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‘From Conception to Birth’ (Doubleday)  29Oct02

 New technology gives a complete picture of a baby’s development

All expectant parents are curious about what is really happening inside during pregnancy, but until recently clear images were nearly impossible to get. Now, new technology is giving us a stunning first time look at a baby’s development while in the womb. Medical images showing the fetus developing in four dimensions use new scientific data from human biology to illustrate the process of birth. The technology and the stunning images of the development of the human fetus are in the book, “From Conception to Birth,” by Alexander Tsiaras and Barry Werth. Read an excerpt below.

THE DRAMA OF LIFE UNFOLDING

What’s happening with the baby now? When our grandparents and even our parents asked this question, the answer was locked in mystery, like the night sky. They knew that as a child grows and develops inside its mother’s uterus, a new life unfolds. But they never anticipated they might someday observe this inner cosmos.

Even if your mother and father had a rough idea about the stages of embryonic development from biology class or brochures in her obstetrician’s office, they couldn’t visualize the wondrous activities stirring within her as she became pregnant.

A clear view from inside the womb

October 29, 2002 — New imaging technology helps give a complete picture of a baby’s development. Author Alexander Tsiaras shows “Today’s” Anne Curry stunning new pictures from inside the womb, found in his new book “From Conception to Birth: A Life

That all started to change in the 1960s. Cameras began going everywhere, including the inmost parts of a woman’s body. Suddenly it was possible to view the stages of unborn life through grainy ultrasound images or marvelous color photos in magazines and on TV. If heavenly bodies no longer were so mysterious in the age of space travel and X-ray telescopes, neither was the creation in utero of human bodies in an era of electron microscopes and tiny endoscopes that could peer inside a woman’s womb.

As the philosopher and ethicist Meredith Michaels observed, the language of space exploration and human embryology inevitably collided. “The blastocyst has landed!” Life trumpeted.

These new images upended the way we look at our own beginnings, by taking expectant parents and others inside the hidden world of procreation and giving them their first glimpses of what happens as cells fuse, then divide and subdivide, to form a new person.

As the baby developed, more and more refined images revealed a profound and beautiful world-part Hubble telescope, part Jacques Cousteau-in which miniscule cosmic voyagers floated in saline seas, reflexively sucking their thumbs. It was thrilling, inspiring, as we searched for familiar signs, experiences, moments, not only in our children’s formation but our own.

Yet the images we saw were biographies of the unborn self, not autobiographies — not the inner experience, viewed from within. As marvelous as our understanding of what was happening with the baby had become, what was really going on-the cell-by-cell, tissue-by-tissue sculpting of a human being-remained all but shuttered from view.

Until now. As the pictures in this book reveal, recent developments in science and technology have vastly enhanced our ability to gaze inside ourselves and witness the drama of early human life-as it unfolds, from conception to birth. As biologists have decoded the molecular basis of life, computer scientists have developed three-dimensional techniques for scanning and displaying the body, which can isolate systems (nervous, skeletal, circulatory, etc.) and allow us to view them down to a molecular level.

What’s happening with the baby now?

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A generation ago the answer might well have been: “Welcome to the dark side of the moon.”
And now?
Feast your eyes.

IN THE BEGINNING
The first primer on the combined topics of sex, science, and reproduction (and thus a valuable forerunner of this book) was published in the United States nearly a century ago, in 1911.

A Child’s Guide to Living Things by Edwin Tenney Brewster was no mere children’s book, however. A Harvard-trained zoologist, Brewster wrote widely on scientific matters, and he sought to provide young readers with a modern understanding of how life begins. Modesty and discretion prevented him from addressing the “facts” of life; he wrote instead about starfish eggs and sea urchins.

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And human embryology remained a primitive, largely forbidden field. But some biologists and doctors had recently begun to explore how cells reproduce and change at the earliest stages of life, and Brewster explained in simple terms what they had-and hadn’t-learned:

So we are not built like a cement or a wooden house, but like a brick one. We are made of little living bricks. When we grow it is when these little living bricks divide into half bricks, and grow into whole ones again. But how they find out when and where to grow fast, and when and where to grow slowly, and when and where not to grow at all is precisely what nobody has yet made the smallest beginning to find out. [italics added]

Now leap ahead 9 decades to a university laboratory in Wisconsin, as an obscure, hang-gliding biologist named James Thomson coaxes cells from a 4-day-old human embryo to reproduce in a glass dish. Since the 1970s, scientists routinely have “immortalized” human cells by tricking them into dividing again and again outside the human body.

But oh, what cells!

Thomson’s “little living bricks” — embryonic stem cells — possess a protean capacity to morph into the more than 200 other types of building blocks that, copied a million billion times and working in magnificent concert, make up a human being. Contained in these microscopic units are virtually all the data needed for answering Brewster’s enduring questions-how do living things know when, where, and how to build themselves?

This was — and is — life’s crowning wonder, and Brewster deserves belated credit for inviting his young readers to ponder it at a time when the most advanced tools for understanding basic biological mysteries were, in retrospect, primitive and crude, the microscope and the X ray.

Yet he, too, couldn’t help but marvel at how a perfect sphere of cells suddenly elongates, inverts on itself, stretches, bends, and molds into elaborate living shapes. Starting from the point of conception-the unseen mingling of 2 coils of chemical information-the transformation defies imagining. Witness the young starfish egg, he wrote:

One would perhaps expect to see the oil and jelly mixture change gradually into a starfish. Instead of this, however, this little balloonlike affair splits squarely in 2, and makes 2 little balloons just alike, and which lie side by side...

In about half an hour, each of these balloons or bubbles, “cells” as they have come to be called, has divided again; so that now there are 4. The 4 soon become 8; the 8, 16. In the course of a few hours, there are hundreds, all sticking together and all very minute; so that the whole mass looks like the heap of soap bubbles which one blows by putting the pipe under the surface of the soapsuds...

Of course, this is only the beginning, a warm-up act. The most spectacular metamorphoses come, Brewster noted, in the weeks that lay just ahead:
If it is an animal like ourselves, this body stuff, before it becomes a body, is a round ball. [Then] a furrow doubles in along the place where the back is to be and becomes the spinal cord. A rod strings itself underneath this, and becomes the backbone.

The front end of the spinal cord grows faster than the rest and becomes larger, and is the brain. The brain buds out into the eyes. The outer surface of the body, not yet turned into skin, buds inward and makes the ear. Four outgrowths come down from the forehead to make the face. The limbs begin as shapeless knobs, and grow out slowly into arms and legs. . . .

Writing for children under age 10 in an era when biologists were better at describing things than explaining them, Brewster might be blamed for oversimplifying-little living bricks, soap bubbles, furrows, rods, knobs. And yet there is something elegant and prescient in each of his descriptions — he seemed to sense some divine infrastructure, some physical laws governing human construction, that modern biologists like Thomson have lately made only “the smallest beginning” to puzzle out.

In fact, as science has shown, we are like buildings, although the structures we most resemble are infinitely more majestic than the grandest brick house. A house is built from the ground up and assembled from different materials imported from someplace else. But people, like all living things, grow from the inside out, transforming as we go.

Imagine yourself as the world’s tallest skyscraper, built in 9 months and germinating from a single brick. As that “seed” brick divides, it gives rise to every other type of material needed to construct and operate the finished tower-a million tons of steel, concrete, mortar, insulation, tile, wood, granite, solvents, carpet, cable, pipe, and glass as well as all furniture, phone systems, heating and cooling units, plumbing, electrical wiring, artwork, and computer networks, including software.

This brick and its daughter bricks also know exactly how much of each to make, where to send them, and when and how to piece it all together. Now imagine further that when the building is done it has the capacity to love, hate, converse, do calculus, compose symphonies, and have rapturous physical relations with other towers, a prime result of which is to create new buildings even more elaborate than itself.

How does this happen? We know that like all else in the universe, not just other buildings, we are built of molecules, which consist of matter and energy but are not what any of us would call alive. What directs our molecules to build?

Science has begun to answer that question, too. Plainly one of the great biological discoveries between the publication of Brewster’s A Child’s Guide and when James Thomson was honored in August 2001 on the cover of Time is the understanding that what tells molecules to make a human being are other molecules.

All living cells are comprised mainly of 2 types of organic molecules-nucleic acids and proteins. Nucleic acids — genes — carry the instructions the cells need to function and reproduce; in other words the overall plans for the building, as well as for each cell’s own small part. Proteins do the work, erecting scaffolding, chopping each other up, recombining, making more proteins.

Indeed inside every cell teems a subuniverse — another skyscraper —comprised of tens of billions of proteins conducting complex chemical reactions at rates of ten billion times per second. Meanwhile, other molecules on the cell’s surface interact with-talk to-molecules on the surface of other cells. Such, literally, is life, which is distinguished from nonlife by the profoundest activity of all: making self-copies. Reproduction.

“Molecules,” as the embryologist Lewis Wolpert puts it, “are the natural language of the cell.”

So we are like buildings, but buildings that replicate. And yet we’re more than that. We’re replication machines. We replicate because our cells replicate. They replicate because their molecules replicate. Everything about us seems to want to replicate. All the time. “The procreant urge of the world,” Walt Whitman called it.
Which is why we love life and love children and love sex.

NATURE’S DESIGN
Like all great buildings and machines, the unborn self combines exquisite architecture and canny engineering.

Start with conception. Because it’s necessary, when wanting a baby, to unite genes from a man and woman, and since these genes are encased in specialized cells inside the human body, it is essential (or was, until the advent of artificial fertilization) to steer two sexually mature bodies into intimate contact. And so what happens? A meaningful look. A seductive Beaujolais. An inviting scent.

Scientists studying sweat lately have isolated chemical secretions called pheromones that signal our sexual ripeness and availability. The point: because our genes need to combine, our egg and sperm cells need to fuse; and enhancing desire while loosening inhibitions is the surest way to improve the chances in humans that both these things will occur.

Throughout the next 9 months-indeed, throughout life-the tools and processes of procreation are similarly optimized. Getting male genes to female genes? No problem.

A mature, healthy man produces several hundred million sperm cells a day, and while the force of ejaculation is generally enough to propel them just halfway toward their goal, each is also packed with a trail mix of rare supersweet sugar to fuel it the rest of the way.

Penetrating the famed zona pellucida, the cunning matrix of sugar and protein surrounds the mature egg like a force field. Molecules on the surface of the sperm heads are designed to bind specifically to molecular “receptor sites”-portals-on the zona, which imbibes one sperm, then stiffens to repel all others. “The egg is sated,” as science writer Natalie Angier notes. “It wants no more DNA.”

Once the egg has been fertilized, the situation recreates itself-again and again, with spiralling complexity. Chemical messages instantly relay the news of the successful penetration to the brain. Molecules talk to molecules, cells to cells, organs to organs.

“Feedback loops” trigger a rush of specialized hormones, slippery secretions, and subtle muscle contractions to help ferry the fertilized egg to the uterus. Unlike Brewster’s starfish eggs, the oocyte, as it’s called, is itself in no hurry.

For the first 3 or 4 days it divides, or cleaves, roughly once a day, slowing gathering into a tightly compacted ball. The ball is hollow. Shape being destiny, this tiny sphere-Brewster’s “heap of soap bubbles”-anticipates perfectly the complex subdivisions to come.

Within a week the thicker end of the sphere glues itself to the uterine wall. Does the uterus “know” what’s arrived? Clearly. The human immune system is programmed to distinguish between molecules that are “self” and “nonself” and to destroy the latter.

The blastocyst, measuring less than one-hundredth of an inch across-a barely visible dot-behaves like a parasite, burrowing into the lining. Yet the uterus, after initially swelling to engulf the embryo and marshalling white blood cells to dispose of it, suddenly turns receptive, even acquiescent.

Its blood vessels engorge with food and oxygen-bearing blood, and its tissues cordon off an area for the invader. Then, as the embryo bores through the small maternal blood vessels in its path, rupturing them, the hemorrhaging uterine tissues respond by releasing a starch that becomes its first meal. At once the embryo gorges itself and starts to grow at astonishing speed-doubling daily in size. Before the expectant mother knows she is pregnant, the basic relationship between mother and child is forged.

To understand what happens next-the budding of the embryo-recall Brewster’s century-old descriptions. How within this tiny nestled dot does an embryonic human being organize itself and take form? How do “furrows” develop into spinal cords, “rods” into backbone? How does a descendant of an embryonic stem cell “know” to become part of an eyelash? Put another way, how does a half-brick know to become a steel girder or a credenza, then get itself to the 150th floor?

BUILDING TOOLS

The scientific answer begins with a process called gastrulation, which occurs in all animals. Suddenly, a few days after implantation, the balled-up cells begin to rearrange and move-migrate.

With magnificent speed and coordination, sheets of cells stream past each other, some migrating inward, others out; some up, some down-until 3 layers emerge: inner, middle, and outer. From these relative positions, cells begin to change, or differentiate, into the building blocks for specific tissues, organs, and systems.

The outer layer produces the cells for the skin and nervous system; the inner layer produces the lining of the gut and related organs like the liver. The middle layer starts to churn out cells that will become the heart, kidneys, gonads, bones, muscles, blood, and the rest of the viscera.

Once these layers are established, the cells interact rapidly with each other, rearranging themselves gradually into the complex communities we call organs.

Poetic-minded embryologists compare this process to origami-the Japanese art of paperfolding. The instructions for rearranging a piece of paper involve only a few simple operations: folding and unfolding.

No one would dream of making a crane’s beak or a Minotaur’s horns in one step from a single flat sheet. But by folding and pinching and refolding, then refolding again and again, it’s possible to make ever more refined and complex shapes.

Lewis Wolpert has been quoted as saying that it is not birth, marriage, or death, but gastrulation that is truly “the most important event in your life.”

He has a point. Everything we become, our whole magnificent design, is predicated on this early layering of cells.

It takes just 3 to 6 weeks to “lay down” the basic body plan. Still less than one-tenth of an inch from top to rump, the round ball of cells curls into a C-shape, a tiny comma. Already, as Brewster observed, a sort of groove has been cut along the length of the back, and it soon closes into a tube. Throughout the embryo, long stringy cells bundle to form nerves, which connect through the tube to the bulge at the top of the comma-the beginning 3-part brain. Two deep narrow slits form at the head-primitive eyes.

To supply the rapid proliferation of cells with energy, a crude circulatory system unfolds. Again, the great triumphs are in shape and structure, just as with molecules. Another tube of new, highly elastic cells takes shape in the region below the dot. The cells have a remarkable ability to contract and release. Within 3 weeks from conception, they have twisted into an S-shaped loop and have started pumping cells filled with oxygen and nutrients to every other tissue in the body. A human heart begins to beat.

Furious folding and refolding happens everywhere, apace. At 6 to 7 weeks, small bulges on the embryo’s flanks morph into recognizable limb buds. With neurons proliferating at the astounding rate of 100,000 per hour, the head grows swiftly. Eye pits deepen, the nasal region expands, the upper limb forms. Where a month earlier there existed a heap of bubbly cells now emerges a discernible face, no different from a chick’s but a face nonetheless. The embryo weighs about the same as a raisin, yet there is little doubt where, biologically speaking, it is headed. Soon finger “rays” appear, and nipples.

And then, at about 8 weeks, just as quickly as it all began, the furious shuffling of cells stops. Assuming that everything has gone successfully, and most often it has, the not yet conscious embryo resembles a mature human being. The head, more rounded, measures about half the total body length, which itself measures about an inch and a half and weighs less than half an ounce. Still, the eyelids and outer ear are fully articulated. The tail disappears, eliminating the last primordial resemblance to other species. The liver, kidneys, lungs, and digestive system are all recognizable. In form, if not character, the embryo is complete, and to make the distinction goes by another name: fetus.

Much, of course, remains to be done. The fetus has to fill out, and its physical proportions must change to prepare for life outside the mother. But in a sense, the architecture is complete. By knowing “when and where to grow fast, and when and where to grow slowly, and when and where not to grow at all,” the building has built itself.

But how has it done it? For Brewster, and for today’s biologists like James Thomson, that remains the key question, the sum of them all.

SEEING THINGS

We live in a remarkable time. Genetics and fertility research have taught us in recent decades how to conceive a baby. Now developmental biology and embryology are teaching us how to build one.

Add to this the recent progress in seeing inside the human body-to zoom through the hidden structures of organs, tissues, cells, even molecules, as if we ourselves were atom-sized-and we become witnesses in places we could scarcely imagine before.

You may wonder how this is possible: How can we look inside objects themselves too small to be seen? Most of the images in this book are not photographs, since photography cannot penetrate the surfaces of things. Instead, they are visualizations, composed through a marriage of powerful medical imaging techniques and passionate art.

The core technologies are familiar-scanning devices like CT and MRI, and computer photoshop software. Yet combined, they illuminate a hidden world. A pea-sized embryo, for example, is scanned head to toe and the information compiled. Since the data reveal differences in density (cartilage is denser than liver tissue, which is denser than blood), it’s possible, with the right software, to distinguish one organ, cell, and even atom from another.

Using other digital techniques, the skilled artist can then isolate any object, magnify it, peel away its surface (“ramp down the opacity”), rotate it so it can be viewed from any angle, and add shading, shadow, and “pseudo-color” until its essence is revealed. In 3-D.

What’s happening with the baby now? From what artist/scientists back to Leonardo da Vinci have suggested about the human form, and from what we can now see thanks to these penetrating images, we might better ask: What’s not?