In addition to being incredibly entertaining and provocative, the popular Orphan Black series is absolutely teeming with science. From human clones and genetic engineering through to DNA barcodes and genetic patents, here's what you need to know about the science behind the show.

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For the uninitiated, Orphan Black is a conspiracy thriller that stars Tatiana Maslany as several human clones. Uncertain of their true origins, the clones struggle to evade the unscrupulous Dyad Corporation as they try to learn more about their past.

And to the show's credit, the writers — with the help of science advisor Cosima Herter — get much of the science right. There's too much to cover in a single article, so we boiled it down to four main topics: human cloning, genetic engineering, the viability of the show's timeline, and the issue of genetic patenting.

The Prospect of Human Clones

To date, no human has been cloned. The act itself would be illegal, and its consequences – for society as well as the cloned individual – are far from clear. That being said, Orphan Black manages to explore a number of ethical and moral issues by imagining a world where viable human clones are a possibility – and it does it with relatively sound science.

For instance, it is a common misconception that clones are produced in vats, or that they come into being as full-grown adults; Orphan Black allows for more accurate scenarios involving established cloning technologies, which bear a far closer resemblance to in vitro fertilization (IVF) than these fantastical alternatives.

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Cloning is the process of creating a biological copy of an organism. Technically speaking, human identical twins are clones, as are single bacterial colonies. In both cases, multiple individuals share an identical genetic code. In the case of Orphan Black, it appears that Sarah and Helena are twin clones (true sisters born to a single surrogate mother), while the rest of the bunch are clones who were born to an unknown set of surrogate mothers.

Cloning may not exist yet for humans, but it has been performed in both plants and vertebrates. In nonhuman animals, it's done in the lab with a technique known as somatic cell nuclear transfer, or SCNT. It works by combining an enucleated egg (i.e. an egg with its nucleus taken out), and the nucleus of a somatic cell (i.e. any body cell other than eggs or sperm) to make an embryo. When done for reproductive cloning, the process can produce a full-grown organism that's genetically identical to the individual that donated the somatic cell nucleus.

As is well known, the first mammal to be created via SCNT was Dolly the sheep, who was born in 1996 at the Roslin Institute in Scotland.

(Credit: Biotechnology Online)

The cloning of a human would require the implantation of an SCNT-produced embryo in the uterus of a surrogate mother, after which it would go through the typical nine-month gestational period, developing into a living, viable human being.

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Reproductive cloning is highly prone to failure, however. Implanting a somatic cell nucleus is a difficult and complex procedure; and even if an implantation is successfully performed, the subsequent development of the clone is not always guaranteed. Dolly represented the 277th attempt at sheep cloning, and she died soon after reaching the age of six – about half the normal lifespan of a sheep. Autopsy results showed she had been aging prematurely. Similarly, the clones in Orphan Black don't appear to be very healthy – not all of them, at least. By the end of season 2, at least one clone has died prematurely, while Cosima battles polyps in her lung and uterus.

Scientists have thus far been unable to clone certain animals, including chickens and primates, but they are inching closer. Back in 2013, researchers from Oregon Health and Science University developed a SCNT technique for producing human embryonic stem cells. A similar technique was devised a year later, by a team of South Korean researchers. These breakthroughs could eventually lead to therapeutic cloning methods for the production of patient-specific embryonic stem cells. These undifferentiated cells could be used to restore a patient's own tissue, or serve as the building materials for bioengineered organs. As for the cloning of an actual person? Assuming the laws that forbid it can be circumvented, it's probably a matter of when, not if.

Custom-Designed Clones, Built to Order

Not only are the clones in Orphan Black genetic duplicates of one another, some (or all) of them may have had their genomes modified, as well.

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In the episode "Pro-clone," Rachel suggests to Cosima that Sarah's ability to have children is unique. (Sidebar: because Helena and Sarah are monozygotic mirror twins, i.e. they split from the same embryo, it's quite possible Helena can also have kids.) That some clones possess biological abilities the others do not suggests the clones are not exact duplicates of an unknown woman, but copies that have been genetically modified in unique ways. We already know that each clone's DNA is inscribed with a barcode designating them as property of the Dyad Institute; perhaps certain clones were also deliberately engineered by Project Leda (in the show, the initial effort to clone humans to be infertile) as a form of reproductive control.

There's also the possibility that the infertility was caused by the same disorder causing polyps to grow in the clones' uteri. But assuming the clones were intentionally modified to be sterile, there are two ways their infertility could have been engineered. The first involves what is called "germline" gene therapy, the second so-called "somatic cell" gene therapy. (NB: Neither method would have existed in the 1980s – more on that below.)

If the Orphan Black clones were modified after they were born, it was probably through what is known as somatic gene therapy, which works by introducing modified genes into non-reproductive cells of the body, and therefore cannot be inherited by the offspring of a treated patient. This technique can be used to treat a number of severe genetic disorders, including various immunodeficiencies, hemophilia, and cystic fibrosis. In the case of Orphan Black, however, the genes would be introduced to enable a genetic disorder, in the form of infertility.

Alternately, the Project Leda scientists could have edited the genome during the cloning and/or in vitro stage, in a manner similar to a new technique by which the genetic information of three parents is used to replace faulty mitochondrial DNA in an egg or embryo with healthy DNA from a female donor. Perhaps a similar technique involving CRISPR/cas9 (a recently developed, high-precision gene-editing technique) was used to modify these clones at an early stage in their development. Having said that, these so-called "germline" therapies, (which don't exist yet for humans, but will soon, unless a recent call for a moratorium is honored), would be heritable – which seems pointless, when the thing you're trying to induce is infertility.

To engineer infertility in the clones, the Dyad scientists would have isolated the requisite target gene (or genes) responsible for infertility. For example, they could have triggered any number of ovulation disorders or uterine/cervical abnormalities. Another possibility is that they somehow disrupted fallopian tube function, or instigated endometriosis.

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We can exclude the possibility that the clones were given hysterectomies, as there's no evidence of such a procedure being performed. And despite popular sentiments to the contrary, nonhuman clones are fully capable of breeding. A clone can also be produced from another clone; recent research shows that mammals could reproduce entirely by cloning.

As for the barcode inscribed in the clones' DNA, that's easy. Back in 2012, geneticists from Harvard and Johns Hopkins Universities developed a novel method of DNA storage, and demonstrated its potential by encoding a 5.27-megabit book containing 53,426 words, 11 jpg images and one JavaScript program with 159-nucleotide chunks of single stranded genetic code. A barcode would be more than manageable.

Timeline Plausibility

According to Orphan Black canon, Project Leda was initiated in the 1970s, apparently in either Canada or the United States. Then, from late March to early April 1984, several female clones were produced from an undisclosed number of surrogate mothers.

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Could this have actually happened back then?

If we stretch our imaginations a little, we can speculate that a primitive form of human cloning might have been possible in 1984, as some of the requisite biotechnologies did, in fact, exist in the 1970s and 80s.

First, a super-quick historical review of major cloning milestones, condensed from this timeline via the University of Utah:

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  • 1885: The first-ever demonstration of artificial embryo twinning, showing that early embryos contains their own complete set of genetic instructions
  • 1902: Artificial embryo twinning in a vertebrate, showing that more complex animals can be "twinned", but only to a certain stage of development
  • 1928: The cell nucleus controls embryonic development, and the knowledge that the nucleus from an early embryonic cell directs growth
  • 1952: The first successful nuclear transfer, resulting in cloned — but abnormal — frogs
  • 1958: Nuclear transfer from a differentiated cell, demonstrating that nuclei from somatic cells in a fully developed animal could be used for cloning
  • 1975: First mammalian embryo created by nuclear transfer, in this case a rabbit; importantly, the researchers developed a glass pipette to manipulate the tiny mammalian eggs
  • 1984: The first mammal created by nuclear transfer, in this case sheep were produced from early embryonic cells
  • 1987: Nuclear transfer from embryonic cell, in which the technique was expanded to cows; at this stage, cloning was still limited to using embryonic cells as nuclear donors (i.e. cloning from differentiated, somatic, cells not possible)
  • 1996: Dolly: The first mammal created by SCNT
  • 1997: First primate created by embryonic cell nuclear transfer
  • 1998-1999: More animals cloned by SCNT
  • 2007: Primate embryonic stem cells created by SCNT
  • 2013: Human embryonic stem cells created by SCNT

Two other landmark events in the history of human cloning: The ability to extract human eggs (which arrived in the 1950s), and the 1978 birth of Louise Brown, the first human born via in vitro fertilization.

Technically speaking, Project Leda scientists may have been capable of human cloning as early as 1984, through the process of splitting an embryo, or possibly via nuclear transfer. Writing in the Genetic Literacy Project, David Warmflash explains:

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[Splitting an embryo is] the same process that leads to identical twins in nature, and it can be done intentionally in the lab, for instance with an embryo produced by IVF that has not yet undergone embryo transfer (implantation into the uterus of the birth mother). Embryo splitting is performed in non-human mammals and has been feasible as a human cloning technique since the 1978 IVF-ET milestone.

A limitation of embryo-splitting, however, is that the number of potential clones is finite. That said, we've only been introduced to a small handful of adult clones in Orphan Black. Charlotte, the eight-year-old clone, was born in 2005, following the development of SCNT.

As for advances made in the early 80s onward (including somatic cell and germline gene therapies), these probably wouldn't have been ready for prime time when Cosima and her fellow clones were created – unless, of course, the Neolutionists covertly developed these advanced biotechnologies decades in advance.

Can Corporations Own Human Genomes?

As noted, the clones in Orphan Black are genetically embedded with a patent barcode that designates them as property of the Dyad Institute. Could a corporation actually do this?

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In a word: no. In the U.S., corporations cannot currently claim ownership of a living, breathing human being. Legally speaking, this has been impossible in the U.S. since slavery was abolished in 1865, with the adoption of the Thirteenth Amendment.

As for claiming ownership over pieces of human genetic fragments? Well, that's a different story.

Patents are routinely granted for tangible things, like mechanical devices; but the patent system has been expanded to include advances brought about by the biotechnology revolution. To date, patents have been granted to fragments of genetic code, methods for identifying DNA or RNA sequences in an individual, nucleic acids, and genetic diagnostic techniques, among other things.

In 2005, MIT researchers Kyle Jensen and Fiona Murray reported that over 4,000 human genes had been claimed in some way by U.S. patents. The practical figure may be much lower, but the larger point is that human genes are being patented. The precise wording that allows for this comes from section 101 of the U.S. Patent Code, which states: "Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title."

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Several years ago, Myriad Genetics used this open-ended wording to claim a patent for two human genes, BRCA1 and BRCA1, both of which are linked to an increased risk of breast and ovarian cancer. They lost the patent in 2010, but won them back again in an appeal. The judges decided that "isolated DNA" was somehow different than "naturally occurring DNA," an interpretation that now allows fragments of human genes to be patented.

However, the patentability of genetic information remains an evolving concept. At the close of the 2012 Prometheus V. Mayo case, the Supreme Court concluded unanimously that a personalized medicine dosing process invented by Prometheus wasn't eligible for patent protection "because the process is effectively an unpatentable law of nature." This could have serious implications for the patenting of genes in the future.

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In the case of Orphan Black, the Dyad Institute could be making the claim that their proprietary processes – whether it be their cloning techniques or their gene therapies – qualify certain aspects of the clones as intellectual property, either in whole or in part.

Additional reporting by Levi Gadye.

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