Scoutmaster of the Boy Scout Troop would have loved walking through the landscape, but unfortunately I was walking to his wake.

We weren't close, but we had a good working relationship. By day he was a high-powered intellectual property attorney, but in his spare time one of his favorite pursuits was developing young men into leaders.  His idea of a great spur-of-the-moment activity would be to head up to the White Mountains for some backpacking.  On the few outings I went on with him, you really could see him morph into an excited teenager, ready for adventure.  He was several years older than me, but just so robust.   So why was I walking through a burial ground?

Mesothelioma. In less than a year and a half the disease had run its lethal course.  Even several months before the final blow, I knew it had devastated him.  The boys had raked his yard as a show of solidarity -- and that yard has abundant deciduous trees -- and he was too weak to come out to say thank you.  

It is hard to think of a cancer with a seemingly stronger 1:1 causal relationship than mesothelioma, but he said he knew of no particular exposure.  So either this was a rare case not caused by asbestos or somewhere an unknown source contaminated his lungs.  When I was a boy my troop had an asbestos glove, which was a wonder because with it you could pick baked potatoes straight out of the fire or even disassemble a campfire.  Asbestos wasn't yet a total bogeyman, though it certainly was already becoming notorious.  

A lot of asbestos removal has occurred, but it sometimes seems never-ending -- I've seen two renovation projects recently that had warning signs for this mineral on them.  When we were clearing my childhood house a few years ago, a brother worried there was asbestos in it.  "Of course!", my father responded -- the  ceramic shingles were made with it.  There was also the sample in my childhood rock collection, which I keep sealed in a plastic bag.

It is rare to non-existent to hear of a biopharma pursuing mesothelioma as an indication.  In the U.S. it would qualify as a rare disease and incidence in men at least is slowly dropping (I found statistics for up to 2008).  But increasingly, mesothelioma is appearing as a disease due to exposure in the natural environment, perhaps abetted by certain genetic vulnerabilities.

As with many cancers, the tumor did not kill alone.  The final blow was a lung infection.  So while my involvement in cancer research is mostly peripheral now (another lobe of Starbase works on cancer), my current quest for new antibiotics might give some of these patients a bit more time and a bit more chance.

The Second Cousin

Every year there is a reunion of the descendants of my mother's paternal grandparents.  I have not gone often, but always enjoy the camaraderie.  Because it encompasses such a broad family tree, the ages of attendees span the gamut, and I am oft nearer in age to those one more rung down than on my own.  There is good longevity in the family; all of the members of my mother's generation are in quite good health.  In sad contrast, my mother is the last of the first cousins on her mother's side still walking the earth.  

I attended the reunion in 2016.  The family member who organizes the event picks the location, and that year it was outside Oak Ridge, Tennessee.  It helps that most relatives -- except my immediate family -- all live in the southeastern U.S. and can drive to such a location.  After the reunion, we headed down to the Great Smoky Mountains, driving through areas that would see terrible wildfires only about four weeks later.

One of my cousins had been living with ovarian cancer for a number of years.  I was excited to tell here about a recent successful trial and promised to give her any other news I had of new happenings.  But not long after my winter cemetery walk I found out the bad news from Mom: she had taken a sharp turn for the worse and succumbed.

Ovarian is one of the more notorious silent cancers, too often going undetected until it has metastasized widely.  Pancreatic adenocarcinoma (PA) is another in that category.  I learned late this year that my undergraduate advisor, whom I had lost touch with, succumbed to pancreatic cancer a few years ago.  It was particularly sad as he was an avid runner and meticulous about his health; PA is often associated with smoking but that certainly wasn't the case with him.  For ovarian and pancreatic, the goal of early detection seems always out-of-reach.  That's one reason I get disgusted by fawning headlines around early-stage detection technologies, such as the whole media storm years back around Jack Andrake.  We desperately need technologies, but so many promising leads have failed after careful clinical testing.  Indeed, my summer internship involved tests once thought to be future screens for both ovarian (CA125) and pancreatic (CA72-4).

The First Cousin

Because my parents married much later than than their siblings, and because I am the youngest offspring of that union, my first cousins were always much older than I.  Several are more-or-less contemporaries of my in-laws.  So I rarely saw my cousins when growing up.  In my adult life, we've sometimes grown closer, sometimes in interesting ways:  one of those cousins old enough to be my parent has a child just barely older than TNG.

L was fifteen when I was born and grew up in California.  I honestly don't remember meeting her in my childhood.  But we connected at a family wedding and then when she came out to Boston to visit a friend.  She lived in the Seattle area, so when I went there once in grad school I looked her up and she treated me to family photos I had never seen and family stories that I had never heard -- the best ones being stories that our parent's generation found embarrassing but we saw as familial color.  Her profession involved physical labor, and her father had been a tall man, and so she had a head or so on me and probably much more of an edge in strength -- but far stronger was her loud laugh.

In 2016 we planned a trip to the Pacific Northwest.  I always intended to connect with my cousin, but didn't try hard enough.  Apparently I was using a dead email address, but the fact was she had a professional office I could have called.  But the trip agenda became more-and-more crowded and connecting became a loose end never attended to.  I will always regret that.

The awful news came in at the end of Thanksgiving break.  L had been at friends and started feeling unwell and an ambulance was called, but she was brain-dead by the time she got to the hospital  What could strike down this vibrant woman?  A pulmonary embolism.  As far as I know she had no particular history or risk factors for such an event, so this would seem a terrifying bolt-from-the-blue.  Just the sort of event that makes me almost completely skeptical of those selling longevity and immortality via scans and tests.  Even if those companies can sort all the incidental finding chaff away from the meaningful wheat, there could always lurk some bad outcome that is undetectable.  And this should be humbling for those of us in biopharma: doom so swift will be nearly impossible to ameliorate by new drugs.

But we must soldier on.  While we may not save everyone or treat every disease, progress can be made for many patients.  And I know too many people with serious issues that represent incompletely met medical needs -- Alzheimer's and Parkinson's and cancer and so many other ails.  Losing too many battles is no excuse for giving up.   So this space will soon return to looking at molecular technologies and genetics and computational biology and all the other topics I write about.  It's the New Year, so time to take heart in new beginnings and renewed energy.


Unknown said...

What a great reminder Keith of the fragility of life. Its an excellent reminder for us to 'number our days' and to make every day count.

Was struck by the Scoutmaster story - strange to hear about mesothelioma in that context, a sad surprise ending to what must have been a remarkable person. (I myself know a very similar person, intellectual property too, involved in Scouting and like your friend very energetic.)


James@cancer said...

Life is cut short for some, and dreadfully short for a few. Whilst we had our Christmas celebrations a friends wife is dealing with colon cancer - the outlook is not great. And last Christmas my mother in law was diagnosed with breast Cancer - her outlook is pretty good - although side-effects of aromatase inhibitor are a problem; arthralgia that appears to be worst in women who respond best and probably benefit most form a full course of therapy, vitamin D supplements and acupuncture may help; but she does not want to stop unless the pain is debilitating.

I'm an early detection fan but would agree the hype is a problem. However Ovarian cancer has an almost 100% rate of TP53 mutation so with sensitive tests we are likely to be abel to diagnose earlier...but it is not clear if we'll catch it early enough. The picture is similar, although not so clear for pancreatic cancer. We might get similar tests for smokers to catch lung cancer early enough for surgery.

All the best for 2018. If all the readers of Omics Omics make their days count we can impact the number of deaths from diseases like cancer.