A Pirate in the Kitchen

The news of Anthony Bourdain’s suicide in France came as a shock this morning.  And yet, somehow, it wasn’t beyond belief– he lived so intensely, so close to the edge, that it seemed almost a matter of time before some event in his life, even a minor one, would tip the scales.  Honestly, I’m glad not to be like that, but his intensity and edginess did serve as an inspiration to me in what I chose to write.

In the late 1990s, I was a mid-career physician with my eye on writing science fiction in retirement.  The books I was reading then were by authors such as Georges Perec, John Irving, William Gass, Jim Harrison and Jonathan Safran Foer.  One day, because of my love of cooking, I picked up Kitchen Confidential out of curiosity, and was immediately struck by Bourdain’s lurid stories of drug abuse, dropping out of college, alcohol addiction, brutal relationships, and the corrupt realities of the restaurant business (all the more vivid now, in the broad wake of Mario Batali, Ken Friedman, Charlie Hallowell and the #MeToo movement).  I learned about the mob’s ties to NYC fish delivery; cringed at the image of a huge pirate-like sous-chef who calmly lifted searing-hot pans out of the broiler with his bare hands; and I learned the horrible truth about what goes into those Sunday brunch buffets.  Kitchen Confidential, much more than the cookbook I was hoping for, changed everything– for me in my world view, patronage of Sunday brunches, and ultimately my fiction writing; and for Bourdain, when its success launched him into the public eye.  CNN signed him to the popular television series Parts Unknown, now cut short in its 12th season.

When interviewed by the Associated Press about Parts Unknown, he said:  “If you think about who the audience is and what their expectations might be, I think that’s the road to badness and mediocrity.  You go out there and show the best story you can as best you can.  If it’s interesting to you, hopefully it’s interesting to others.  If you don’t make television like that, it’s pandering.”

That is exactly the argument that ran through my mind almost a decade later, when writing Fourth World, the first novel in my science fiction trilogy.  Reading it over, I noted the density of medical technology (for example, genetic engineering with multi-species recombinant DNA) and discussions of related ethical questions (debated in 2018, but settled by law in 2196).  In that book, I even invented a space engine– necessitating a new, fictitious subatomic particle– in order to allow Benn and Lora to fly from Mars to Earth in only four weeks!  Was I going too far, risking the alienation of my readers?  To me, that would be better than waving a hand and simply issuing the order, “Warp nine– engage!”  Wasn’t it preferable to stay true to my own vision of the novels– to be a pirate in my own kitchen?

But who was the audience?  Who were my readers, and what might their expectations be?  If I edited the novel to suit some hypothetical, “average” reader, Anthony Bourdain would call it pandering and a road to mediocrity.  And indeed it would be.  With the conviction that this was my one, best shot at writing, I decided that if the content was interesting to me, then hopefully it would be interesting to others as well.

A few weeks ago, I spoke to two sixth-grade classes about the Fourth World series and writing (see my blog post Kids These Days!).  I advised the potential writers among them to read as much as they could, in order to absorb some of the vocabulary and craft of writing.  Also, they should write about what they know– in my case, medicine, science, colonialism, geopolitics, food and wine.  What I omitted was the importance of being true to themselves, to write what came from within, and not for the sake of external acceptance and positive reviews.

(I know, I know:  marketing!  For all those professional writers in the blogosphere who are now groaning at my remarks, I apologize and readily acknowledge that it’s easier to ignore ratings when you’ve already had a career in medicine).

Should I, or shouldn’t I, have taken an axe to potentially challenging material?  You be the judge.  Here’s the passage from Fourth World with which I wrestled long and hard, before deciding to leave it in, completely intact:

After hanging around the engine room aimlessly for a couple of days, Benn finally asked a sympathetic engineer for a tour.

“All right, Benn, I’ll give you a simplified version.  To start with, let’s consider these subatomic particles as such, although we analyze them as waves.  Flowsorb takes a variety of hyped-up particles, by-products harvested from the fusion reactor (efficient, right?) and fires these particles from the central initiator, where they first enter the cyclic counter-current mechanism. Meanwhile, at the terminal emitter, each compatible, or what we call candidate, particle degrades to a capacitron:  you remember that’s a cousin of the anti-proton, capable of absorbing energy like a sponge, storing that energy until a specific threshold is exceeded, then discharging it. Following me so far?”

Benn nodded uncertainly.

“See, the Flowsorb mechanism exploits the power of the Almighty Exponential,” said the engineer, bowing his head only half in jest.  “Changes in particle direction are forced by plasma nano-platforms, which are folded by powerful magnetic fields. These folds are embedded in thousands of larger platforms which fold into larger convolutions, and they, in turn, fold upon themselves– and so it goes, over and over.

“The repeated folding forces streams of energized particles to pass streams of capacitrons traveling in the opposite direction, millions of times over, each time transferring a portion of energy back toward the center.  Finally, a new cycle begins– but with their energy multiplied in each cycle, these exponentially-accelerated particles asymptotically approach the speed of light. You see?”

The engineer, now multiplying his own energy level, waved his hands in the air.  “Particle velocities literally explode by orders of magnitude! Then we eject these particles into space, and the rest relies on Newton’s Third Law:  you know, action and equal-slash-opposite reaction. Major thrust is what I’m talking about!  And that enables us to reach Earth in only four weeks, a journey that used to take more than seven months!”



Opioid of the People

Karl Marx called religion the opium of the people, its drug-like influence blinding them to the realities of the world, and therefore advocated atheism.  Also fearing an opiate effect on his audience, Bertolt Brecht used entfremdungseffekt, or alienation, in his theatrical productions in order to avoid sweeping the audience into a make-believe world.  It might be argued whether religion or theater was closer to an addictive drug historically, but in recent times, the opioid of the people turns out to be much more literally so.  It is the drug OxyContin, manufactured by Purdue Pharma.

Starting in medical school (I graduated in 1981), it was drummed into students that opioids are addictive, dangerous, life-changing, not to be prescribed lightly, a last resort only.  We grew up disciplined, ready to tackle the tough decisions, morally rigid and a bit self-righteous.  We were automatically skeptical whenever patients demanded stronger pain meds, and in steadily escalating quantities.  Of course we knew real pain existed, and we were sympathetic– but at the same time, there were sure to be malingerers, addicts, and those who would resell prescribed narcotics for a huge profit.  The fear of treating pain insufficiently was often eclipsed by the fear of being taken advantage of, as health care providers.  As we gained experience, some became better judges of character, but no one ever knew for sure; I remember a couple of seemingly reliable patients forging my signature for Demerol injections in the Urgent Care Clinic.

Then came a blizzard of editorials in medical journals and the lay press– sometime in the ’90s, as I recall– excoriating doctors for their callous under-treatment of chronic pain and pressing for a liberalized approach to the prescription of opioids.  It felt like a public shaming of our profession for its paranoia and lack of compassion, and was taken by many as welcome permission to loosen up our self-imposed standards.  But despite a universal sense of relief, a rational approach to opioids remained elusive.  It made sense that terminal cancer patients should never be denied a narcotic for their excruciating pain, but elsewhere on the spectrum of pain, the same uncertainties prevailed.

Now with the opioid crisis making daily headlines, the pendulum has swung all the way back.  The public is outraged about the ubiquity of opiates and resulting societal problems; over-prescribing doctors and the pharmaceutical companies share the blame. And it seems that Purdue Pharma had knowledge of the dangers and abuse of their product long before admitting it to drug regulators.  Huge profits and corporate greed attached to OxyContin, not surprisingly, outweighed public health concerns.

In my Fourth World novels, the drugs in question are psychopeptides, the proteins made by translating recombined multispecies DNA– including DNA discovered in Martian fossils.  The giant pharmaceutical company Eunigen discovered those fossils and secretly manufactures these products.  Here’s an excerpt from Fourth World:

“Thor Ibsen, my name is Dr. Walther Beame.”  He was speaking more rapidly now. “I am about to give you a higher dosage of a drug very similar to Deep Coma.  Is that all right with you? I should tell you that there may be a substantial risk of serious side-effects at this high a dosage, including rash, headache, fever, abdominal pain, death, incontinence, loss of taste, and loosening of the nails.  All right then?” Beame smiled thinly at Trip and nodded encouragingly as he spoke.

“Yes.  Q.”

“Note that informed consent was obtained,” Beame murmured to 0749, who duly marked a box on his datadisc.  Without further ado (except for an audible gasp from 0749), Beame then applied the Dermamist injector and emptied the entire contents of the white vial into the subject’s carotid artery.

It took only a few seconds for the effects to begin.  Trip’s eyes slammed shut, his jaw clenched, his lips pulled tightly back in a grimace reaching almost ear-to-ear and revealing gold-capped molars on either side.  Nice, thought 0749: designed to match his gold chin cup and nostril ring. Trip’s tremulous hands grabbed onto the seat, knuckles white; his back arched against the plastic restraints pinning down both shoulders; his feet kicked violently against securely tightened leg straps.


That wasn’t quite a seizure, thought 0749, but it was close.  He searched his datadisc. Seizures were not listed among the side-effects.

“Dr. Beame, just what are we observing here?  I mean, what are we expecting to happen to the subject?  Do you think the higher dose of drug will result in a more prolonged extra-corporeal experience?  And will the withdrawal therefore be more painful than the previous?” 0749 tried to suppress the rising anger so familiar by this point in his short career at the Repro Division.  He really should get around to filling out a transfer application, and soon.

Beame continued to stare at Trip’s contorted face, as he considered the question.  0749 was struck by the resemblance between Beame’s face and that of the subject: the tightness of its expression, the mouth drawn back, the look of one greedily searching for something in the obscure distance.    Finally, the director explained matter-of-factly to his conscience-plagued lab technician, “Don’t worry yourself, 0749; he will not experience any painful withdrawal this time. Extrapolating from results so far in our titration protocol, you can rest assured that this time the subject will successfully expire.”


Kids These Days!

I just got back from a reading and discussion of the Fourth World trilogy (final installment pending) in two separate sixth-grade classes today.  Frankly, I hadn’t expected very much engagement; to me, Fourth World seemed much too dense with 22nd-century medicine, genetic engineering, stem cell technology and even the mechanics of space engines, to appeal to students in sixth grade.  But the intro and Q&A sessions covered the art and science of both sci-fi and medicine, which seemed to draw rapt attention– something for everyone.  About two-thirds of the class said they preferred the arts, while one-third classified themselves as science-heads.  Anyone want to write as a hobby or professionally?  Quite a few hands shot up.  How about doctors?  Almost an equal number– amazing, at this age.

For those who denied any interest in writing, I advised keeping an open mind:  years from now, they may find that writing has become one of their greatest passions.  My advice to the nascent writers in the class:  first and foremost, read a lot!  In junior high school, some books I read for fun were Moby Dick, A Tale of Two Cities, The Foundation Trilogy, some Kurt Vonnegut, Dune and Lord of the Rings.  But To Kill a Mockingbird has had the greatest influence to this day.  Love of reading does not lead to good writing any more than love of music leads to composing skills or mastery of a musical instrument– but in the absence of high-quality reading, good writing is impossible.

Second, write what you know:  that is as old as the hills and twice as dusty– but still valid.  Of course I wrote Fourth World drawing from my experiences in medicine, bench research, patients’ stories and so on.  Although too young to have accumulated much experience of that sort, most sixth-graders have gone through the gamut of family struggles, (cyber)bullying, good and bad relationships, lack of confidence, and personal loss.

Third, know what your theme is before you write.  When students were asked what they would write a book about– or would like to see in a book written for teens– recurrent themes included character growth through the school years and entering professions such as medicine.  Those were expected, as well as themes oriented around gaining control of one’s life, as well as the fear of death.  More surprising, one student who had lost her father recently said that she hated doctors for failing to save him– but wanted to become a doctor herself.  Another student– thanked by the teacher for sharing– wished for a book about a girl who was constantly abused by her mother, then discovered superpowers in herself.  Yet another planned to solve, and write, murder mysteries.  In the end, there was universal enthusiasm for an ethnic cookbook– food conquers all!

Then came my reading from both novels.  When given a choice of passages, the overwhelming majority of kids chose Benn’s discovering a scene of horror in a locked medical ward (from Fourth World Nation).  I thought they would!  A baseball game played on Mars came in second, and no one wanted to hear about a band of young children fleeing an invading army (now that I had not expected).

These students, maybe ten to twelve years old, were very bright, definitely engaged, and not shy about speaking up.  They understood various references, albeit not in detail, that I made to artificial intelligence, genetics, space and medicine.  In contrast, when I was ten and entered sixth grade, as far as I can recall, I had no knowledge of anything.  It must be the energy and generous spirit of their teacher, supplemented by the Internet Age; the whole time I thought my readings would fall on deaf ears, I needn’t have worried at all.

Three paragraphs above, I mentioned a book about a mother’s abuse of her daughter, who subsequently gains superpowers.  Here’s a mercifully brief excerpt from Fourth World, in which Benn mulls over his strict upbringing:

“Honestly, his father’s long absences were a relief to Benn, as Owen’s oppressive approach to child-rearing (traditional among the Chinese, Benn had learned from a library book on psychosocial development) included caning his son when he broke the rules, or slapping him for asking impertinent questions.  Benn rubbed the back of his head, imagining a dent where Father had once applied his shoe. The effect, however, was the diametric opposite of what Owen intended: as a child, Benn reacted to physical punishment by further rejecting the rules, his impertinence growing with every blow.”

To the girl who requested that book:  Benn does develop extraordinary abilities later in Fourth World, and to a degree, justice is served.  Keep on reading!


Testing One-Two-Three

The patient’s spiking fevers had lasted over two weeks, and all efforts to diagnose an infection (the most common cause of fever) had yielded nothing.  She was admitted to the hospital for further workup, and late one evening, I was asked to see her, as the rheumatologist on call.  The electronic health record showed a normal admission physical exam (except for her temperature) and dozens of normal blood tests.  The only abnormality was a markedly elevated erythrocyte sedimentation rate, which is a nonspecific indicator of inflammation– it can be high in infections, malignancies, autoimmune diseases etc. and did not narrow down the diagnosis by much.  The inpatient ward team’s primary question for me was:  Out of all the numerous lab tests associated with rheumatologic diseases, which should they order?  ANA?  SSA/B?  RF?  ANCA?  aCCP?  What’s the best rheum test to diagnose an autoimmune disease? they earnestly inquired on the consult request.

After taking a detailed history of her illness, I looked at her skin, her mouth, nose, ears, felt for lymph nodes, listened to her heart and lungs, pressed on her abdomen– most are routine features of the physical exam– without finding anything abnormal.  It seemed the admission exam was accurate, and it was going to be a long evening.  Then I threw back the bed covers, to take a look at the legs.  The abnormal finding was immediately obvious:  her right foot was pointing at the ceiling, while the left foot was pointing at the door.  Hard as she tried (with me cheering her on), she could not point it upwards.  How long had that been going on?  Oh, about two weeks, she said– was it important?

She had what is called a foot-drop!  I went back to the electronic record, which made no mention of it (“Neuro, nonfocal,” it said).  And yet her conspicuous foot-drop, a result of a condition known as mononeuritis multiplex, led to the correct diagnosis of vasculitis (after a biopsy):  PAN, polyarteritis nodosa.  Long before the biopsy result came back, the patient’s fever had already resolved on treatment begun later that night.  Further blood tests did not contribute to her care; the “best rheum test,” it turned out, was throwing back the bed covers.

What brought this episode to mind was an article by Dr. Abraham Verghese in today’s NY Times, How Tech Can Turn Doctors Into Clerical Workers, in which he warns of the downside of electronic health records and artificial intelligence, in terms of mistakes made, the temptation to cut corners by simply making a keyboard click, the decline in the interpersonal aspect of patient care, and physician burnout.  It is human nature, I suppose, to seek the fastest path to a solution; to order more and more tests rather than look at the patient’s feet; and to write the daily progress note electronically by replicating the previous day’s note (with minor additions), assuming that the admission note had not missed anything.  In 2018, we seem to rely less on ourselves, our senses, our analytical skills, and more on all our ingenious inventions– our computer algorithms, antibody screens, DNA sequences, cell counters, all our technology– and in this way, we become subservient to them.

In the dystopian society of the Fourth World trilogy, machines use A.I. to make the diagnoses and prescribe the treatments.  Here’s an excerpt from the first novel, Fourth World:

“The patient, W.P., is a 64-year-old transportation executive who complains of severe, sharp pains and tightness in all of his muscles, of eight months duration.”  Kai began his presentation, reading from his open da-disc to the small group of interns, who were supervised that Friday by Dr. Hol Chan. W.P. was sitting hunched over on the hard examining table, wrapped in a short white cellulose gown, hands spread on his exposed knees.  He had been through this ritual ordeal so many times before. Less than a meter away, his wife sat stiffly upright on a short metal step stool. Standing just to her left, Benn observed her jaw muscles, clenching and unclenching. A state of agitation. Her middle and distal knuckles showed the bony enlargement of mild osteoarthritis.  There was a tiny growth on her forehead, which he diagnosed as a seborrheic keratosis; the Probot would have concurred. Because the room had been designed to accommodate only the patient and one physician, Dr. Chan and her interns were forced to crowd around.

“He is previously healthy, except for a very brief period of PsySoc rehab in his twenties, and his social and family histories are non-contributory.”  Kai glanced nervously at Dr. Chan, who, having heard Kai’s presentations before, watched him with an expression of deep concern as she activated the wall projection.  Kai continued, “I have put W.P. through the Probot twice, and both times the results were identical: signals of tissue injury or regeneration, inflammation, pre-mutagenesis and metabolic derangement are completely absent.  Epigenetic expression, including at the micro-RNA level, is normal. Risk loci mapping and haplotype structure are unremarkable. You can see on the next screen that the central and peripheral chi are not in any way obstructed.  I entered the patient’s history, systems review, family history, physical exam and lab data into the analyzer and found no matching diagnosis. And so, without a suitable coding of his diagnosis, there is no way to initiate the billing process.”

Dr. Chan, studying the wall screen, nodded in agreement.

Kai looked up from his da-disc and shrugged.  “In fact, W.P. is perfectly healthy, even though obviously he is persisting in his illness behavior.”


They Are, Therefore They Think II

This weekend, the director of Stanford’s Artificial Intelligence Lab, Professor Fei-Fei Li, made a speech in which she referenced an article she wrote for the NY Times, How to Make AI That’s Good for People.  In her plan for “human-centered A.I.” the first goal is for artificial intelligence to better reflect the complexity, richness and sensitivity of human intelligence.  Along those lines, my March 23rd post on this blog, They Are, Therefore They Think, addressed a robot’s sense of humor, while contributor Sean Noah focused more on the capacity for introspection.  Both are felt, at least for now, to be uniquely human characteristics, but would probably fit well into any imagined human-centered AI.

Dr. Li’s second goal is to have A.I. enhance us, not replace us:  we would automate the “repetitive, error-prone and even dangerous” aspects of jobs, while leaving the “creative, intellectual and emotional roles” for humans.  In my first novel, young Benn Marr, on his way to medical school in 2196, muses about the vanishing role of humans in medical practice.  Here’s an excerpt from Fourth World:


The medical field essentially consisted of tailoring and applying these peptides in clinical situations.  Diagnostics had long ago been relegated to machines, which scanned, analyzed, and diagnosed the patient. They even prescribed the appropriate therapeutic plan.  Frankly, the production of theragenomic peptides could also easily have been taken over by- and, in fact, seemed particularly suited to- the medical computers. What remained were the sensitive tasks- acknowledged haltingly by the most advanced teaching hospitals- of deciphering patients’ wishes and guiding them through the pitfalls of treatment.

“Wishes” meant the patients’ attitudes toward both disease and treatment, resulting from a global summation of their personalities, prejudices, neuroses, education, religious beliefs, family dynamics, and a host of other factors not amenable to analysis by computers.  After all, physicians had to balance the purely technical or algorithm-driven approach with personalization of care. Didn’t they? Wasn’t the admirable desire to do something for the patient best complemented by a healthy skepticism and sensitivity to the patient’s wishes?  In Benn’s application essay, “The Vanishing Role of Humans in Medical Practice,” he had pointed out that technology did not supply social awareness, creativity, or idealism.  Wasn’t the physician also a humanist? he had asked. A historian, digging out, interpreting and telling individual stories? The essay had focused on this tiny corner of the field of medicine, and while conceding the value of face-to-face human interaction, had also predicted that it would continue to fade away.


Dr. Li’s third goal for A.I. is to ensure “that the development of this technology is guided, at each step, by concern for its effect on humans.”  Machines should not be our competitors, but instead “partners in securing our well-being.”  She is concerned about effects on labor, biases against minorities in machine learning, privacy rights, and geopolitical implications.  Debating and resolving ethical challenges should not be outstripped by the fast pace of A.I. technology– a problem we are already seeing in other fields, such as genetic engineering and stem cell applications.

The Fourth World trilogy imagines a dystopian future:  there are three major laws governing genetic engineering (but laws– including Isaac Asimov’s famous Three Laws of Robotics– are meant to be broken, and therein lies a large part of the story).  In contrast, at the turn of the 23rd century, Q.I., or quasi-human intelligence, is far less fettered by ethical constraints; the concern for its effects on humans has a lot to do with monitoring the population, as China and others are already doing in 2018 with facial recognition, social media and big data; suppression of any dissenting views; and, inevitably, the development of weapons.

My third novel (the working title is Child of the Fourth World), will conclude the trilogy.  A fascinating conversation I had recently with someone who consults on US weapons development led to the following passage (apologies if you are having breakfast):


If Najib were now in Shanghai, he could have chosen from a range of much more sophisticated tools to carry out the assassination.  True, the century-long setback to technological research and development caused by the War of Unification had returned warfare to a more primitive state.  The PWE, faced with widespread pockets of rebellion, had spent substantial resources simply to maintain the status quo. But they had also managed to develop a few fiendishly clever QI weapons on a small scale.  He thought of the virtually unstoppable SHIVA Destroyer (the acronym was especially appealing to Najib, whose ancestors had practiced the Hindu religion). The Single Highly-Identified Victim Aerial Destroyer was a high-speed drone the size of his palm.  It could be launched from as far as three kilometers away, and was capable of individual facial/retinal recognition; assessment of circumstances surrounding the target, including the presence of “friendly” combatants; correcting for evasive and weapon-based countermeasures; then acquiring and attaching to the target’s head with a 99.97% success rate.  Having done so, SHIVA would unleash a directional microwave blast calibrated to melt the target’s cranium and reduce its contents to a viscous liquid resembling hot oatmeal. It was highly effective, but sadly, unavailable to him at the moment.


Ah, the wondrous benefits of technology.  But sometimes we seem like three-year-olds sitting behind the steering wheel of a speeding Maserati; technology is empowering, of course, but if only the human species were mature enough to avoid crashing into the nearest tree!



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.


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?”