CHAPTER 11
Are the Ledas Really
Genetically Identical?
PAUL: There’s nine of you.
SARAH: No! There’s only one of me.
—“Parts Developed in an Unusual Manner,”
season one, episode seven
Several of the Ledas in Orphan Black—Alison, for example, in “Variation Under Nature” (season one, episode three)—say that they are genetically identical. But that claim is not 100 percent true.
How can that be? Isn’t having identical genes what being a clone means? In somatic cell nuclear transfer, or cloning, the genes in an egg’s nucleus come from a single source that forms the embryo of a future human clone.
We’ve already discussed one important genetic difference in the Ledas, as indicated by the show itself: the unique DNA tag, added by scientists at the time of cloning, by which each clone can be identified. But there are other ways in which a clone ancestor’s genes are not reproduced exactly, or expressed in exactly the same way.
WHAT CLONING CANNOT REPRODUCE
To begin with, two embryos with the same DNA will always, atomically, reveal minor variations. Atoms combine to form molecules that in turn compose enzymes and proteins. For example, according to most chemists, the probability that any two hemoglobin molecules (the protein in red blood cells) in a human body are the same is close to zero. So even though the greater gene structure of two identical clone embryos would be very similar, at the molecular level there would already be differences.
The probability of any two cloned humans being identical down to their last cell is even lower, because the probability of any two things being exactly identical drops further as those things’ complexity increases. When the jump is made even just to the cells that molecules form, much less the bodies composed of those cells, complexity jumps exponentially.
As New York Times science writer George Johnson explained:
Even cloned cells, with identical sets of genes, vary somewhat in shape or coloration. The variations are so subtle they can usually be ignored. But when cells are combined to form organisms, the differences become overwhelming. A threshold is crossed and individuality is born. Two genetically identical twins inside a womb will unfold in slightly different ways. The shape of the kidneys or the curve of the skull won’t be quite the same.
He does note, though, “The differences are small enough that an organ from one twin can probably be transplanted into the other.”
MORE GENETIC INPUTS
In addition to these differences on the molecular side, there are differences in a cloned embryo’s actual genes, depending on the egg into which the nucleus is implanted.
An embryo’s genes do not come just from the implanted nucleus. As noted in chapter six, the egg itself contains mitochondria, the energy source of cells, and inside these mitochondria are a small number of genes. Although mitochondrial DNA accounts for less than 1 percent of the resulting person’s overall genes, such a contribution so early in life can make a big difference later as an adult. It is like a child growing up with or without fluoride in his or her drinking water; the former can result in almost no cavities for life.
There’s also the issue of gene activation. In a female embryo, there are two X chromosomes, one inherited from each parent (or, in the case of a clone, one from each of her ancestor’s parents). Early on in female embryonic development, each cell randomly inactivates one of the two X chromosomes: About half of the cells inactivate the maternally derived X and about half, the paternally derived X.
Once a cell inactivates a particular X, that X remains inactivated in all cells descended from it via mitosis. But because the population of cells is not enormous at the time that chromosome inactivation occurs, the resulting distribution of cells inactivating the maternal X and those inactivating the paternal X is not always 50:50. So even in the Ledas, whose X chromosomes are identical, we would see differences in activation. One Leda might express the maternal X in 70 percent of her cells and the paternal X in only 30 percent, while another expressed the maternal X in 60 percent of her cells and the paternal X in 40 percent.
Something similar happens with the other twenty-two chromosome pairs, as well. For each gene on a chromosome, humans have two alleles, or gene variants. Because of something called genetic imprinting, one of those two alleles is sometimes not expressed. For example, a paternal allele can be imprinted and suppressed, so only the maternal allele is expressed. So cloned embryos start to differ from each other very early on.
All these small differences in early embryos caused by genetic imprinting, combined with the presence of different mitochondrial genes from different eggs and, in females, chromosome inactivation, could account for surprisingly significant differences in hair color, complexion, height, and even personality—creating, in the case of the Ledas, many radically different people from Kendall Malone’s genes.
Even with cows created from the same cloned embryos, the model that geneticists use to predict similarity in milk production forecasts only a 70 percent match in taste and quantity. And human identity, with many more potential environmental inputs, is much more complex than cow’s milk.
Sarah Manning’s Four Mothers
There are four women who might justifiably call Sarah Manning their daughter: Amelia, the surrogate mother, the African American woman who gestated her; Mrs. S, Siobhan Sadler, the raising mother, the woman who nurtured Sarah from infancy to adulthood (and who, in an act approaching sainthood, totally uprooted her life and moved from Ireland to North America to protect Sarah and Felix from unknown enemies); Kendall Malone, the major biological mother, from whose cells Sarah was cloned; and finally, the minor biological mother, the woman whose egg was used to host the nucleus of the ancestor’s nucleus, whose identity we do not yet know.
Which one of these four women gets to call herself Sarah’s “real” mother? Asking the question this way is really just asking which mother is most important, or rather, which element of mothering is most important. From the major and minor biological mothers come the genetic components of who Sarah is; from the surrogate and raising mother, the nurture to the others’ nature. All four elements are necessary. Our societal definition of mother assumes one woman will be responsible for all four of these, but that is certainly not the case for many children—not only clones like Sarah and her sestras.
Perhaps the most tactful conclusion is to say that each of the women were contributing mothers and mothers in a special way.
THE ROLE OF EPIGENETICS
The most substantial way in which the Ledas differ is explained by epigenetics. What is epigenetics? In every human body, there is a layer of proteins called histones that wrap DNA; this protein layer is called the epigenome. This wrapping carries chemical tags that tells genes when to turn on or off. How tightly or loosely batches of DNA are wrapped in the epigenome shapes the physical structure of the genome, activating some genes and shutting down others.*
While the underlying genetic base of all the Ledas is the same, inevitably their individual epigenomes must also vary, because the epigenome is modified by events in one’s environment. So, for example, whether certain genes of a six-month-old fetus are turned on, and then expressed, depends on things like how the mother eats, her stress level, and whether another fetus inhabits her womb.
Another, maybe better way of putting this is to say that our epigenomes have evolved over millions of years to allow our genomes to respond to the challenges of survival and reproduction in varying surroundings, by expressing the best underlying genes for a specific environment. (A rigid, one-way-only method of gene expression might have doomed humans, who live in sometimes radically changing environments.)
So again, small differences during the formation of the embryo, during gestation, and during the first two crucial years of life, as well as when hormones flood the body during the teenage years, could easily lead to adults who share the same underlying DNA and genes appearing as different as the sestra clones in Orphan Black.
For example, the Ledas seem to have different textures of hair. Also, there may be biochemical reasons why the Ledas differ in susceptibility to addiction. We know Alison has such a problem and so does Sarah. But it does not appear that Rachel or Cosima or Krystal do.
Some of the most exciting research in biology today concerns epigenetics and a version of “self-evolution”— though not of the sort promoted by Orphan Black’s Neolutionists! This self-evolution concerns what individuals can do to turn on or turn off telomeres, the tips of chromosomes that shorten and thereby age our cells. A ton of research has been done on this topic, and thousands of anti-aging claims have been made, but the distillation of all the research is that two things are good for telomeres in mice and also good for humans: green tea and red grapes (and to a lesser extent, red wine). In other words, drinking green tea and eating red grapes can modify the way your underlying genes are expressed. Perhaps red grapes and green tea activate cancer-suppressing cells or help telomeres stay long. Whatever the mechanism, they seem to have a healthful influence on one’s inherited genes (at least, enough of one that I’ve switched from soda to green tea and from green grapes to red ones).
Almost all other claims about anti-aging schemes fail except one: severe caloric restriction. Such a “survival diet” seems to turn on reserve genes that we’ve inherited for surviving famine and catastrophe. (We don’t know the exact mechanisms here, just that it works with caged monkeys, who, when starved, live much longer.) The obvious problem, however, is that few people want to live on 1,800 calories a day, much less a low-fat, non-dairy, vegan diet of mostly fruits and vegetables. But the impact of the survival diet does illustrate epigenetics: how environmental stresses (including ones we choose voluntarily) can turn on hidden genes and turn off others.
DELAYED AND CONJOINED TWINS
The late, renowned Harvard biologist Stephen Jay Gould, who is known for his attention to the complex interactions between heredity and environment, once claimed that some living, identical human twins are more identical than cloned humans would be. This is because, for two people to be identical, it would require not only an identical genotype inserted into an enucleated egg, but also the same inheritance of mitochondria in the cytoplasm of that egg, the same womb and exposure to the same unusual events in the womb (e.g., alcohol consumption, falls), and the same parents, in the same geographical place and time. (As Gould asked in a Natural History article, “Does anyone believe that a clone of Beethoven would sit down one day to write a Tenth Symphony in the style of his early-nineteenth century forebear?”)
Even in cases where the mother is the same, differences in her behavior and environment during gestation make a difference. As I have argued elsewhere, the best way to think about a person originated by cloning is as a delayed twin of an ancestor. Delayed twins are actually something that has happened in reality many times, using assisted reproduction. One of two identical human embryos is gestated to birth by a woman and then, sometimes as long as seven years later, the twin is similarly gestated to birth, giving the firstborn a much younger twin. And as with the Ledas, the environmental differences during pregnancy and beyond always substantially alter the final phenotype of the second twin.
Even in the case of conjoined twins, who originate from the same zygote and share both the same womb and exactly the same environment for life, two people with the same genome sometimes manifest very distinct personalities as adults. Take, for example, the original conjoined twins Eng and Chang, who were born joined by a thick mass at their chests and were never separated. Amazingly, one was a morose alcoholic, and the other, a benign and cheerful man. The two were married to different women and had separate houses in the rural Appalachian mountains of North Carolina. They alternated houses every other week, fathered between them twenty-one children, and lived to the age of sixty-three.
Like Eng and Chang, the famous Tocci twins had different personalities. Like Eng, Giovanni Tocci drank beer in considerable quantities, while Giacomo did not like beer and preferred mineral water. (The Tocci twins had separate livers and circulation; Eng and Chang shared a liver.) Giovanni was introverted and fond of sketching; Giacomo was an extrovert, a big talker, and also had a volatile personality (if he found some fault in Giovanni’s sketch, he would kick the drawing off “his” knee). Similarly, the conjoined twins Abigail and Brittany Hensel, who share a common body below the neck, feel hungry and sleepy at different times, sometimes get different grades on exams, and have different personalities, with Abigail describing herself on Facebook as “girly” and “outgoing,” whereas Brittany describes herself as “not too girly” and “shy.”
If conjoined “identical” twins can have such different personalities, just imagine how different two originations from the same genotype have the potential to become! When identical nuclei are inserted into different eggs, and the resulting embryos are gestated by different women, adopted by different families, and grow up in different cultures or times, the “identical twins” will differ substantially.
VARIATIONS ON A CLONAL THEME
Was it dramatic considerations or scientific facts that drove the creators of Orphan Black to differentiate the various clones as widely as they did? Only they know. But those differences are far from scientifically impossible. While Alison’s claim that the clones are genetically identical is somewhat correct, that does not mean that their phenotypes—the embodied expression of those genes—are identical. In resisting genetic reductionism, Orphan Black offers a valuable lesson in epigenetics to all of us.