CHAPTER 5 “Ipsa Scientia Potestas Est”

The Scientific Pedigree of Cloning

To understand why we feel so strongly about human clones, you should understand the earthshaking furor that has surrounded every advance in biology over the last half century. Reproductive medicine has been especially controversial; Luddites have challenged every breakthrough. As you will see, it’s both sad and hilarious how often the Chicken Littles of the world claim the sky is falling over even the most modest advance in helping people have children. (It’s also amazing how often scientists try to become famous by faking their results.)

One of the most startling aspects of the modern science of cloning may be how everything is politicized, which is something Orphan Black gets right in spades. Dr. Aldous Leekie and pro-clone Rachel Duncan boast that the Dyad Corporation has lobbied Congress and the Supreme Court to create laws favoring biotechnology and their interests. Similarly, it is no accident that the main religious group opposed to cloning is the Proletheans; their name refers to pro-life movements around the world that abhor abortion and have a very expansive view of what counts as murder of a person, including a one-day-old embryo (and hence they see IUDs and morning-after pills as instruments of murder). Nor is it an accident that both the Leda Orphans and the Dyad Corporation see the Proletheans as their enemy, because the traditional Proletheans, led by Tomas (pre-Henrik), oppose both.

The Latin title of episode five of season two, “Ipsa Scientia Potestas Est,” taken from the writings of scientist and philosopher Francis Bacon, loosely translates as “knowledge itself is power.” Every issue in bioethics, every breakthrough in science, and every setback in medicine has a pedigree. To understand a tree in the present, you need to understand who planted the seed and the placement of its roots. This is truer of human cloning than any other issue of its kind. Likewise, to understand cloning and the public’s reactions to it, as well as why Dyad and Topside are so interested in this technology, we first need a little background about assisted reproduction, the history of (and early false claims about) cloning, and stem cells. Along the way, we will also touch on some controversies that these issues introduced.

ASSISTED REPRODUCTION

To understand cloning, you first need a little knowledge about assisted reproduction. Hard as it might be now to believe, people in the early 1970s did not distinguish between helping to create a natural child by combining sperm and an egg in a lab dish outside the womb before inserting the embryo into a woman’s uterus—a form of assisted reproduction common today that has helped create millions of wanted babies—and cloning a person from someone else’s cells. As Richard Brown, father of the first child produced by in vitro (“in glass”) fertilization, said, the former is just “helping Nature along a bit”—something very different indeed from Brown cloning a copy of himself from his own cells.

After Brown’s daughter Louise was born in 1978 through the work of scientists Patrick Steptoe and Robert Edwards, her birth was condemned by not one but two Nobel Prize-winning scientists: Max Perutz, who won the Nobel Prize in Chemistry in 1962 and worked at Cambridge University, and James Watson, who in 1962 shared the Nobel Prize in Physiology or Medicine for his work on DNA. Watson predicted that dangerous events would follow Louise Brown’s birth. He feared that future in vitro fertilizations would lead to deformed babies who would then have to be raised by the state in custodial homes, or might even be victims of infanticide.

In all the books in which Watson has been featured, including his own famous memoir The Double Helix, he is shown to be arrogant, obsessed with hard science, and narcissistic. As an example, for decades Watson scorned fellow Harvard biology professor E. O. Wilson—the founder of sociobiology and a leading environmentalist—because he considered Wilson’s work soft and mushy, not real science like his own. Watson also notoriously took too much credit for discovering the double helix and gave virtually no credit to fellow scientist Rosalind Franklin, toward whose work he is widely regarded as having had sexist attitudes. Perhaps surprisingly, Watson said decades later that he regretted his premature, impulsive condemnation of IVF.

CLONING

Before Dolly the sheep was cloned, the field of cloning was rife with fraud. For example, in 1978 writer David M. Rorvik claimed in his book In His Image: The Cloning of a Man, that Max, a millionaire industrialist, and a host mother, Sparrow, had gestated a child from an embryo clone of Max. In 1982 a federal judge in Philadelphia ruled that his book was “a fraud and hoax.”

When an egg is fertilized, its cells have the potential to become any type of cell in the body; as those cells begin dividing, the new cells differentiate, becoming liver cells or bone cells or tissue cells, to build the fetus. These undifferentiated cells are referred to as stem cells, first because they can regenerate themselves in a way that most cells cannot and second because all other types of cells stem from them. Hence, they are the magic that makes cloning possible. (We’ll talk further about stem cells, and their different varieties, below; see “The Definition of Cloning.”)

If you looked in physiology and cell biology textbooks from 1996 or earlier, you would find a “law” of biology stating that differentiated cells could not be returned to their primordial, undifferentiated, pluripotent state. That impossibility seemed such an ironclad fact that many promising biologists had fled old-fashioned embryology for the more promising field of molecular biology (although the American ban of federal funding for research on human embryos also hurt).

Returning differentiated cells to a pluripotent state was once the Holy Grail of developmental biology because finding these stem cells in the body was extremely difficult; when they were found, they were few and hard to grow more of. If you could reverse the process of cell differentiation, then you could create gobs of pluripotent cells that could then be teased to develop any differentiated cells you required—say, to build a new liver (or a clone)—that could precisely match each patient’s body and needs.

Remarkably, it was precisely that “law” about cell differentiation that Ian Wilmut—building on the work of British scientist John Gurdon and Danish scientist Steen Willadsen—overturned when creating Dolly. Back in the mid-1960s, Gurdon laid the groundwork for later stem cells and cloning research by transplanting frog-egg nuclei and, although he never used the word clone, creating the first functional embryo via cloning. He was followed by Willadsen, an apparently brilliant if contrarian and reclusive guy who, instead of memorizing stuff in biology textbooks, set out to prove them wrong. A Danish scientist working in Texas, he successfully created the first mammalian embryos by transferring nuclei of differentiated cells into eggs of cows in which the previous nucleus had been removed; his embryos even survived to become fetuses. However, he didn’t pursue this work and was shy of publicity.

Wilmut went a step further, showing definitively that a differentiated cell from a lamb’s udder could be the source of a nucleus that, inserted into an enucleated lamb egg, could produce an embryo that grew to a living, breathing adult lamb—Dolly.

The Definition of Cloning

Cloning is an ambiguous term, even in science, and may refer to molecular cloning, cellular cloning, embryo twinning, or somatic cell nuclear transfer.

In molecular cloning, strings of DNA containing genes are duplicated in a host bacterium. In cellular cloning, copies of a cell are made, resulting in what is called a cell line, a very repeatable procedure in which identical copies of the original cell can be grown indefinitely. These senses of cloning match the popular sense of the term—exactly reproducing or copying a thing in an easy, repeatable way—but are not what we mean when we talk about cloning an animal or human being.

In embryo twinning, an embryo that has already been formed via sexual reproduction is split into two identical halves. Theoretically, this process could continue indefinitely, but in practice this twinning occurs only a limited number of times. This is also how we get identical twins.

(One thing of interest to Orphan Black viewers: Embryos divide and produce identical twins, as with Helena and Sarah, far more often than most people realize, meaning that many people have ghost twins in the womb that they never know about, which we’ll talk about further in chapter thirteen. Some biologists speculate that this is because, due to limited resources, only the strongest of these twins is able to survive. Another fascinating fact about embryo twinning: Recall that Henrik discovers that Helena and Sarah, although genetically identical and both gestated in Amelia’s uterus, have organs that are mirror images of each other. So if Sarah’s heart is on her left, Helena’s is on her right. If one is left-handed, the other will be right-handed. This is a real medical condition that happens sometimes with identical twins, called situs inversus.)

Finally, there is somatic cell nuclear transfer, a process in which the nucleus of a differentiated adult cell is implanted in an egg cell from which the nucleus has been removed. If successful, and it often is not, this creates an embryo. This is what John Gurdon and Steen Willadsen had been working on and what Ian Wilmut brought to fruition with Dolly.

Cosima uses these exact words, “somatic cell nuclear transfer, cloning,” when she describes to Scott what Henrik did with the biological material he stole from Ethan Duncan. What biological material did Henrik steal exactly? We are not sure. But we can assume Henrik must have used a nucleus from one of his own cells, put it in an enucleated egg, and then used a surrogate mother on his farm to gestate Abel, his cloned son who dies and whose grave Sarah disturbs while a wounded Mark watches. (As we shall see in the next chapter, given the problems of getting normal primate embryos from somatic cell nuclear transfer, it is realistic that Abel died shortly after birth.)

A variant of somatic cell nuclear transfer called fusion describes a version of this process in which donor cells are put next to an enucleated egg and a tiny electric current is used to “fuse” the two. The electric pulse also activates egg development, and a blastocyst—a pre-embryonic cluster of about a hundred cells or less—results. (This is the type of cloning that was used to produce Dolly.)

CLONING DOLLY

Before his success in 1996, Wilmut had spent years trying to clone just one lamb.

Where others had failed, Wilmut and his team succeeded in cloning Dolly by synchronizing the cell cycle phases of both the donor nucleus and recipient egg cell. During these phases, DNA starts doubling—before mitosis begins dividing cells to form the cell cluster that will eventually become a fetus. When other scientists had attempted nuclear transfer via fusion during this rapidly changing process, mitosis broke down, producing broken chromosomes and, consequently, mutants and defective embryos (this may be why Henrik’s clone, Abel, died). So Wilmut starved egg cells to dormancy, rendering them inactive, and only then inserted a donor nucleus. In this way, he finally got mitosis to continue undisrupted, producing a healthy embryo.

While Wilmut did succeed, his methods were inefficient. He started with 277 sheep embryos, but only 29 embryos lived even a few weeks. These matured into thirteen fetuses, out of which three lambs grew to near birth size. Only one, Dolly, survived. As well, additional clones produced via his techniques have frequently suffered large-offspring syndrome, where the clones are so big that they can’t be birthed normally (a condition that, in nature, can be lethal). This syndrome could be caused by nuclear transfer or by something in the uterine environment or cell culture. The lambs that died shortly after birth, unlike those that did not survive gestation, were, however, chromosomally normal.

The success of Wilmut’s experiment established three important points about cloning:

The genes would not come from both a man and a woman but just one ancestor.
Accordingly, there would be no random mixing of two sets of genes, as occurs in sexual reproduction.
The creation of the embryo would occur, as in most forms of assisted reproduction, outside the womb in a Petri dish.

Wilmut made his claim of being the first person to have cloned a mammal from a differentiated cell cautiously, for two reasons. First, a lot scientists had been skeptical when, two decades before, Steptoe and Edwards first claimed to have created Louise Brown by in vitro fertilization, as in vitro violated similar so-called laws of nature as cloning did. Previously, several scientists had falsely claimed to have done so and had been exposed.

Second, Wilmut knew some people would not want his claims to be true, especially people such as Leon Kass, the arch-conservative bioethicist who, as we saw in chapter two, felt that cloning was against God’s will, repulsive, and, above all, scary. Wilmut’s success, and the specter of human cloning it introduced, galvanized Catholic and conservative Protestant theologians, who vowed not to be surprised as they had been in 1973 by the US Supreme Court’s legalization of abortion; as other scientists tried to clone other mammals and as people speculated about cloning humans, they declared that here was an ethical bright line beyond which society must not trespass.

Wilmut was careful to document his claim; he had living proof of his achievement and he encouraged reporters and other scientists to visit and interact with Dolly. He also encouraged other scientists to duplicate his results.

Dolly was actually born in the summer of 1996, but Wilmut did not announce it until February 1997. Why not? Because he was also being careful about the patents he had filed with British authorities about various aspects of the processes he had used to create Dolly. It wasn’t until his patents were approved in 1997 that he made his announcement.

SENSATIONAL CLAIMS ABOUT CLONING

When Wilmut announced Dolly’s creation and birth via cloning in 1997, many people feared that a human would soon be born the same way. Many politicians then wanted to criminalize all forms of human cloning (even animal cloning). Fortunately, this never happened.

But that was just the beginning of the furor about cloning. Shortly after Wilmut’s announcement, Chicago scientist Richard Seed announced to NPR’s Joe Palca that he would clone himself. Seed was not only a physicist but had also helped found a company that assisted breeders in transferring cattle embryos (the same techniques used in Orphan Black by Henrik Johanssen to harvest Helena’s eggs and then impregnate both Helena and his daughter Gracie).

Richard Seed embodied every trope of the mad scientist. He narcissistically said he wanted to clone himself “as a step toward immortality,” he didn’t feel he needed anyone’s permission to do so, and he seemed unaware of how his actions scared ordinary citizens. Seed’s announcement about human clones being on the horizon alarmed everyone because he had expertise in the field, he had clear motives (narcissism, self-perpetuation), and, worst of all, he looked the part of a Hollywood-cast, elderly, creepy scientist, with his wild beard, huge head with drooping eyes, and disheveled clothes. In reality, Seed wasn’t that smart and wasn’t technically sophisticated in biology, so his fame soon faded—but he’d already kicked off both an international debate and paranoia about human cloning.

Next, a bizarre cult called “the Raëlians” entered the scene and claimed that it, too, would clone a child. This cult was led by Claude Vorilhon, also known as Raël, a former French racecar driver who had almost exclusively female followers living with him and with whom he liked to exercise in the nude. Add religious piety to Raël and you’d get Henrik and his rural compound with lots of young women and their children running around.

Like Henrik, Raël also had some seemingly competent female assistants, especially a biology professor and chemist named Brigitte Boisselier, who became the scientific director of Raël’s company, Clonaid, which, through its mailbox in the Cayman Islands, received deposits from infertile people hoping to clone themselves or a child.

They were far from the only scammers to do this: Cypriot Panayiotis Zavos—whose PhD was in working with turkey sperm—and Italian researcher Severino Antinori also took money from clueless, infertile couples, claiming they could give the couples cloned children in their (largely fake) fertility clinics.

Throughout all this, the public had a hard time determining which claims were legitimate and which were not. The Raëlians in particular were masters of manipulating the media, and Raël and Boisselier appeared on hundreds of television programs. And why not? Every time they appeared on television, they seemed to grow in credibility and more gullible people sent Clonaid money. Even higher-ups in government were fooled. When I testified before Congress in 2001 against making human cloning a federal crime, Raël also appeared at the far end of the table.

In 2002, Clonaid falsely claimed that it had successfully cloned a human baby, whom it had named Eve. Taking it seriously, a Florida attorney asked a judge to appoint a guardian ad litem for Eve and threatened to sue Clonaid, because he feared it would treat Eve as a lab rat. But eventually, this attorney, the media, and everyone else realized that Raël and the rest of these claimants were just media-hungry frauds.

REAL ADVANCES IN STEM CELLS

Although claims of human cloning proved false, there were real scientific advances taking place in a related field: stem cells.

As mentioned in the discussion of cloning earlier, stem cells are primordial, unspecialized cells that help an injured body grow new cells. For example, after blood loss, the body can activate stem cells in the blood to make new blood. In theory, stem cells could be directed to form new bones, neural cells, and cardiac tissue, and to cure sickness. This is the powerful stuff extracted from Kira’s bone marrow that is being used to treat Cosima’s respiratory illness.

Scientists believe that stem cells might be created using the same technique that was used to make Dolly; in fact, the original goal of Ian Wilmut and many others was not cloning, but rather finding a way to create stem cells.

But understanding what stem cells are, what they could do, their many kinds, and how to get them has taken scientists many decades. Before 1998, scientists knew that the human body had some stem cells (mainly in embryos or bone marrow), but they had no easy way to grow them. Then, in what Science magazine called “the scientific breakthrough of the year,” John Gearhart of Johns Hopkins University and James Thomson of the University of Wisconsin discovered how to make something called an immortalized stem cell line using cells originating from human embryos. Essentially, their new scientific process allowed embryonic stem cells of a particular type to be continually produced, like a little biological factory. Previously, such stem cells had to be derived, individually and tediously, from minute amounts of tissue from embryos or aborted fetuses.

ADULT STEM CELLS DISCOVERED

In 2001, some scientists suggested that stem cells already existing in the body might be just as good for medical purposes as embryonic stem cells. Found in blood, bone marrow, and the umbilical cord, they called these adult stem cells, to differentiate them from embryo-derived stem cells. Such adult stem cells become specific kinds of cells more quickly than their embryonic predecessors. Unfortunately, most human organs contain few adult stem cells, not nearly enough to use medically; moreover, adult stem cells are even harder to grow than embryonic stem cells. Indeed, when Gearhart first investigated stem cells in the mid-1990s, he found adult stem cells so rare and difficult to extract that he decided to focus on using embryonic stem cells in his research; his production of an embryonic stem cell line was his means of assuring himself a steady supply.

The biggest benefit of adult over embryonic stem cells was political. Pro-lifers consider a human embryo to be a person, and anything that destroys such embryos is murder. Using adult stem cells in research rather than embryonic ones allowed researchers to avoid controversy.

It is adult stem cells that Sarah allows Delphine and a pediatrician to harvest from Kira’s bone marrow to help Cosima in Orphan Black. It seems as if they are making Cosima better, and we hope they will work. In theory, they could; this isn’t purely speculation. In May 2015, USA Today reported on the alleged recoveries of two legendary heroes of sports: National Hockey League star Gordie Howe and National Football League star John Brodie. After suffering massive strokes, both traveled outside the country for injections of stem cells from aborted human fetuses—a procedure illegal in the United States but permissible in some other places. Brodie went to Russia, Kazakhstan, and Mexico; Howe just went to Mexico. After the injections, each man’s family claimed remarkable recoveries.

PLURIPOTENT STEM CELLS

Biology progresses in fits and starts: two steps forward, one step back. Because it is so much easier to be against progress, so much easier to be a naysayer rather than a yea-sayer, and so much easier to raise alarmist ethical objections than to provide ethics cover, it is sometimes a wonder that any progress occurs in medicine at all.

Thomas Kuhn, in The Structure of Scientific Revolutions, proved that paradigm shifts move science forward, such as from the pre-Galileo belief that the Sun revolved around the Earth to the modern understanding, first forwarded by Copernicus, that the opposite is true. The cloning of Dolly was one such Copernican Revolution in biology.

Another such revolution occurred in 2007, when researcher Shinya Yamanaka of Kyoto University discovered how to use four genes to tell skin cells to revert back to pluripotent cells, or induced pluripotent stem (IPS) cells. In other words, Yamanaka learned how to make a differentiated, somatic cell revert back to a primordial, undifferentiated stem cell—which then could turn into anything. What this Nobel Prize-winning achievement meant, practically, was that medicine no longer required embryonic stem cells, derived from actual embryos, and no longer required eggs from female donors to create new embryos, because these powerful IPS cells eliminated the need for both. We can use IPS cells derived from our own cells as medical therapy for ourselves without the need to create, or destroy, human embryos.

WHAT DOES THE NEAR-FUTURE HOLD?

We don’t know why Topside began Projects Leda and Castor, but in the real world, cloning was only a means to an end, and that end was proving that stem cells could be manipulated to do what scientists needed to use them as the body’s own medicine. This is medicine’s Holy Grail. Why? Because what we all really want is (let’s be honest here!) not to clone ourselves or a relative or Ian Wilmut, but to be able to use cells from our bodies to (choose one): reverse aging, heal severed spinal cords, inject new neural cells into aging brains, and, in general, to become our own individualized fountains of youth.

Anyone allowing us to do this would make billions of dollars and be awarded Nobel Prizes. On the darker side, if such stuff (or the knowledge to make it) actually existed, we can easily imagine that very rich and powerful people, especially those whose loved ones suffered terrible injuries in accidents or from hereditary diseases, might do almost anything—and pay any price—to secure such life-changing biotechnology. It would be a biological Lazarus, capable of staving off death for decades, if not raising the dead.

And we are getting oh-so-close.

As Princeton molecular biologist Lee Silver once wrote, in making fun of past naysayers: “Understanding the true nature of the gene is ‘beyond the capabilities of man,’ they said in 1935; it is impossible to determine the sequence of the complete human genome, they said in 1984; it is impossible to read the genetic information present in single embryonic cells, they said in 1985.” Of course, all these “impossibilities” and more proved possible. With new federal funding under President Obama for the National Institutes of Health, with restrictions largely lifted on embryonic and stem cell research, and with computers assisting biologists with big data at every level, we are in a new dawn of biological revolution, which Orphan Black makes exciting and real.

Cloning, adult and embryonic stem cells, and the new pluripotent stem cells are all actually part of the same new explosion of interest in the nascent embryology of human life: about how changes to incredibly tiny embryos can create huge changes later on; about how to use cells of an existing person to recreate a genotype; and about how, after we are struck down by disease or accident, to tell our bodies to heal.

So let us give Orphan Black a little slack and accept that, somehow, Ethan and Susan Duncan, or Dyad and Topside, have, in the process of their cloning experiments, lucked into something like the biological Holy Grail of regenerative medicine in Helena and Sarah, and now Kira, too. It is an exciting premise and promises great future plots for the show.