Blood Matters

by Masha Gessen

  The idea was this. A human egg cell contains forty-six chromosomes, twenty-three of which it expels on its way to fertilization. So if a woman is heterozygous for a gene, then by looking at the discarded part of the egg researchers would know whether the embryo contained the gene with the mutation. If, for example, the woman was a BRCA carrier and the discarded part of the egg contained the “bad” copy of the gene, then the embryo would not be affected: “If this is yellow, we know exactly where will be red.” This worked for recessive conditions, too—to an extent: If both parents were known to be carriers—that is, if both carried just one “bad” copy of a gene—and the “bad” gene was expelled by the egg, the embryo would not be affected; if, however, it was not expelled, there was still a 50 percent chance the embryo would be healthy, since it may inherit a “good” copy of the gene from the father as well.

  Verlinsky started running experiments. By the late 1980s he had performed this kind of test for women going through in vitro fertilization. By the early 1990s Verlinsky developed a technique for removing one of the cells from a six-to-eight-cell embryo and testing it for chromosomal and genetic abnormalities. He had also left Michael Reese Hospital and started the Reproductive Genetics Institute. Then the Soviet Union collapsed, and Anver Kuliev accepted his old friend’s long-standing offer and came to join him in running the Chicago institute—which, by the time I visited it in the summer of 2006, was offering prenatal testing through chorionic villus sampling and in vitro fertilization with preimplantation genetic testing for more than 120 conditions, as well as testing that would allow couples to have babies who would make suitable donors for their sick siblings.

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  In his brief on ethics Anver Kuliev compared preimplantation genetic diagnosis to such primary prevention measures as adding folic acid to the diet of women of childbearing age—a step that can vastly reduce the risk of giving birth to children with congenital abnormalities. The beauty of such measures, he argued, was that “they provide the actual gain in infants free of congenital malformations rather than the avoidance of birth of affected children.” In other words, if a woman discovers she is carrying a fetus affected with chromosomal or genetic abnormalities, she might have an abortion. If a woman discovers that one of her embryos obtained through in vitro fertilization is affected, she will opt to have another, unaffected embryo implanted and go on to have a healthy baby. This is an overargued way to express a simple truth: It is far easier for humans, whatever their ethical and religious beliefs, to reject embryos than to abort fetuses.

  The clinical sterility of such discussions is a luxury compared with the human torment geneticists witnessed, sometimes experienced, and often tried to alleviate back in the days of prenatal testing. “I will never forget the spinal muscular dystrophy case,” said Barbara Handelin, who ran the first commercial genetic testing laboratory in the Boston area in the 1980s. “One of the first cases we did was this young couple whose daughter had died about six months before they knew, before we knew that we would be offering prenatal testing. They were our first prenatal case. And we said, ‘You know, the thing is, we have to have tissue from your daughter, so if there is a muscle biopsy, we’ll try that,’ which we did and we were not able to get DNA out of it: It was a tiny section that was left and it had been formalin-fixed in paraffin, and we were not able to get enough useful material out of it. So I had to call her and say, ‘Can’t do it.’ And she said, ‘Well, what about hair?’ And I said, ‘You mean, like a lock?’ And she said, ‘Well, I have her neonatal baby cap that I kept. And there is quite a bit of hair in it.’ One of the first signs is hair loss. And she said, ‘If I take the hair out, would you be willing to try that?’ I said, ‘Yeah, we will, but I’d hate for you to give up the only thing that you have.’” Barbara had tears in her eyes when she told me this story twenty years later.

  “So the day we got DNA out of that hair sample—oh! People were running through the hallway: ‘Got to call her and tell her!’ And then her CVS sample arrived, and people held their breath for a couple of weeks. So when we got those results—she was carrying a carrier, not affected—that was a very happy day. And she sent a postcard with a photograph after the baby was born. That—I still have that.”

  There was another case Handelin remembered in detail two decades later. “There was a woman who had polycystic kidney disease—one of her siblings had died of renal failure. She was actually doing very well herself. But she didn’t want to pass it on.” The condition is what it sounds like: a disease that causes fluid-filled cysts to form on the kidneys, and sometimes on other organs, reducing kidney function and ultimately leading to kidney failure. Hereditary polycystic kidney disease can be caused by either a dominant or a recessive gene. The woman who came to Handelin’s lab had the more common dominant form.

  “The first time we did her case—I mean, it was depressing: depressing for the tech who gets the results, and they bring it to you, and we go over it in a lab meeting and say, ‘Well, you know, bad news, bad news for this lady.’ And then, a year later, her case comes in again, and bad news again. And you think, ‘Okay, this will be it, she is not going to be able to take this anymore. Or maybe she’ll just go ahead with this pregnancy.’ And the third time she got pregnant, I just felt like, really, we can’t take it!”

  The genetic counselor working with the woman asked Handelin to meet with her: The counselor wanted to tell the woman to stop, but the rules governing genetic counseling forbade that. “So I did talk with her, and she was just so incredibly determined, and I said, ‘We are just feeling for you.’ And she said, ‘I’m okay. Do your job. I cannot bring children into the world with this hanging over their head.’” It took five years and four pregnancies.

  These days, either woman would have been able to seek in vitro fertilization with preimplantation genetic diagnosis either through polar body biopsy, as the Miróinspired technique is called, or embryo biopsy—or both, as the Reproductive Genetics Institute usually does it to get the most reliable results—then picked a healthy embryo or embryos, and gone on to have the healthy baby she sought without the torment to which both women were subjected in the 1980s. This is very much how Verlinsky and his colleagues saw preimplantation genetics: If the technical opportunity was there, it had to be used, for its benefits were tangible while its risks were really just other people’s fears.

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  Preimplantation genetic diagnostic procedures are banned in Austria, Germany, Italy, and Switzerland. “I think Germans collectively are unsound,” wrote the journalist Martha Gellhorn in 1990. “I think they have a gene loose, though I don’t know what the gene is.” Germans clearly hold a similar opinion of themselves, as do other countries that either chose fascism or know themselves to have aided it. “It’s really more about a fear,” Karen Avraham, a geneticist at Tel Aviv University, explained to me. “It’s because of what the Nazis did, and eugenics. And there should be fear. Because if any of those tools get into the wrong hands...” She trailed off.

  Israel, being the opposite of Germany, Austria, and Italy, not only allows preimplantation genetics but, in some cultural way, encourages the practice. All Israeli general hospitals have their own fertility units; public health funds cover the cost of producing two babies for any infertile woman under the age of forty-five, and the standards of what constitutes infertility tend to be very liberal. “In Israel people want a child—they have fertility done,” said Avraham, who was born and raised in the United States. “People don’t wait a year to see if they can get pregnant. And you see a lot of twins.” Prenatal testing in Israel is performed routinely, regardless of the pregnant woman’s age: The quest for perfection, or at least for health, overrides the economic considerations that, in other countries, limit prenatal testing to pregnant women over a certain age. Nor are there any religious obstacles to preimplantation genetics: A fetus is not considered a human life before forty days’ gestation—and this is also one of the reasons Israel has been able to make grea
t strides in stem-cell research.

  Avraham herself studies the genetics of deafness, one of the most ethically fraught issues even in Israel’s permissive climate. One out of twenty-one Ashkenazi Jews carries a mutation in the connexin 26 gene, a gene that codes for one of the proteins known as connexins, which are essential to hearing. That would mean that roughly one in eighteen hundred Ashkenazi babies would be born deaf. That makes what is called “nonsyndromic deafness”—hearing loss that is not associated with any other symptoms—one of the most common genetic disorders among Ashkenazi Jews. But screening has been a matter of some controversy.

  Dor Yeshorim, the wildly successful Jewish premarital genetic screening program, holds to a principle of testing only for conditions that are life-threatening. That standard was relaxed slightly when the program began testing for Gaucher’s disease, which can be mild but can also be debilitating. Deafness is isolating, limiting, and difficult to overcome, but it is neither life-threatening nor physically painful. Some people argue that deafness provides for an alternative form of communication that should be protected. The active deaf community in Israel has been consistently opposed to developing genetic therapy for deafness, but there are also deaf and hearing-impaired scientists at Avraham’s laboratory working on this research. Premarital, preimplantation, and prenatal genetic testing for deafness, though, goes to the question not of whether deafness should be treated but whether deaf people should be born.

  Michal Sagi, who ran the genetics unit at Hadassah, told me in 2005 that her program had solved the dilemma the ostrich way: by omitting deafness mutations from the list of available prenatal genetic tests lest it look like a recommendation for testing—and possibly for the termination of pregnancy. So much for full disclosure, one of the basic tenets of genetic counseling.

  Genetic tests for deafness mutations are, however, available to pregnant Israelis who ask for them. If they ask, it is usually because they already have deaf children. “There is a physician who had two deaf children, and he decided they were not going to have another deaf child,” Avraham told me. The physician had apparently been very public about his story, even using it to aid in fund-raising efforts for Avraham’s work. “So they were going to have prenatal diagnosis. They were not negating their first children, but they felt they couldn’t provide for their first two if they had another deaf child. Such a burden. We discovered the mutation, we worked with the clinic, they did the diagnosis: The child was hearing. The fetus did not have the mutation. They carried the pregnancy, the child was fine. But they do say that if they found the fetus had the mutation, they don’t know that they could have had an abortion. My guess is they would have done it, because it would have been just too much of a burden.” Deaf children whose parents want to integrate them into hearing society require time-consuming, difficult, and expensive training: Mothers quit jobs, families go into debt and sometimes run out of resources.

  What makes us uncomfortable about stories like these is the question of selection. A woman or a couple who choose an abortion because they do not want a child at all are somehow less ethically suspect than people who do not want a child with particular characteristics. For decades, Soviet women used abortion as their means of birth control; Russian women still average 2.43 abortions in a lifetime. Yet distasteful as this is, it is not frightening in the same way as abortion resulting from prenatal testing—or even embryo rejection resulting from preimplantation diagnosis—because it does not raise the question of our criteria for the suitability or the worthiness of life.

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  Most people with whom I talked as I did research for this book claimed to have specific ideas about the dividing line between suitable and unsuitable criteria in screening potential offspring. Sex selection is one of the usual border posts, and a mainstay of prenatal counselors everywhere: If a woman’s or a couple’s apparent primary reason for seeking a prenatal test such as amniocentesis is to learn the sex of the fetus, the test is normally denied. “I’m not a criminal investigator to try to find out what reason they have to transfer this embryo or another one,” bristled Yury Verlinsky: His clients learned all sorts of things about their embryos, including their sex, and they made choices to which, he felt, they were entitled—like to transfer a healthy embryo that was male or female.

  Not only that, some of his clients had sound medical reasons for seeking sex selection: A woman who carries an X-chromosome-linked mutation, such as the one associated with hemophilia or “bubble boy” syndrome, or a variety of others, could reasonably choose to give birth only to daughters, who would not be affected by the genetic disease. One of Verlinsky’s earliest successful experiences with preimplantation diagnostics involved identifying a female embryo for a couple in which the woman was a carrier for hemophilia.

  In some societies, preimplantation sex selection for social reasons has gained acceptance. In India the practice is called “family balancing,” although it may more reasonably be called “boy selection”—a service for families already burdened with girl children in a country where boy babies are prized. Israel’s first approved case of preimplantation sex selection was a perfect Talmudic case study. It involved an Orthodox couple in which the husband was infertile. The couple wanted to have a child by using donated sperm, but the situation was complicated by the fact that the future father was a Cohen, whose son would be expected to play a certain role during synagogue services. But the Cohen heritage is passed on to biological children only: One cannot become a Cohen by dint of adoption, marriage, or any other nonbiological relationship. If a boy was born, therefore, the father would face a dilemma: Either allow him to be treated as a Cohen, thereby perpetrating a lie, or tell the community that the child was not his biologically, which was not something he wanted to do. The obvious solution, the rabbinical authorities agreed, was to have a girl. Since then, authorities have also allowed couples who have four or more children of the same sex to seek preimplantation sex selection.

  “Some people do it the natural way.” Verlinsky laughed. “Trish, our secretary, she has seven children: She did six boys until she got a girl. One of the ways to do sex selection.” He had a point: People have always engaged in sex selection of some sort or another. Every culture has its superstitions regarding when and how boys or girls are most efficiently conceived. To argue that just as humankind has finally acquired something it has sought all along—a truly effective way to choose boy or girl babies—it should be banned, seems hardly logical and entirely unnatural.

  Selection for intelligence raises another universal objection. The obvious objection to this objection is that the most common understanding of the most common prenatal test—amniocentesis—is to avoid giving birth to a child with Down syndrome, at least in part, and possibly primarily, because these children have mental retardation. The common amendment to the selection-for-intelligence objection aims to exclude children who would be mentally retarded: Giving birth to a child like that, the logic goes, requires a different sort of parent-child relationship, one that is far more demanding, much less rewarding, and largely devoid of development.

  But for the past twenty years and more, potential parents in the United States have been routinely aborting fetuses that would develop into children of below-average intelligence. These are fetuses identified either through amniocentesis or through chorionic villus sampling as having an abnormal set of sex chromosomes: a lone X; three Xs; two Xs and a Y; and one X and two Ys. The abnormalities carry different prognoses: XXYs are males who are usually infertile; single-X females (or females with a partial second X chromosome) tend to be infertile, often fail to develop secondary sex characteristics, are usually of short stature, and often have heart problems; triple-X females tend to be tall and to have behavioral problems; XYY males are just what you would expect: very tall and exceedingly active. Two things unite all the sex-chromosome abnormalities: The affected individuals tend to have learning problems and intelligence just below average, albeit in the normal range; and
fetuses identified as having a sex-chromosome abnormality are usually aborted—a twenty-year study of prenatal testing in the United States showed that between 1983 and 2003, 60 percent of such pregnancies ended in termination. Presumably, at least some of the decisions are attributable to a general discomfort with abnormalities, especially ones that have some relationship to sex and gender. But the weeding out of these fetuses is most certainly a form of selecting for intelligence.

  “Nobody knows,” objected Verlinsky. “There is definitely the biggest percentage of the triple X in the psychiatric institutions.” But selection for mental health, with its perpetually shifting definition, seems an even more precarious proposition than selection for intelligence.

  Preimplantation genetics skirts the issue, in a sense. Chromosomal abnormalities are usually spontaneous, not hereditary, which means that a set of half a dozen to a dozen embryos might contain several normal ones and one or a few with chromosomal abnormalities. Most of the abnormalities would be incompatible with a normal pregnancy—these would be embryos that, under natural conditions, either would not have implanted or would have been spontaneously aborted—but in any case, a couple going through in vitro fertilization would never have a reason to choose to transfer, say, an XXY embryo, which might have occurred naturally and would, if it successfully implanted, develop into an overweight, infertile, and intellectually rather slow male, over a normal healthy one.