Saturday, August 4, 2012

Little Tommy

Bill and Susan Barton strode into the fertility center at the appointed time Thursday morning. But their confident outward demeanor belied an anxiety just below the surface.

In a moment, one of the young assistants entered the waiting room and announced that the doctor would see them.

The two kept up the charade of confidence as they entered into a plush office. A balding middle-aged man in a white coat peered at them through a pair of wire-rimmed glasses from across an expansive desk.

"Mr. and Mrs. Barton, my name is Dr. Seabram. So, it seems you are interested in conceiving through our meiotic selection procedure?" he prompted them.

"Well, yes, Dr. Seabram, we are certainly interested," said Susan, "but we would like to know a bit more first."

Susan and Bill looked like the stereotypical patients Dr. Seabram encountered every day, day in, day out :  nervous, middle-class, mid-thirties, want to know more. He began his well-worn explanation.

"Well, the meiotic selection procedure is not actually an engineering procedure, as far as the genetic material is concerned. Which is why we can do it, perfectly legally, within the parameters of the Cold Spring Harbor Protocol. Very safe. It's simply a way to sort out more promising gametes -- reproductive cells -- from among the possible cells each of you are capable of producing.

"We take a sample of cells from each of you -- a blood sample, very simple -- and grow them in culture, where we induce them to undifferentiate back into stem cells. We then transfer them to new culture media where they are induced to undergo meiosis. Meiosis is the process where the genes segregate to produce the unique combinations that unite at conception to produce a unique person.

"These thousands of unique meiotic segregants are separated from one another and used to establish vegetative lines" -- here he carefully avoided the word 'clones' -- "which we test with a parallel genetic analyzer.

"The analyzer is just basically a big machine designed to analyze many samples all at once and output the results to a computer. It checks both the genetic content of each line, and also the integrity of the cells, just in case there might have been any unusual rearrangement in the segregation process. Because we have established lines of each segregant, we can match the results back to the specific line, and pick out the best candidates for you two to conceive a child.

"The chosen lines are induced to continue differentiation to form fully developed reproductive cells -- sperm and egg, which we check for genetic integrity once again -- and combine in a routine IVF procedure and implant into the uterus. Nine months later, you've got your little baby," he said, with a smile at the end.

"But, what about all the other little embryos?" asked Susan.

"There are no other embryos," said Seabram confidently, "the only embryo formed is the one implanted into you."

"I see," said Susan, hesitantly.

"What exactly can you tell -- genetically, I mean -- about the different segregants?" asked Bill.

"You know, my husband studied genetics in college," said Susan, confidently squeezing Bill's leg.

"That was a long time ago, honey; things have changed since then," he said, a bit impatiently.

"And that's just where the rubber meets the road, isn't it?" began Seabram "Things are changing because we have been learning more -- which begs the question 'Just how much do we really know?' And I would not be being totally honest with you if I told you that we could tell you everything you wanted to know about your future offspring. Because, frankly, there's a lot we still don't know about how genetics works. In fact, I'd even venture to say that we probably won't ever know everything. There will probably always be a large element of mystery to these processes.

"We can tell you what genes are there, to the extent we have identified certain sequences as genes. Unfortunately, we can't say for sure that we've got them all yet, and we can't always say what the outcome will be of having any particular gene -- or even if we have established a proper definition of what a gene is! We haven't really learned all the ways that different sequences of DNA can interact to produce biological characteristics. We are always learning more, but there is simply a very great deal that we don't know at this time.

"On the other hand, there is quite a bit that we do know, and this procedure can greatly reduce the probability that your offspring will suffer from those genetic diseases which we do understand. We can also give your child a better chance at being able to achieve more in life by stacking the deck in his favor in terms of those genes which we have identified that can confer particular advantages -- an above-average IQ and such. But we can't in general predict just how the particular combination of genes will turn out, and outside of this genetic deck-stacking -- which, really, is fairly narrow in terms of the overall genetic content -- the rest is up to chance."

"Hmmm..." said Susan, pensively.

Bill leaned forward, his complexion taking on a keen squint of a gaze at the doctor. "What about your pre-selected lines?"

"Bill," said Susan, in a tone of warning, "we talked about this."

"I'm just asking," said Bill, turning back towards the doctor.

"Well," said the doctor, adjusting his glasses and straightening up in his chair. "I'm glad you asked. It sounds as if you've been doing you homework.

"In the course of our practice, as well as research, we have accumulated an extensive collection of meiotic lines, some of which have already undergone extensive selection. Now, when -- or I suppose I should say 'if' at this point -- if we were to perform a meiotic selection on one or both of you, no doubt that with a large enough sample, we would identify some lines which contained a 'better' set of genetic material -- on average, at least, and if 'better' is really the right word -- than would be at all likely if you were to produce a child the old fashioned way.  As a matter of chance, some lines will contain considerably more of those advantageous genes, and fewer of the genes likely to cause trouble.  Which, of course, is why we do the selection in the first place!

"But you have to understand -- the human genome contains a lot of DNA, and a lot of genes.  Neither of you appears to have an overt genetic defect, but chances are that each of you carries at least a few genes that would kill you if you didn't have a complementary gene to make up for the bad one. Probably also several more that wouldn't really be very good for you. Fortunately, the probability of having two such genes is rare; unfortunately, natural meiosis is non-selective and these things persist, every now and then causing some poor individual a great deal of trouble.

"Our procedure would likely be able to identify at least a few of your own segregants which were mostly free of such defects -- again, at least of the ones we know of.  But, let's say for argument's sake, you've got seven potentially lethal or otherwise deleterious genes you are trying to exclude.  Right off the bat, we're talking about the elimination of over 99% of the lines we produce -- before we have even started trying to select for advantageous characteristics!  This is pretty typical.  Now, you don't necessarily have to get rid of all the bad genes, so long as you can ensure they wind up in a background where they won't cause any trouble.  But it illustrates the principle of the thing -- the more cards you are trying to stack, the tougher it gets, and we often wind up having to make tough decisions and weighing one thing against another.

"Our pre-selected lines can help with this process immensely. They are actually the result of several such procedures -- they are derived from individuals whose lineage has been undergoing this type of selection for several generations. These lines contain no known genetic defects, but in addition, contain a disproportionate number of those genes which have been identified as particularly beneficial or advantageous, in that they can confer what many people would consider more desirable characteristics. Some are positively stacked with these genes.

"With one of these lines as the complementary line to one of your own, everything becomes much more flexible. It isn't so critical that the stars align, and you have a lot more options. We have a wide selection of such lines, for starters, which you can search to find one that is most compatible with the genetics you have to offer, and in whatever line you choose, at least one good gene at every known locus. You can start thinking about particular combinations that work together that maybe wouldn't otherwise be possible, without worrying so much about the deleterious genes."

"But it wouldn't really be our child, would it?" asked Susan, more as an assertion than a question.

"I'm afraid you've entered philosophical territory with that question," said the doctor. "If you want my perspective, I deal with this stuff every day, so it's sort of lost its magic for me. And I have an adopted daughter whom I love very much. I think you have to answer those kinds of questions for yourself."

Susan squirmed in her seat a little, and there was a rather long, awkward silence.

"I'll tell you what," began the doctor again, "I'll put it to you this way. You basically have three choices -- You can use all of your own DNA, from both of you, or you can use half of your own DNA, from either one of you, or you can use none of your DNA, using two of our own pre-selected lines --"

"People do that?" asked Susan, in a tone of amazement.

"Oh my, yes," said the doctor. "You're chances of having a prodigy for a child are practically guaranteed. If that is what you are looking for, naturally. Of course, it is not the most popular choice. The most popular is to use one of our lines with one from one of the parents. As I said, this allows for a great deal more flexibility, and in all likelihood a very promising offspring in terms of the potential for high achievement.

"And since most families that have children have more than one child, there are always opportunities to include the genetics of the other parent in subsequent children. But if do you choose to use both of your own in the same child, the child will still probably stand a good chance at having the potential for at least above average achievement, and will be spared a great deal of anxiety over suffering from heritable diseases or passing them on to his own children. It is up to you."

"So, wait, you mean we could have, say, a son with Bill's DNA, and a daughter with mine?" said Susan, apparently warming to the idea a little.

"Oh yes," said the doctor, "we do just that all the time -- selecting the sex and everything. It's one of our most popular plans."

Bill and Susan looked at one another for a moment. "I suppose we've got a lot to think about," said Bill.

"How about this," said the doctor. "What we can do is get samples from both of you, and create the lines. We can do some hypothetical computer matchups with these different options, so that you can see what kinds of choices you are really looking at. That can maybe help you to decide what you want to do. As it is, you don't really know your own genetic backgrounds, so all of this is a bit hypothetical at this point. Neither of you have been tested before, have you?"

They both shook their heads.

"OK," he continued. "We can do this free of charge, the only catch being that once the lines are created, they become our property, whether you decide to use them or not. How does that sound?"

"What will you do with our lines?" asked Bill.

"Probably nothing," answered the doctor. "If you do a selection, the lines of your child would be far more valuable to us -- and we do ask that they be donated, should you make such a decision. But since you are both from the general population, most of your own lines will contain too many defective genes to be of much use as a pre-selected line. We'll probably wind up throwing them all away. There's always a chance, though."

"But..." said Susan, timidly, "what about..."

The doctor smiled. "Don't worry," he said, "they are nothing more than tissue lines. Your own bodies are doing the same thing as we speak, turning over potential reproductive cells. That is all we're doing, making reproductive cells, not embryos. That has to wait until you are actually ready for the baby."

The Bartons assented to this plan of action. The doctor showed them into a clinical room, where they signed release forms and a nurse drew blood from each of them. An assistant gave them some informational brochures, and the couple was on their way.

Later that evening Bill Barton examined some of the material, and looked up a website with additional information. He found a webpage that gave a brief history of the technique. It was fascinating.

Apparently, about twenty years ago, a very wealthy elderly couple set up a trust for genetic research, with the explicit aim of alleviating -- or better yet, eliminating -- genetic disease from the human population. Both their families had been rather aristocratic, and wracked with heritable diseases -- his with Parkinson's, hers with Alzheimer's and heart disease.

But the money came with strings attached -- no unethical means could be employed, either in the techniques developed, or in the research which went into developing the techniques. This meant that no embryos could be created outside of the express purpose of producing a human life, and no human cloning. Embryos were not to be created for experimentation or for use as genetic tools, and the prohibition on cloning eliminated the standard recombinant strategies of genetic tailoring.

For most researchers, this was too much of a straightjacket. But one promising geneticist agreed to the challenge -- one Dr. John Anderson. Dr. Anderson pitched his idea to the trust, and it was off to the races.

At that time, methods for manipulating cellular differentiation were already being developed, and within a few years he had already perfected the technique in mice. He experimented for some time with cultures of his own cells until he had mastered the process of differentiation, induction of meiosis, and conversion into reproductive cell lines. By all measures he could devise, they were indistinguishable from naturally occuring egg and sperm cells.

He then gathered together a group of volunteers -- ten couples committed to raising large families. He performed his technique with each couple, producing a first generation of meiotically selected children. All pregnancies went texbook-perfect. No birth defects, and a clean bill of health on every baby, genetic and otherwise. Among them, the incidence of deleterious genes was drastically reduced, and as all combinations had been pre-screened for compatibility, the possibility of a known defective combination in any particular child had been eliminated.

But he did not declare victory over genetic disease and stop there. Recognizing that these children represented a pre-sorted 'genetic pool,' he used cells from this generation for a subsequent generation, implanting the embryos back into the original mothers to produce a second generation within only a few short years of the first. The result was a complete eradication of all known deleterious genes within this generation -- and a substantial improvement in the frequency of known advantageous alleles. A few years and a few generations later, and Dr. Anderson had isolated multiple highly-sorted lines -- some still in use today by couples like Bill and Susan -- and delivered over a dozen child prodigies. Five generations of selection -- in a fraction of a single human lifetime.

Only twenty years ago, and already the technique was so advanced and widespread! The impacts on human health were already being felt. The incidence of birth defects and heritable disease among children fell like a stone. And as the genetic segregation was permanent once established in individual people, the suppression of the frequency of defective genetic loci would persist whether or not children of these couples opted for the procedure themselves.  The frequency of defective genes in the population at large was being permanently reduced.

But there were other effects as well. The standardized test scoring systems were thrown into a tailspin. Public schools did not know what to do with the enormous influx of 'statistical outliers.' Religious and political groups began to question everything from the morality of the procedure to the 'fairness' of its availability only to the 'privileged' groups that could afford it. Some groups wanted it banned; some to make it manditory and a crime to conceive by other means. Charities were set up to subsidize the procedure for poorer families -- and burned down by militant fringe church leaders proclaiming 'judgment' and bloody apocalypse. All told, it was an intensely controversial and socially disruptive development.

It was the drive of aspiring middle-class families like the Barton's -- always looking for a perceived 'competitive advantage' to propel themselves and their children into the upper-echelons -- that pushed the technology into the mainstream. Almost overnight, a cohort erupted demanding the procedure, their demands backed up by dollars. The procedures therefore remained legal and took place; the propelling, not so much, as there is only so much echelon to go around. In the span of twenty years, it had become a commonplace. By the time Bill and Susan were having their samples drawn, it was no longer unusual, though still controversial.  Some of their friends were having it done, but not all of them.

Two weeks later, they were contacted by email that their results were in. They were directed to a website that showed them their 'best-ranked' possibilities, as generated by a computer algorithm.

As it turned out, Bill and Susan were not all that compatible, which they were informed was a fairly typical result. Each of them carried a number of genes which could potentially confer a particularly favorable set of characteristics if present in the right combination with other genes, but these complementary genes were not present in their partner. And Bill in particular carried a number of rare but debilitating genes that severely restricted the number of lines they would really want to use from his segregants.

However, there were a number of compatible pre-selected lines that could provide a useful genetic background for each of them. This way of doing things would allow the couple to better utilize it's own genetic assets to produce healthy children without sacrificing possibly advantageous combinations.

In the end, Susan and Bill settled on the last approach -- they would first have a boy using one of Bill's segregants and a pre-selected line, and then a girl with one of Susan's in the same manner. They set another appointment, at which time they were presented an enormous bank of computer generated choices using the center's library of cell lines. After some agonizing, they made their selection, and within a few days were summoned back to the clinic for implantation.

Nine months later, little Tommy Barton was born, and as soon as Susan saw him, she could tell he had his father's eyes.


  1. The difference between the right word and the almost right word is more than just a fine line! it's like the difference between a lightning bug and the lightning!