Dear Jean

Dear Jean

I couldn’t leave my students to say farewell. Our friends told me it was one of those miserable days before the daffodils bloom along the Cambridge College Backs: Scots would call it a “dreich day”. Pronounced correctly, everyone knows exactly what they mean.

So much water passed under the bridge in thirty years. You’d be amazed to see my hair now—but better a silver noggin than a shiny nut.

As summer grows old, I’m feeling sentimental and looking back on salad days again. I never forgot the first time you showed me a human embryo. Alive! Gazing down the microscope I needed your help to see the tiny ball of cells floating in a pink ocean of culture fluid. You hovered behind me, probably worried that a green student might spill the precious mite you had just created by in vitro fertilization. It took five more years of struggling research until your breakthrough with the embryo that became Louise Brown. Now there are millions like her.

Jean and Bob arriving at Gare du Nord, Paris, for a conference
Jean and Bob arriving at Gare du Nord, Paris, for a conference

Did you ever mind standing in Bob Edwards’ shadow? He was generous with compliments, saluting you as the third pioneer of IVF beside Patrick Steptoe and himself, but as the assistant to a famous scientist and a gynecologist (and being female) you didn’t have much visibility with biographers and the press. The longer you are away the deeper the mystery of your part in the program, and now that both men are gone there is no one left to tell the full story.

Why did you quit nursing? Why did you switch to a lab job for which you were hardly qualified? Of course it wasn’t any ordinary job. Bob’s goal was no less than to forge a medical revolution, and Patrick was aiming to help infertile couples that his profession had virtually abandoned because it had nothing to offer them. Your work was accused of being unethical, “playing God,” and was excoriated in the press, by doctors, and from church pulpits. I wondered what your friends said, what your family thought, and how you coped with it all.

All those struggles were quickly forgotten when it all came right, but then you couldn’t foresee the triumph at the end of the tunnel of nearly ten disappointing years of trials, working long hours and often away from home until Louise was born. Besides the immense challenge of nurturing embryos in the dish and the thicket of critics, you had to glue two different personalities together, for if Bob and Patrick had parted nothing would have been achieved.

I guess you seasoned the setbacks and stresses with humor. I remember you used to laugh when we goofed in the lab, and when you struggled to spell the name of the Philadelphia biologist, Beatrice Mintz, you posted attempts on your bulletin board. It’s funny how trivial things get stuck in my memory. Visitors would remark about your “humor station” before Mintzstepping past to Bob’s office for some heavy scientific discussion. Once when I was sitting in his office soon after Louise was born and you were setting up Bourn Hall Clinic I asked him how he managed to publish his huge tome, said to be the bible of reproductive medicine. He nodded towards your desk, which you leant over, cracking a cheeky smile that was so endearing.

I always knew you had a sterner spirit under the sunny exterior. One day during the public hullaballoo about banning the South African national sports teams from international tournaments I saw you in a heated debate with an overseas visitor who was defending apartheid. Afterwards, I realized you felt the same passion for patients depending on you, and Bob had hired you over more qualified assistants because he saw what you were made of.

I wish I had asked if you ever wanted to be famous. Had you stayed you would have been queen of the realm—earning awards, dinners in your honor, and guest lectureships everywhere. I guess you were happy to be spared that kind of attention, preferring the undisturbed backroom where you could counsel patients and care for their embryos. You were content for Bob and Patrick to be the front men. Bob will go down in history as a scientific pioneer. Patrick passed away too soon to share the Nobel Prize and earn a knighthood, but won’t be forgotten. I’m told that quite a few patients from Bourn Hall still wander across the lawn to stand reverently at his graveside outside the chapel. He’s lying just 15 minutes away from you, but no one makes that journey.

Some of our nurses in America inquired about your story a few years ago. They only knew you were first in the field, but that was enough to create the Jean Purdy Visionary Award. I shared everything I knew for their introductory speech for award-winners, but my knowledge was threadbare and I never managed to find your family to fill the gaps. They have vanished. I found an unrelated woman called Jean Purdy in London; she works as a magician, but you were the real thing. The award was a wonderful naming legacy and I’m terribly sorry that it too has disappeared. You would just put your arm over my shoulder to console me, saying it doesn’t really matter.

If I could go back in time I would love to ask how you felt when you started working with human embryos. The first were experimental because you needed to check they were healthy before Patrick dared to give them a chance of making a pregnancy. I heard you had a devout faith, though I didn’t know your church denomination. Did you ever have qualms about making and destroying embryos? For myself, I believe they deserve respect, but could never understand people who wanted to endow full human rights from the moment of fertilization. Moral philosophers and theologians are still arguing the point, although every nation I can think of has either legitimized IVF or turned a blind eye to the practice. Since your time, embryos have been used to create stem cells for regenerative medicine, which Bob dreamt about half-a-century ago and George W. Bush tried to can a dozen years ago. Although it really started in your lab, I doubt you ever imagined that your work might one day help to cure the incurable. If you read nothing else in this post I would want you to know your endeavors weren’t wasted.

Human blastocyst
Human blastocyst

When I asked a friend at the Hall where I could find you she offered to drive me to Grantchester. I hadn’t visited the village since I was a student. Then I used to cycle over from college or punt on the Granta against the stream, feeling I deserved a drink at The Green Man when I arrived. It was mead in those days. Sometimes I joined students enjoying a cream tea under the apple trees in The Orchard, which is still associated with Rupert Brooke. His patriotic war poems fell out of popularity long ago, but his own tragedy still draws me to his romantic verse, even the schmaltz about his Grantchester home.

The church at Grantchester. Thanks to Kay Elder
The church at Grantchester. Thanks to Kay Elder

And laughs the immortal river still

Under the mill, under the mill?

Say, is there Beauty yet to find?

And Certainty? and Quiet kind?

Deep meadows yet, for to forget

The lies, and truths, and pain? . . . oh! yet

Stands the Church clock at ten to three?

And is there honey still for tea?

The Old Vicarage, Grantchester by Rupert Brooke (1912)

I ask myself why it has taken so long to write to you, and why now? Perhaps Bob’s passing is prompting me (Blog date April 2013). Perhaps news of Louise’s 35th birthday last month nudged me. But I think it is because the book I finished today jogged something in my unconscious. You might have enjoyed the life story of a remarkable but long forgotten New York surgeon.* Had I more data, I might have started your biography next. Stories of people who made a difference but now lounge in obscurity fascinate me so much more than those still celebrated. They resonate with the last lines George Eliot wrote in her tribute to Dorothea, … the effect of her being on those around her was incalculably diffusive: for the growing good of the world is partly dependent on unhistoric acts; and that things are not so ill with you and me as they might have been, is half owing to the number who have lived faithfully a hidden life, and rest in unvisited tombs.

When we reached Grantchester churchyard I could imagine the dreich day when you were laid under the grass beside your mother. It’s a rather unkempt, inauspicious corner with nothing to draw the eye of casual visitors who meander between the stones. Had I been asked to order your memorial I would have insisted on a granite carving, Here lies Jean Purdy, the World’s First IVF Nurse and Embryologist, died 1985 aged 39. But your name painted on a gray headstone is being eaten away by rain and wind, the plastic flowers the most cheerful feature of that bleak spot. Rupert Brooke would have walked over from his rooms at the Vicarage to compose an ode.

Jean's grave

*A Surgeon’s Story by Roger Gosden and Pam Walker will be available on Amazon soon. See Jamestowne Bookworks for news.

Next Post: Gold in my Garden

Baby’s First Picture

The first picture of a baby is usually in the mother’s arms soon after delivery, and becomes pasted into an album for posterity.  My mother missed out on that snapshot since I was born in austere post-war London when a box Brownie camera was a luxury my parents couldn’t afford. Roger and MumBut nowadays the picture is taken earlier and with a much more expensive camera.  My granddaughter, Pippa, was snapped by an ultrasound scanner when she was barely past the fishy stage in her mother’s womb. The next picture taken a few weeks later showed her looking like a real child, and the obstetrician could confirm everything was fine, including beating heart and nuchal transparency. Pictures reassure us all is well, even if we can’t put absolute trust in them.Pippa 3 month fetus

The first picture can be taken even earlier nowadays – in fact, as early as can be. For most of her thirty years as an embryology lab director, Lucinda gave prospective parents of IVF children a picture of their embryos which she had taken immediately before medical staff transferred them to their Mom’s body. These were embryos that had been fertilized in a Petri dish and grown to a ball of about 8 cells in three days, or had formed a blastocyst with about a hundred cells after a slightly longer incubation. Giving these photos to patients is now a common courtesy in fertility clinics, and more and more couples are having this extraordinary preview. Last year there were over 60,000 babies born after IVF procedures in the USA alone, or 1% of all births.

Human 8-cell embryo
Human 8-cell embryo

For such couples (and single mothers undergoing the same treatment) pictures of their embryos probably find a temporary place of honor on a kitchen bulletin-board until the next picture at the six week ultrasound scan – or taken down if the pregnancy test proves negative. But for embryologists and physicians, pictures of embryos are records of the best-looking in the bunch which they hope stand the best chance of getting Mom pregnant.  Generally one or two are chosen (sometimes three) for transfer from the half-a-dozen eggs (more or less) that were fertilized, but these pictures say so much less about the embryos’ prospects than my first picture or Pippa’s, and even ours hardly say anything about things that most matter to us – future health, vigor, brains, and beauty.

Upwards of 50% of all human embryos conceived in the IVF lab (and probably the same in the body) have abnormal sets of chromosomes, and therefore no chance of making a healthy child. It is possible to genetically screen embryos so that only the healthy ones are placed in the uterus, but although this can be helpful it is far from foolproof. Some embryos are mixtures of normal and abnormal cells, meaning that a test produces misleading results if only one cell is removed, which is all that most embryologists dare take. And then there is the unanswered question of whether certain kinds of abnormalities can correct themselves spontaneously, implying that embryos could be discarded unnecessarily.

The upshot of this uncertainty is that deciding which one to transfer is still mainly based on how they look at the time when the photo is taken. It’s a beauty contest which Machiavelli would have derided because “men in general judge more from appearances than from reality.” Unfortunately, “reality” is much too deep to plumb, and so, despite the best efforts, the embryos with the best chances of success are not always chosen.

A single snapshot at the end of a growth process that had been going on for days mostly unseen inside the lab incubator is not much to go on. We wondered if a picture is worth a thousand words, perhaps a thousand pictures would better convey the whole story.

Back in the 1990s Lucinda had already started making movies of embryos in Petri dishes, but had to build her own equipment and record them on magnetic tapes. When I joined the project some years later, digital time-lapse recorders, more advanced microscopes, and miniature incubators were available for the job. We could take a snapshot of individual embryos every few minutes, which over five days added up to over two thousand frames. Imagine how eager we were to compile them for a motion picture of the first days of human embryo development! But we didn’t anticipate surprises, accustomed as we were only to static images, but the embryos educated us.

On the first day nothing seemed to be happening, although appearances are deceptive because there was a lot of activity at the sub-microscopic level. But the next day the fertilized eggs made an almighty heave and in a strange contortion never to be repeated divided into two equal halves within their shells. They tolerate only so much fragmentation of cells at this stage, which you can see in the movie. The next division to make four cells started later in the day, and more divisions created a ball of tiny cells without any net increase in overall size. Clinics are now using customized equipment to monitor the rate of embryo development to help to choose which to transfer.

On the fifth day, healthy embryos became blastocysts, hollow balls of cells with a tiny knot at one side that make up the embryo proper. The movies revealed that blastocysts undergo cycles of swelling and collapse rather like a beating heart, although far more slowly and not from muscles contracting because no such cells exist yet. Just as a heart sound or pulse is a sign of life, the blastocyst’s beat is a sign, and probably a better token of vitality than a static picture ever gave.

We had another surprise after pressing the PAUSE button at a random frame if the embryo looked sick, its cells more opaque and less plump. Sometimes it really was unhealthy and had reached the end of the road to development, but in other cases when we pressed RESUME the embryo would shrug off its frumpy appearance to continue growing, often even turning out to be a beauty. So Plato was right for embryos too – beauty really is in the eye of the beholder. A sad-looking embryo might have been discarded or, at the very least, frozen in reserve if its fate had hung on only one picture. Besides, we already knew that, like judges scrutinizing models on a catwalk, embryologists don’t always agree on their scores for embryos. They can tell you stories about patients who produced only a very few scrawny-looking embryos which were transferred to wombs “just in case”, only to find that at least one was successful and made a bonnie baby.

What about the rest, the ones that never survived long enough to be photographed? We seldom mourn things that pass beyond the focus of our eye or camera lens, nor give a moment’s thought to the far, far greater slaughter going on day-in and day-out in the wombs of the world where most embryos never thrive. Embryos may have started out looking hopeful after fertilization and even grow some, only to perish in the dish unnamed and unknown in a Greek tragedy of their own.

Sometimes I am moved to wonder about wasteful nature. I wonder why I can watch in deep sympathy a bee writhing after it has strayed into an insecticide spray or an earthworm wriggling its last as it dries out on the pavement, while we never spare a thought for the anonymous multitudes ending their lives prematurely by being trampled physically or chemically.

I suppose it is the connection with individuals, especially at tender ages, that makes the difference. No matter how alien to the subject we feel there is a biological link and by witnessing the life and death struggle of another creature we are jolted into thinking about our own. Patrick Steptoe (1913-88), who was Bob Edwards’ clinical partner in pioneering IVF, pondered the same thoughts as I do in idle moments. I remember him playing at a conference his musical elegy, For a Dying Embryo. Steptoe_PCS Before striking a key he told us he was sad for the couple who would never have that proud picture of their offspring, but he also had some sort of feeling for the embryo in his care, wondering what it might have become and achieved. Thank goodness Pippa and have pictures so we can muse in the future how we got here.

Next Post: Stem Cell Stuff

Seventeen Year Itch

Back in 1996, Bill Clinton was still in his first term of office, Charles and Diana agreed to divorce, the Unabomber was apprehended, and Ella Fitzgerald died. That year I hadn’t even dreamed of moving permanently to North America: I was living in Yorkshire where mad cow disease was seizing the headlines in England. While so much history has flowed through newspaper presses since then, Brood II cicadas were all the while secretly sucking at tree roots waiting for the calendar to flip over to 2013.

I encountered the brood a couple of weeks ago at a rest area on the I-64 west of Richmond.  The first thing travelers noticed after stepping out of their cars was a chirping racket coming from every direction. I had heard the sound only once before when a 13-year brood of cicadas was emerging near home in 2011. This year it is the turn of the 17-year ensemble to sing.cicada on grass

For a few weeks every 17 years local residents have sleepless nights. The noise can be as loud as a passing truck, and at 90 decibels reaches a level at which the Occupational and Safety Administration warns we should not be exposed to for more than 8 hours a day to avoid hearing damage. Not being respecters of regulations, male cicadas chirp round the clock.

They are among the great wonders of the insect world, but not only because they have one of the longest life cycles. The question that intrigues me more is how they manage to coordinate mass emergence.  When ground temperatures rise above 64 °F (18 °C) in the Year of the Brood, the fossorial cicada nymphs start to burrow upwards, breaking the surface first at the southern edge of their range (North Carolina) and progressively towards northern limits (Connecticut).  Soon there are incalculable billions above ground, more than a million per acre, but during intervening years you are unlikely to see any at all.  So precise is their timing that local residents can plan when to be on vacation in 2030 during the next big pulse.

They look scary and are the biggest of their kind. They are an inch-and-a-half long with bulging red eyes, orange wing veins and leg stripes, and through their transparent wings you can see a black cigar-shaped body.  They look like bugs in zoot suits and were given the marvelous scientific name, Magicicada septendecim.

I was a member of a naturalist group heading for a wildlife center in the Blue Ridge, but the cicadas in the car park – not you would think the most auspicious place to watch wildlife – were the most memorable sights of the day. They were thought to be a bad omen by superstitious early colonists, who assumed (wrongly) that they were the same as locusts in the Bible which warned in the Book of Revelation: “Then from the smoke came locusts on the earth …” I guess that every seventeen (or thirteen years) there were particularly fiery sermons from the pulpit about the seven last plagues of Armageddon.

For all their fearsome appearance, they are harmless insects. They don’t bite or sting, nor do they eat vegetation as true locusts do. They can cause minor tree damage from “flagging” (browning) during nest-building, but are generally rather beneficial. Soon after mating and egg-laying the adults die, providing food for critters and fertilizing the soil. The only remaining cicadas are immature “instar larvae” hatched from eggs. These nymphs fall from the tree canopy to the ground where those that avoid predation burrow underground to find juicy roots to suck on … and on … and on until the calendar turns.

For the most part, the distribution of 17-year broods and 13-year broods don’t overlap, although they evolved from a common stock a few million years ago.  Today there are 15 broods in North America, twelve with 17-year cycles and three with 13-year, and you will not find them anywhere else.  Of the 3,000 species of cicada worldwide, only seven have periodical behavior.

Burrows and shells from which cicadas emerged in the car park
Burrows and shells from which cicadas emerged in the car park

We watched hordes of them lumbering up tree trunks and walls; we saw many flying unsteadily like old flying boats, often crashing into branches or to the ground where robins were waiting to pounce. For a small bird, a cicada is hamburger-sized (and probably just as nutritious), so the eaters were soon sated. Everywhere across the hard-trodden ground there were holes, about ten to the square yard and a little larger than earthworms make. These were the burrows from which cicadas had recently emerged, and scattered close by were the transparent brown shells (exuvia) which they had worn for so many years underground. They gave us a spectacle I may never see or hear again.

The greatest enigmas are how they know the time, and why coordinate their emergence instead of being independent like most insects. We know of genes that regulate daily cycles in animals, but I can’t understand how molecules make a 17-year timer. And if cicada nymphs were synchronizing eruption by communicating with each other underground, it stumps my imagination.  Perhaps it serves to overwhelm the appetites of predators so that at least some survive to breed, although that theory is controversial. A similar explanation has been offered for mast seeding of long-lived plants. Last year was a mast year for oaks, with acorns lying so thick in our yard that every step sounded like walking on cornflakes.  But mast years are unpredictable – they can be consecutive or after long gaps – whereas cicada years can be written into almanacs for years, even centuries, ahead.cicada on blue

There are few pat answers in nature and the life sciences. That was frustrating when I was a student preparing for exams, but now I think the mysteries are far more wonderful than the facts.

Next Post: Baby’s first picture