Friday, November 11, 2016

HGP Counterfactuals, Part 1: An Introduction

My new correspondent, Kumar Thangdu, has posed some challenging questions with regard to the Human Genome Project.  He's been good enough to capture my initial tweet stream over at his blog, which was my initial defense.  I then followed up with my note on my one paper in proteomics, which I received favorable feedback on  from one of my co-authors.

Kumar has pointed out that he doesn't question the value of the HGP, but rather whether the return on investment (ROI) was good. Scientists don't really like thinking about ROI, which in turn is a proxy for the hard question of opportunity cost -- if the effort hadn't been spent on the HGP, what could it have been spent on that might have advanced biomedicine further?

These are hard questions but important ones.  The approach I'm going to take is to try to explore alternative histories (also known as counterfactuals) of the HGP in a set of seven posts.  This is perhaps the most ambitious series I've ever attempted here.  There have been times in the past when I declared I was going to do a series, but I was never bold enough to lay out the precise scope of the series in advance.  So when my effort petered out, it wasn't readily apparent.

Counterfactuals have a somewhat tawdry reputation in serious historical studies, from what I have learned by reading them.  After all, we can't re-run events with changes or switch between parallel universes.  So alternate scenarios can never be truly tested.

On the flip side, whenever we declare that something was "a turning point in history", then we are implicitly invoking that other outcomes were possible, if only a different decision were made or a chance event had been slightly different.  Even very small stories can suggest multiple alternatives.

For example, I know a romantic story with four main characters, which has a touch of humor and a bit of tragedy.  During the Roaring Twenties, a young schoolteacher in a rural Kentucky town liked to go to parties.. She remarked to a friend of hers that she lacked a date for a party she wanted to go to, and the friend offered to set the schoolteacher up with her "kid brother". But this brother had a sad backstory; he had married but his wife had died just days after giving birth to a daughter, who was being raised by the deceased mother's family.  It was dark when the young man picked up the schoolteacher, so she did not get a good look at him.  She was taken aback by the constant stream of jokes the man told on the drive; he did not seem like a serious prospect.  But when they arrived at the party, he stepped into the light, revealing his World War I doughboy uniform.  He looked dashing, she fell in love with him, they married and they went on to have one daughter.

On this 98th anniversary of World War I ending, look back at that story for the contigencies and alternatives apparent within. A shell flying a little differently, and the doughboy never leaves France.  Given the time period, we know that all four characters in the story (doughboy, schoolteacher, friend and deceased first wife) survived the 1919 influenza epidemic, which millions did not.  If the first wife survived whatever killed her, then the doughboy would have been staying home with his young family, not going on dates. The schoolteacher would have certainly married someone else and had a very different later history.  Perhaps most starkly, the daughter of the union of the schoolteacher and doughboy, as well as her children and grandchildren, would simply have never existed.  All humans are products of numerous contingencies, but this is a particular clear-cut example.

Now think of the bigger stage that touched on this.  World War I was ignited when Archduke Franz Ferdinand and his wife were assassinated in Sarajevo. The assassin had failed in previous attempts to get near the royal pair; it was a wrong turn by the driver that happened to put them at point-blank range to assassin.  If the royal couple hadn't been murdered, would a World War have broken out?  There are plenty of reasons to think it might of, and equally good reasons to think it might not have (The War That Ended Peace is a very good exploration of the long lead-up from the Congress of Vienna to World War I).

In his contribution to a volume called Virtual History, which he also edited, Niall Ferguson explores what might have happened if the British Expeditionary Force (BEF) had not been sent to France at the beginning of the war.  The two nations had no formal military cooperation treaty, and the British Cabinet was deeply divided as to whether to send the BEF or not. Ferguson imagines the BEF being held back, with the Western Front running much as the Franco-Prussian War had.  France conquered and only a brief European war.  No trench warfare, no introduction of poison gas.  No defeated Germany left to fester, and no gas-injured insane corporal to take advantage of festering post-Versailles conditions.  No entry of the U.S. onto the world stage -- and no doughboys. Perhaps no 1919 flu epidemic, if various post-war conditions contributed to its spread. Collapse of the Russian, Austro-Hungarian and Ottoman Empires doesn't occur in the same way. All three empires were probably doomed, but perhaps would fail less spectacularly.  No Communist Revolution?  No Sykes-Picot agreement carving up the Middle East with arbitrary lines?  Millions of people not killed or maimed.  The ripples of The Great War are fossilized endlessly on modern maps and in modern memories.

It should be obvious that the farther one goes from the initial change, the less predictable things are. Too many contingencies are disrupted. For Want of A Nail explores what would have happened if General John Burgoyne had won the Saratoga Campaign and snuffed out the American Revolution; the earlier parts aren't bad but it gets a bit silly long before the end of the book a century later. Or imagine Ferguson's short WWI scenario.  Would Kaiser Wilhelm have been satisfied with the spoils he could have extracted from France, such as overseas colonies?  Or would he have been driven to even greater heights of megalomania, fomenting another war to take British possessions or perhaps extract more territory in the center of Europe?  Perhaps he would have tried to pick apart Austria-Hungary.  Would a humiliated France have embarked on a new round of militarism and tried to avenge its losses?  

However, by carefully exploring these gedanken experiments in history, and perhaps running them over relatively short times, it is possible to at least think about which events and decisions perhaps weren't as critical.  Which things might not have been contingent.

The second installment will explore the "forgotten maps", important products of the HGP that were not strictly sequences but quite critical to the sequences being useful.  The third installment will look at the strategies that were used for organizing the sequencing; it is in some ways a replay of the forgotten maps but different in the details.   Fourth, I'll look at the actual sequencing technologies that existed when I was first seriously exposed to the HGP, and how it was effectively the sole technology only a few years later.  How did one win?

Chapters five and six will explore two counterfactual scenarios with caveats and provisos.  In one, opponents of a public HGP prevail.  In the other, the project sticks to developing technology to make the project more cost-feasible.  How might these have played out?  Finally, I'll wrap up in a seventh missive to try to collect any lessons I've discovered.  Oooof.  That's a big agenda to keep on schedule. I'd have been smarter to get the whole thing assembled before announcing it, but only part two is actually drafted.

My goal is for you, the reader, to find this series interesting and enlightening.  Perhaps you'll be stimulated to contest my assertions, or point out what I've failed to consider or a key fact I didn't know.  Perhaps you'll write your own counterfactual.  Some who read this might ponder the contingencies that have shaped their life.  But if nothing else, I hope I've entertained you with the story of how my maternal grandparents met.

The doughboy proudly holding his regimental colors at stateside training camp.

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