This week’s gift from a neighbor’s chicken coop included one extra-large egg. After hard-boiling and cracking open we found a double yolk, which some say is a good omen on our wedding anniversary. The following conversation over a meal would be unlikely in most homes, but perfectly natural in ours.
“Have you ever seen a giant human egg?” I asked my wife, Lucinda Veeck. I have only had a few hundred eggs under my microscope, but Lucinda has examined tens of thousands over a long career in her IVF lab.
She said it happened once. It was obviously immature because there were two nuclei in a cell enclosed by a membranous ‘box’ (the ‘zona pellucida’). A normal egg contains one nucleus and it vanishes shortly before ripening at ovulation by ejecting a surplus set of chromosomes in a cytoplasmic bleb. This elimination is so a fertilizing sperm can add a matched set to restore the pair.
Now here’s the thing. Her giant egg was not a microscopic version of the cooked egg. If a hen bird ovulates two yolky eggs simultaneously, which happens occasionally, they are quickly bathed in albumen, then enclosed in a common membrane and a shell during their journey down the oviduct, a process that takes about 24 hours to laying. As the nuclei are in separate yolks, the outcome is a normal genetic makeup with two chicks hatching from the same egg, although the cramped space affects their viability . The closest parallel is when non-identical human twins are conceived after a double ovulation.
But the nuclei in Lucinda’s giant shared the same cell, so their DNA would be inherited together. Had it been mature for fertilization the embryo would likely have three sets of chromosomes (two female and one male), called digynic triploidy, and fail to develop.
We explored explanations for its origin. If you have seen densely packed eggs in biopsies of young human ovaries you might wonder how they manage to grow independently instead of being swayed by neighbors, like people jostled in a football crowd. Sometimes they lose autonomy. I have seen two or more eggs combined inside follicles of every species examined, up to 14 in dog ovaries, although some looked unhealthy from the competition.
When boxed inside their own membrane eggs can’t fuse to make giant eggs. They have unique genetic makeups, just like eggs from separate follicles that go forward to make non-identical twins. But what happens when they coexist in a ‘box’ and don’t fuse to form a single cell?
Lucinda saw an example five days after an IVF procedure. It was a double embryo at the blastocyst stage with about 64 cells each. If separated for implanting in the womb, it seemed likely they could make non-identical twins, but if they had originated from a fertilized egg that had split instead of from two separate eggs they would make identical twins. It’s possible that they could unite (or reunite) to make a singleton pregnancy, and, if originating from two fertilized eggs, the baby would inherit mixed genetic lineages, a known condition called chimerism.
In the interests of being (somewhat) intelligible, I avoided more abstruse explanations and outcomes. With so many ways that development can go awry, it is a marvel that we turn out well, or mostly, and I am thankful for my genesis otherwise you wouldn’t be reading this post. I usually avoid writing technical stuff, but correspondence is welcome from readers who like to crack eggs.
Dr. Howard Jones passed away a year ago today in his 105th year. The following is extracted from the prologue I wrote for “Howard & Georgeanna” (2015) to remind us of our loss.
Since pioneer days, very few doctors and scientists have left a legacy large enough to be remembered for long, or one that endures beyond their lifetime. For most people who make a great discovery, their sun suddenly breaks out of obscurity to shine brightly for a while before it is eclipsed again by clouds. There are not many men or women whose sun glows constantly from a series of discoveries through a long working life. The Joneses were those kinds of doctors, and their story reads like a history of 20th century reproductive medicine. When Howard was still working into his 105th year, it seemed there would always be a Jones shining in the sky.
Georgeanna made her first research breakthrough in the 1930s during her days off as a student. Howard’s career as a surgeon and gynecological oncologist took off at the same time until he was deployed in the 1940s to care for dreadfully wounded soldiers on the Western Front. From the 1950s through the 1970s, Georgeanna was discovering new causes and treatments of infertility, while Howard pioneered reconstructive surgery. Together, they wrote numerous papers and edited books and journals. And in the 1980s, they established the first in vitro fertilization clinic in the nation, and trained many of today’s leaders in assisted reproductive technology (ART). When I recently asked Howard which advance was most important, he had no hesitation. It was ART because it “conquered the grief of infertility and has a huge societal impact.” I can’t think of any other pair of doctors whose crowning achievement was made after “retirement.”
When they hung up their white coats in the 1990s, they were still busy in the field of human reproduction, or at least Georgeanna was as far as the hard road of her final illness allowed. People like us who were lucky to spend parts of our careers with them remember how they encouraged junior staff and visiting faculty, and had an uncanny knack for solving problems.
I was a beneficiary of this wisdom when I joined their faculty in 2001. I hoped to launch an online master’s degree in clinical embryology and andrology, because it seemed a good fit to the reputation of the Jones Institute and I had created the first program in the UK. But the school was unwilling to invest a penny in the idea. It would have been stillborn had Howard not persuaded the Jones Foundation Board to stump up funds to get us started. Now, a dozen years later, the course draws embryologists and physicians from around the world, and almost three hundred have graduated. Where others saw risks Howard grasped opportunities, and his judgment was rarely misplaced.
We wondered what philosophy animated their energy, boldness, and generous hearts. Perhaps owing to the experiences of living through World War II, they were eager to make the world a better place, and when resources were limiting they knew how to make do.
Their paths to medical careers were paved by family members who worked in the profession before them. But being raised in comfortable homes wasn’t a preparation for the physical and emotional suffering they encountered in their medical practices, which, although such is the lot of everyone in the caring professions, they faced abundantly in combat injuries, oncology wards, birth abnormalities, and infertility. Their devotion to work was, I think, driven by an existential belief in the nobility of labor after witnessing hard times in the 1930s and ‘40s. They understood Chekhov’s Irina, who told her sister: “The time will come, and everyone will know the meaning of all this, why there is all this suffering, and there won’t be any mysteries, but meanwhile, we must go on living… we must work, we must work!” (The Three Sisters, Act IV).
Their work was demanding in time and energy but never a grinding existence, because they had help for managing their household and raising three children. They were passionate to apply their knowledge and skills, and took immense pleasure in helping people build families with the new reproductive technologies. Howard once said, “If I have a legacy, it is of someone who thoroughly enjoyed his work.”
After his first residency in general surgery at Hopkins, he switched to gynecology so he could be closer to Georgeanna. From then on, they were almost inseparable apart from his military service in Europe and Asia, and their collection of letters in the memoir War and Love shows what an extraordinary bond they enjoyed. And yet they were more like the opposite sides of a coin than two identical peas in a pod. She had the more scientifically penetrating mind, and he had the charisma to lead and inspire people; he was the organizer and she was more quietly and effectively laid back; he was fun-loving and she was elegant and decorous. Perhaps it was these opposite natures that attracted, but in every other way they were soulmates. This success as a pair fascinated us as much as their careers. We thought their communion was an art form, like a harmonious pair of dancers who deftly spin around a hall and never let go.
See how the couple whirls along the Dance’s buoyant tide,
And scarcely touches with wingëd feet the floor on which they glide…
Friedrich von Schiller (trans.)
People who never knew the Joneses might wonder if they had out-sized egos on their shoulders to match their achievements. No, not all! They were as much at ease with the office janitor or a child as they were with a visiting dignitary, and they embraced their clinical team like a second family.
At staff journal clubs at their home, Georgeanna was the gracious hostess while Howard sat cross-legged on the floor, only raising his authoritative voice at 9:00 pm sharp with a clap of his hands, announcing “Time for bed!” to scoot everyone out! And when the Jones Institute hosted baby reunion parties, they would mingle with former patients and their children on the lawn, and on one occasion he dressed up to look silly like the clown they invited.
House guests always received warm hospitality, but after Asbury and the Joyners retired as their helpers, you couldn’t count any longer on a fine home-cooked meal. They never had time for that, but he might pull out some dusty bottles of wine given by grateful patients years and years before. They may have been a fine vintage at one time, but age had turned them to vinegar. He thought this hilarious.
It was this attitude that reminded us they were not judgmental people when others blundered, and they always tried to put a positive spin on a mistake. There were life lessons to be learned in their company for people who didn’t think they already knew everything.
Everyone who knew them has a favorite story about the Joneses, and many wonderful vignettes appear at the end of this book. Lucinda treasures stories from the times she traveled with them to conferences overseas.
On a trip to Taiwan, the trio was collected in a limousine by a professor from a local hospital who asked with a heavy accent how a “wombat” was used in the Norfolk lab. That was what Howard thought he had heard after lately taking an interest in a marsupial of that name during a stop in Australia. When he realized his mistake, that the question was really about a “warm bath” for preserving cells, he bent double laughing and alarmed the man, who thought his distinguished guest was having a seizure.
On another occasion, they were together in Stellenbosch, South Africa. The desk clerk at the hotel apologized that the Joneses and Lucinda would have to share a bathroom with another couple from an adjacent room. As there was only one other couple in the dining room, Lucinda marched over to ask if her group could have first use of the bathroom in the morning because they had an early flight. Unfortunately, this was not the couple next door, but another who were occupying the bridal suite, and they immediately ran to see the clerk. Howard almost passed out laughing that time too. Georgeanna said he never could control himself in a droll situation, and remembered embarrassing episodes from his days in amateur opera. If someone accidentally knocked over a prop during the performance, he started giggling uncontrollably on stage.
Howard reserved at least a day on conference trips for exploring the city or countryside. He planned every hour for the party, which Georgeanna accepted in good grace even if it was occasionally an ordeal. When they arrived with Lucinda after a 31-hour journey from Norfolk to Auckland, the women were ready to collapse into bed, but he wanted to leave the bags unopened in the hotel and for everyone to head straight for a museum before it closed. He was then already in his late seventies, but never lost a combination of verve and curiosity!
Like other energetic people, the Joneses understood the importance of relaxation and would go swimming at the end of a long day. They had a gift for shifting from the gravity of the clinic or laboratory to the conviviality of home and recreation with friends. When they arrived at my home for a Devonshire cream tea they looked serene, like graceful Southern aristocrats. And at my Burn’s Supper where we had country dancing and bagpipes, they were eager to try a Scottish haggis manufactured in Florida.
Friendships struck with team leaders often wither when the juniors move away, like scions cut from a tree, but the Joneses were different. They kept up a large correspondence with many of their former associates, who were often promoted to friends for life. People craved to be close to Georgeanna and Howard, and we loved them. They had an amazing way of making visitors feel important by giving them undivided attention, and Howard drawing from his memory the tiniest details from their last meeting. They sent Christmas cards to many of their former patients, some of whom remembered how Georgeanna would comfort them in the O.R. by holding onto an anxious hand during a surgical procedure. When we visited their home in Portsmouth in later years, he still greeted us from his wheelchair with outstretched arms, exclaiming in a huge voice that hardly faded since the days he sang opera, “Hey, Cinda and Roger!” and bundling her in his embrace for a kiss. On our final visit, he was lying dreadfully weak in a hospital bed on his last full day, but one of the first things he asked was, “How are your families?” He also inquired about the manuscript for this book: “Is it worth pursuing?” Of course!
The Joneses were around so long they seemed immortal. Some of the staff they had trained was already retired, and most of their peers had passed while they still occupied their offices, although only Howard remained for the past decade. Their longevity and lasting good health baffled us. Perhaps it helped that they had no worries at home, and never seemed to be stressed. They didn’t offer formulas for a long life or dietary advice, and stopping at a fast-food outlet for fried chicken or an occasional hamburger and fries was okay! In an interview for Yale University the year after he became a centenarian, Howard said the secret of longevity is “unique to the individual,” and it takes “the right genes, an exciting and interesting profession, and a serene family life.” Sadly, it is not a combination we can engineer.
When Georgeanna died at age 92 in 2005, he was looking frail after a bout of flu and everyone worried that he too would sink, as elderly carers often do. How could he dance any longer without his life partner? But a few weeks later, he was more his old self again; his voice was coming back strongly, and there was the old twinkle in his eyes. He returned to his office nearly every day for the remaining decade of his life. He read medical journals, attended the journal club, received visitors and journalists, made calls and texts on his iPhone, and dictated manuscripts to Nancy Garcia. There were three more books he wanted to write, including this one, and he was mentally engaged with ethical and legal controversies in medicine. His office looked the same as ever. The desk was well-ordered, usually with an open manuscript he printed from his own computer, the shelves behind his desk were lined with books, and the framed degree certificates still hung on the wall alongside a sword in its scabbard, gifted by a Middle-Eastern friend. Of course, there were pictures of Georgeanna.
She began slipping away mentally more than a decade before she died. She was diagnosed with Alzheimer’s disease, which is no respecter of intellectual brilliance, and during those final years Howard cared for her at home. The image of two bright people, one caring for the other who is fading away intellectually, brings another famous couple to mind. The philosopher and novelist Iris Murdoch was cared for by her husband too, the Oxford don John Bailey, and their story is widely known through his book and the movie, Iris. But theirs was a very different “open” marriage, and neither of the Joneses would have understood Iris when she wrote, “The absolute yearning of one human body for another particular body and its indifference to substitutes is one of life’s major mysteries.” The Jones marriage was complete and sufficient.
Howard managed the challenge as he had so many others in life, with sagacity, patience, and love. The first signs of her illness were subtle. She began losing her place in lectures, which was so extraordinary that those who knew her were first to notice the difference. She admitted to her former office nurse, Doris Gentilini, she was forgetting things, and this became obvious when she lost her way home from a hair appointment at Ward’s Corner in Norfolk, just three miles away. At the tenth anniversary celebration of the first IVF baby in Norfolk, she was uncomfortable in the crowd and retired to rest.
Howard knew that patients with this disease suffer from anxiety, becoming distrustful and suspicious, so he kept their lives highly structured and predictable to give her security as she grew more disoriented. She retired from work, stopped driving, and they moved to a one-bedroom condominium. He watched her diet so she wouldn’t lose weight, and gave her a couple of hours to finish a meal, if necessary. Doris came out of retirement to help. Yet, they still traveled together to conferences around the country and overseas, where she recognized old friends. She seemed to be engaged when listening to lectures on highly technical subjects if they were familiar from years gone by, even as she forgot if she had ordered a salad.
Howard initially kept her diagnosis private for the sake of those who loved her, but the story couldn’t be hidden forever and eventually he spoke openly of it because her memory loss was obvious.
She could joke in the early stages about her confusion, like the time they were in Egypt when she asked if they were on the River Severn or the Chesapeake Bay.
Howard replied, “No, Sweetie, it’s the Nile.” She chuckled heartily.
On another occasion, when he was unfolding a napkin before a meal, she pleaded, “No, no, no!” He reassured her it was alright.
“That belongs to my sister,” she said, staring at the napkin.
“It’s OK, Ginny,” he replied. She then dropped the objection.
Flashes of humor continued for a long time, and her old graces were well-preserved because lifelong social skills are deeply engrained. He was never heard to raise his voice in frustration, and always looked on the positive side, trying to make a tough situation special. But he admitted, “She was a wonderful conversationalist, and that’s what I miss most.”
In those days, she still occupied an office next to his, but instead of editing papers and arranging slides of ovarian tissue, she worked on jigsaw puzzles or drew with colored pens that were laid out in neat rows with their caps carefully replaced. After a while, she would nod off in her chair, and Howard would say, “Look at her! She’s so darned sweet!” He believed Alzheimer’s disease laid bare a person’s true nature.
He was still interested in scientific riddles, social concerns, and family matters. Why do eggs age? Why don’t more insurance companies cover infertility? How were his children’s jobs doing, and his granddaughter’s soccer league? If he had frustrations with growing immobility and the complications of diabetes he hid them, perhaps along with other conditions only shared with his personal physician, but which must be expected at a great age. He never whined except to say that perhaps it is easier to pass from life in the way his wife had rather than decay with a fully preserved mind to the end.
Have you noticed how towards the end of life people are often drawn towards water? Some settle in retirement communities overlooking a river or lake, others downsize to a home in a seaside town. Perhaps it is the peaceful flow that pulls them to the waterside like time itself, or the infinitude of the sea and pounding of surf against round pebbles on the beach. Sometimes, it is the happy memory of vacations around water that is so fascinating.
The people along the sand
All turn and look one way.
They turn their back on the land
They look at the sea all day.
The Joneses kept their membership of the Norfolk Yacht and Country Club long after their sailing days were over. When I joined the Jones Institute, they often invited me to join them at the club for casual dining in The Deck. We would meet on the upper floor with Mason and Sabine Andrews, an admirable gynecologist and his wife, a founder of EVMS, and former city mayor. We chose Thursday evenings because it was quieter and we could take a window seat to look down on the marina and out towards the Bay.
Our table was spread with a white cotton cloth and neatly arranged cutlery and napkins. A waiter soon arrived to pour ice-water into our glasses and take our orders. Maryland crab cakes, chicken, and salad were popular choices, and Howard always chose soft-shelled crab soup for Georgeanna’s starter.
Then the conversation would start up about almost anything. We’d talk about town politics, the hospital expansion, medical care, and even my stem cell project. While we talked, Georgeanna sat silently watching us and smiling to show she was engaged. These four were old friends from Hopkins days, but they never made a younger buck like me feel out of place, and did much to help me settle in Norfolk. They were lively spirits and enlightened company who, as much as they enjoyed looking back on past achievements, looked forward to new goals. They had not stopped working as Improvers and Encouragers.
After the meal, we’d rearrange our chairs in an arc in front of the full-length windows to enjoy the scene. Below us, hundreds of white boats of all shapes and sizes were drawn up in tight rows along the slips at the end of day. The rigging of yachts slapped against their masts, and sea rods on motor launches leaned forward like the antennae of giant aquatic bugs gently nodding in the breeze. A fisherman lugged a heavy bucket of fish from his boat over a gangplank with its water sloshing over his gumboots. He waved at a friend on a late boat chugging into an adjacent berth. It was often like that.
The conversation would fall quiet as we’d study activity in the dock below, but as the light faded we would raise our eyes to the skyline. Georgeanna would gaze very intently into the distance. Perhaps she hoped to see the sail of a yawl coming into harbor; then perhaps she could climb onboard and sail off once more to the Chesapeake Bay of deep memory.
Our meal was timed to finish with the sun setting over the shining waters of the Lafayette River until it dropped behind the silhouettes of dockyard cranes at the container terminal. Those evenings always seemed miraculously clear with barely a cloud scudding across the sky. If you ever watched a sunset closely on such an evening you will know how slowly it traces an arc to earth. It starts as a fiery yellow orb which was high in the heavens all day, but makes its descent almost imperceptibly until you notice some of heat has gone out of it and it is turning orange before becoming blood red. For a moment it looks like it will rest on the edge of the earth and scorch it. But then, and rather suddenly, it is swallowed up and the horizon where earth meets sky turns a royal purple.
When the show was over, we’d rise and take the elevator to the ground floor. There was nothing more to say after the spectacle and we stepped outside in silence, Howard leading Georgeanna with her arm curled around his. Walking into the darkening parking lot, we looked for their car with the “2DOCS” license plate. The first evening stars twinkled overhead.