Genomena

On 9 March, President Obama issued an executive order to lift hobbling restrictions on embryonic stem cell research  imposed by his predecessor, George Bush. In its own right, Obama’s order enacts a substantive and welcome change, jumpstarting an exciting and clinically promising line of biomedical research. But the revival of stem cell research can also be seen as part of a larger, ongoing effort to strip away religiously motivated fetters placed on many fronts of American science by the Bush administration.

Sadly, despite some real progress, these fetters continue to ominously hinder the American public discourse on science — even on occasions, such as the the new executive order on stem cell research, that should be clear victories for empiricism.  Like other reversals of Bush policy that have reinstated sound, empirically driven policy on such matters as greenhouse gas regulation, the stem cell order conveys a clear grasp of the societal value of the ever skeptical mode of systematic inquiry that we call science.  Yet, in remarks at the signing ceremony, Obama was careful to solemnly profess his ‘faith’. In doing so, he likely meant to console opponents of stem cell research, many of whom are religious. Reaching out to opponents is a laudable goal, and one that Obama consciously cultivates in his role as a `uniter’. Yet it is frustrating that, in a national ‘teachable moment’, Obama could apparently find no better way to reach out to do so than by emphasizing a pat solidarity rooted in shared baseless beliefs.

And that wasn’t the only way in which, even while redressing another case of scientific sabotage by his predecessor, Obama shrank from fully championing a reasoned approach to policymaking.  As a sign of specific future policy intentions, Obama’s latest profession of faith may have been less telling than his use of the signing ceremony to harshly, but emptily, condemn the prospect of human reproductive cloning.  Speaking with customary force, but without laying out a chain of reasoning such as we’ve come to expect from him, he declared that ‘[cloning] is dangerous, profoundly wrong and has no place in our society or any society.’ Obama’s mention of cloning as a foil to stem cell research reinforced a pattern that has emerged in American politics, in which the two issues seem to have become joined at the hip, appearing together with the rote predictability of a pantomime hero and villain. This rhetorical conflation (which is nearly always resolved with some dramatic flourish of contrast) may serve mainly to let supporters of stem cell research distance themselves from an ostensibly obvious evil, thereby reassuring us of their credentials as decent members of the human race. But if stem cell research is right, must reproductive cloning be wrong? Perhaps this moment — punctuated, as it is, by a major change in federal biomedical research policy — is a good one for reviewing the question.  Below is an attempt, in several parts, to do just that.

Two years before Obama’s executive order to rescind limits on stem cell research, Senator Orrin Hatch introduced bill S.812, the ‘Human Cloning Ban and Stem Cell Research Protection Act of 2007’. Though unmistakably right-wing, the veteran Hatch is renowned for shrewdly wielding the political olive branch (he famously joined Bono’s well-heeled campaign for foreign aid debt forgiveness; recorded a hearty get well song for Ted Kennedy; and stood up fairly early in support of Barack Obama’s embattled attorney general nominee, Eric Holder). It was no surprise, then, that Hatch front-loaded bill S.812 with a title aimed squarely at what has become known as ‘purple state’ America. In admirably forthright wording, Hatch’s title evoked a sense of sober, considered balance: one could picture Justice herself, pausing for a moment’s due consideration before lifting a brightly glowing vial (stem cells) in one hand and discarding a soiled diaper (human cloning) with the other. In 2007, as now, American adults, eager for a therapeutic boon, tended to favor stem cell research; the same electorate, however, strongly opposed reproductive cloning — and, sadly, remained largely oblivious to key differences among stem cell lines that stood to greatly limit the pace and scope of their therapeutic payoff.

In particular, much of the public appeared unaware that some stem cells — the most developmentally versatile ones — are culled from young embryos (only those slated to be discarded), while others are collected later (usually after birth). Seen in this light, Hatch’s title, with its reference only to ‘stem cell research protection’, carried a deft ambiguity. In public rhetoric, Hatch and other Republican leaders often silently, but pointedly, exploit the distinction between embryonic and non-embryonic stem cells: their insistence that they are ‘pro-stem cell research’ is asterisked with a qualification — only grudgingly voiced to anyone beyond their religious-right ‘base’ — that they mean ‘adult’ stem cells only.

But the invocation of ‘stem cell research’ in the title of bill S.812 turned out to be even more strikingly devious, once one actually read beyond the title. In the body of the bill, the term ‘stem cell’ appeared exactly twice: once, in a recursive mention of the bill’s title, and once in a boilerplate section defining ‘unfertilized blastocyst’ — which, as the definition rightly noted, is not a stem cell (nor is it a golf ball, as long as we’re keeping track…). Perhaps other references to stem cells were stripped from Hatch’s bill during last-minute backroom revision, with someone forgetting to change the title. Or maybe the reference to ‘stem cell research protection’ was to be read as an oblique threat, conditioning future Republican cooperation on any actually substantive stem cell research initiative to passage of S.812 (much as a mafioso might profess interest in the protection of kneecaps). In any case, the body of the bill did indeed mention ‘cloning’ (28 times); indeed, every substantive clause aimed squarely to ban attempts — therapeutic or otherwise — to make a human embryo by cloning. And in this sentiment, bill S.812 was far from new.

Since 1998, the Senate had already seen at least three major motions to ban human cloning, each mirrored by a sibling bill in the House of Representatives. Each time, the House bill passed, but enough senators balked at the proposed ban to give a reprieve to the apparently non-existent technique of reproductive cloning. The round of legislative fuss over reproductive technology that preceded Hatch’s 2007 bill culminated in the 2003 passage of a House bill banning cloning. Right around that time, a tellingly relevant nugget of news went largely overlooked here in the US. It was a spat that played out in the British press; the words were lively enough, but it lacked in visual fireworks, so was hardly tabloid grist, and hardly registered as a blip in the American press. Looking back, though, one might say that the affair laid bare a clash of ideas at the core of our society’s debate over technology itself.

The trouble started back in December 2002, when the BBC aired a documentary film that openly probed the tenets of a popular sect. The day after the broadcast, Crispian Hollis, a cleric who worked for the sect in question, denounced the British state broadcasters for airing a film that dared to publicly challenge his beliefs. Hollis alleged that the filmmakers had indulged in `unfounded guesswork’ — and he fumed, sensibly enough, that passing off any such guesswork as documentary fact is `not only unscholarly but runs the risk of undermining [journalistic] integrity.’

But closer inspection of the offending broadcast suggested that Hollis’s indignation might have been misplaced. In discussing their subject matter — the dogma of the sect in question — the filmmakers had actually made it a point to favor definitive evidence over unfounded hearsay. What sort of hearsay had they tried to get to the bottom of? It turns out that Hollis and his fellow clerics swear:

• that there is an invisible male ape watching over all of earth, in great detail, at all times (presumably never sleeping).
• that this ape parses all human conversations (and even unspoken thoughts), in all languages, simultaneously.
• and that the ape in question has been doing all this since being born — asexually — more than two millenia ago.

So what evidence is there to support these claims? Sadly, the BBC filmmakers were apparently unable to reach the ape himself for comment, and the leaders of Hollis’ sect insist that their claims rest on eye-witness accounts written by several men who interacted with the ape early in his life, when he was living in southwest Asia (rather than, say, in the sky). Though varying in some details, the cited accounts all portray the ape as readily visible, susceptible to sleep, and not — to the outside eye, at least — especially interested in, or even aware of, the everyday life of anyone in, say, Guatemala or Korea (to name two places where the sect in question has become particularly popular).

As hearsay goes, Hollis deserves points for boldness. In the annals of medicine and peer-reviewed research, there is little, if anything, that could rival his sect’s claims. Let’s take the two thousand year-plus lifespan detail, for example. That would be roughly eight-fold overripe even for a Galápagos tortoise, thought by most biologists to be the longest lived animal with eyes. Which brings us to the question of the ape’s remarkable worldwide vision. Most primates do indeed have quite good eyesight; nonetheless, watching the whole surface of a ball-shaped planet at once would seem to pose problems for the architecture typical of paired vertebrate eyes.

And then there’s the asexual birth bit. Some birds (turkeys, for example) may do it. And, indeed, bees do it. But, so far, there’s no clear evidence of asexual reproduction in any wild (i.e., non-laboratory) mammal. Moreover, even if a female mammal could bear asexually conceived young, she would have to pull off a pretty neat trick to make a son, in particular: one of her X chromosomes (or some other part of the genome) would have to mutate, wholesale, into a Y chromosome, in order to masculinize the developing fetus. Birds — lucky them — don’t have this problem, as it is their females, not males, who have two highly distinct sex chromosomes like our X and Y.

So it seems understandable that the foregoing claims by Crispian Hollis’s sect might provoke some skepticism. But if we’re to gauge the boldness of a claim by the degree of hand-wringing among its makers, then it is the apeness of the ape that really stands out. When formally endorsed by the sect in 1996 — ostensibly to square its dogma with a vast weight of empirical evidence on the matter — the fact that humans are apes was officially fudged with an `ontological leap’. This was apparently done largely to quell horror, among the sect’s adherents, at being (versus merely descending from) animals. Hollis’ all-seeing sky ape, being a man (if an unusual one, in having been born asexually), was thus separated from all non-human apes by some sort of unprecedented evolutionary jump — a qualitative material difference that the sect, conveniently, has declined to try to characterize in any concrete and testable terms.

Here it’s worth noting that such careful dogma-pruning has long been used to help priesthoods stay afloat amid occasional tidal waves of new human knowledge that threaten to obviate pulpits themselves, along with fossilized bronze-age cosmologies. Hollis’s sect, for example, had already conceded, centuries earlier, that the earth revolves around the sun, rather than vice versa, despite the absence of this basic fact in the sacred texts that the sect typically relied on. But theological revision has limits — and when further tweaking would appear to gravely threaten priestly interests, smart clerics throw a trump card familiar to all parents (virgin or not): believe because we say so. And so many a sect, including Hollis’ own, extols as virtue the belief in some ever-dwindling suite of empirically groundless claims, coddling the willful ignorance that is `faith’.

The same winter that saw controversy over the BBC documentary on Crispian Hollis’s sect, another claim was foisted on the world by another sect, who likewise urged others to believe their claims without evidence. On 26 December 2002, the day after a birthday celebrated for Hollis’ allegedly asexually born boy, along came an asexually born girl. Or so said a priest in a newer, far less popular sect. Flush with a potent mix of giddiness and apparent relief, chemist-cum-cleric-cum-CEO Brigitte Boisselier crowed to journalists that she had overseen the birth of a healthy girl who, if true to billing, was the first primate cloned from a somatic (i.e., non-germline) cell.

Pending so-called ‘independent’ confirmation (which never came), Boisselier declared that day that the world had only a week to plausibly call her a fraud. And so began an intense, if brief, inquisition (perhaps enough to do the BBC proud, but Torquemada might have been unimpressed). Pressed for proof of her cloning claim, Boisselier retorted that any such evidence she might offer would be dismissed out of hand, presumably due to her priestly subjectivity and/or direct financial stake in the matter.

The rest of Boisselier’s sect put up a stiff front of secrecy regarding their claims, too, and a safe consensus emerged among pundits: Boisselier’s announcement had been a lie, serving as a commercial publicity stunt for her and her colleagues. And, indeed, in the several years since the birth announcement, the only major nugget of followup detail that the sect has offered publicly is that the asexually born child and her mother have, like their forerunners in Hollis’s sect, allegedly found refuge somewhere near Jerusalem.

So what sort of evidence could Boisselier release to made her claim credible? Decisive evidence would comprise DNA sequences, from across the human nuclear genome, amplified in parallel from somatic (i.e., non-egg) cells of the alleged mother and daughter. Only if their genotypes matched each other perfectly in an overwhelming majority of cases (allowing for a few mismatches, for reasons we’ll get to below), and the derivation of sequences were proper and clear (there’s the rub, for Boisselier and any anonymity-minded sample donor), could one soundly infer that the donors derived from the same fertilized egg, and were, given their age disparity, most likely clone and clonee.

Absent such evidence, pundits understandably scoffed from the start. Belittling the chance that anyone — a non-MD to boot — might have pulled off such a rash stunt, talking heads shook scornfully, and took pains to mull the implications of human reproductive cloning in hypothetical terms only. Other empirically groundless claims of Boisselier’s sect — that humans have non-earthling forebears, for example — became fodder for doubting her truthfulness a priori. Suddenly, outspoken empirical rigor was in refreshing vogue!

And, perhaps miraculously, Crispian Hollis’s own priesthood called shotgun on the skeptics’ bandwagon. Vatican spokesman Joaquín Navarro-Valls burdened himself to speak for empiricists everywhere, declaring that `[Boisselier's] announcement without any element of proof has already raised the skepticism and the moral condemnation of the greater part of the international scientific community.’ Such newfound skepticism made sense, too; after all, Navarro-Valls’s and Hollis’s own asexually bred darling hadn’t been born yesterday.

Duly steeled against falsehood, the world still awaited real tests of at several human cloning claims; no verdict came, and at least one alleged clonee cited lawsuits as deterring her from further disclosure, fueling talk of a charlatan hoax. But whether or not Boisselier, or anyone else, has yet cloned a woman using a skin cell nucleus, a sense of inevitability looms around that endeavor. Skepticism of human cloning claims, however fiercely it persists, may eventually look less like sincere evidentiary concern than like craven denial. Perhaps then, at this pregnant hour in the advent of human reproductive cloning, a broader survey of surrounding myths — not just those which are two millenia old — could help us decipher all the frightening scrawl on the wall.

Let’s start with the worn chestnut of identity. Ethicist Robert Williamson has posited `that there is a personal right, ethically based, to individuality, autonomy, and identity…[and that r]eproductive cloning crosses a significant boundary in removing the single most important feature of autonomy: the fact that each of us is genetically unique.’ As is well reported, monozygotic siblings — so-called identical twins, triplets, &c. — seem to pose a challenge to the assertion to any such right, which convention would deem a universally inborn attribute (at least within our non-universal little branch of life’s tree). Williamson skirts this problem, distinguishing violations of rights by `nature’ from those `reproduced deliberately by man.’ Ignoring dilemmas raised in trying to justify or even rigorize such a distinction, he retreats still further, exempting monozygotic siblings as a special case because `even if they closely resemble each other, they do not resemble anyone else.’ Unfortunately for Williamson’s argument, the same can be said of clones and their clonees (except, say, if one of them happens to have a monozygotic twin, too…).

But even beyond the problems of defining rights, the identity question is moot. Simply put, clones are not genetically identical. To understand why, first recall an admonition that often pops up in the cloning debate: that environmental factors ensure the uniqueness of individual personality, aptitudes, and other large-scale (read: `non-genetic’) traits. If, for example, you rue the hackneyed vision of an army of Michael Jordan clones turning professional basketball into a Midas’s hell, check the numbers for a real life clone-of-a-sports-superstar. Outfielder Osvaldo Canseco hit exactly zero home runs in his major league baseball career; over the same seasons, his injury-prone monozygotic twin José hit 73, and swatted 389 more while Ozzie was relegated to the minor leagues or the celebrity impersonator circuit.  Incidentally, José has reportedly written that both he and Ozzie used anabolic steroid supplements during their careers; while that particular environmental factor may have helped José considerably, it apparently did little for his twin.

Vagaries of environment turn out to affect more than athletic performance (which, of course, has genetic underpinnings too); they also affect the genome. Because genomes mutate, each potential clonee has a mildly genetically diverse population of cells from which to clone; further mutation during the development of a clone itself nearly assures its genetic uniqueness. Bottom line: assuming plausible rates of cell division and random mutation, fewer than one in ten billion newborn clones would have even one cell genetically identical to the sperm-fertilized egg from which he or she was derived.

Moreover, cloning — especially for males — may require eggs whose proteins (which influence gene expression, and, thus, subtleties of development) and non-nuclear genomes (such as those of mitochondria, the rife bacteria which long ago established symbiosis within ancestors of our cells) differ from those of the fertilized egg that became the clonee. A somatic genome transferred into such a tabula non rasa egg has its own pattern of functionally meaningful chemical modification (called genomic imprinting), too, which typically needs thorough overwriting for cloning. More bizarrely still, many living humans are technically chimeras, harboring small numbers of somatic cells derived from a mother, child, or even sibling; such cells sometimes cross placental barriers during gestation, engrafting amid much larger populations of cells derived from another zygote.  In all the above cases, a clone derived from a single somatic cell represents a truly novel mix of heritable molecular inputs.

All told, the lack of strict genetic identity between clones and clonees voids any claim that cloning violates a right to genetic individuality. More importantly, it gives us more reason to treat clones as unique individuals, rather than to saddle them with overwrought expectations based on their genetic likeness to those we already know.  Sadly, Brigitte Boisselier’s sect announced their own plans for the latter: to try to shoehorn — wholesale — the unique personalities and memories of clonees into the uselessly novel brains of their wards. Cloning’s own technical challenges pale next to those of such a cruel endeavor; and such doubly vain goals alarm those who fear cloning as a means to human eugenics.