Swing, Batter, Swing!

The SF Giants’ pathetic lack of offense in a 1-0 loss last night had me grinding my teeth, against the advice of my dentist (probably a Dodgers fan).  Then, in this morning’s NY Times, comes an article (How Do Athletes’ Brains Control Their Movements? by Zach Schonbrun).  Two Columbia University neuroscientists, Sherwin and Muraskin, have been using EEGs to look at a batter’s decision to swing at a pitch (the moment he makes that choice shows up as a burst of neural activity on the EEG), and then correlating their measurements with performance outcomes.  They are applying what is known as rapid perceptual decision-making to the sport of baseball.

Schonbrun points out that a 95-MPH fastball travels 60 feet 6 inches from the mound to home plate in just 400 milliseconds (the blink of an eye), and by then, given the maximum speed of nerve conduction/activation, the time available to react has already been cut in half.  A good batter has to respond to his nerve activations in a very different way than normal people.  Quick:  Is this a fastball or a slider?  At which millisecond does the batter decide to swing at, versus to take, a pitch?

In my second novel, Fourth World Nation, Benn Marr– who possesses certain uncanny abilities due to his unique genetic makeup– has his turn at bat:

Suppressing his excitement, Benn nodded at Hank, picked up a bat and stepped up onto the field.  A thousand hostile baseball fanatics, many wearing black PWE uniforms, glared at him. A metallic voice announced the substitution, to a chorus of catcalls and booing.  Even the programs clutched in the fans’ hands—supposedly there to provide objective analysis of the game—reacted poorly. The crowd rained scorn on Benn as he stood at home plate, their expletives addressing everything from his Asian ethnicity to the “gouging” water rates set by Hydra.

Benn, however, focused his thoughts and heard none of the noise; to his ears, the diamond was still and quiet. Behind him, the mobile QI umpire adjusted his mask. The catcher shifted stealthily to the outer half of the plate, his shoes grinding into the red clay. The pitcher Helmut rolled the ball deep in his glove, his fingers seeking its seams.  To Benn’s eyes, events unfolded as if in slow motion: he anticipated the limited wind-up; the delivery from a low release point; the seams spinning centrifugally; the appearance of a red dot at the center of the ball. It was a slider, unhurried in its journey toward home plate, where Benn waited patiently. He flexed his knees, shifted his front foot forward, then planted his lower body firmly.   As the ball curved low and away, Benn extended his arms and kept his body balanced. On impact, the bat exploded into a hundred shards.

“There it goes, a high fly ball!” yelled the robotic announcer, whose positronic eyes calculated the arc of the ball’s flight, its velocity leaving the bat, and the distance to the warning track, where it bounced off the wall above the leaping right fielder.  All this data was instantaneously transmitted to the fans’ programs, which murmured their grudging admiration. “The Giants have a double!” the announcer added, when the play was over. “So the game is tied up at two runs apiece. Ladies and gentlemen, please… further throwing of trash from the bleachers will result in ejection from the park.”  Discarded programs continued to land on the infield. Many of them were still gushing about the inside-out swing and the broken-bat, opposite-field RBI double.

 

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Choosing a Sharper Blade

Bacteria, it seems, rule our health, living as they do at the interface between our protected internal selves and the wide external world.  We all know that they can act as harmful pathogens, but often they also function as mediators, brokers, an essential part of normal health and homeostasis.  At the time of my retirement from Rheumatology in 2015, an ever-increasing understanding of the role played by the microbiome– the bacterial population of our intestinal tracts– in driving autoimmune diseases such as rheumatoid arthritis and systemic lupus gave me pause:  should I retire, just as such an interesting and important field was opening up?

For example, there is a bacterium called Enterococcus gallinarum that can migrate from the gut to tissues such as lymph nodes and liver, where it triggers autoimmune processes and inflammation; an antibiotic or vaccine against this bacterium reverses its effect on autoimmunity, at least in genetically susceptible mice.

And recently, a team at Yale has looked at a protein called Ro60 in lupus patients.  Ro60 is found in bacteria from the mouth, skin and gut of these patients, where it induces the immune response and antibody production.  In theory, a topical antibiotic might be designed to target Ro60-containing bacteria and thereby suppress the autoimmune process in lupus.

Both of these examples herald a paradigm shift in our understanding and treatment of rheumatologic conditions (and other autoimmune diseases)– diseases where a wayward, dysregulated immune system attacks one’s own tissues, such as kidneys, lungs, brain, skin and joints.  When I was in training in the 1980s, treatments consisted largely of poisoning the immune system with chemotherapy agents and steroids.  As in cancer chemotherapy, we would bludgeon the target, stopping just shy of dangerous toxicity.  Not until the turn of the century did the biologic agents come along:  a new class of medications that finely targeted proteins along the complex inflammatory pathway, cutting with smaller and sharper blades where previously we had operated with dull machetes.

And now, antibiotics and vaccines for autoimmune conditions?  Examining these diseases with ever-greater resolution leads to better identification of culprits and “surgical strikes” with a minimum of collateral damage.  In teaching residents and medical students about lupus and RA, I would often use this analogy:  you’re enjoying a peaceful stroll through the park, when suddenly you encounter a boom box lying on the ground.  It’s playing a type of music you hate (for me, until recently, that was rap), and playing it very loudly.  In the 1980s, I would have taken a sledgehammer and pounded that boom box to bits.  In 2000, I would have found the volume dial and turned it way down.  In 2020, they will be figuring out how to change the radio station– or rather, the live stream.

No matter how far we think we’ve gotten in advancing the field of medicine, there will come a day when we look back at current practices with a mixture of amusement and horror.  In that same vein, here’s an excerpt from my sci-fi novel Fourth World, the first in a trilogy:

“Dr. Vincent?” the intern ventured.  “I understand why you would combine the gene fragments from the biogenome menu to make therapeptides?  And how the therapeptides correct the deficiency state? But you would have to keep administering the peptide indefinitely, right?  Because it wears off?”

Dr. Vincent, unaccustomed to interruptions, stared at him with eyebrows raised.  “Yes, of course, there is a finite half-life for every therapeptide,” she replied warily, sensing the question to follow.  “They have to be administered periodically. But they can be engineered to have extremely long half-lives, as you know.”

“Yes?  But wouldn’t a better solution be to transfer the PerMutation into a stem cell?  Then introduce the stem cell into the host, you know, to grow actual tissue? Once the genetically modified tissue took hold?  The patient could then, you know, make his own permanent supply of the therapeptide?”

Vincent’s face reddened as she consulted the seating register at her lectern.

“No… Mr. Messler.”  Her smooth delivery had been brought to a sudden halt by his naïve- no, appalling- question.  “That would not be a better solution. Not at all! You haven’t studied medical history much, have you, Mr. Messler.  The PerMutations obviously consist of multispecies DNA. Multispecies Proteomics- and subsequently the use of the protein products as pharmaceutical products- is a well-developed field.  But not the incorporation of PerMutations themselves into human beings. It has been over ninety years since the first attempt at introducing multi-species DNA into humans. Can anyone here please tell us what the consequences were?”

Benn and Lora looked at each other blankly.

An intern sitting across from them, a bearded black man a few years older than his peers, spoke up:  “I believe you’re referring to the Boston Gene Project. In one experiment, chimeric DNA, part mouse (from a strain of New Zealand mice with hyper-immune traits) and part human, was inserted via stem cells into patients suffering from a variety of immune deficiencies.  Balancing deficiency with excess: it seemed a straightforward idea. But there were nucleotide sequences in the DNA, previously considered ‘junk’ or nonsense, and even some non-genetic material, such as the associated proteins you mentioned earlier, which turned out to be important.  Ninety percent of DNA doesn’t code for proteins, yet remains biochemically active: for example, directly regulating- or coding for RNA which regulates- gene expression. The ‘junk” interacted in unpredictable ways with the patients’ genes, sometimes destroying them, or worse yet, re-sequencing them and changing the end-products.  In the Boston experiment, subjects developed unexpected consequences: aggressive auto-immune diseases, multiple cancers, and even bizarre body changes involving… non-human tissue.”

“Yes!  And therefore, in vivo application of multi-species DNA became illegal, Mr. Messler- it’s a major violation of the genetic engineering code.  In fact, the law forbidding this application is second only to the universal ban on human cloning! Does that answer your question?”

 

April’s Fool

We each need our own coping mechanisms to deal with the chaotic Trump presidency, from ranting about it in blogs to taking powerful antidepressants.  Over the past year, at particularly poignant (or pungent) moments, I have sometimes resorted to distracting myself with the music of Mary Poppins, which stubbornly repeats in my mind until the crisis has abated.

On Inauguration Day, this is what I heard over and over:

Super-callous narcissistic ex-reality show host, um diddle diddle, Donald Trump, diddle ay…

The lyrics have evolved over time, of course.  For example, during Trump’s exchange of childish insults with Kim Jong-Un over the threat of nuclear annihilation, I heard:

Please oh please don’t go ballistic with North Korean boasters, um diddle diddle, diddle bomb, diddle pray…

For several weeks now, the Trump administration has clashed with California over ICE raids in sanctuary cities; the census to include a question on citizenship; Obama-era tailpipe greenhouse gas emissions and vehicle mileage requirements; and the transfer of federal lands for development and drilling.  Add all of that to the many Trumpian threats to immigrants, net neutrality, air and water quality, etc. already facing California (see my previous blog, Most Likely to Secede), and no wonder I can’t get Mary Poppins out of my head:

He’s anti-Calif pugilistic blasting tweets ferocious, um diddle diddle, piddle dump, in the middle of the bay…

And now Donald Trump– of all people!– is declaring April Sexual Assault Awareness and Prevention Month.  This despite being credibly accused of sexual harassment and assault by so many women.  It’s not only ironic, it’s laughable!  Today’s outraged mantra:

While keeping tally of his antics loudly braggadocious

This groper’s wiping Stormy’s lipstick off the White House sofas

Awareness Month?  He’s schizophrenic!  Hypocrisy atrocious!  Um liddle liddle, liddle Trump, liddle ay…

Thanks again for coming to the rescue, Mary Poppins!  I’m sure I’ll hear from you soon!

And now, back to work on my real writing project:  the Fourth World trilogy.