Lessons and Triumphs of 1996
My Unofficial Investor’s Letter, December 2024
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 — I think — the 15th yearly letter.
The fund had a pretty good year. I’ll get to business in a bit.
But first a story.
On a cold November night in 1996, Priya calmly walks onto the stage of the Grand Opera House in Macon, Georgia, shakes hands with the conductor of the Macon Symphony Orchestra, bows to the audience, and sits down to play Rachmaninoff’s Piano Concerto №3 in D minor, opus 30.
The Opera House is vaguely familiar to me. It dates to 1884. Ninety years later, the Allman Brothers Band records and tapes a concert there for television, which I record on a portable cassette player from the TV and listen to over and over again. I take guitar lessons and learn how to play an Allman Brothers song called Jessica, and join a band named Machine.
Returning to 1996, I start to see patients with recurrent pregnancy loss, to experiment using in vitro fertilization with preimplantation genetic diagnosis, or PGD of the embryos. The idea is that many, if not most, of these pregnancies are genetically abnormal, never destined to grow to term, and that by performing a sort of pre-amniocentesis on each embryo and transferring only those that are genetically normal, we can greatly increase the chances of a successful pregnancy.
A lot of orchestras program the Rach 3rd in 1996: earlier that year it’s featured in the movie Shine, during which a conservatory student suffers a breakdown trying to master the piece. Indeed, it is one of the most technically difficult piano pieces in all of classical music, usually played by large, athletic men with huge hands who play it over and over again through their careers — sort of their personal greatest hit — each performance a special event, full of dark minor chords and big man Russian mystery.
Machine books its first big performance, playing on a Saturday night for the ice skaters at the South Mountain Arena in West Orange, NJ. I wheel my amplifier, a sixty pound Fender Super Six Reverb with 100 watts of power, to a small riser at the far end of the ice and plug it into a frayed extension cord which is plugged into the wall thirty feet away. I plug into channel one and our bassist, Marlo Newman, plugs into channel 2. After a few seconds of air raid siren feedback, the amp settles into an angry electric hum.
The problem with PGD in 1996 is that we can only test five chromosomes: X, Y, 13, 18 and 21. The technique involves removing one cell from each of the eight-cell embryos that we have grown over three days, then squashing the cell on a microscope slide mixed with fluorescent dyes that light up different colors, depending on which chromosome it stains. Then we shine a fluorescent light on the cells and count the colored dots.
Priya travels a lot, and I’m her road crew. I carry long dresses through airports, and hide pages of sheet music on the soundboards of the pianos hours before the shows start. On tour in India, a newspaper profile mentions Priya’s “American doctor husband.” During the performances, I lose myself in her music, but also catch glimpses of the audience, a mouth open in wonder during a particularly fast and fluid passage, the back of a hand spreading a tear across a cheek, a couple shares a smile and a “did you hear that” raise of the eyebrows. (I think about my sister’s reaction when first seeing Priya perform: “I Can Not Believe That She Is Marrying…..YOU!”)
(She smiles when she says it.)
For a week before our gig, the marquee outside the arena says “Saturday: Live Rock Music with Machine.” We attract a lot skaters and a few dozen people who sit in the hockey stands just to listen. We run through our set: Rick Derringer, Eric Clapton, two spacey songs that our drummer, Ray Yadlowsky, wrote, and then we get to the Allman Brothers section: Ramblin’ Man and Southbound and Jessica. Marlo gets excited and steps out onto the ice, the cord from the amp to his bass trailing through puddles.
PGD works. For women over 35 with three or more pregnancy losses, the miscarriage risk drops below that of women who never had a miscarriage. Then we use it for single gene pediatric disorders and prevent sickle cell disease, cystic fibrosis and spinal muscular atrophy with close to 100% precision. Patients come from across the country, Europe and Japan.
Promotors book at least a year in advance, and while I don’t remember all of the important life events of 1996, I do recall a day when Priya and I compare two calendars and realize that the Macon performance of the Rach 3 will be even more special than normal.
Marlo’s head bobs side to side. Not realizing that he is standing on the cord to his bass, he lifts his bass towards the ceiling. The metal jack at the end of the cord pulls out of the guitar and skips across the ice, creating sparks and painful feedback from the amplifier. The lights flicker and the skaters stop and Marlo bends down to pick up the metal end of the electrical cord, his feet in a puddle of water…
Then we apply PGD to chromosomal translocations, swapped pieces of chromosome that result in genetically unbalanced embryos that implant but stop development at seemingly random times, one pregnancy loss after another. For 300,000 years of human existence, a translocation is a curse, a black cloud; each pregnancy carries less hope, more dread and resignation.
In Macon I ask for a seat on the aisle, just in case I’m needed. As Priya walks across the stage to the piano, the polite applause grows louder, and the audience sits higher in their seats. I hear a few “wow’s” of appreciation. The conductor raises his baton. The strings play the first swirling bars of the their intro. Priya places her hands on the keyboard and starts to play.
The feedback in the ice rink ends abruptly as my amplifier blows a fuse. The lights return to their normal brightness. Marlo is saved from death by electrocution; he picks up the metal end of the cord and plugs it back into his bass. The session is over; a hockey team needs the ice for practice.
Not all of the translocation patients have successful pregnancies the first time, but most of them do. We publish the results and three years later we start a company, the first of many in what becomes a major industry within an industry, one that removes curses, dispels clouds, restores hope, and replaces dread and resignation with joy.
The piano score for Rachmaninoff’s Piano Concerto №3 in D minor, opus 30, contains 29,035 notes, and on a cold night in November of 1996 in Macon, Georgia, Priya played every one of them, perfectly, powerfully and magnificently, and she did it when she was eight months pregnant, farther away from the piano than she had ever had to play before, her arms outstretched in a way that no large athletic man with huge hands ever could. And the crowd stood and cheered and called her back onto the stage. And I was awed and proud and happy (and immensely relieved that she had not gone into labor on stage.)
PGD was renamed PGT and is now performed in more than half of the IVF cycles in the United States.
Machine disbanded shortly after the South Mountain Arena concert. Marlo lives in Arizona and sells real estate. Ray stayed in music, and played for many years with Meat Loaf and occasionally backing up Bruce Springsteen. He also released several albums of children’s music as Mr. Ray.
Priya and I became parents when Nikhil was born at Saint Barnabas shortly after the Macon concert. Tarana joined us three years later. Nikhil is a Johnny Cash fan, although he is known to tilt his head in recognition when he hears Rachmaninoff. Where has he heard that before? Tarana joined her dad as a member of Priya’s road crew. You can sometimes see her on Seventh Avenue pointing the scalpers towards the people who waited too long to buy their tickets.
And oh yeah, the fund did just fine this year.
Wishing you all the best for 2025.
David
