August at the Lake

It’s August at the Lake.

I should be writing about our recent houseguests, a family that includes two delightful teenagers. Yes, there are really nice teenagers. I know this from direct observation.

And, I would like to describe the clear cool water, the loons diving for their dinners, the four-pound smallmouth that took a surface popper on the first cast a couple of nights ago, and the eagle that has nested across the way. All these things are beautiful, lyrical, like the sky in the few minutes after sunset, still glowing with the memories of pleasant days.

But…I just had lunch. I fixed it and ate it by myself. It was a pretty mundane lunch: extra-crunchy peanut butter and mixed berry jelly on whole wheat with a small bottle of fizzy water. So, while I crunched, I entertained myself by reading the July issue of Nature Biotechnology.  This is not as technical as your average Car and Driver, but still, it’s pretty technical. The news items included a piece on chimeric antigen receptor T-cell therapy and another one on protein scaffold drugs, relatively small polypeptide chains that maintain the binding specificity of antibodies. Then I turned to another item describing the conjunction of artificial intelligence and drug discovery.

Then I stopped, and tried to think for a minute. What do these bits of news mean and, more importantly, what do they imply for the future? Of course, the future is an assumption highly dependent on the statesmanship of leaders like Kim Jong-un and Trump the Donald. As Nat King Cole wrote, “Tomorrow may never come/ For all we know,” and old Blue Eyes answered, “The fundamental things apply/As time goes by.”

I digress. First, these news bits show us the incredible pace of change in biotechnology. Remember, kids, it has less than 75 years since Pauling’s work on protein structure and just 64 years since Watson and Crick described the structure of DNA! What a ride!

But what does this news imply for the future? I don’t mean, what will the next rabbit to come out of the hat look like? Much more important than that, I mean what happens to our society when having a good job means that you have to understand some physical and organic chemistry, a smattering of X-ray crystallography, and have a nodding acquaintance with deep-learning algorithms?

I just spent a week with my younger son, Drew. While he recovered from a total hip replacement (so much for eugenics!), we had plenty of time to talk. He teaches young adults in New York City who want to attempt the TASC (Test Assessing Secondary Completion) exam that leads to a High School Equivalency Diploma. These students, and millions more like them across the country, are totally unprepared to deal with the STEM (science-technology-engineering, math) material that’s required today for employment in the modern world. They don’t have the academic skills, the basic reading and math knowledge, to learn STEM material.

Economic inequality is real, and it’s easy to measure and show on a graph  . But for tomorrow, the critical issue will be educational inequality. Yes, they are highly correlated, but they don’t have to stay correlated. We could try to make sure that the next generation has a chance to acquire better academic skills, that they don’t go to school hungry and come home to violence.

Oh, but that might take some government interventions. Whoops.

Are scientists innately boring and out of touch?

 

The popular viewpoint seems to characterize scientists as dull. The popular media often give the impression that scientists, a.k.a. “nerds,” or “geeks,” insulated from the real world of apps, ride-hailing, and rap by their glasses and pocket-protectors, aren’t much fun.

I’m working on editing a memoir that my friend, Bernie Witholt, left unfinished, and wildly unstructured, when he died two-plus years ago from pancreatic cancer. Bernie was a full-fledged scientist. He spent much of his life in the lab, studying the biochemistry of bacteria. PubMed lists 179 separate publications for him; he held many patents, and his colleagues remembered him as a remarkable salesman for his ideas.  “With visionary lectures, he convinced policymakers and companies to invest. He was a fantastic advisor for, and initiator of, numerous successful biotech start-ups, and was the founding father of the Zernike Science Park in Groningen. In 1992, he established [a laboratory] in the Institute of Biotechnology of Swiss Federal Institute of Technology in Zürich (IBT, ETH Zurich) and worked on alkane-degrading bacteria, biocatalysis and bioplastics until 2005 when he retired.”

In addition to his science, Bernie was an avid oarsman. We rowed together at Amherst, and for the summer of 1963 we rowed a double scull for Vesper Boat Club in Philadelphia. He continued rowing in Zurich with gusto and considerable competitive success.

He and his second wife, journalist Renske Heddema, were an elegant couple with an active social life.

My task in editing his memoir is to communicate the joy of living the scientific life and of asking questions and finding one answer that leads to a dozen new questions. But beyond that, the real scientist also finds joy and excitement in seeing how the world fits together, in knowing about history and the arts as well as science.

Christine Rosen, writing in The New Atlantis in 2006, said, “It is not, alas, the stuff of great memoir, so severed has the actual practice of science become from the broader concerns that animated many early scientists — the wonder at life in its fullness, the observable mysteries of the natural world.”

She nailed the issue! Today’s science involves questions that require detailed technical knowledge that the general public does not have. Yet many of the scientists I know do, indeed, “wonder at life in its fullness.”

I would be delighted to hear from readers who have ideas or suggestions about successfully writing about scientists.

Summer Reading. (Not required, but worthwhile)

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What did you think about over the past two major holidays, Memorial Day and the Fourth of July?

As I often do, I spent a lot of time wondering how we got to this strange point in our national history, and a smaller time hoping that the federal bureaucracy, in its nautical role as our national ballast, has sufficient inertia to hold the course in foul weather.

I’ve just finished reading two books that I want to recommend; both are appropriate for the packet. They are not new, but ripe for reading now.

The first is Fredrik Logevall’s Pulitzer Prize-winning Embers of War, a history of Viet Nam that focuses on the period from the end of WWII to 1959, at the beginning of the second Viet Nam war, the one the US fought.

The three main players of the story include war-weakened France, struggling to retain its colonial domination over Viet Nam, a home-grown independence movement desperate for military and economic support, and the suddenly superpower, the cold-war United States, operating on the basis of the “domino theory” and committed to halt the spread of “Communism.”

As Logevall tells the story, the players cannot shed the blinders that limit their vision and condemn them to act out their roles, no matter what the consequences. France poured blood and treasure into Viet Nam that could have helped stabilize her in Europe. Ho Chi Minh made a Faustian bargain with the Chinese, after his efforts to lead his country to independence were rebuffed by the US. Meanwhile, with the US caught up in the madness of McCarthyism and the “loss of China” political finger-pointing, the irrational political pressure to support first the French and then Ngo Dinh Diem and the South Vietnamese was overwhelming.

Logevall, a history professor, writes clearly and unobtrusively. As events unfolded, as a reader I could only shake my head, wondering, “Why?”

The second recommendation is Jean Edward Smith’s Eisenhower in War and Peace. Smith focuses much of the book on Eisenhower’s military career, an important approach in order to understand how Ike functioned as President. Eisenhower was extraordinarily fortunate throughout his career in gaining brilliant senior military men as mentors, probably because they recognized his extraordinary capabilities.

Smith emphasizes Ike’s skills at the card table, his perspective in structuring “carrot and stick” decisions for both his peers and his subordinates, and his ability to delegate responsibility.

The two books, taken together, help to clarify the complex path that led to the United States involvement in Viet Nam. The relationship between Eisenhower and DeGaulle, the political pressures within the Republican Party, the pressure to use tactical nuclear weapons, all played a role.

What’s my message here? We live with our successes, and with our mistakes. Americans should celebrate the 4th of July. The essential document of the day, the Declaration of Independence, stands as a remarkable example of our successes. And on Memorial Day, the Civil War and the Viet Nam War stand as stunning examples of the consequences of our mistakes. It takes about a half-century, a reasonable time for the dust to settle, to see how the mistakes were made.

The photos are all from Havana, Cuba. I think they speak to some of the issues. The lady in the rain was photographed on the grounds of the Hotel Nacionale in a sudden downpour. The red Buick was originally, I believe, a 1954 Roadmaster. The missile is an SA-2 Guideline surface-to-air missile of the type that shot down Rudolf Anderson’s Lockheed U-2 aircraft over Cuba on October 27, 1962,during the Cuban Missile Crisis. The wrecked engine of the U-2 is displayed below the missile.

“Outside of a dog, a book is man’s best friend. Inside of a dog it’s too dark to read.” ― Groucho Marx

About a year ago, two reviews of Annie Proulx’s novel, Barkskins, appeared in the New York Times. Neither was particularly favorable.

I bought an audiobook recording of the novel and have listened to it, all 26 hours of it, while driving up and down I-75 from Ann Arbor to the Upper Peninsula. I finished the last disc a few days ago driving west on M-28.

Two of Proulx’s previous works, The Shipping News and Brokeback Mountain, have won a Pultizer Prize and a National Book Award. Barkskins probably won’t scale those heights. Nonetheless, the book appealed to me at several levels.

First, Proulx is now over 80, and any octogenarian who has the dedication and energy to write and publish a 717 page novel spanning 300 years is OK in my estimation. Second, the tale is a prolonged, slowly intensifying, protest against the wholesale exploitation of natural resources for corporate profits. It’s a protest that might be more effective at a fraction of the length, but it certainly conveys the intensity of her feeling. At this stage of life, having intense feelings about issues seems to me extraordinarily admirable. And from time to time, she delivers positively lyrical descriptions.

Finally, though, I was drawn to her failure to get the story ended. I’m sure we have all sat through to one or another piece of classical music in which the audience raises its’ collective arms, ready to applaud and get the damn thing over with, only to have the orchestra continue on, repeatedly swelling toward but not achieving a grand finale. In the last chapters of Barkskins, Proulx just can’t stop the music.

Most stories often have natural endings. The detective solves the crime. The traveler returns home. The horse wins the race. But Barkskins won’t end for Annie.

I find that appealing. She doesn’t want to hang it up, to say, “There, that’s all I have to say about that.” Good for her!

I don’t think many Weekly Packet visitors will head to the local bookstore to buy this very long novel. You just won’t have time to read it. So, here’s an offer you can’t refuse. Anyone who is facing a long drive, for instance, New York to Los Angeles by way of New Orleans, can let me know. I’ll send the audiobook to the first reader I hear from. You’ll enjoy it.

Aargh! By AARP

 

 

 

 

 

 

I have several medical journals open on my desk with interesting topics that I thought I might mention in “The Weekly Packet.” By and large, the open journals are now properly aged, like pieces of meat at a fine steakhouse.

Nonetheless, they will have to wait. The most comment-worthy item to come along this week was in the AARP weekly flimsy.  Painful truth: my wife and I joined AARP to get the substantial discount offered by our local optometrist’s shop on new glasses. Even more painful truth: I was pulled in by the headlines about “why do drugs cost so much?”

I did not have high hope for a rigorous exegesis in the AARP journal, but the presentation was actually quite balanced. The writers covered the long timelines from drug discovery through clinical trials and the FDA approval process, and even covered phase 4 studies. They also touched on the vast amount that “big pharma” spends on marketing. In all fairness, they at least mentioned that Medicare cannot, by law, negotiate drug prices and touched on the strange role that “pharmacy benefit managers” play in the US system.

What’s my point? An AARP member who actually spent some time carefully reading the article would have a basic vocabulary, would become familiar with some of the players in the market, and would have been introduced to two key facts: pharmaceutical costs are only about 10% of overall health care costs, and big pharma spends as much on marketing as on basic research. Not bad. Although the authors did not point out to their readers that without this industry, their diabetes, high blood pressure, high cholesterol, and cancers could not be treated.

More importantly, what the AARP reader would NOT know, struck me last week when I attended the Clinical Leader Forum in Philadelphia. The pharmaceutical industry, particularly the clinical research organizations that have proliferated in the past couple of decades, exemplifies the new economy.

Let me try to explain. In one lifetime, mine, pharmacology has gone from a collection of empiric facts about medicinally useful herbs like digitalis or compounds, like sulfa, to an integrative science and technology focused on identifying “drug targets” in pathophysiologic processes.

From this point of view, the new drugs that pharma generates are the physical tokens, the representation of knowledge and of enormous amounts of data. The patients are not really paying for the drugs, they’re paying for the data. I think eventually, we will work out something more functional for drug pricing. But take a step back, and look again.

Kids who under-achieve academically will not find jobs in this industry. What I saw during last week’s meeting was a relentlessly driven technological and sociological wedge splitting the workforce into those who could deal with complexity and those who could not.

And I’m sure that other industries are similar.

There is no going back. No matter how much we would like to idealize the post-WWII economy, it’s gone.

Here’s the really scary thing; there’s good evidence most AARP members don’t understand what this kind of industry means for our society.

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Time Travel is REAL!

This time last week, I was in Havana.

This is not a report from last week. It is a report from the late 1950s or early 1960s. If you don’t want to take my word for it, read Carlos Manuel Alvarez in the New York Times. 

Packet-style breaking news from Cuba: we Americans have been involved in armed conflicts twice there, in the Spanish-American War in 1898 and in the 1961 Bay of Pigs invasion. The count so far looks like one and one. After 1898, Cuba shook off Spanish rule to become a unique and vibrant society, and most Cubans seem to view that intervention positively. Plus, San Juan Hill gave Theodore Roosevelt an enormous boost.

By the mid-1930s, Fulgencio Batista, strongman, dictator, and certainly a friend of the mob, consolidated his hold on Cuba. He eventually brought rampant gambling and widespread corruption to Cuba. Although the US government supported Batista, revolution was in the air by the mid-1950s. A young lawyer, Fidel Castro, and his brother Raoul, along with Che Guevara, led the successful overthrow of the Batista government in 1959.

In April of 1961, a Nicaragua-based, CIA-sponsored, 1400-man anti-Castro “brigade” invaded Cuba at the Bay of Pigs. The invasion was a disaster. Over 1100 of the brigade were captured. “14 were put on trial for crimes allegedly committed before the revolution, while the others were returned to the U.S. in exchange for medicine and food valued at U.S. $25 million. Castro’s victory was a powerful symbol across Latin America, but it also increased internal opposition primarily among the middle-class Cubans who had been detained in the run-up to the invasion. Although most were freed within a few days, many fled to the U.S., establishing themselves in Florida.” https://en.wikipedia.org/wiki/Fidel_Castro

Having seen the terrain around the Bay of Pigs, including the dense Cienaga de Zapata, it’s not hard to understand why the invasion stalled. Most Cubans seem to view the Bay of Pigs for what it was, a fiasco.

After the events of 1961, time stopped. In fact, with the fall of the Soviet Union, from 1990 to about 2000, time went backward. This was Cuba’s “Special Period,” when support from the Soviets ended and the entire country fell into dire straits, short of everything.

Today, what we saw was how Castro’s unrestrained idealism, with the best of intentions, nearly destroyed a country. Cubans have universal education, universal healthcare, and no homelessness. But in this society, the infrastructure has crumbled; housing stock has steadily deteriorated, and the highly educated are vastly under-employed and underpaid.

The current government has reduced restrictions on free enterprise. Independent restaurants, “paladars,” flourish in Havana (see the photos). Some restoration and refurbishing is happening. But the work to be done is daunting!

High points of the trip: the Hemingway museum at Finca Vigia  and the National Museum of Fine Arts in Havana.

If you click on any of the photos in this post, you should get a slide-show view that will have nice size and detail. I have almost 900 photos sitting in Lightroom; more to come.

The Day After April Fool’s

True confession. If one refuses, and I do, to write about current political events, then finding subjects can be challenging. As I wondered how to appropriately memorialize the day after April Fool’s, I thought about my recent reading. “Gosh, I thought, I haven’t read much lately.” Then, I looked around the room I call “my office.” (My wife calls it something rather different; let’s not go there.) I really have read quite a lot, but mostly related to “The President and the Poet,” a project that is worth checking out  if you are not familiar with it. (Also, have a look at Reunion ’64 and please consider some modest support, $10 or $20, for the project on Kickstarter.)

Then, I thought about my Kindle. Yes, I’ve read a good bit on it, too. Most recently, I completed Aldo Schiavone’s Pontius Pilate. Deciphering a Memory. The book received a nice review in the New York Times, but there are two problems. First, the translator was very fond of obscure academic English terms. He lost me, not once, but several times, in a dense fog of theological scholarship. Second, the entire historical record can be summarized in two sentences. Solid historical evidence indicates that a Roman, Pontius Pilate, governed the territory around Jerusalem around the time that we have arbitrarily picked as the beginning of the “common era.” A brief interaction between Pilate and an itinerant Jewish teacher named Jesus resulted in the latter’s death. Building a full book from those sentences requires injecting a lot of material that, at the best, could be called ‘scholarly interpretation.’  Not highly recommended.

So then, I really looked around the office. I’m struck that the books I keep coming back to are the ones I should write about. The two that never get far off my desk these days are Daniel Kahneman’s Thinking, Fast and Slow and Leonard Mlodinow’s The Drunkard’s Walk. How Randomness Rules our Lives.

Back in the early 1980s, I thought that game theory might offer a useful approach to understanding clinical decision-making. I published a little-known paper about this, but the real bonus was that the background reading lead me to Kahneman. I have been a fan ever since.

I found Mlodinow after I started working at Scios and realized that I was so inept at statistical thinking that I did not even know how to ask statisticians good questions. This ineptitude became embarrassing when it was revealed on an almost-daily basis, and it accounted for my purchasing a number of books. Mlodinow’s is one of the better ones; his strength is that his language makes critical concepts accessible for lay readers.

So, as I look around the office, I’m going to come up with a new rule. I hope you know some of my old ones, for example “Sicker patients do worse.” Or, “Non-fatal diseases generally get better.”

Here is the new rule, based on the concept of “presentness,” (last post) and the two books I have just discussed…

“Any intuitively obvious conclusion based on present data is very likely incorrect.”

CAT

Presentism

In high school, I learned that writing offered an opportunity to display one’s vocabulary, and thus, presumably, one’s erudition. Complex sentence construction was laudable, save for the dreaded “comma splice.”

Then I arrived at Amherst, where Theodore Baird dominated my freshman year. Baird lived in a Frank Lloyd Wright “Usonian” house, and was a friend of Robert Frost. In his course for freshmen, English 1-2, Baird taught writing. He rewarded simple straightforward sentences. He derided complex constructions.

A few years ago, Dan Chiasson reviewed Baird’s book, English at Amherst, and said, “It would be an exaggeration to say that getting Frost right was the great mission of English 1-2. For one thing, the course read no Frost. In fact, after its early, provisional years, it read nothing: no literature, no text of any kind. But I think it is true to say that the air of Robert Frost pervaded English 1-2.”

I agree.

With this background, I was drawn into a recent New Yorker book review titled “The Illiberal Imagination” by Adam Gopnik, a long-time staff writer for the magazine. He pulled me in with two sentences. “Of all the prejudices of pundits, presentism is the strongest. It is the assumption that what is happening now is going to keep on happening, without anything happening to stop it.”

The review covered three books: Pankaj Mishra’s Age of Anger, Joel Mokyr’s A Culture of Growth, and Yuval Noah Harari’s Homo Deus. I understood very little of Gopnick’s commentary, which was obviously erudite and involved quite a lot of Rousseau and Voltaire. On the other hand, I really liked the concept of “presentism.” More accurately, I liked Gopnick’s identification of the concept as faulty.

“That’s what I’ve been trying to say!” I thought. That’s what I had in mind when I wrote that I wanted to capture the perspective of the reader who is delighted to have a month-old newspaper arrive on the mail packet.

Thinking about presentism seems important to me. The past is debatable. For instance, the slogan “make America great again” seems patently false. What was great about the Depression, polio, segregation, the Cuban missile crisis, or the Viet Nam war?

The future is, by definition, unknowable. This leaves us with the present. Here and now is what we have to work with, and where we have to become engaged. We must not fall into “the assumption that what is happening now is going to keep on happening.”  Presentism is disheartening, paralyzing.

But this is when the month-old newspaper arrives, like the cavalry coming over the hill. We read it. My goodness, that was terrible! But whatever it was, it ended. By now, something else has happened. The present, whatever it is, will change. How invigorating!

Shaping the outcome of today, shifting a bit toward something better, becomes the relevant question for us. This is the antithesis of presentism. How do we bend toward better without breaking something? Ah ha! Read the month-old paper, carefully. Did yesterday’s crisis require solution, or did it self-resolve? How did the leadership muddle through? Just as important, what were the unintended consequences of what they implemented?

Chiasson had another thought about Theodore Baird. He wrote, “If you can convince a large number of 18-year-olds that making up sentences is an act of deep moral imagination, you do it, no matter how much work that entails.” By extension, recognizing good sentences when reading can also be important. So thank you, Mr. Gopnick, for those good sentences.

“Déjà vu all over again”

In keeping with longstanding Packet policy, I’m offering readers some well-seasoned news for the sake of context. This is not intended as humor, although some may initially view it as such. My point is serious. Without the context of the past, we have no basis for evaluation for current events.

The facts for this post, and all of the otherwise unattributed quotations, come from Robert Strauss’s book, Worst. President. Ever., a history of James Buchanan’s term as President of the United States.

The first year of James Buchanan’s term, one hundred sixty years ago, was not a good year for the United States.

First, two days after the inauguration, came the Dred Scott decision from Chief Justice Roger Taney and the Supreme Court. “In March 1857, in one of the most controversial events preceding the American Civil War (1861-65), the U.S. Supreme Court issued its decision in the case of Dred Scott v. Sanford. The case had been brought before the court by Dred Scott, a slave who had lived with his owner in a free state before returning to the slave state of Missouri. Scott argued that his time spent in these locations entitled him to emancipation. In his decision, Chief Justice Roger B. Taney, a staunch supporter of slavery, disagreed: The court found that no black, free or slave, could claim U.S. citizenship, and therefore blacks were unable to petition the court for their freedom.” Buchanan, before his inauguration, had vigorously lobbied the Court justices for a broad and binding decision; they went along with him.

Buchanan chose a mediocre cabinet. “There was not a rival or a grand thinker” among them. Lewis Cass, his choice for secretary of state, “was growing senile and Buchanan would essentially be his own secretary of state.”

The Panic of 1857, one of the periodic major financial downturns that plagued the country, was largely a response to Buchanan’s reduction of tariffs. “The Panic of 1857 was … caused by the declining international economy and over-expansion of the domestic economy. Because of the interconnectedness of the world economy by the 1850s, the financial crisis that began in late 1857 was the first worldwide economic crisis.” Buchanan’s  (ineffective) solution was to reduce the physical size of U.S. coins. These smaller coins required less gold and silver to mint. Thousands lost their jobs, and several major companies went bankrupt.

“Buchanan’s personal attitude [was that] …rugged individualism would triumph over adversity; the buoyancy of youth and the energy of the people would enable them to recover.”

As the year wore on, a dispute in the Utah territory between Mormons and federal justices became heated. Without any effort to determine the validity of the Mormon’s claims, Buchanan sent federal troops to “defend American law.” Brigham Young “formed an army of his own and ordered them to burn everything – every building, every tree, every piece of hay – that the federal force might capture on the way toward the presumed invasion.”

“Thousands of Mormons …lost their homes and livelihoods, scorching all, as Young had ordered, and fleeing in the face of the army.” The Mormons, for their part, were responsible for the deaths of more than 120 innocent settlers on their way to California, the Mountain Meadows massacre.

BEAR
Russian Grizzly and her cubs, 8/19/2013. KZM photo.

In summary, 160 years ago, in his first year of his first and only term, Buchanan had a mediocre cabinet, a Supreme Court crisis, and a major financial crisis precipitated in part by the fact that America had become part of a global economy; in addition, he directed the power of the federal government against a specific religious sect.

So, we’ve got that goin’ for us, which is nice.