The first classical album I ever owned was a copy of Beethoven’s 9th Symphony that I bought for 99 cents from the used album shelf in the old Urban Outfitters warehouse in West Philadelphia. I needed background music to study for the MCAT, and the 9th was alternately thoughtful and lively, good for absorbing chemistry and physics.
Before that, classical music meant the Hungarian Rhapsodies played in Bugs Bunny cartoons, and the aria from Pagliacci that I learned in fourth grade as a member of the West Orange Top Twenty Choir, that we performed, dressed as Italian peasant children, at the Paper Mill Playhouse in Millburn with the New Jersey State Opera.
I added the 5th and the 3rd and the Pastorale, the Violin Concerto, the Emperor Piano Concerto, and the Kreutzer and Spring sonatas. Beethoven led to Mozart and Bach, then Mendellsohn, Schumann and Chopin and Mahler. I listened to a CD of the Brahms D Minor piano concerto over and over on a long plane trip, which a year later let me hold my own talking to a pretty New England Conservatory student one afternoon in Boston. But that’s a story for another time.
I saw the Atlanta Symphony and Choir perform the 9th at Avery Fisher Hall during my chief resident year. Watching the orchestra, the string sections passing the melodies to each other, the winds and percussion adding punctuation, the themes introduced and recalled in different ways, I saw the architecture of the symphony as a whole, how it methodically build from the sunrise of the opening notes through the turbulence of the middle sections to the cellos’ first whispering of the Ode to Joy theme, which gets passed from section to section, from individual voice to small group to chorus, merging loud with strong, fireworks with exclamation points.
I approached music differently after that. No longer content to let it just pass through me on a journey from one side of the room to the other, I held on to it for a while, looked for the big picture, for theme and variation, key and tempo changes, the unique structures of a concerto versus a sonata versus a symphony, and how the language of a trio differed from that of a quartet or duet. I took apart pieces of music and put them back together like a kid playing with an old toaster. I saw the structure of DNA in the violin and viola duets of Mozart’s Symphony Concertante, and the chaos and aftermath of battle in the third movement of Brahms’ first piano sonata. I even found Bach hiding in the opening chords of The Beach Boys’ California Girls.
Two to the fifth came and went. I finished medical training, met and fell in love with Priya. My friends and I grew older, shared joy and sorrow, succeeded sometimes and failed sometimes and eventually stopped keeping track. Nikhil and Tarana arrived, filling our world. My parents passed away.
The Boston Symphony performed Beethoven’s 9th at Tanglewood last summer, and the four of us spread blankets on the lawn under a tree and settled in. I had only seen it that one time 32 years before, and had not heard it played start to finish since. I looked forward to watching it unfold, and comparing it to how I remember seeing it so long ago.
But instead of watching and analyzing, I closed my eyes and I listened, and I stopped thinking, and I just felt. Instead of locking my gaze on the different orchestra sections just before I knew they would pick up a melody or add a harmony, I blurred my vision and let the music come to me, as a whole. Priya was a few feet in front of me and just to the right, Tarana next to her and Nikhil sat at my side, his head occasionally leaning into my shoulder. The symphony surrounded and enveloped us, lifting us a tiny bit off of the grass. For the next hour the world was just the four of us in the sunshine, and the 9th: no conductor, no audience, no musicians, no stage.
The 9th Symphony was first played in 1824, in Vienna. Beethoven died three years later, on March 26th, exactly 137 years to the day before I was born. Thirty-two years after that I saw the 9th performed. Then thirty two years later, for the first time, I truly heard the ode to joy.
A happy two to the sixth to all who celebrate.
Every year about this time I send out an unofficial end of year investor's letter -- "unofficial" because 1) it does not get sent to my investors and 2) it usually has little to do with investing. (This is not an official business correspondence)
I’ll get to business in a bit.
But first a story.
It's just after 7:00 on a December morning at the 50th Street subway stop in Times Square. The line outside the Stardust Diner stretches to Broadway, rounds the corner and stops just short of the stage door of the theater where The Music Man is playing. The Stardust is where the waiters and waitresses stand on the counter and sing show tunes.
Rachel from Friends worked there.
As I walk by the Stardust on my way to work, the Spotify algorithm serves up an old Cat Stevens song.
I left my happy home, to see what I could find out
I left my folk and friends, with the aim to clear my mind out
One hundred and eighty miles to the northeast, there's an iron gate at Brown University. New students go through the gate onto campus the first day of school freshman year and go back the other way at graduation. In between the gate stays locked.
The name of the song is On The Road To Find Out.
Depending on traffic, state trooper presence and the beat of the music playing on the car sound system, it takes between two and a half and three hours to drive up I-95 to get to Providence. The most memorable drive was the Covid evacuation pickup in March of sophomore year, the cars double-parked, clothes stuffed into Hefty bags -- students now refugees fleeing the oncoming viral army.
Well, I hit the rowdy road, and many kinds I met there
Many stories told me of the way to get there
The Stardust opens at 7 and it's already full, so the people I see on line will be the second sitting. There are no reservations. Lots of strollers on line and lots of sweatshirts and varsity jackets. Ohio State, Arizona. Lots of accents and dialects.
Tarana mentored two sisters from a Providence grade school, recent immigrants from Senegal. She'd pick them up and take them to campus and one day they decided to do field research, studying (if I remember right) something like the relationship between mood and sleep. They surveyed students and staff and professors, then tabulated the data and came up with a conclusion.
The sisters were 11 and 13 years old.
My office is about a ten minute walk from the Stardust diner, and that particular morning, with Cat Stevens singing in the background, I envision drives to airports in Texas and Colorado and Dublin and Madrid, taxis from JFK to the Marriott Marquis, QR coded tickets to Phantom of the Opera and Wicked and bookmarked pages from Trip Advisor that summarize which days the museums close and which hop-on hop-off bus tour stops where.
Cat Stevens released Tea for the Tillerman in 1970, when I was in middle school. I first heard it when we visited by father's old friend Carl Tasch, who had a son, Ira, who was my age. He played the album start to finish, which relieved us of having to find something to talk about.
On the Road to Find Out is the fourth song on side two.
I reach the office. A card in my wallet unlocks the elevator button to our floor, an action that creates one more data point in the building's security log.
What was the relationship between mood and sleep in a sample of the twenty or so people surveyed one Spring afternoon in Providence? How was the data analyzed? What was the conclusion?
The elevator opens, the work day starts.
Well, in the end I’ll know, but on the way I wonder
Through descending snow, and through the frost and thunder
I listen to the wind come howl, telling me I have to hurry
I listen to the robin’s song, saying not to worry
Of course the sleep data was never the point, and neither is the total amount of time spent on lines on a trip to New York. What matters is that two young girls will remember how easy it was to approach a bunch of older and very foreign acting people, to talk to them and to ask them questions a couple of miles and a world away.
So on and on I go, the seconds tick the time out
There’s so much left to know and I’m on the road to find out
Regarding business?: Not a great year, but it will be fine.
Wishing you all a happy and fulfilling holiday season, a successful and engaged 2023, and forever safe passage on the road to find out.
(Previous letters in the series: www.dbsable.com)
Every year about this time I send out an unofficial end of year investor's letter -- "unofficial" because 1) it does not get sent to my investors and 2) it usually has little to do with investing.
I’ll get to the funds’ performance in a bit. First, let’s pick up where we left off last year.
You’ll recall that Priya, Nikhil and I survived Tarana’s trip to the bridal gown store in the mall in Dartmouth, Massachusetts to buy a prom dress. More about that later.
Years ago a friend sent me a copy of a book with a “read this chapter” note. The important part was a story about an old man who liked to dance. If I remember right he used to go to a community center or some place like that and, no matter what kind of music was playing, he would go out on the dance floor and close his eyes and spin around and do whatever the music made him feel like doing. The way the old guy danced was nothing like the move-as-little-as-possible, keep your hands at your sides and, heaven forbid, don’t let anyone think you are enjoying yourself style that I had perfected years ago. His way was better.
I read the story, put the book on the shelf and figured I’d come back to it another time.
My father gave me a piece of advice: sometimes it’s best not to let everyone know what you’re thinking. I took that advice to heart. Maybe I learned it too well. I missed the part where if sometimes its best to keep things to yourself, then ― at other times― letting the world in is okay, and sometimes it’s a lot better than ok. Nikhil always understood that. A good example: we stopped at a town square during a festival in the Netherlands on our way to Kröller-Müller and Van Gogh a few years back. Nik and I wandered to the bandstand as the music started. His dancing involves a lot of jumping and pretty soon he had a bunch of bikers in leather jackets over black t-shirts, with long beards and dark sunglasses, leaping up and down with him to the beat of what was actually a pretty good band playing old Motown. A few songs, lots of spilled beer (theirs, not his) and many high fives and fist bumps with his new Dutch friends later, we were off. He was about fifteen the time.
I still have my friend’s book, which I have read through many times, and it’s easy to bring back the image of the old guy out on the dance floor. I thought about him again a few weeks after the David’s Bridal Shop episode.
The after-prom party for the Chapin class of 2018 was held in someone’s parents’ second or third house’s huge backyard, somewhere up in horse country. I think the story included shuttle buses and an enormous sloping lawn and a big tent and paper lanterns. Not burdened with the awkwardness of boyfriends and girlfriends and the before the after prom issues of is this a date date or a prom only thing (I am making this part up and it may have no relation to reality), the girls were free to be happy and to be loud.
Only not too loud. There was a neighbor and a phone call and maybe a police car, and the sound system, probably louder than Woodstock, had to be turned off. But the story ends well: a Bluetooth system switched on, dozens of headphones handed out, and the class of ‘18 and their guests spread out over the lawn dancing with abandon, neon glow sticks around their wrists and in their hair. To those of us watching from afar, a silent dance party on a starry starry night, a marvelous night for a moondance.
Oh yeah, before I forget, both funds did just fine this year.
Jumping the gun to wish you a great end of 2019 and happy, prosperous, and a choreographed with abandon 2020.
The American Society for Reproductive Medicine kindly invited me to give a keynote address on The Business of IVF. A video of the talk can be found here:
A few words about sixty. But first, a story.
During internship, if I was fortunate enough to have slept during a Friday or Saturday night on call, I'd bike across the park the next day, to 65th and Broadway. There was a theater on the east side of the street that ran Eric Rohmer and Stephen Frears films. Shakespeare and Company was a few blocks north and Lincoln Center was a few blocks south, and right across the street was an enormous Tower Records where you could lose yourself for hours, in rock or Broadway, pop or jazz or classical, each type of music in a separate area, arranged with glass walls and sliding doors and on different floors, so that one type of music never drowned out another. Bernstein's quartet from West Side Story here and Talking Heads there. Classical downstairs, the cello solo from Brahm's third piano quartet, the CD box on the counter underneath a cardboard sign with "now playing" written in black magic marker. On a Saturday afternoon I could discover REM or hear Chopin for the first time, or rediscover Billy Cobham or Larry Coryell until fatigue sent me to the cashier and back out onto Broadway where I unlocked my bike, reattached the front wheel, and pedaled back back to York Avenue, where I carried the bike on my right shoulder into the elevator, a bright yellow plastic Tower Records bag swinging from my left hand.
There was one problem. 1980's compact discs sounded terrible, their highs clipped indiscriminantly, the sizzle of the cymbals traded away in exchange for the disappearnce of a little background hiss that we had already trained ourselves not to hear. They were also too small and too shiny, so we hid them on little mechanical drawers that disappeared into the front of the CD players. And they only had one side, with no break in the middle.
We made a bad trade when we switched away from record albums, which we rightly encased in artwork, handled with an almost religious gentleness, touched only on the edges and not on the grooves, cleaned with velvet Dustbusters and D3 fluid. Watching the record spin was as much a part of the experience as hearing the music, the tone arm balanced, barely touching the vinyl, the signal whispered from needle tip to cartridge to preamp to amp to speakers, every tone, music or pop or scratch, reproduced without judgement, somehow landing in the room as if the musicians themselves had knocked on the door and politely asked if they could come in, set up and use your apartment to practice.
And all the albums had a beginning (side one), a middle (turn the album over) and an end (side two), and the middle, the moments when you lifted the tone arm, flipped the record, dusted it off and lowered the needle to play side two were the filled with the best, purest, most sublime sense of anticipation. The best of those feelings came the first time you played a new album, something you only got to experience once per record, once in your life. You heard Baba O'Riley for the very first time. You turned over the record not knowing that Won't Get Fooled Again is on the other side. You listened in wonder as you first hear Kitty's Back-- having no idea that Incident On 57th Street and Rosalita were just a few minutes in the future. You flip over Sergeant Pepper. Could you possibly have imagined A Day In The Life?
All you had to do was turn over the record.
You can get to sixty from anywhere. It's divisible by 1, 2, 3, 4, 5, 6, 10, 12, 15, 20 and 30. Multiply just about any two or three small numbers and eventually you'll land on sixty. But like forty and fifty before it, sixty is not a destination. While you're there, its just the middle, coming after what came before and coming before what will come after, which may still be new and different and great. There are even more directions away from sixty as there were paths to it.
Time to turn over the record and hear what's on side two.
1) Espresso is single task.
2) Espresso should only be poured into a glass.
3) Espresso is never ordered to go.
4) In the Nicomachean Ethics, when Aristotle discusses magnificence on a small scale, he means good espresso.
5) Second espresso, clean cup.
6) Espresso is best consumed in a coffee shop that does not have a kitchen.
7) You can make good espresso or good tea, but not both.
8) Do not look at your phone while drinking espresso.
Every year about this time I send out my unofficial investor's letter -- "unofficial" because 1) it does not get sent to my investors and 2) it usually has nothing to do with investing.
I’ll get to the fund performance in a bit. First, a story.
We spent a long weekend in Newport back in May, and a heavy downpour that Saturday led us to the Dartmouth Mall in New Bedford, Massachusetts. More specifically, and improbably, it led us to David’s Bridal Shop.
Tarana’s school has a formal graduation ceremony, with hymns and speeches and limited seats for parents, grandparents and nannies (you need tickets to get in), and a commencement address, and each girl wears a long white dress. By tradition each dress is unique (there was a scandal involving a duplicate dress this year but I am not allowed to talk about it) and as March became April and April turned to May, finding the right dress rose higher and higher on the to-do lists for the members of the Chapin class of 2018.
Priya and Tarana were on top of this, but Nikhil and I were blissfully (and appropriately) unaware. The occasional white dress reference over dinner was easily lost in other transition talk as our family planned for both kids to move out of the apartment later in the summer, Nik into his own place and Tarana off to college.
For me, with the kids leaving, this was a year of vigilance for signs of overwrought sentimentality, which, whatever “overwrought sentimentality” means, sounds like a good thing to avoid. I kept an eye on myself for new obsessions and the emergence of odd hobbies. Indeed, I developed a passion for swapping out hard drives and upgrading RAM in old computers, but otherwise showed few signs of decompensating.
I dropped Priya and Tarana at the store and drive off to the far reaches of the many-acre parking lot, hoping that it would take so long to park that by the time Nik and I walked with our umbrellas back to the store, the dress would have been chosen, bagged, and paid for and the two guys in sandals, shorts, and hooded sweatshirts with Montauk printed on the front (Nik’s in green, mine in blue) would not have to see their daughter and kid sister prematurely wearing a wedding dress.
It was not to be.
David’s bridal is the Library of Congress of wedding dresses, rows and rows and rows. There were lots of fitting stations, each with a three-fold mirror and platform, and each with a little bleachers section so that the bride-to-be’s entourage could watch and weigh in. The women (all women, at each station, no best guy friends like in the movies) were split into two groups. One group, usually the mother and one best friend, gave their opinions right away, before the bride. The rest waited until the core group made up their minds, then cheerfully reinforced whatever was already decided. Dress after dress was unwrapped, modeled and rejected, until “the one” emerged, eliciting a roar from the bleachers, hugs and tears and the ringing of a loud bell (Nikhil and I laughed when we heard the bell the first time, drawing angry looks.)
But all of this activity faded when we reached the back corner and found Priya and Tarana and a saleswoman in cat glasses. I felt a sense of relief, because it looked like Tarana was playing dress-up, pulling costumes out of a fake cardboard storage chest in a friend’s attic. Nikhil and I looked at each and exhaled. The foundations of our existence remained intact, unthreatened by images of a future we were not yet prepared to see.
Then all of a sudden “the one” emerged, and we were no longer in someone’s parent’s attic. The women in next fitting station turned their heads towards Tarana and nodded and smiled and raised their eyebrows, the saleswoman put the right earpiece of her glasses to her lips, and Priya took a picture, then another one.
For Nikhil and me, the image we had feared was indeed remarkable, but it revealed the present, not the future. It was a graduation dress after all, found in an unusual place, but for worn for the right reasons at the right time. There were hugs but no tears.
And no one rang a bell. Nik and I made sure of that.
Regarding the fund: it was indeed a year of living (a little) dangerously. That said, the fund has done just fine.
My dear friends and colleagues – wishing you happy holidays and the best for 2019
(Below: Tarana is far right, second from the top; below that — Nikhil and I having survived David’s Bridal)
Eat Drink Son Daughter: A Saturday Morning In The Kitchen
It’s a recent September Saturday morning and I’m by myself in the kitchen thinking about a 1990’s movie from Taiwan. The sun is up, a window is open. The sailboats from the 79th Street boat basin are moored well past 100th Street, and the West Side Highway is weekend morning quiet.
I’m making an omelette, eggs scrambled into a mixing bowl, the other ingredients chopped or sliced in their own little plates waiting to be poured into hot oil one after the other, the order and timing based on size, protein and fat content (how quickly they cook), trying to coordinate each being done just right so the ingredients in the omelette will arrive at done-ness all at the same time.
Kitchens are the best chemistry labs. All of the ingredients are in the pan now, melding together. Fatty acids separate from glycerol from contact with the hot oil. Proteins unfold and unwind in what used to be the nuclei of the eggs. I lower the heat, run the edge of a spatula around the perimeter of the pan to keep the omelette from sticking, turn on the ventilation fan, open another window and hit the button on the Nespresso machine, pretending I’m making espresso with a burr grinder and the real Gaggia machine that I struggled with for years before sticking it in a high shelf in the pantry. I flip one half of the omelette onto the other, trying but not quite succeeding to make the edges match so that the top melds to the bottom, making it into one.
In the movie, a father prepares dinner for his three adult daughters. It’s a Sunday, he does this every week. While he collects vegetables from his garden, strips leaves from various plants and grinds them into spices and arranges a drum set’s worth of kettles and pans and pots over the stove over a huge stove, we learn about each of his daughters, and the challenges they face. Gradually each makes her way home. They eat together, plates of food and words and smiles and raised eyebrows crossing the table rapidly, managing never to collide.
I’ve seen the movie a couple of times. It’s more of a still photo than a film for me, the four characters pausing life for a couple of hours and recharging their energies together. It’s a beautiful image, and one that means much more to me now than in 1994, three years before Nikhil and six years before Tarana.
It’s a good omelette. I clean up and head out, feeling content in that sunny and breezy September morning way. Nikhil and Tarana are both settled in their new homes, working and studying and moving forward. I’m thinking about cooking and kitchens and making sure that they keep coming back.
A Violent Encounter With Transparency And Other Adventures In Biotech Fund Management: My Unofficial Investor Letter 2017
Reliable Deli is on the north side of East 54th Street, midway between Park and Madison. It has a rust-colored awning with white lettering, with a string of Christmas lights strung around its edges that blink on and off year-round. I've gone there four or five times a week to take out breakfast or lunch for the past 8 years. It's a bustling place, one of those places where you can get hot food, cold food, toothpaste, batteries, boxes of cereal, sandwiches, wraps, spicy Korean chicken, fake crab meat, and real duck. Deep metal pans under heat lamps. Sneeze shields over the buffets.
You get the idea.
Reliable has two tall glass doors that can swing in or out, like saloon doors, only much thicker and much heavier. One day this summer I must have had difficulty deciding which way I wanted to open the door so I just walked into it as if it wasn’t there. Right knee and forehead met the thick, thankfully shatterproof glass while I accelerated from a standing start. I bounced off the door, shook my head back and forth like a puppy hearing itself bark for the first time, while soaking up the collective concern and secondary embarrassment of everyone inside.
The staff sprung into action. A small stack of clean napkins was quickly applied to my forehead. A first aid kit appeared, its contents probably long expired. A heavily accented New York voice repeated over and over: “Get him to an emergency room. He needs an MRI. I'm a nurse. I know”
I had no intention of going anywhere except back to my office across the street. I felt okay. I am not a stranger to concussions, having suffered one while ice skating with my son years ago, and I somehow knew that the door had enough give to have not made my brain rattle around inside my head. The skin on my forehead, however, was not so fortunate. Just to left to the midline on the mild frontal bossing over my eyebrow there was a terrific gash, the result of the impact followed by a little bit of a smush and tear. I folded the stack of napkins to hide the soaked-through part, applied pressure again and this time successfully exited Reliable Deli.
I was quite a sight in the elevator, going back to the office, holding a white plastic bag containing the styrofoam container with my lunch in one hand and the other hand pressing the folded stack of bright napkins against my forehead. Thirty minutes later I sat in the exam room of a nearby urgent care center. A half hour after that I am back on the sidewalk, having replaced the paper dinner napkins with a folded stack of sterile gauze pressed against my forehead, dismissed from the Urgent Care Center and directed to the nearest emergency room. (“Too deep. And you need an MRI.”) I stood on Second Avenue, left hand against head, right hand holding cell phone, speaking to a helpful representative of my insurance company, who reassured me that as far as United Healthcare was concerned, I could choose between the equidistant emergency departments of Cornell Medical Center and NYU Medical Center, confident in the knowledge that my co-payment, deductible, access to care for the rest of my life, and future list of pre-existing conditions would be the same.
I went north to Cornell. “I used to work here,” I said over and over, eliciting a flash of semi-interest from the security guard at the door, the triage nurse, the admitting nurse, the intern who took my history, the attending who retook my history, and the volunteer whose job seemed to be to observe me for any signs of rapid cognitive decline.
I turned down the MRI and was content to let the intern place four interrupted stitches (it may have been silk or vicryl but I forget) into my forehead, although I was offered a plastic surgery consult. At that stage in my training, I could have thrown those stitches in my sleep. The intern’s handwriting was good so I figured his hands were steady.
I returned to the office with a bandage wrapped tightly around my head, returned to the ER a few days later to have the stitches removed, filled out a nice evaluation online about the quality of my treatment at the hospital, and ignored the monthly solicitations for donations that came for the rest of the year.
The next day, I was a celebrity at Reliable. Breakfast was on the house, as was lunch. The cashiers, the short order cooks, the stock guys all greeted me with warm smiles and curious glances to the scar on my forehead. Menus were taped on the glass doors at eye level.
I made a point of joking about the incident and repeating over and over again that I had been careless and preoccupied and stupid and that it was my fault. And that I was fine, no crazier than before, no ringing in the ears, and certainly no intention of talking with a lawyer.
After a few weeks, the menus came off of the glass doors, and the customers of Reliable Deli were again trusted to use their hands or back sides to enter and exit. The scar slightly to the left of the midline just above my eyebrow faded away. The Intern, who by now has rotated to the Intensive Care Unit or to one of the med-surg floors, had done a good job. Whatever acute or chronic damage that my brief violent encounter with the glass door may have caused will forever remain undetected by the MRI scan that I refused to have done.
Every semester, as my students get to know me better, their questions get more and more personal. Towards the end of each semester I get asked wisdom questions, about success and happiness. I’m no expert, but I do think that humility and the ability to laugh at yourself are good places to start. Also: the fund did just fine this year.
(A speech I gave to the American Fertility Association in 2000.)
In planning to speak about advances in the field of assisted reproduction I have two conflicting images in my mind: the first is filled with impressive slides and graphs, detailing what is new in ART and, more importantly, what is coming. The second, and more real, is the disturing and disquieting image of a detached doctor, close in proximity but miles apart from the hearts and minds of his patients.
I spend many nights staring at the ceiling, thinking about the two challenged that face RE's. The first and obvious challenge is pushing closer and closer to the holy grail of our field, that of a reliable, predictable procedure with low risk and consistent outcome, one that is easy enough to place on an actuarial table so that insurance coverage becomes not only an easy ethical choice but an easy business choice as well. We have taken many steps in that direction over the past few years, and we can be justifiably proud of the development of ICSI, blastocyst transfer, single sperm freezing, preimplantation genetic diagnosis, assisted hatching with fragment removal and cytoplasm transfer.
But to inch closer to where we need to be, to the only truly acceptable set of goals for our science, we need to find some huge pieces of the puzzle. In the short term, we need a better means of assessing whom we can help and whom we cannot help. Two years ago I wrote an internet piece on FSH testing and our means of assessing eggs, in which I lamented the limited means we have to counsel many of our patients on what we can do for them. Every RE who will speak to you today knows that it is far easier to counsel an auditorium full of 500 couples on their chances of a good outcome than the one couple who sits across your desk.
In the longer term we need to better understand what makes some eggs, and some sperm, "good" and others "not good" and find ways to either rejuvenate those with lesser potential or make new eggs de novo. Now there are people, none of whom probably need this type of technology, who get uncomfortable with this type of talk. Some of these bold steps might need to use "cloning" technology. And we all know that anything that needs cloning technology, or even brings us to the possibility of speaking about the need for cloning technology, or even makes us think about the need for cloning technology should be banned and outlawed and never spoken or thought of again. Or should it?
A thirty one year old woman sits in my office, a survivor of leukemia or lymphoma or some other disease whose treatment left her not only infertile but menopausal. She and I discuss the very real and wonderful possibilities of her onceiving through egg donation, and we both silently say thanks that we live in the year 2000 and can offer this possiility to her. But what of the undeveloped option of using her "own" eggs? But did we not just say she has no eggs? And since women are born with all the eggs that they will ever have, how can we even think about or talk about using her own? Well, why don't we make new ones? Now, thankfully I have already passed my reproductive endocrine boards so if any board examiners are in the audience I cannot be blackballed, (at least I hope I cannot.) But let's for a moment propose for one of our long term goals the development of techonology that allows us to not only swap the nucleaus (and therefore the genetic material from my patients' eggs to donor eggs) and therefore make new "good" eggs but to swap a brand new nucleus from a stomach cell (yes, I know it has twice the needed number of chromosomes and is **gasp** technically a clone cell) and then zap it with electricity or an enzyme or two so that it DIVIDES and becomes.... a new egg. And my lovely thirty one year old patient can now have her own babies.
But we have used cloning technology! We have stepped onto the slippery slope that will lead to an Orwellian nightmare of genetic engineering and online ordering of blue eyes and perfect skin and high SAT scores. Or maybe we have just refined a technique enough to allow my 31 year old to have her own babies. And if, in so doing, we have allowed 41 year olds to have their own babies more rapidly and with higher percentages, than I am all in favor of that too. And if it allows us to say to our patients with really high FSH levels who cannot respond to stimulation regimens or to women whose endpometriosis has aged their ovaries by an extra two decades to have their own babies then that's a good thing too. But but but... if you can take the cell from a woman's stomach and make an egg with her chromosomes and she can get pregnant and have a baby when before she could not, could you not take the nucleus from a man's stomach and make an egg for him too? uhhh,, yeah. So we're perfecting a (**gasp**) cloning technology and we're allowing men to have eggs and we're supposed to let this just happen, knowing full well that we have stepped onto the slippery slope that will lead to an Orwellian nightmare of genetic engineering and amazon.offspring.com etc etc etc....
No, we are finding ways to help couples to have babies where before we could not. In 1995 we started larger scale use of preimplantation genetic diagnosis for the detection of abnormal numbers of chromosomes. If I can manage to deliver some reasonably well matured eggs to Dr. Cohen's lab, and he can grow the resulting embryos for three days and deliver one good cell from that embryo to Dr. Santiago Munne, then Dr. Munne can tell me and my patient and her partner the likelihood that that embryo will have an extra number 21 chromosome, or only one X and no Y chromosome, or pass on Muscular Dystrophy. We can also do, with pretty much 100% accuracy, sex selection.
With the enormous amount of information that we will soon have from the human genome project we may be able to greatly reduce the risk for breast cancer within a family, or the risk for diabetes. But this uses a technology that allows accurate sex selection, which as you all know, is a step onto a slippery slope that will lead to Orwellian nightmares of.... oh forget it.
The point I am trying to make is that there are enormous opportunities to help people and locked inside some of our more "dangerous" technologies. The challenge is not to suppress the technology, or to outlaw it; the challenge is to use it well. Just as we can choose to use a sharp object to remove a diseased appendix we can use a fluorescent in situ hyridization probe to prevent the passage of disease. And we can use intracellular manipulation to help families have babies.
That's the future-- now what about the present? A long time ago I wrote an article called "Reflections of an RE." It probably should have been called observations of an RE because that's all it really was, but a lot of my patients read it and commented on it. I had noticed certain periods during infertility treatment that tended to recur one patient to the next-- I called them emotional crisis points. They are pretty obvious: a first failed treatment cycle with injectable medications, a painful diagnostic test, that sort of thing. In discussions with my patients after that, we looked at another side: strategies for infertility treatment survival. To finish my talk today, I would like to share some of the lessons I have learned from my patients.
Ten tips for surviving your IVF cycle
1. Take yourself off the hook. Recognize that there is nothing you can do the will screw the process up. Entry fee to the "I screwed up my own IVF cycle" club:
2. Don't sweat the small stuff. Realize that there is no one right way and that a minor deviation from what happened last time can still be ok. There are a hundred valid ways to overlap lupron and the birth control pill. 10,000 units of HCG is probably 5000 more than you really need, so if a tiny drop dribbled down the side of your rear end it will not make a difference.
3. Lower the bar. Remember when you thought that your Algebra II final exam was like your final grade in Life? Your IVF cycle and its outcome are extremely important and you have invested tremendously of yourself in doing it. It is not everything though.
4. Repeat after me: the limitations are in the technology. If my IVF cycle cannot use your eggs, the problem is my IVF procedure, not your eggs.
5. Be as stressed as you want to be. Recognize that a major dose of stress is unavoidable during your treatment cycle. Don't try to deny it away and don't let its presence become a further source of stress for you. Look stress in the eye and keep it in its place.
6. Speak your mind but keep your composure. Remember "please" and "thank you" and if you page your doctor in the middle of the night, preface your question with, "I am really sorry to disturb you." Don't do this for the doctor. Do it to show him or her, and the rest of the world that even though you are going through IVF, you are dealing from strength.
7. Win both ends of the IVF cycle doubleheader. The greater goal is pregnancy and children, but a short term goal is to beat the evil treatment itself. Infertility treatment can chip away at self-image, can rob of us our positive self-image and cause us to question some of the more important decisions we have made as to how we run our lives. Let your actions show the world that you will not let the uncertainty turn you around. (h/t to Jackson Browne)
8. Let yourself be amazed at how well your spouse is putting up with everything. Be over the top in the way you support your spouse. Say nice things to your friends about him or her within his or her earshot.
9. Don't save up the love and attention. It is not going anywhere.
10. Take a crayon and draw a picture of yourself getting a progesterone injection. Make yourself look really silly. Take another crayon and draw a picture of whatever sperm collection technique you employ. Make everyone look really silly. Next take another crayon and a piece of paper and draw the head nurse talking on the phone. Give her really big hair and a cartoon balloon coming from her mouth and make her say, "blah blah blah blah blah blood and ultrasound" and make her look really silly. Next take another crayon and draw a picture of your doctor doing an ultrasound while you, the patient lie on the table with a thought balloon in which you hit him or her over the head with the probe. Make yourself look really powerful and make him or her look really silly. Then hang the pictures on the refrigerator with magnets.
The most impressive part of the advances in reproductive technology is the way IVF patients channel their strength and determination into grace, humility and humor. The rest of us can learn a lot from you.
David Sable MD
writer, teacher, fund manager and retired reproductive endocrinologist