by Simon Mawer
He handed the diagram to Bratranek. “There. I have added my own supposition of their inherited characters, but otherwise that is just as I was told it. It fits my ideas perfectly. Unlike garden peas, in mankind it would seem that the character of reduced growth dominates over the normal. I would consider delivering a talk on the matter to the Society, but I fear it would anger the Abbot. What do you think?”
Bratranek peered at the diagram. His expression was stern. He pursed his lips and pulled at his chin and frowned in the same way that he frowned at idle and foolish students. Mendel watched anxiously. “What do you think? Magda’s mother is unknown, as you may see—Magda was abandoned as a child outside the caravan of circus folk, so they told me. Anyway, assuming both Magda and Big Johann to be hybrids, and assuming my theories to be correct, they would expect to give rise to normal children in a ratio of three dwarfs to each normal, and the fact that Magda did not produce a normally heighted child is no more than the workings of pure chance. Further, it would seem that any dwarf of the non-hybrid kind is of the nature A, that is, pure—although unable to breed and thereby demonstrate such purity of type because of early death. What do you think?”
“What do I think?” Bratranek gestured helplessly. “They are mere monsters, deformities, things against the perfection of nature. And where does it come from, this character? I mean, normal people do not make dwarfs.”
“Ah, that’s a question!” Mendel leaned over the thin man’s shoulder and pointed to the figures. “Look at Birgit’s husband. As far as I could ascertain, he came from parents who were both normal. So in a sense these people are normal. They differ only in this one thing, and that difference could happen to anyone. Exactly how it arises I do not know, but there is no doubt that it does happen. I guess it to be something occasional and spontaneous, a change in the inherited characters owing to some error—a sport. A normal character transmogrifies into an abnormal one, and despite not having inherited diverse characters from his parents, the new carrier becomes a kind of hybrid. Contrary to Darwin’s assertion—the poor man is far off the track with his ideas of hybridization—this kind of transmogrification I would assume to be exceedingly rare.”
“What has Darwin to do with it? These are aberrations—”
“My dear Bratranek, this is every bit as important as Darwin’s theory, I can assure you. And in contrast to his, this idea is precise, almost mathematical. It calls other matters into question. Are we just children of chance? Are we merely products of mathematical probabilities, little different from the tossing of dice?”
Bratranek snorted. “That is mere foolery. If that were so, how could such a perfect thing as a human body ever be produced? If it were mere chance, then all of us would be monsters!”
“And there’s this: Should I have warned the family that within their makeup lies this character for normality, which for them is anything but welcome? Magda herself was lucky. Her daughter Heike, as yet unrealized as a woman and a mother, carries the factor hidden within her body. It may be that a tortured childbearing lies ahead of this poor creature who appears so alien to us, but who differs in nothing more than a single inherited character.”
In the lab the refrigerators hum, the ultra-centrifuges whine, the suction evaporator whirs. Patricia Primer, now revealed as plain Pat Storey, her gestures still awakening Benedict the goat, crouches over a rack of tubes and injects liquid from a micropipette. She flips the used pipette tip into a bin, snaps on a replacement, sniffs up another sample. Mere microliters. She glances round and smiles, the precise movements of her hand barely pausing. Her smile has the same effect on me as her gestures. What would she think, I wonder and have often wondered, if she knew about Eve? What would she think if she knew how I lust after her? Would she be surprised? Shocked? Flattered? Disgusted? Perhaps all those things.
“There’s a box arrived by courier. I put it over there.”
“Box?”
“From the States. Maybe it’s those cultures we’re waiting for.”
“Why didn’t you open it?”
“Not in the habit of opening other people’s mail. It might be love letters. Or dirty magazines.”
“Packed in dry ice?”
“Hot stuff.” Back to the work.
Ochre Codon (Olga Conlon, you will be pleased to learn, but known to many as Olga Condom) emerges from the sterile room with a medical flat in which a pale yellow culture liquid slops. She is large and loose, having been through at least two of the other postdocs and one of the project leaders in the last year. I have wondered, of course. Benedict the goat has watched her plump knees and wondered about her plumper thighs. She sweeps past toward the incubators, drawing after her a particular scent, as sweet and corrupt as a blown rose. Vincent Vector, Eric Venables in real life (tried with Olga and apparently failed; she is free but not easy), crosses her path, moving from PCR thermal cycler to electrophoresis gel, carefully stepping each time. over an expanded polystyrene box that lies almost in the center of the lab floor. Green lights on his PCR machine plot the rise of temperature—76, 77, 78, 79—and record the number of cycles, while the tubes inside, clutched by a heating block, proliferate DNA fragments on the rocket trajectory of an exponential curve—2, 4, 8, 16, 32, 64, 128 … After thirty-two cycles you have 1,073,741,824 identical copies of the original molecule. It seems like getting something for nothing.
“I’m doing that family from Edinburgh,” he says.
“The one with the homozygote?”
“That’s right.”
Benedict the goat, Benedict the propositus, humps the box up onto a bench and clambers onto a stool to open it. “Just like Christmas,” he says.
“Hanukkah,” says Olga over her shoulder.
The sender-label on my Hanukkah present says THE REDUCED HUMAN STATURE FOUNDATION, CHICAGO. As I remove the lid, the ghostly breath of dry ice rises to greet me. Couched within the mist, packed among steaming slabs of dry ice, are thirty plastic tubes, each red-capped, each labeled, each with a small plug of white matter in the tip. The plugs are made of frozen white blood cells cultured from five families with achondroplasia. The pedigrees, carefully cross-referenced to the tubes, have already been downloaded over the Internet.
“When can we …?”
“Oh, crumbs,” says Pat helplessly. “I can’t possibly deal with them for a week at least. We’ll have to store them.”
“Get one of the graduate students to do them.”
“Probably bugger them up.”
It is a mundane world, a world of inconsequential chat while you follow a protocol that has been followed a hundred times before and can be followed now without thinking. Like cooking, very like cooking. A protocol, with its echoes of diplomacy, of law, of etiquette, is actually a recipe. You are constructing a sauce béarnaise. As with cooking, the uninitiated get it wrong and the sauce béarnaise curdles. Mere repetition is necessary to get it right, like Mendel with his cross-pollinations, hundreds and hundreds of cross-pollinations with a ninety-nine-percent success rate (“a very few [errors] … among more than ten thousand”3). You or I would get it right about once in every ten attempts, until we had repeated it dozens of times, until it had become routine …
“How’s the library lady?” Olga asks. As she passes by, she ruffles my hair. Whether this is something I love or hate, I have never decided.
“She’s fine.”
“You seem … quite close.”
“She’s an old friend. From home.”
The conversation dies away as she pulls on latex gloves (two pairs) and positions a Perspex screen between her and her rack of tubes and begins to make up a radioactive probe. Someone—is it Pat?—begins to hum a tune. In the silence everyone works.
It is a game of patience, this search. A game of watch and wait, of dealing the cards and reading the messages traced out in the cryptic bands of radioactive DNA probes. You deal and deal again. The patients queue up in the clinic, a whole circus assembly of the dwarfed and stunted, to f
ill in forms and surrender blood samples. White blood cells are spun like a merry-go-round, and lysed4 and digested and amplified,5 and the little samples of DNA, translucent like semen, glistening like seed, are sorted and tagged and identified. The secret of life in a speck of jelly. Once upon a time the mystery was enshrined in the tabernacle on the altar, in a sliver of wafer. Now it lies, stripped open for mankind to read, in a polyacrimide denaturing gel.
Great-great-great-uncle Gregor would have understood.
Finding the Gene
You extract the DNA from cells. Then you use specific enzymes (called restriction enzymes) to chop the whole lot up into manageable pieces. These enzymes cut at specific, known places in the DNA message. I have a catalog at hand that lists ninety-three such enzymes; we have fifty different ones stored in the fridge. I am not talking about the frontiers of science here. Nowadays these things are commercially available. Using the enzyme of your choice, you carry out a digest, and then, from the whole mess, from the tens of thousands of different genes present in the gelatinous blob of DNA, you try to pick out the one that interests you.
Analogies, metaphors, similes. Searching for a needle in a haystack, that’s the obvious one. There are 3.3 × 109 base pairs in the human genome. Thirty-three billion letters. Do you need a yardstick? Does your brain seize up when people start talking about the number of centimeters from here to the moon and the total length of all the blood vessels in the human body, that kind of thing? Well, I have a copy of the Bible on my bookshelf—it must be a copy that Jean left behind, because, let me assure you, I’d never have bought it—and I have done a rapid estimation of the number of letters in that edition. Fifty letters a line, fifty-five lines a page, 1,668 pages. Number of letters? Four and a half million, more or less. It includes the Apocrypha. So the human genome, the sum total of all the human genetic material, is some thousand times as big as the entire Bible. Only a fraction of those letters actually code for genes, but still, finding a single gene is difficult enough. Like searching the Bible for a single sentence.
Or how about this one: searching for a murderer among the whole population of a city?
Ah! You are closer now, aren’t you? You can immediately play the flatfooted policeman and think of some kind of strategy. You know that this person exists, you know what he has done (a serial killer, perhaps), but you don’t know where he lives. You can think of ways you might start, can’t you? How about a door-to-door search, starting at Abbess Close and running through the A-to-Z to end up at Zoffany Street? Takes forever. You want to narrow down the search, increase your chances of getting it right, look only in those parts of the city where he might appear …
Just as the city is divided up into districts, so the human genome is divided into chromosomes. The first step is to identify the chromosome on which your gene lies. So we find families with achondroplasia and pick through their DNA. Like policemen looking for possible associates of the unknown man, we are looking for specific, known genetic markers and hoping to find one that tends to be inherited with the crime. The genetic markers are known as Restriction Fragment Length Polymorphisms (RFLPs), but they are referred to, always referred to as riflips. It sounds like something a jazz drummer might play: “Give me a riflip, man.”
You follow the riflips with radioactive DNA probes. At first it is purely a matter of luck. There are RFLPs known throughout the whole human genome, in every district of the city. It is pure chance whether or not you choose to follow one that is actually linked to the gene that interests you. It may take a few weeks, it may take years. You just keep guessing and keep trying. Like any police investigation, the work is repetitive and painstaking. Like any police work it has its share of luck, good and bad.
Once you have found a linked marker, you find out which chromosome the marker came from. And once you know that, you know in which area of the city the suspect lives. You find other, closer, more intimate associates. And finally you can find the street.
It has taken us one year, almost exactly, to get our first linked marker. It is named, prosaically, D4S412, and it lies on chromosome 4. Precisely, the marker lies in the short arm of the chromosome. We need markers on either side of the gene, we need markers nearer the gene. We can begin walking the chromosome toward our goal. We are closing in, focusing on my own existence. Soon we will have identified the street, and then finally the house number, so that one quiet afternoon when there is no one around, when the children are all at school and the housewives are out at the shops, we can walk up the path to the ordinary front door and ring the bell.
1. Twenty amino acids, and the command STOP.
2. Two trivial differences between nuclear DNA and mitochondrial DNA.
3. Mendel, Versuche über Pflanzen-Hybriden, 1868.
4. SDS lysis, proteinase K digestion, phenol/chloroform extraction, ethanol precipitation, and Tris-EDTA resuspension.
5. PCR using 1 U Taq polymerase and 30 cycles of denaturation, annealing, and elongation.
One day Jean didn’t appear at work. I happened to go into the library for something, and she wasn’t there behind the desk.
“Where’s Miss Piercey?” I asked the head librarian.
“Who’s Miss Piercey?”
“Miller. Mrs. Miller.”
The man shrugged. “Phoned to say she was ill.”
I imagined an alluring fever, the cheeks flushed and the bedclothes awry. But later in the morning there was a call put through to the lab. “It’s me,” said a voice. “Jean. Can we meet?”
“Meet? Where are you? Aren’t you at home?”
“Not really.” Not really? How could you not really be at home? The words made me angry. She did make me angry at times, with her willing stupidity, her calculated determination not to understand, not to think for herself, not to realize that she too had a brain. How, in God’s name, could you not really be at home? “I’ll explain when I see you,” she said.
“Where?”
“The pub?”
“But why didn’t you—”
“Just meet me there at the usual time. And make sure there’s no one with you.” There was a murmur of determination there, just a faint gleam of iron. “Just be there.”
At The Pig and Poke I took my drink and a slice of quiche and retreated to what, over the weeks, had become our corner. “The missus left you, has she?” Eric called across as he pulled a pint of bitter. “Hey, how about this one? This’ll grab you. How do you tell the sex of a chromosome?”
“Look up its genes.”
His face fell. “You’ve heard it already.” Then he brightened up as another regular entered. The joke was repeated, with roars of laughter to signal the punch line and gestures of acknowledgment in my direction. “Jeans and genes, you got it? That’s what the professor there does, looks up the sex of genes, isn’t that right, Prof?” he shouted.
I agreed that it was, more or less. A group of Belgian tourists came in to provide a blessed distraction. I turned back to my drink and the disconsolate slice of quiche; and Jean was sitting beside me on the bench. There was an insubstantial quality to her apparition, as though she had not come in by normal means but had slipped, ghostlike, through the walls. She held her head in profile, tilted slightly forward as though she were examining very intently something that lay on the floor in front of her. The mouse-white skin across her cheekbone was reddened and swollen; her upper lip was puffed up, bringing a sudden and unfamiliar irruption to the modest curves of her mouth. “He hit me,” she said quietly. “I don’t know what to do. I don’t know where to go. I need help, Benedict.” I’d never realized that weeping could be such a silent thing. As I sat there helplessly, I wondered about the physiological basis for it, that soundless and incessant seepage of liquid from two tiny ducts in the eyelids. It seemed bizarre. I fumbled for things to say, but they fell to pieces in my hands and I was left only with useless fragments.
“I don’t want to stay here,” she said. “Where can we go?”
“I ca
n’t go anywhere. I’ve got a lecture straight after.” Then inspiration struck. I searched around in my pocket and found the key to my flat. “Here, take this. Take a taxi. Have you got some money?”
She had some money.
I told her the address. “You can rest at the flat for as long as you like. I’ll join you after the lecture. You’re welcome to use the place …”
The tears had become tears of gratitude. How could I tell that? How can tears change their identity? She took the key without saying anything. I must admit to a certain tremor of anxiety. I didn’t want her poking around within the doors of 28A Pearson Street, within the confines of my cave, and coming across my carefully tended collection of unusual photography and videotapes. Was Winsome Wanda, I wondered desperately, still lying with her legs splayed artlessly across my bedside table? But one must take risks in life. “I’ll be back at about five,” I told Jean. “You just make yourself comfortable till then.” Which implied, somehow, that after that I was going to make her uncomfortable. She got up from the stool and turned away from the bar and went out through the door.
“Was that Jean, then?” Eric called. “She seemed all in a rush, didn’t she?”
“Got an appointment.” I turned back to my quiche, no longer feeling very hungry, wondering a whole lot of things. Miss Piercey was no longer mousy; but at what cost?
Doctor Benedict Lambert lectures at Imperial College on the latest developments in linkage analysis and homeobox genes. He lectures to a packed house, for the diminutive Doctor Lambert, the vertically challenged Doctor Lambert, the deformed and pitiable Doctor Lambert, has, ironically, a growing reputation. There is standing room only. The aisles are packed. People peer in through the glass panels in the doors and see that there is no more space. But don’t imagine for one moment that they have come to hear about the HOX7 gene and Wolf-Hirschhorn syndrome. I mean, who would be interested in such a thing? No, they have come to see the performer. Oh yes, I can offer them some good slides of fruit flies with antennae growing out of their heads and mice with stunted legs, but the monster they have come to see is there on the lecture stage, disappearing behind the lecture bench on occasion, cracking jokes about reduced stature in albino mice and showing slides to prove it, waving his magic wand at projection images of a homeodomain protein and how it might bind to the chromosomal DNA during the regulation of gene expression. The spotlight is on the midget; the hanging gardens roar and clap. It is little better than the circus.