Transmogrification

Abstract

Advances in nanotechnology and biotechnology hold the promise of a brave new world, but also one in which threats to humanity could be of a uniquely terrible kind. Hodgson’s famous story provides the modern reader with a hint of the sort of horror that biotechnology could unleash.

Appendices

Commentary

William Hope Hodgson had a particular interest in the transformation of the human body. From childhood, Hodgson was fascinated by the sea (stay with me—the connection with bodily transformation will become clear) and when he was just 13 he ran away to join the navy. He was caught and forcibly returned home, but a few months later his father allowed him to begin an apprenticeship as a cabin boy. Hodgson, however, was short in stature—even as an adult he was only 5′ 4″—and he was, furthermore, in possession of movie-star good looks. This combination almost guaranteed that his fellow crew members would bully him. And they did. Most men might have given up and jumped ship. Hodgson, though, took up bodybuilding. It wasn’t long before any seaman trying to bully Hodgson found to his cost he was dealing with, pound-for-pound, the strongest man in the navy. Hodgson went on to found a “School of Physical Culture”, where he trained others—including police officers—to strengthen their bodies and improve their physique.

Hodgson’s method of implementing physical change through exercise depended of course upon conscious control. The horrifying bodily changes described in his 1907 story “The Voice in the Night” were involuntary—the result of a terrible fungal infection. Although I’m not aware of there being anything quite like the fungus described in this story, there is at least one disfiguring disease that causes similar visual outcomes. Indeed, I wonder whether an encounter with a sufferer during one of Hodgson’s voyages might have sown in his imagination the seed of the story?

The disease epidermodysplasia verruciformis (EV)—also referred to as Lewandowsky–Lutz dysplasia (after the dermatologists who first described it in 1922) and as treeman syndrome (after the visual appearance of sufferers)—is an extremely rare disorder. The medical literature contains only a few hundred reported cases. Currently, perhaps the most notable case is that of Abul Bajandar from Bangladesh (see Fig. 2.1). However, the best documented case of EV is that of Dede Koswara, an Indonesian man whose arms and feet were covered in the warts and thick horns that typify the disease. Koswara died from complications of EV in 2016, aged just 42. During his relatively short life he was the subject of numerous television documentaries, and no viewer could consider his plight to be anything other than both heartbreaking and shocking. Much of the skin on Koswara’s body had the appearance of bark; his hands and feet resembled the gnarled branches of old trees. When I look at photographs of Koswara, I’m put in mind of the unfortunate couple in Hodgson’s story.

Fig. 2.1

A photograph of Abul Bajandar taken in February 2016, when Bajandar was 25 years old. The lesions on his hands are clearly visible. In 2017, surgeons at Dhaka Medical College succeeded in removing 5 kg of the wart-like growths during 16 operations on Bajandar. Unfortunately, by 2018 the growths had started to reappear (Credit: Monirul Alam)

The terrible skin lesions characteristic of EV are caused by repeated infection with the human papillomavirus—a virus with many subtypes, some of which can persist and cause warts. If a person has an abnormal or impaired immune response to certain subtypes of the wart virus then, in some unlucky cases, the result can be EV. In some individuals with EV the impaired immune response is the result of HIV infection or of drugs used to suppress rejection following organ transplants. The disease is then said to be acquired. In most patients, however, the disease is the result of an inherited condition. The problem in these cases is caused ultimately by a mutation in certain genes, with the so-called EVER1 or EVER2 genes being particularly implicated. The condition is recessive, which means that in order to be affected a person must receive two copies of the abnormal gene on a non-sex chromosome; if only one abnormal copy is inherited then the individual becomes a carrier rather than a sufferer. So a child born to two carriers has a 25% chance of being completely unaffected, a 50% chance of becoming a carrier, and a 25% chance of being affected. Dede Koswara was one of the unlucky individuals who received two copies of an abnormal gene, one each from carrier parents.

Treatment of the condition is about alleviating symptoms. Surgeons can sometimes operate to remove the lesions, and this might permit a patient to recover the use of fingers and feet, but even if surgery is successful there can be no guarantee the warts won’t return. There is no cure for EV.

Bioscience, however, progresses at a dizzying pace. The same morning I sat down to write this commentary to Hodgson’s creepy story, news was published of an exciting development in gene editing techniques. The development represents the first step on a journey that might lead not only to a cure for diseases such as EV but also to more general control over the workings—and even appearance—of the human body.

A team of Chinese bioscientists made the advance. They were investigating the rare but serious blood disorder β-thalassaemia, which is caused by a so-called point mutation: it requires the base adenine (A) to be switched to the base guanine (G) at a particular point in the HBB gene. This mutation does occur in the Chinese population, but it’s relatively rare; it’s much rarer to have someone receive two copies of the mutation—and, as with EV, the disease is recessive so a person must receive two copies of the mutated gene for the disorder to manifest itself. The Chinese team wanted to investigate the disorder in embryos, so their first challenge was simply to source embryos that had two copies of this rare mutation. The team proceeded by identifying a patient with β-thalassaemia, extracting some of the patient’s skin cells, and then developing 20 embryonic clones each with two copies of the mutation. They then employed a new base editing technique, a procedure that has been called “chemical surgery”. The team built on a gene-editing method called CRISPR-Cas9, which was developed in 2012 and allows bioscientists to use enzymes to cut genes with accuracy. The Chinese team’s modification of the CRISPR-Cas9 technique can guide an enzyme to specific gene sequences, and then simply swap G to A (or the base cytosine (C) to thymine (T)). No cutting involved. In 8 out of the 20 cloned embryos, the offending G could be switched to A at the relevant spot in the HBB gene. And fixing just one of the two faulty genes would be enough to cure a recessive disease.

Clearly, a huge amount of work must take place before this technique can be used in medicine; many questions are still to be answered. But this proof-of-principle experiment shows how base-editing techniques might correct a disease mutation. In future, rare diseases such as treeman syndrome might be prevented by editing an at-risk embryo; if the disease is already present in an adult, techniques might be developed to swap out the faulty genes. If the unfortunate married couple in Hodgson’s story were living today, they might hope for a cure.

But, as with every scientific advance, there are dangers.

For centuries people have been using artificial devices to transform the human body, and we can expect this phenomenon to continue. Some transformations are entirely unremarkable (vision correction, for example); some are currently noteworthy (advanced prosthetics); some are seemingly science-fictional (the addition of non-anthropomorphic structures such as wings). We can expect some future humans to undergo a level of “cyborgisation” because throughout history people have used whatever technology has been available in order to alter their bodies. Ultimately, though, these transmogrifications are transformations of the individual. What makes the advances in genetic engineering so powerful—and potentially so dangerous—is that they have the capacity to affect the entire human species.

Science fiction writers have been in the vanguard of examining the opportunities and threats of biotechnology as applied to human transmogrification. They’ve contemplated changes in form even more bizarre than those imagined by Hodgson in “The Voice in the Night”. As long ago as 1983 Greg Bear, in his award-winning novelette “Blood Music” (later expanded into a novel of the same name), discussed one possibility.

In Bear’s story a rebellious bioengineer manufactures a simple biological computer based upon his own white blood cells. His employer, nervous about the direction of this work, orders him to destroy the computers; instead, the bioengineer injects the computers into his bloodstream and smuggles them out of the company lab so he can continue work on them in his own time. Once inside his body, however, these artificial cells evolve and develop self-awareness. They start to alter their own genetic material, and the bioengineer begins to transmogrify. At first, it’s all good: better eyesight, greater strength, improved skin, quicker brain. He infects others and they find that their health improves, their muscles strengthen, their intelligence increases—again, all good. Except that these mutant cells infect more people, then more, and eventually go on to assimilate much of the biosphere!

Bear’s story was one of the first visions of the grey-goo scenario—the notion that technology at the molecular or nanoscale level (the realm where biotechnology takes place) might cause the end of the world through a runaway effect.

The threat of a gray-goo doomsday, and similar runaway effects, can surely be alleviated. If society pays serious attention to the problem now, while we have the luxury of time, then safeguards can be put in place—just as engineers implement safeguards for all new technologies. The power of biotechnology, however, gives rise to one problem humanity might struggle to avoid.

The problem involves the quite staggering rate of progress in biotechnology. To appreciate the scale of this progress, recall that the double-helix structure of DNA was discovered as recently as 1953. The Human Genome Project—the campaign to determine the sequence of base pairs that make up human DNA—was launched in 1990, cost about $2.7 billion, and took more than a decade to succeed. Today, companies can sequence your genome within about an hour for $1000 or so. These unprecedented advances in biotechnology have occurred within a typical person’s lifespan: 1953 was the year of Queen Elizabeth’s coronation, after all, and as I write Elizabeth is still on her throne. If this rate of progress continues then the cost of sequencing a genome will soon be pennies.

Here is another example of progress in biotechnology. Starting in 1989, bioscientists began to investigate gene function by using “gene targeting”—they’d inactivate, or “knock out”, an entire gene in an animal, replace it with a piece of artificial DNA, and then observe any effects on the animal. In 2012, this expensive and time-consuming technique was revolutionised with the introduction of the CRISPR-Cas9 gene editing technique mentioned above. In 2017, as we’ve seen, scientists showed how to swap individual base pairs. In the future, it seems likely that any reasonably competent undergraduate biology student will be able to tinker with the fundamental chemicals that define the make-up of a human being.

So what’s the problem? These biotechnological advances will, after all, transform medicine: people will have access to personalised treatments, dreadful diseases such as EV will be eradicated, and it will be difficult for readers to even imagine the sort of world described in “The Voice in the Night”. Unfortunately, those same biotechnological advances will become so cheap and so widespread they’ll be readily available to terrorists, criminals, or simply the unhinged. The bad guys as well as the good will have ability to alter existing life or to create new life. Unfortunately it’s not difficult to imagine a future fanatic creating a deadly pathogen in the kitchen of his bedsit, and releasing it on an unsuspecting population. How can we protect ourselves against such a threat? We should start thinking about it now.

If an artificial pathogen were inflicted upon us, by either accident or design, what would happen to our civilisation? Well, we might face a world not dissimilar to the one depicted in Chapter 3.

Notes and Further Reading

• the transformation of the human body—Bodily transformation is a venerable theme in literature. The Latin poet Ovid wrote beautifully about such flux two thousand years ago in Metamorphoses, which ranks as one of the most influential books ever written. Melville (2008) is a good English translation of Metamorphoses. Marina Warner (2004), in a wide-ranging volume, analyses themes of transformation in literature since the time of Ovid.

  In Shapeshifters (2018) Gavin Francis, a doctor, has written about human alteration from the perspective of a medical professional. His patients—pregnant women; menopausal women; those suffering from anorexia; people transitioning—visit his clinic in the hope he can influence what is changing in their bodies.

• Hodgson was fascinated by the sea—Sam Gifford (n.d.) runs a blog that contains a large amount of interesting information about William Hope Hodgson.

• the best documented case of EV is that of Dede Koswara—The unfortunate Koswara was the subject of a hard-to-watch documentary called Half Man, Half Tree (TLC 2007) and soon after another documentary called Tree Man (ABC 2008).

• a procedure that has been called “chemical surgery”—About two-thirds of documented human diseases are the result of the sort of point mutations described in the text. So base editing, if it becomes routine, could give rise to exciting developments in medicine. The correction of β-thalassaemia in embryos using a base editing technique is described in Liang et al. (2017).

• as with every scientific advance, there are dangers—There are many potential abuses of biotechnology. One obvious cause of concern, which I haven’t had the space to discuss in the main text, is the prospect of “designer babies”. Science fiction writers have been interested in this since at least the 1930s, when Aldous Huxley (1932) published his satirical novel Brave New World. The development of CRISPR-Cas9, and the subsequent development of base-swapping, means there will come a time when embryos can be edited. Whether this prospect is years or decades away depends on advances in technology (these techniques are, after all, still in their infancy) and on the regulatory framework imposed by governments (obvious ethical concerns surrounding gene editing are combined with a general public distrust). But it seems likely that at some point, in a lab under some jurisdiction somewhere in the world, scientists will be allowed to manipulate the basic building blocks of human life in order to prevent or treat genetic disease. The worry then becomes that embryos will eventually be edited not only to remove the possibility of disease but to possess features society deems attractive—blue eyes, blond hair, improved athletic ability, or those features that happen to be in fashion. Several ethical issues spring to mind with this scenario. Will the health gap between rich and poor increase within society and between nations? Will parents be influenced by society to choose various features for their children? If it turns out, as seems likely, that there’s a complex relationship between genes and traits such as personality and intelligence, will people start “tweaking” embryos just to try and give their offspring an advantage in the genetic sweepstake—and what if that tweaking goes wrong? And then there are the unforeseeable but probably inevitable unintended consequences of dabbling with DNA …

  Even if the technology behind gene editing turns out to be ineffective, society will still need to debate the potential promise and peril of designer babies because a quite different genetic advance provides an efficient and cost-effective method to allow parents (or the directors of hatcheries, as in Brave New World) to choose traits for their babies. Instead of getting parents to produce a single embryo, and then editing the genetic information, the simpler approach is for them to produce lots of embryos and screen all of them for their genetic potential. The desirability of an embryo marked as high-IQ, low-risk for asthma, high-risk for male-pattern baldness might be weighed against an embryo possessing the possibility of athletic prowess but low-IQ and a susceptibility to diabetes. Choices, choices. Society must soon debate these ethical and moral issues in earnest.

• For centuries people have been using artificial devices to transform the human body—The use of spectacles or contact lenses to improve vision is of course entirely unremarkable; the use of prosthetic arms and legs to improve the quality of life for those who have lost limbs is becoming more common; soon we shall see the everyday application of devices to augment the natural abilities of individuals who are entirely healthy. It seems likely that in the future many people will choose to undergo some form of “cyborgisation”. Professor Hugh Herr, head of the biomechatronics group at the MIT Media Lab, researches this idea. Herr himself uses specialised prostheses, the result of having both legs amputated below the knee following a climbing accident. (The story of Herr’s accident, and his single-minded struggle to recover from the loss of his legs, is recounted in Osius (1991).) Using these devices Herr can effectively change his height, and attempt climbs that would previously have been impossible. In a sense, Herr has taken a first step towards cyborgisation. At TED2018 (available online; see Herr (2018)) he talked about his vision for humanity in the 21^st century: “Humans may … extend their bodies into non-anthropomorphic structures, such as wings, controlling and feeling each wing movement within the nervous system. … During the twilight years of this century, I believe humans will be unrecognizable in morphology and dynamics from what we are today.” This idea, of course, has been investigated by SF writers. In Man Plus, for example, Frederik Pohl (1976) described how an astronaut’s body might be transformed for the rigours of life on the Martian surface: genitals would be removed, cloaca added, lungs revamped … Advances in biotechnology mean our species might son change in ways we can barely foresee.

• Greg Bear, in his award-winning novelette—See Bear (1983).