Biologists have been mixing the DNA of different animals since the 1970s, but the idea of injecting the genes of animals into humans remains taboo. Called transgenics, it's a practice that could cure illness in the future -- and eventually reshape our species. Here's what you need to know about it.
Illustration by Jim Cooke.
Transgenics has been around for a while now. It's the use of any number of recombinant DNA techniques to introduce new characteristics -- via genes -- into organisms that weren't present before. These changes can either alter the germ cell line, passing new traits down to offspring; or they can affect the somatic cell line, which just changes the individual who receives treatment. Transgenesis can involve the entire organism, or a few individual cells.
Transgenic animals are sometimes called chimeras or hybrids. These genetically-mixed animals are often used to model specific human diseases, produce novel materials and tissues, and engineered to withstand diseases, among many other things.
A Criminal Act?
Currently, while it's (mostly) acceptable for researchers to manipulate the DNA of animals with transgenes, it's definitely not ok to introduce animal genes into the human germ line.
Transgenics: Not about creating monsters. (Splice (2009))
In some countries, like Canada, it's actually a criminal offence; its Assisted Human Reproduction Act (2007) prohibits:
- The use of non-human reproductive material in humans
- The use in humans of human reproductive material previously transplanted into a non-human life form
- The creation of chimeras made from human embryos
- The creation for reproductive purposes of human/non-human hybrids
It's more ambiguous in the United States where this issue is governed by local and federal agencies. In contrast to the situation in Canada, the US National Academies of Science has suggested the outright prohibition of only two types of chimeras: those in which embryonic stem cells of any origin are introduced into human blastocysts, and those created by the introduction of human pluripotent stem cells in non-human primate blastocysts.
Prohibitions aside, the reluctance to engage in animal-to-human transgenics tends to overlook one crucial aspect, namely the incredible benefits that are to be had by integrating nonhuman DNA into the human gene pool. Before we get into this, however, it's important that we do a quick review of transgenics to see how it works.
Tools of the Transgenic Trade
Some forty years ago, scientists learned how to transport genes into plants and animals by 'piggybacking' those genes on viral or bacterial DNA. As early as 1974, Ralph Brinster was creating chimeric mice made up from two different strains. By 1982, biologists were melding goat and sheep to create "geep," and creating so-called "super mice."
A Geep, via My Petting Zoo/Facebook.
Over the past several decades, biologists have refined their transgenic techniques, including the introduction of DNA microinjection, embryonic stem cell-mediated gene transfer, and retrovirus-mediated gene transfer.
More recently, scientists have figured out how to modify the DNA of plants and animals to much greater degrees of precision. While techniques using bacterial and viral DNA enabled scientists to transport genes into the chromosomes of various organisms, the precise target for where the transgene was to eventually land could not be controlled. The CRISPR/Cas9 system, which normally allows the bacterial immune system to store DNA 'fingerprints' of viruses, now enables scientists to choose a specific region of the genome for either gene disruption (a gene knockout) or insertion (creating a more-precise transgenic organism).
This technology is extremely powerful because the original genes of an organism (its endogenous genes) provide a direct entryway for scientists to control, or edit, an organism's biology. For instance, if someone has a mutation that causes a disease in a particular type of cell, using CRISPR/Cas9 to replace the mutant gene with a normal gene could theoretically cure that disease. Likewise, it could be used to introduce a foreign transgene.
So, for example, scientists have used CRISPR/Cas9 to correct B-thalassemia (a condition similar to sickle-cell anemia) in human blood cell lines. They also used it to fix a mutation causing a liver disease in mice (though their technique only corrected 0.4% of mutated liver cells, these cells were able to rescue liver function). Additionally, researchers recently used the technique to create programmable antibiotics that selectively targets undesirable microbes.
Chimeras Among Us
Today, transgenic organisms are used for a number of purposes, from toxicology and the improvement of plants and livestock to the creation of animals that simulate human diseases. They can be divided into three major functions:
- To obtain information on gene function and regulation as well as on human diseases
- To obtain high value products (recombinant pharmaceutical proteins and xeno-organs and xeno-tissues for humans) to be used for human therapy
- To improve animal products for human consumption.
As noted by Emily Anthes , author of Frankenstein's Cat, genetically engineered animals could do real good for the world. As she notes in The New York Times, scientists have created transgenic salmon that can reach their adult size in a year and a half, rather than three years. There's also the famous "spider goats" -- hybrid goats that secrete exceptionally strong strands of spider's silk, and transgenic glow-in-the-dark pigs and rabbits that use jellyfish DNA (the point of which kind of eludes me).
Boxer et al.
Perhaps most profound of all, scientists have been able to give adult, male squirrel monkeys (who are normally dichromatic) trichromatic vision using a virus carrying a human gene for a missing, particular opsin. Opsins are the proteins that detect light in our retinas, and male squirrel monkeys lack the third type of opsin, L-opsin. Humans have three types of cone photoreceptors, giving us trichromatic vision. Each cone cell expresses a different type of opsin.
The virus carrying a human L-opsin gene was injected into the male monkeys' retinas. Crazily enough, five months later, these male monkeys could suddenly see reds and oranges that they had previously been blind to. Furthermore, in spite of the neural circuitry of these monkeys' eyes remaining pretty much the same (they were adults monkeys), these animals could properly complete colour-discrimination tasks as if they had had trichromatic vision all along. There was no need to rewire the circuit for apparently functional trichromatic perception.
One of the implications of the squirrel monkey study is that -- assuming this technology could be safely adapted for humans -- one could imagine injecting genes for additional opsins to improve peoples' colour vision. Two years ago scientists finally identified a rare subset of women who had increased colour acuity, thanks to the possession of a fourth, mutant opsin. This also could conceivably be used to correct colour-blindness (which tends to affect men).
Transgenic Medicine for Humans
These many examples raise two important considerations. First, DNA works similarly for all animals; so in theory, the transgenic techniques described earlier also apply to humans as well. Second, there appears to be tremendous potential for a wide variety of transgenic interventions and augmentations that could work in humans -- from medicines and vaccines through to physical and even cognitive augmentations.
Say, for example, we discover an animal that has a built-in genetic immunity to a particular disease. Scientists could isolate those markers and transplant them into human DNA. Novel medicines based on animal DNA could be developed, including ways to stave off the effects of ageing and metabolic disorders, including diabetes. Other speculative applications could involve changes to physical appearance, metabolism, and even the improvement of physical capacities and cognitive faculties such as memory and intelligence.
Rise of the Planet of the Apes (2011)
For example, chimpanzees -- a close relative of ours -- are much stronger than we are. Their muscles work around five to seven times more efficiently than ours. Our muscle fibres are far smaller and weaker than those of our primate cousins -- roughly an eighth the size of those seen in macaques, for example. Also, chimps are freakishly good at memorization tasks, consistently faring better at memory tests than human subjects. They're also better at strategic reasoning than we are. So rather than envisioning a Planet of the Apes scenario, it may be more plausible to propose a kind of animalization of human characteristics (if you'll forgive the speciesist term).
Obviously, I could go on and on about other nonhuman animals and their desirable characteristics, but I'm going to stop here at the risk of getting too speculative. Suffice to say, conferring these traits via transgenesis and gene transfers would be a monumental task -- one that would carry tremendous risks.
Indeed, traits that relate to physical characteristics -- say, the shape of the teeth, the acuity of the eye, the strength of muscles -- have not been easily linked back to particular genes. At least not yet. Many traits rely on dozens of genes acting in concert, and it has been a struggle to identify how one might engineer a better hand or a smarter brain. For something like immunity, a genetic modification solution (such as perhaps engineering in a particular antibody to a disease) may be more costly than simply using a vaccine.
Also, sometimes biology takes a roundabout route with maintaining the health of some part of an organism. For instance, if the body misregulates inflammation or pain, this could create a struggle for brain function. The problem would manifest with maybe a cognitive defect, but the source of the problem would be indirect.
And as bioethicist Linda MacDonald Glenn told me, there's the heightened risk of the transmission of fatal zoonotic diseases -- that is, diseases that can be passed between animals and humans because of shared genetics.
"Ebola, Lyme disease, Rocky Mountain Spotted Fever are just a few examples of zoonotic diseases that jumped from animals to humans," MacDonald Glenn says. "Increasing the further integration of animal DNA into human DNA could lower the barrier for transmission of zoonotic diseases."
Bioshock "Pick Your Plasmid" poster.
I also spoke to Anthes to get her opinion, and she's also worried about the risks.
"Animals have all sorts of characteristics that we humans don't possess, and it's certainly possible that would could boost our own health, skills, and talents by strategically integrating animal DNA into our own genomes," she told io9. "I don't worry too much that adding a non-human gene to our own genomes will insult to our 'human dignity,' but there is always the possibility of unintended health consequences. Human transgenes have sometimes led to serious, unanticipated health problems in animals, and animal genes could potentially cause nasty side effects in us. That's not to say that such outcomes are inevitable -- merely that they're possible. It will very much depend on the genes we use and how they're expressed."
Not Human Enough?
As noted by Anthes, there's also the ethics to consider and the potential moral backlash. For some, the intermingling of human and animal DNA is seen as an affront to human dignity, and a violation of our genetic heritage. Canada's AHRA is a testament to this stance, an act designed to protect human dignity, individuality, health and safety, and the integrity of the human genome.
But as noted by Maneesha Deckha in a critique of the legislation, much of this has to do with what she calls "species anxiety" -- a phobia that "individuals manifest at the thought of the human body intermingling with another species at the reproductive, genetic, cellular, or other body part level, in spite of the fact that interspecies biological interface happens routinely."
Which is actually an amazing point; the human genome, via the process of endosymbiosis, is a massive amalgamation of tinier organisms.
At the same time, some are framing the debate in terms of individual freedom and the right to use germinal choice technologies. A case can be made that transgenics is a component of our reproductive and morphological freedoms.
But the critics are not having any of it. Back in 2005, ethicist Jeremy Rifkin and Stuart Newman of New York Medical College attempted to win a patent on a (hypothetical) laboratory-conceived animal -- a so-called "humanzee" -- that would be part human and part animal. The claim was rejected by the U.S. Patent and Trademark Office, which was exactly what Rifkin and Newman were hoping for. Their goal was to set a legal precedent that would keep others from profiting from any similar "interventions."
The Island of Dr. Moreau (1996)
In addition, ethicist George Annas has suggested that we need to set up an international criminal tribunal that will ban genetic engineering and xenotransplantation, along with other forms of possible alterations of humans for fear of endangering the species or the creation of a slave race. And the International Olympic Committee has expressed its concerns that athletes will soon use genetic engineering to boost their performance among any number of physical domains.
The debate also raises some important questions: At what point is a human no longer "human" enough to warrant status as a human? Is it wrong to 'humanize' other animals, such as nonhuman primates and rodents? And if not, would they be deserving of human-like rights if their newfound capacities warrant it?
MacDonald Glenn put it to me this way: "Just how many genes does one need to be considered human? Considering 97% per cent of our genome consists of the genes we share with other species -- chimps, fruit flies, even common brewer's yeast -- do these questions even matter?"
To which she added, "Further advances in the blending of nonhuman animal and human DNA could result -- intentionally or not -- in chimeric entities possessing degrees of intelligence or sentience never before seen in nonhuman animals. Would an intelligent, sentient creation be property or a person? Could he/she/it be patented?"
Clearly, we have a long way to go in answering these questions, not to mention the difficulty in developing safe and effective transgenic interventions. But one thing is becoming increasingly clear, and that's the insufficiency of the term "human" as the signifier of some kind of moral delineator. Rather, we should adopt a non-species approach to the issue and start looking out for the interests of persons instead.
Or as Glenn further posited at the Yale Personhood conference last December: "Boundaries will blend and blur, and the question will not be who or what are persons, but what sort of beings do we want to be?"
Additional reporting by Levi Gadye. Sources: "Use of Transgenic Animals to Improve Human Health and Animal Production," L. M. Houdebine | "The methods to generate transgenic animals and to control transgene expression," L. M. Houdebine [Frankenstein's Cat, Emily Anthes | "Holding onto Humanity: Animals, Dignity, and Anxiety in Canada's Assisted Human Reproduction Act," M. Deckha | "Chimeras and 'Human Dignity'", E. Eliot | "When Pigs Fly? Legal and Ethical Issues in Transgenics and the Creation of Chimeras," L. MacDonald Glenn | "GM to Order," L. Gadye | "Neuroscientists Probe CRISPR Transgenics and Treatment Paradigms" [Zoonotic Disease: When Humans and Animals Intersect, CDC [Forum on Microbial Threats. Microbial Evolution and Co-Adaptation: A Tribute to the Life and Scientific Legacies of Joshua Lederberg: Workshop Summary, Institute of Medicine (US).]