Blood Matters

by Masha Gessen

  An organization like Dor Yeshorim sets its limits at life-threatening or extremely debilitating early-onset diseases that are inherited through a recessive gene. The logic is clear: One needs grave reasons to interfere with a marriage, and a disease that is not particularly severe, or one that sets in later in life—by which time treatment may be available—is just not grave enough. Testing for dominant disease-causing genes would be unfair because carriers, under the Dor Yeshorim system, would be marked as unmarriageable.

  Preimplantation testing demands a different set of rules. There is no reason to exclude dominant diseases. Is there reason to exclude late-onset diseases such as hereditary breast cancer? I asked Verlinsky whether he would undertake in vitro fertilization for the purpose of weeding out embryos affected with my mutation. “Sure,” he answered. “It’s a predisposition, it’s high risk, and why do you have to give your child the same worries you have?” Seriously, why would I consider saddling a daughter of mine with the nighttime fears, the obsessive medical examinations, or, worse, the surgeries, or, worse yet, the torturous treatment for breast or ovarian cancer? Any parent wants her children to grow up as free of worry as possible—and especially to be free of the fears that plague the parent. The thing with in vitro fertilization is, the child or children are theoretical—few of us are capable of thinking of eight cells in a dish as a human life—while the genes, and the risks they carry, have names, identities, and tangible consequences. Weeding out any embryo with impaired chances for turning into a healthy, long, and successful human life is easy and painless by most people’s ethical standards.

  For those whose beliefs hold an embryo to be a human life, there is Verlinsky’s method of testing the chromosomes shed by the maturing oocyte. Even German law allows this method. It is not fool-proof—in particular, it cannot weed out any genes on the father’s side, which makes it possible to pass on dominant disease-causing genes, and it cannot catch chromosomal errors that occur at conception—but it is effective in preventing most conditions.

  The more stringent one’s ethical demands, the more expensive it is to meet them. The economic hierarchy is clear: Amniocentesis, which can lead to a second-term abortion, is cheaper than chorionic villus sampling (roughly a thousand versus fifteen hundred dollars), which forces the decision to terminate a pregnancy into the first trimester and is in turn cheaper than preimplantation genetics (roughly ten thousand dollars for the entire fertilization procedure), the cost of which is raised further by testing the polar bodies discarded by the oocyte. For more than twenty years of its existence, chorionic villus sampling has remained an expensive procedure limited to the moneyed and the informed, but in vitro fertilization, at least in countries like the United States and Israel, is fast trickling down to the insured masses. Most of Verlinsky’s early diagnostic work was supported by research grants; now his research is supported by insurance fees paid for in vitro fertilization. With parents getting older and increasingly impatient, in vitro fertilization is on its way to becoming the standard of care. That means only the uninsured will have abortions—or children who carry genetic abnormalities.

  ***

  The Reproductive Genetics Institute’s Web site has a list of single-gene disorders for which an embryo can be screened. The list is alphabetical, and the first condition on it is achondroplasia, a bone-growth disorder that results in very short stature and disproportionately short limbs and large head. There are sound reasons for wanting to avoid passing on achondroplasia: The pregnancy and especially the birth can be very complicated, and life for extremely short people can be difficult. Each disorder on the list is a hyperlink. I clicked on achondroplasia and landed on the Web page for Little People of America. It opened with what looked like a family picture: a man, a woman, and three children with achondroplasia, all hugging and looking very happy.

  I remembered a conversation I had almost twenty-five years ago. It concerned a news article about a group of scientists who claimed to have determined that homosexuality is genetic. I thought it was interesting, and vaguely affirming. My first girlfriend, who read the article with me, was appalled. “There is nothing like being the last of your kind,” she said. I imagined Little People of America knew that feeling.

  Every now and then a couple will ask Verlinsky and his associates to help them have a baby with a congenital abnormality. Several couples, said Verlinsky, had come in wanting to have a child with Down syndrome to provide companionship for an older affected sibling. Verlinsky had refused. Others had asked for congenital deafness syndrome or achondroplasia. Verlinsky had always refused: “Our role is to diagnose disease and avoid it, not to create disease.”

  Verlinsky could not have taken a different position—both because he runs a medical institution (though he is not a medical doctor) and because of the legal climate that is taking shape in the United States and some other Western countries. Since the late 1970s American courts have usually awarded financial damages in so-called wrongful-birth lawsuits, directing doctors to pay the parents of children born with birth defects that could have been identified or predicted during the pregnancy. Some people, the legal logic goes, should never have been born. The courts have stopped short of saying that some people should not be alive—they have generally rejected so-called wrongful-life lawsuits, where the plaintiffs are disabled children themselves—essentially creating a grandfather clause for the existence of people with congenital defects.

  But if it is wrong to enable the birth of a child with abnormalities, is it always right to enable the birth of a healthy child? In the whole field of preimplantation diagnostics, there is probably nothing that scares people as much as so-called spare parts babies, whom professionals in the field prefer to call “designer babies”—children born to serve as donors for an ill sibling. The first such child, Adam Nash, was born in August 2000 with the help of Reproductive Genetics Institute. Stem cells from his umbilical cord were transplanted to his six-year-old sister Molly, effectively curing her Fanconi’s anemia, a fatal bone-marrow disorder. Over the course of the following six years, about fifty more designer babies were born, about a dozen of them conceived at the Reproductive Genetics Institute, but the controversy over the commodification of human life did not quiet down.

  Neither Verlinsky nor Kuliev had much patience for discussing the ethics of creating designer babies. “Usually families spend years looking for an identical donor,” said Kuliev. “Often the child is dead before they can find the donor. Maybe somebody is lucky, but they can never be 100 percent identical: It’s more or less close, and it gives some side effects. And this is 100 percent identical. There was a spectacular case, diamond-blackfan anemia—you can imagine the misery. Now that child no longer needs any supplementation. And that Molly, she is going to school. And Adam is five, and he is fine.”

  ***

  Of all the diseases in the world, Kuliev had to mention diamond-blackfan anemia. Five years earlier, distant relatives of mine came to Moscow from their far northern town because they had been referred to the big children’s hospital here. Their daughter, Diana, was a month older than my daughter, Yael. They stayed with us most of the summer: The girls played together, had babbling conversations of sorts sitting in their high chairs, and sometimes struggled for control over toys. Diana was a bit thinner and less than an inch shorter than Yael, but, on the whole, she did not seem unhealthy. But then every couple of weeks she would spike a fever and grow weak and helpless. Then she would get a blood transfusion that brought her back to life. It was a hellish roller coaster, but it did not prepare her parents or anyone else for hearing that the child had a fatal disease. She was diagnosed with diamond-blackfan anemia, a disorder in which the bone marrow fails to make red blood cells. Only about six or seven hundred people worldwide were known to be living with it. They lived from transfusion to transfusion. About half of them could get some help from corticosteroids, which stimulated the bone marrow, but at a great cost: The steroids made their bones brittle, ultimately co
ntributing to the body’s overall weakness. Some people lived into their twenties; most died earlier.

  After Diana’s parents had the diagnosis confirmed, they returned to their hometown. Diana was lucky: Corticosteroids worked for her. They made her bloated and stunted her growth—by the age of five she was almost a head shorter than Yael—but they reduced her need for transfusions. She was a happy, smart girl, a born dancer. Her parents, who were in their early twenties when she was born, sometimes tried to talk to doctors about the possibility of having another child, and of perhaps obtaining a bone-marrow transplant for Diana. The doctors tried to discourage them: An outside donor would be hard, probably impossible to find, and a second child might also be born with the disorder. How would they take care of two severely ill children?

  After I met with Kuliev and Verlinsky, I wrote Diana’s mother a short, dry e-mail message, explaining that I had visited a place where designer siblings for children with Diana’s disorder had been conceived. She wrote back the next day. There was no anguish, no hand-wringing over the ethics and the difficulties of having a designer baby. In fact, there was no time to waste. There was only a chance to save her daughter.

  Acknowledgments

  AS I WORKED on this book, I posted chapters to a blog that was read by a small group of people, some of whom are my friends while others I had never met. They caught errors (some of the readers were, fortunately, trained in the fields into which I had carelessly ventured), pointed out logical inconsistencies, suggested edits, and generally kept me company while I worked. I owe many thanks to Ellen Todres Gelfand, Nikolai Klimeniouk, Ilya Kolmanovsky, Mark Schoofs, who actually took the time to edit entire chapters, and Lena Shagina. Katya Krongauz on several occasions saved me from collapsing under the anxiety of producing this book. As always, my father and brother, Alexander and Keith Gessen, were among my first and most important readers. And many thanks to my amazing agent, Elyse Cheney, and Becky Saletan, the most thoughtful of editors.

  Glossary of Key Terms

  Allele. A sequence of DNA code that occupies a given position in a chromosome.

  Autosome. A non-sex chromosome. People normally have twenty-two pairs of autosomal chromosomes. Each pair contains two copies of every gene, one inherited from the mother and one from the father.

  Carrier. Someone who has a single copy of a gene that determines a recessive trait. A child of two carriers has a 25 percent chance of inheriting the gene from both parents and therefore exhibiting the trait or being affected with the disorder.

  Chromosome. The building block of the genome, a single DNA molecule that contains many genes, regulatory elements, and other nucleotide sequences. People normally have one pair of sex chromosomes (XX in women and XY in men) and twenty-two pairs of autosomal chromosomes.

  Complex trait. A trait whose expression is dependent on the presence of more than one gene.

  Consanguineous marriage. Unions between people who are second cousins or more closely related. The practice, common in a number of closed populations around the world, increases the risk of children who are affected with recessive conditions because the children are certain to be homozygous in a significant part of the genome.

  Dominant trait. A trait caused by a single copy of a gene. For example, brown eye color is a dominant trait: A person who inherits a copy of the gene from either parent will have brown eyes. The genes that are linked to Huntington’s disease or hereditary cancers are also dominant.

  Endogamy. The practice of marrying exclusively within a social, religious, or ethnic group.

  Eugenics. A social philosophy pioneered by Sir Francis Galton in the late nineteenth century. Its adherents advocate aiding the human race through improving its heredity. The eugenics movement was very strong in the United States in the first half of the twentieth century, leading to the adoption of sterilization laws in a number of states and the implementation of immigration policies aimed at selecting migrants with the best hereditary characteristics. The Nazi regime in Germany relied on eugenics to justify many of its policies, rendering the very concept of eugenics suspect. Many modern practices, however, follow the spirit of Galton’s philosophy. These include premarital genetic testing and prenatal and preimplantation testing.

  Exon. Any part of a gene that is actually transcribed to the final messenger RNA.

  Gene therapy. Treatment based on inserting genes into a human organism to replace a deleterious allele with a functional one. Several techniques of gene therapy have been tried since 1990, some of them successfully, but all methods are still considered highly experimental.

  Genetic drift. The idea that chance is primarily responsible for a given allele’s becoming more or less common in a population. The smaller the population, the greater the potential influence of genetic drift. Many geneticists believe genetic drift is the primary reason small closed populations may have a high prevalence of a genetic condition rarely found elsewhere or may entirely avoid a genetic condition that is considered common in other populations. For example, the Amish of western Pennsylvania have a high prevalence of the rare disease glutaric aciduria Type 1 but have zero incidence of cystic fibrosis, the most common genetic disorder in the world. A corollary to the concept of genetic drift is the concept of selective advantage.

  Genome. All the hereditary information of an organism as encoded in DNA.

  Haplotype or haploid genotype. A set of alleles that are transmitted together. Certain haplotypes are believed to pinpoint a person’s geographic and/or ethnic origins.

  Heterozygous. Possessed of two different copies of an allele.

  Homozygous. Possessed of two identical copies of an allele.

  Mendelian inheritance. The mechanism of genetic inheritance described by the nineteenth-century Moravian monk Gregor Mendel. His two laws are the cornerstone of the modern understanding of genetics. Mendel’s first law holds that alternative versions of genes explain variations in inherited characteristics, that an organism inherits two alleles for each characteristic, and that if the alleles differ the one accounting for the dominant trait will be fully expressed. Mendel’s second law holds that different traits are inherited independently from one another.

  Mitochondrial DNA. DNA that resides outside the cell nucleus and is inherited from the mother.

  Polymorphism. A mutation—a distinct form of an allele—that is present in at least 1 percent of a given population.

  Recessive trait. A trait expressed only in the presence of two copies of a gene. Blue eye color is an example, as are a variety of disorders that occur in children born to two carriers.

  Selective advantage. The concept at the root of the theory that natural selection, not genetic drift, is the primary reason an allele becomes common in a population or gets entirely washed out. Mutations that are deleterious in homozygotes, the theory holds, are beneficial to heterozygotes—confer a selective advantage on them—hence the allele is carried forward through the generations. An example is the mutation that causes sickle-cell anemia in those who inherit two copies of the mutant gene but, it is believed, helps protect carriers (those with just one copy) from malaria.

  Stem cell. A sort of cell that has the ability to renew itself and to differentiate into any number of kinds of cells.

  X-linked. Mutations that reside on the X chromosome. Females have two X chromosomes, inherited in equal part from the mother and the father, and males have one X chromosome, inherited from the mother, and one Y chromosome, inherited from the father. If a woman carries an X-chromosome allele with a deleterious mutation, she herself will not be affected, nor will her female children: They all have another, healthy copy of the allele, inherited from the father. Male children, however, will invariably be affected, since they are certain to inherit the X chromosome from the mother and will not have a healthy copy of the allele. Examples of X-linked disorders include a form of hemophilia and “bubble boy” syndrome, a severe congenital immune deficiency.

  Notes on Sources

  CHA
PTER 1: MY MOTHER’S FATAL FLAW

  The search for the breast cancer gene is described in Kevin Davies, Michael White, Breakthrough: The Race to Find the Breast Cancer Gene (John Wiley & Sons, 1996).

  On lifetime risk for mutation carriers and on earlier age of onset for successive generations: Mary-Claire King, Joan H. Marks, Jessica B. Mandell, The New York Breast Cancer Study Group, “Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2,” Science 5645 (October 24, 2003): 643–646.

  The function of the BRCA genes: K. Yoshida, Y. Miki, “Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage,” Cancer Science 11 (November 2004): 866–871.

  Nonviability of BRCA homozygotes: Srdjan Denic, Lihad Al-Gazali, “Breast cancer, consanguinity, and lethal tumor genes: Simulation of BRCA1/2 prevalence over 40 generations,” International Journal of Molecular Medicine 10 (2002): 713–719.

  Some cancers in mutation carriers are more aggressive than in noncarriers: M. O. Nicoletto, M. Donach, A. De Nicolo, G. Artioli, G. Banna, S. Monfardini, “BRCA-1 and BRCA-2 mutations as prognostic factors in clinical practice and genetic counseling,” Cancer Treatment Review 5 (October 2001): 295–304.

  Male breast cancer in mutation carriers: N. Wolpert, E. Warner, M. F. Seminsky, A. Futreal, S. A. Narod, “Prevalence of BRCA1 and BRCA2 mutations in male breast cancer patients in Canada,” Clinical Breast Cancer 1 (April 2000): 57–63.

  On the risk of developing cancer for mutation carriers: A. Antoniou, P. D. P. Pharoah, S. Narod, H. A. Risch, J. E. Eyfjord, J. L. Hopper, N. Loman, H. Olsson, O. Johannsson, Å. Borg, B. Pasini, P. Radice, S. Manoukian, D. M. Eccles, N. Tang, E. Olah, H. Anton-Culver, E. Warner, J. Lubinski, J. Gronwald, B. Gorski, H. Tulinius, S. Thorlacius, H. Eerola, H. Nevanlinna, K. Syrjäkoski, O.-P. Kallioniemi, D. Thompson, C. Evans, J. Peto, F. Lalloo, D. G. Evans, and D. F. Easton, “Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: A combined analysis of 22 studies,” American Journal of Human Genetics 72 (2003): 1117–1130.