STAT recently released a phenomenal three-part video series on biomedicine in collaboration with Retro Report. The latter is known for their bite-sized documentaries that follow up on old stories and explore how they figure into today’s news. In this series they recount the hopes and aspirations associated with sequencing the human genome and precision medicine, and retrace the often tortuous history of biotechnologies past and present, from gene therapy to burgeoning gene editing tools like CRISPR.

In Part 2, we’re reminded of the discomfiting story of Jesse Gelsinger, whose death set the field of gene therapy back more than a decade. Gene therapy is one of our earliest attempts to correct for disorders arising from our DNA, with the first clinical trial conducted in May 1989 by the National Institutes of Health. At bottom, gene therapy tries to reverse the course of genetic disorders and other diseases, usually by inserting a working gene variant into the body to compensate for a faulty one.

Huntington’s disease, for example, is a rare neurodegenerative disorder caused by a mutation in the huntingtin gene on chromosome 4. (Naming genes by what goes wrong when they mutate is a popular convention in genetics.) Humans have two copies of this gene, one from each parent. If just one copy has the mutation that gives rise to the disease, the individual will inherit the disorder. We call this an autosomal dominant disorder, which according to the rules of inheritance, means that any child of an affected parent has a 50% chance of suffering the condition. Cystic fibrosis, on the other hand, is an autosomal recessive disorder, requiring two copies of the mutated gene to express the disease.

What gene therapy aims to do is supply the cells with a normal or non-mutated copy of the gene(s) responsible for these and other disorders. This was the goal behind Jesse Gelsinger’s treatment in 1999. The 18 year-old Gelsinger suffered from OTCD (ornithine transcarbamylase deficiency), a metabolic condition that impairs the body’s ability to process nitrogen in the blood. As with the others mentioned above, OTCD has a genetic explanation: it’s caused by a mutation in the OTC gene located on the X chromosome. Its inheritance is X-linked recessive, meaning men more commonly suffer from the condition than do women.

In a clinical trial overseen by James Wilson, founder of University of Pennsylvania’s former Institute for Human Gene Therapy, scientists used a viral vector to deliver an unmutated copy of the OTC gene into Gelsinger’s blood. The antigenic presence triggered a massive immune response, sparking a deadly high fever and lethal levels of blood clotting. Gelsinger did not survive.

Wilson and his research cohort quickly found themselves on the wrong end of political stilettos. The FDA, NIH, a Senate subcommittee, and his own university launched investigations and held hearings to probe the ethical, legal and scientific implications of gene therapy. Wilson, in addition to being sued by Gelsinger’s family and the Justice Department, was slapped with a five-year ban from human clinical trials. Around the same time, two others died in Europe from therapeutic DNA delivery, almost shuttering the field for good.

In the case of Gelsinger, his immune response and subsequent death were the result not of the insertion of the functioning allele but of the delivery mechanism — the viral vector. James Wilson’s team used what are called adenoviruses, specialized viruses that take up the functional DNA before being injected into the host. What we think happened is that Gelsinger had already been exposed to the particular adeno-associated virus used in the study. When the particles made it to his liver, his previously acquired antibodies induced the body-wide bout of inflammation that overwhelmed his immune system.

We still use viruses to deliver DNA in gene therapeutic trials. But Wilson and others have made great strides in the time since Gelsinger’s death, discovering a number of viral candidates far better suited for genetic treatments. The ones in use today are not only more efficient and provoke little to no immune response, they can also be tailored to specific types of human tissue, from muscle tissue to the liver and even the brain. Subjacent to a 2013 article by Carl Zimmer are a number of examples of disorders currently being treated by gene therapy interventions, including hemophilia, muscular dystrophy, blindness, and even nicotine addiction. To date, over 2,500 gene therapy treatments have been approved for clinical trials.

Gelsinger’s story underlines the at times tragic cost of clinical trials in exchange for future cures. As you’ll see in the videos below, many of the participants in these trials volunteer knowing that their decision could ultimately prevent others from suffering as they have. There are never guarantees in these arrangements, but the possibility of successful treatment of a debilitating disease often outweighs the risk for many patients.

Retro Report’s recap of the fall and rise of gene therapy helps set the stage for CRISPR, a genetic engineering tool that’s become a remarkably powerful way to edit DNA in any species. One key distinction to keep in mind when it comes to gene therapy and its successor, is that, unlike CRISPR, gene therapy doesn’t actually repair broken genes; it simply provides a working variant alongside the defective one. That is, the mutated one remains in place. With CRISPR, we are actually changing the DNA in living cells.

Because of this, it’s always been unclear how long gene therapy treatments, if successful, will last. In the case of one woman in the documentary who was treated for ADA deficiency at a young age, we learn that the therapeutic benefits subsided over time, and that she’s had to continually receive treatment over the course of her life. This is important because a successful gene therapy trial does not mean that the patients were cured or that the benefits they received from the treatment are persistent.

With CRISPR and other gene editing kits (there are several flavors), the mutated code is snipped out and replaced with healthy DNA. Rather than rely on viruses to deliver the DNA, CRISPR makes use of Cas9, an enzyme that can cut DNA directly. When the enzyme’s guide RNA finds a match within a selected strip of DNA, it deletes the matching portion, disabling it. A 3D illustration does wonders for understanding how this system works: Genome Editing with CRISPR-Cas9 by the McGovern Institute at MIT is still my favorite.
 

 
While CRISPR is currently being put to extraordinary use by humans, we didn’t invent this technology. We discovered it by studying bacteria, which have been using it as a defense against viruses and other foreign elements for hundreds of millions of years. Scientists have simply co-opted this natural mechanism by changing the guide RNA to match the specific DNA sequence we want to cut in an organism’s genome.

Where it gets interesting is what happens after the molecular scissors excise the target DNA. Normally, the cell’s repair mechanisms kick into gear and attempt to reconstitute the missing section of DNA. This process can introduce mutations that often end up disabling the gene altogether. Sometimes, knocking out the defective DNA is all that’s needed and we can stop there. In other cases we might want to replace the mutant gene with a healthy copy, effectively editing the DNA sequence. This is the step that’s proved a bit trickier in practice.

When Chinese researchers attempted this in human embryos, CRISPR managed to cut DNA in only a fraction of the 71 embryos that survived, out of a total of 86, and only in a fraction of those 71 did cells manage to take up the new DNA. In other words, 28/71 were successfully spliced, but only a few of the 28 ended up with the intended DNA. (Note that the Chinese team used non-viable zygotes only — i.e., the zygotes were fertilized by two sperm, so they had an extra set of chromosomes.) The ability of cells to take up a desired sequence of DNA without introducing off-target effects is where the rubber meets the road right now in genetic engineering.

CRISPR and other high-profile biotech have undoubted potential and are amazingly cool. But we still have a long way to go before we’ll be rewriting the DNA underlying SNP-related diseases like cystic fibrosis, sickle-cell anemia, Tay-Sachs disease, or breast cancer, or curing neurological disorders such as Alzheimer’s and Parkinson’s, to say nothing of enhancing or regulating traits controlled by multiple genes (see polygenic trait). The time required to refine our understanding of gene-based treatment, moreover, will provide us the necessary opportunity to assess these technologies at the level of ethics and define the boundaries of permissible application and misuse.

The hope is that one day these more precise molecular techniques now at our disposal will eliminate common genetic diseases entirely. But comparing today’s headlines with those of yesterday suggest that, in some ways, we’ve been here before. The under-delivered promises made alongside advancements in gene therapy and the $2.7 billion Human Genome Project should remind us of the untold complexity that awaits us as we delve ever deeper into the labyrinthine realm of biomedicine.

Enjoy STAT’s series The Code below.
 

External link:  ‘The Code’: roots of today’s most promising genetic technologies

Further reading:

• Gene Therapy Emerges From Disgrace to Be the Next Big Thing, Again
• Genome Editing with CRISPR-Cas9
• CRISPR: Gene editing and beyond
• How CRISPR lets us edit our DNA | Jennifer Doudna
• Breakthrough DNA Editor Born of Bacteria
• Biologist Explains One Concept in 5 Levels of Difficulty – CRISPR | WIRED

 
 
The Harris-Klein conversation was posted yesterday (audio + transcript here). Clocking in at over two hours, the duo give their best attempt to resolve their disagreements in real time. As I suspected in last week’s post-mortem, that didn’t happen. And in truth there is very little of note that wasn’t already fleshed out in the commentaries leading up to this debate. What we do hear is recapitulation with minor elaboration and a few moments of palpable frustration as the arguments refuse to land. So to the extent that one is still getting up to speed on this story, my previous post should do the trick.

What’s clear from the outset is that Harris’s ego is still perhaps the central problem blinding him to many of his own strong biases. This is literally how he frames the conversation from the get-go:
 

“I’m not saying that everyone who did the work, who listened to the podcast and read all the articles would take my side of it, but anyone who didn’t do the work thought that I was somehow the aggressor there and somehow, in particular, the fact that I was declining to do a podcast with you was held very much against me. That caused me to change my mind about this whole thing, because I realized this is not, I can’t be perceived as someone who won’t take on legitimate criticism of his views.”

 
Heaven forbid there is someone out there who thinks Harris backed down from a challenge. For someone so ostensibly committed to defending a person who subscribes to the intellectual inferiority of African Americans, Harris seems positively paranoid about any affront to his own intellectual standing. Imagine that. Better yet, imagine being the subject of Murrayism. Alas, this is more of a character quirk than substantive criticism of his ideas.

The reason this conversation never really made it off the ground is that their emphases are in different places and, where they overlap, are out of register with one another. Harris thinks Klein is underestimating the reputational hazards that attend participation in questions about the science of race and other precarious topics. Klein thinks Harris underappreciates the intricate social and historical context waiting around every corner of a conversation like the one he and Murray had. Harris, moreover, thinks these conversations run independently of one another; Klein thinks they’re more or less indissociable. And round and round they go.

Klein summarizes what he thinks is going on this way:
 

“Here is my view: I think you have a deep empathy for Charles Murray’s side of this conversation, because you see yourself in it. I don’t think you have as deep an empathy for the other side of this conversation. For the people being told once again that they are genetically and environmentally and at any rate immutably less intelligent and that our social policy should reflect that. I think part of the absence of that empathy is it doesn’t threaten you. I don’t think you see a threat to you in that, in the way you see a threat to you in what’s happened to Murray. In some cases, I’m not even quite sure you heard what Murray was saying on social policy either in The Bell Curve and a lot of his later work, or on the podcast. I think that led to a blind spot, and this is worth discussing.

I like your podcast. I think you have a big platform and a big audience. I think it’s bad for the world if Murray’s take on this gets recast here as political bravery, or impartial, or non-controversial. What I want to do here, it’s not really convince you that I’m right. I don’t think I’m going to do that. It’s not to convince you to like me, I don’t think I’m going to do that either, I get that.

What I want to convince you of is that there’s a side of this you should become more curious about. You should be doing shows with people like Ibram Kendi, who is the author of Stamped from the Beginning, which is a book on racist ideas in America which won the National Book Award a couple of years back. People who really study how race and these ideas interact with American life and policy.

I think the fact that we are two white guys talking about how growing up nonwhite in America affects your life and cognitive development is a problem here, just as it was a problem in the Murray conversation. And I want to persuade you that that some of the things that the so-called social justice warriors are worried about, are worth worrying about, and that the excesses of activists, while real and problematic, they’re not as a big deal as the things they’re really trying to fight and to draw attention to. Maybe I’ll take a breath there and let you in.”

 
This cuts right to the chase. The Murray conversation was problematic not merely for its presentation of the mainstream science, but for its neglect of the social and historical considerations with which that science intersects. This is hardly a pardonable oversight given the context. If their chosen topic had been about, say, genetic biomarkers for cancer, no one would have chastised them for not bringing up racism in America. The topic they discussed, however, was race-related differences in IQ. And the reason the additional context matters — and why its omission can’t be overlooked — is firstly because the underlying science has often been used to justify the status quo and advance contemptible political agendas, and secondly because the past and present inequality of American life has contributed to and is responsible for the very outcomes we observe today.

In his opening remarks above, Klein fully concedes that while certain strands of leftist activism are “problematic,” they pale in comparison to the societal ills conspicuously absent from the Murray-Harris podcast. He further traces this imbalance in perspective to Harris’s deep-seated concerns about being misrepresented and the smear tactics of which a number of his ideological adversaries frequently avail themselves. For these reasons, Klein argues, Harris sees in Murray a fellow traveler, even if he doesn’t sign onto the raft of social policies Murray recommends.

To his credit, Klein seems equally adept at navigating the scientific and social dimensions to these issues, while Harris seems none too interested in the latter. Indeed, he even claims at one point that “[t]he weight of American history is completely irrelevant [to the scientific discussion of race and IQ]”. Klein notes that it can’t possibly be irrelevant when the weight of the science points to environmental influences as accounting for measured differences in racial IQ. Here we have another ironic twist in that Harris, who often chides others for denying the tiniest genetic influence on IQ differences across groups, is arguing that the natural experiment of American history is totally disconnected from observable outcomes. Somehow I doubt anyone actively studying race-related questions, including Murray, would go this far.

Klein also came prepared, having spoken on the record with both James Flynn and Eric Turkheimer prior to doing the podcast, both of whom reiterated their scientific disagreements with Murray. True to form, Harris is quick to paint these disagreements as ‘PC culture’ run amok, claiming that these actually are political considerations taking the place of serious scientific criticism. This, of course, is the same Harris who accuses others of claiming to read minds. But when Harris makes the same implicit claim, he is apparently reasoning from a place of good faith.

Which brings us to the last substantive critique of Harris that I want to highlight, which Klein lays out nicely here:
 

“Here’s my criticism of you. I don’t think you realize that the identity politics software is operating in you all the time and, I think it’s strong.

When you look at literature on the conversation about race in America, you often see the discussion broken into racists and anti-racists. That’s something that you’ll read often in this debate. I think there’s something else, particularly lately, which you might call anti-anti-racism, which is folks who are fundamentally more concerned, or fundamentally primarily concerned, with the overreach of what you would call the anti-racists. And, actually that’s where I think you are.

One of the things that I hear in you is that, whenever something gets near the questions of political correctness — the canary and the coal mine for the way you yourself have been treated — you get very, very, very strident. They’re in bad faith. They’re not being able to speak rationally. They’re not being able to have a conversation that is actually going forward on a sound evidentiary basis. The thing that I don’t think that you’re self-reflective enough about — and I apologize, because I know that “I” statements are better than “you” statements, but I do want to push this idea at you for you to think about it — is that there are things that are threats to you. There are things that are threats to your tribe, to your future, to your career, and those threats are very salient.

You see what happens with Charles Murray, the kind of criticism he gets, and that sets off every alarm bell in your head. You bring him on the show and you’re like, “We’re going to fix this. I’m going to show that they can’t do this to you.” You look around and you say, “Ezra, you think we shouldn’t take away all efforts to redress racial inequality? But that’s a bias. You’re just being led around by your political opinions, where I am standing outside the debate acting rationally.”

To me that’s actually not what’s happening at all. I think you’re missing a lot, because you are very radically increasing the salience of things that threaten your identity, your tribe — which is not the craziest thing to do in the world, it’s not a terrible thing to do, we all do it — without admitting, or maybe even without realizing, that’s what you’re doing.

I think that there is a lot of discussion like this in the public sphere just generally at the moment. There are a lot of white commentators, of which I am also one, who look at what’s happening on some campuses, or look at what happens on Twitter mobs, or whatever, and they see a threat to them. The concern about political correctness goes way, way, way, way up. Then the ability to hear what the folks who are making the arguments actually say dissolves. The ability to hear what the so-called social justice warriors are actually worried about dissolves. I think that’s a really big blind spot here. I think it’s making it hard for you to see when people have a good faith disagreement with you, and I also think it’s making harder for you to see how to weight some of the different concerns that are operating in this conversation.”

 
I think we do in this conversation get a better sense of Harris’s understanding of ‘identity politics’. For him, it’s something that other people engage in to lend unjustified credence to their arguments and positions. While he describes the phenomenon as using one’s skin color or gender to gain undue leverage in debate, in practice he often uses the term as simple code for tribalism, or to describe people whose motives for engagement are suspect and unfounded.

At the same time, he sees himself as somehow immune to these impulses. He honestly sees himself as sitting above the fray, reasoning from a purely Rational™ standpoint. His position is borne of sound principles, the other side’s of ideology. His views are dispassionate, unbiased, and uncorrupted, while the opposition — which must include the many well respected scientists who’ve responded to Murray’s work over the years — is contaminated by identity politics and extrascientific agenda.

When Klein offers that confirmation bias and motivated reasoning might just be at work in Harris’s own approach to these conversations and, indeed, might explain why he is so quick to ascribe bad faith and malice to his detractors, including Klein, Harris demurs and doubles down, insisting that he’s “not thinking tribally.” Rather, the default explanation is that he and Murray have been unfairly maligned by dishonest parties who happen to share all the same concerns about the social implications that he does.

The fact is that anti-social justice (what Klein refers to as “anti- anti-racism”) is its own tribe, with its own tendencies toward cognitive fallacies and moral panics and all the rest. And Harris has always seemed more concerned with defending this particular tribe (read: his tribe) than using his intellectual capital and zeal to speak truth to the injustices and abuses of power that actualize social change movements. As Klein suggests more than once, this might be because Harris sees a part of himself in folks like Murray. He feels threatened by the march of social justice, anxious that he’ll be the next Murray-esque casualty in the crusade against destructive speech.

One of Klein’s gifts is his ability to step back and analyze ensuing debates and disagreements and set them in wider contexts, whether it be racial disadvantage in America fueled by discriminatory policies or the flaws in our own human psychology. The excerpts above demonstrate this well. Harris seems utterly incapable of — or unwilling to engage in — that level of panoramic depth or self-examination, preferring to beat the same dead horse relentlessly until it wakes up and apologizes for not seeing matters his way. I think Harris is so invested in his views that he can’t introspect enough to see or own up to his own cognitive and perceptual limitations.

I had hoped against all odds that Sam’s conversation with Ezra would be a turning point. I hoped Sam might at last acknowledge that he, like every one of us, is susceptible to his own set of tribalist tendencies. Instead, it became an exercise in navel-gazing, and yet another seized opportunity to rant against the identity politics he sees as operating in everyone but himself.

External link:  The Sam Harris debate

Further reading:

• Sam Harris Still Can’t Take a Hint
• The Bell Curve isn’t about science, it’s about policy. And it’s wrong.
• I begin to sense a pattern
• Sam Harris and the Myth of Perfectly Rational Thought

Image credit:  samharris.org

 
 
Color me saddened, but not at all surprised, to see that Sam Harris is still the insufferable egoist he’s always been. By airing another of his long-winded email tantrums — this one directed at Ezra Klein, Vox’s editor-at-large — he’s let his childlike petulance further erode his status as a public intellectual, and, by doubling down on his defense of Charles Murray, resumed his rightward pull in the process. Whatever we might think of Murray’s science and Harris promoting it, one thing is certain: it takes an inflated sense of self-importance to think publicizing this joust like so much dirty laundry was a good idea.

We’ve been here before, of course. He pulled the same stunt with Greenwald and Chomsky, and my impression hasn’t changed. To wit: Harris sounds like an annoying mosquito that won’t stop buzzing around Klein. Harris, for whatever reason, walks away feeling sufficiently vindicated to post the exchange on his blog. Klein walks away relieved that the mosquito isn’t buzzing around him any longer.

And this time, Sam may have finally jumped the shark. Ezra Klein seems an unlikely target for scorn, but Harris’ feverish preoccupation with deplatforming and political correctness helped secure this fate. His endorsement of Murray’s scientifically dubious and morally damaging theses about race, his incessant huff-fests about social justice culture in academia, his chummy nature with Ben Shapiro, and his defense of free speech absolutists like Milo Yiannopoulos have earned Harris a fair number of alt-right fans, including Trump supporters. In fact his audience has grown so full of them that he’s had to address them on several podcasts. You don’t get here without dabbling in and expressing some patently right-wing rhetoric.

So how did we get here exactly? To bring latecomers up to speed, here’s the play by play in a nutshell. Sam Harris had political scientist Charles Murray on his podcast. After Vox published a piece responding to the science presented in Sam’s discussion with Murray, Harris went after Klein directly via email. Some half dozen missives later, a stalemate ensued, culminating in this week’s post-mortem of the whole affair by Klein.

Based on their correspondence, it’s clear Harris regards Klein as a bad-faith actor, when any honest reading of their exchange demonstrates the opposite. Harris’ self-absorbed nature and near-pathological inability to admit a wrong commits him to seeing malice and Tartuffery where mere professional disagreement exists. The message for any hapless soul daring to engage New Atheism’s beloved pansophist is clear: you either bask in the radiant wisdom of Sam’s polemic, or you’re an evil scheming liar — there is no middle ground.

It has to be mentioned that I know of no one else who can boast of such a consistent pattern of failed interactions with reasonable, highly intelligent, widely respected individuals. His back catalog of podcasts is an absolute junkheap of conversational carnage, and reflects poorly on his ability to communicate. That Harris has such an infamous record of public impasses and burned bridges with diverse voices and thinkers says more about him than it does about anyone with whom he’s sparred. At some point you have to admit that he’s the common denominator here, that he might be the problem and not everyone else.

There’s also his strange obsession with publishing private email exchanges. Not only does it smack of voyeurism and self-seeking drama indulgence, it’s also incredibly lame, unbecoming of a serious intellectual, and possibly exploitative since he did not receive Klein’s permission to do so. Once again, as so many times before, Harris utterly fails to impress.

On the other hand, Ezra Klein’s latest, in which he responds to these controversies, is unremittingly brilliant, and one of the best commentaries on the intersection of America and racism I’ve read in a long time. Few can write like Klein, and I’m grateful he has brought his talents to bear on these critical issues. His masterful expatiation deserves to be shared widely and read often, even if you’re new to this topic and have no interest in questions about the relationship between race and intelligence. This is the “care and context” missing in the discussion between Harris and Murray.

Klein points out that any discussion of race and IQ which fails to acknowledge America’s centuries-long struggle with racism, including slavery, segregation, and institutional violence, is bound to be woefully incomplete and ahistorical.
 

“Over hundreds of years, white Americans have oppressed black Americans — enslaved them, physically terrorized them, ripped their families apart, taken their wealth from them, denied their children decent educations, refused to let them buy homes in neighborhoods with good schools, locked them out of the most cognitively demanding and financially rewarding jobs, deprived them of the professional and social networks that power advancement.”

 
And that’s all before you get to the more nuanced conversations about heritability, the interaction between genes and environment, and whether it even makes sense to talk about ‘racial’ discrepancies — as opposed to geographic discrepancies — in intelligence or other DNA-quantifiable traits. Notably, Klein declines to weigh in on these more science-oriented questions. As he makes clear in his exchange with Harris, neither of them are geneticists, and intellectual discretion dictates we leave those matters for more capable hands. What he does feel compelled to relate are the environmental influences that have shaped the trajectory of African Americans in this country and the grievous ways in which racist actors have used and abused genetics to further oppression of marginalized groups.
 

“Here is my view: Research shows measurable consequences on IQ and a host of other outcomes from the kind of violence and discrimination America inflicted for centuries against African Americans. In a vicious cycle, the consequences of that violence have pushed forward the underlying attitudes that allow discriminatory policies to flourish and justify the racially unequal world we’ve built.

To put this simply: You cannot discuss this topic without discussing its toxic past and the way that shapes our present.

Whatever the future holds, the idea that America’s racial inequalities are driven by genetic differences between the races and not by anything we did, or have to undo, is not “forbidden knowledge” — it is perhaps the most common and influential perspective in American history. It is embedded in our founding documents, voiced by men with statues in their likeness, reflected in centuries of policymaking. It is an argument that has been used since the dawn of the country to justify the condition of its most oppressed citizens. If you’re going to discuss this topic, that’s a history you need to reckon with.”

 
For his part, Sam Harris seems more concerned about the politics within academia — attributing the controversy surrounding Murray’s research to “dishonesty and hypocrisy and moral cowardice” — than he is with the actual scientific value of what Murray is claiming. That’s why he classifies scientific arguments against Murray as evidence of academia discriminating against Murray, and not as genuine scientific arguments. Klein addresses Harris and Co.’s mushrooming concerns about “PC culture” head-on, and cuts them down to size.
 

“One problem with the political correctness debate, however, is we’re quick to demand a sense of proportion and prudence from college protesters even as we ignore related sins of partiality and overreaction in nationally recognized commentators. I often see pundits — Harris included — who seem far more afraid of “PC culture” than the problems PC culture is trying to address. On some level, that’s understandable. If you’re a white male pundit who trades in controversial opinions, PC culture probably does pose more of a threat to you than the inequalities it means to fight.

Perspective is key here, though. The victims of the toxic idea that Americans with dark skin are biologically destined to be, on average, intellectually inferior to Americans of light skin are not the white men who have promoted it but the black Americans who have endured it. And when your explorations of these debates don’t seem to understand that, you feed the worst fears of the PC culture you’re trying to calm.”

 
Klein nails it. Whatever misgivings we might have about leftist overreach must always be tempered by the more consequential concerns about the injustices and misuses of power those movements are working to face down. It’s precisely this unfeeling misappropriation of outrage that permeates Harris’ rhetorical repertoire. Over the course of several years, he has used his sizable platform not to advocate for equality and fair treatment for those less fortunate, but to rail against the activist left. Given the right’s inexorable slide into authoritarianism, idiocracy, and wealth and justice inequality, there is simply no excuse for framing social justice activism as the central problem of our time.

And it’s here that Klein truly outshines whatever presence Harris seems to think he occupies in this conversation. He flips the script, redirecting the spotlight away from Murray and his alleged bad rap and onto the history of racial injustice to which less privileged Americans owe their unequal outcomes. There’s a certain diplomatic eloquence on Klein’s part as he explains why there’s nothing remotely brave about two white men sitting around chatting about race-related differences in IQ when it is they who have been the principal beneficiaries of the racist policies on which those conversations have historically relied. His finishing stroke:
 

“In this country, given our history, discussions about race and IQ need more care and context than they get. As a starting point, rather than being framed around the bravery of the (white) participants for having a conversation that has done so much damage, they should grapple seriously with the costs of America’s most ancient justification for bigotry, and take seriously why so many are so skeptical that this time, finally, the racial pessimists are right when they have been so horribly wrong before.”

 
Perhaps what’s most regrettable about this whole saga is that it was unnecessary and avoidable. Both are clear thinkers who eschew facile arguments and care earnestly for truth and civil discourse. But thanks to his penchant for verbal conflict, Sam has now pitted Klein, a natural ally, as a sworn enemy, and his rabid fans are all too keen on treating Klein accordingly. The vitriolic mood with which Harris approached and characterized their exchange ensured this outcome, closing off any possibility of future collaboration. While I could have imagined some interesting cooperation on future projects where their values and political views overlap, that seems unlikely after this very public, very messy ordeal. I’m afraid I can’t see anything positive or productive coming from a podcast at this point either, especially since I’m unable to recall a single instance of Harris changing his tune with someone for whom he’s already summoned the pitchforks. And if his series of self-coronating tweets this week are any indication, it doesn’t look as though a merging of minds is in the forecast. It’s a shame, really, albeit predictable given Sam’s track record.

Post-Script: What’s This Debate About Anyway?

For those who may not be up to speed on the longrunning scientific debate around group variation in intelligence, my admittedly lay understanding, in obnoxiously paraphrased form and subject to heavy revision, is as follows:

As with most uniquely human traits, genetics and environment are both surely involved in determining intelligence. When it comes to measured differences in IQ among racial or ethnic groups, the “debate” (which has actually been settled for quite some time) is over which factor matters more, and how much we should emphasize each factor regardless of the size of its actual effect. The balance of evidence to date strongly suggests that the mean differences in IQ scores across human populations — and indeed, human variation in general — are best explained by environmental or cultural differences, not genes, even if we can’t slap precise percentages on these variables. This makes sense given that Homo sapiens as a whole has relatively low genetic diversity — four times lower, in fact, than our closest living relative the chimpanzee — leaving nongenetic factors to account for these observed differences.

Harris & Murray et al often put up a straw man by saying their detractors deny any genetic basis whatsoever for group differences in IQ, and that this denial stems from a left-leaning political agenda. In reality, intelligence researchers are open to the possibility of genetic explanations but see nothing persuasive in the evidence — which is to say there is no known genetic basis for any gap in any data set of IQ scores. Meanwhile, pretty much every well designed study that looks at environmental factors and intelligence finds something significant. Detractors of Murray & Co. argue that race is a biologically invalid concept, that the IQ gap between black and white Americans is predominantly environmental in origin, and that we shouldn’t be having this discussion anyway without properly contextualizing the sordid history of racism in human societies.

So the crux of the debate is over how significant a role DNA plays and the degree to which we should recognize the role of culture and socioeconomic circumstance in shaping both group IQ differences/other outcomes and the genetic patterns themselves.

Obviously, there is much more to say on the subjects of race and IQ, so I’ve assembled below a loosely chronological compilation of resources that should help prepare those who wish to follow along the next time this heated topic inevitably arises.

External link: Sam Harris, Charles Murray, and the allure of race science

Further reading:

• Charles Murray is once again peddling junk science about race and IQ
• No Voice at VOX: Sense and Nonsense about Discussing IQ and Race (counterpoint)
• There’s still no good reason to believe black-white IQ differences are due to genes
• How Genetics Is Changing Our Understanding of ‘Race’
• How Not To Talk About Race And Genetics
• Denying Genetics Isn’t Shutting Down Racism, It’s Fueling It (counterpoint)
• Sam Harris responds to Ezra
• Race, Genetics and a Controversy
• The Fault in Our DNA: ‘A Troublesome Inheritance’ and ‘Inheritance’
• Letters: “A Troublesome Inheritance”
• A Troubling Tome
• The myth of race: Why are we divided by race when there is no such thing?
• 11 ways race isn’t real
• Racecraft: The Soul of Inequality in American Life
• Race Unmasked: Biology and Race in the Twentieth Century
• The Myth of Race: The Troubling Persistence of an Unscientific Idea
• Solving the riddle of race (pdf)

Feature image credit:  Javier Zarracina/Vox

 
 
Faced with questions of personhood and human identity, there is perhaps nothing more unequivocal you could point to than your genome — your personal genetic signature. But what if there isn’t just one genetic signature to which you play host? And what if one or more of those signatures is from another person entirely?

A series of recent studies promises to pile additional layers of complexity onto the already heavily ramified field of genomics. In the NY Times, Carl Zimmer introduces us to evidence that will change how we think about the human genome.

We often think of our cells as specialized entities serving different functions but all housing the same genetic information. It may come as a surprise, then, to know that a cell swabbed from our cheek can have an entirely different genetic code from that of a plucked hair, for example, or from a neuron in the brain. In fact, if you were to sequence a random sample of cells from the same host, you might find a potpourri of genomes, with some even belonging to another person.

The pair of phenomena associated with these intra-organism variations are formally known as mosaicism and chimerism. We’ve known about the former since the 1930s when American geneticist Curt Stern demonstrated the occurrence through mitosis, a natural cell process utilized by every eukaryotic organism.

© Garland Science

When a female egg is fertilized, a single genome — a marital blend of the two parent genomes — emerges. At this stage, there is just one cell with one genome, called a zygote. That cell then divides to form an embryo, but mitosis is an imperfect and infrequently sloppy process. The replicants are often not perfect clones of their parent cells, and genetic dissimilarities can arise. The mutant cells of course also divide, thus birthing the embryo and resulting organism with different sets of genetic instructions. One set may grow into the tissue that forms the lungs, while another may develop into a vital organ.

This scenario is known to occur not only during embryogenesis, but at any stage of a species’ life. Put simply, these mosaic derivatives can pop up at any time as a function of the disorder inherent in various stages of cell division.

Chimerism, by contrast, also occurs in utero but is the result of two or more zygotes swapping cells back and forth in the womb on their way to becoming an embryo. If these cells make mitotic headway in certain locations in the body, twins may share certain cells in common.

Another manner in which a foreign genome can be introduced and spread is from an organ transplant. One study at Innsbruck Medical University found that 74 percent of patients contained the genome of the donor in addition to their own, a full nine years after the transplants were performed.

While initially received with little skepticism, the idea that any cell taken from anywhere in the body will have identical DNA is now just too simplistic a view of biology. Until recently there simply hasn’t been enough original research into this area to conclude how widespread mosaicism and its cognates are.
 

We have also found that many women harbor cells that contain Y chromosomes. How is this possible? It turns out that genetic material can be passed from fetus to mother. The placenta — nature’s all-in-one life support system — allows for bidirectional exchange of various nutrients and fluids. Embryonic cells can also be left behind after the birth of a child, which can then multiply and assimilate into neighboring tissues.

“It’s pretty likely that any woman who has been pregnant is a chimera,” Dr. Randolph said.”

Indeed, these are not fringe cases which demand unique explanations, but evidenced by several focused studies to date. Zimmer recounts one such study conducted last year.

“In 2012, Canadian scientists performed autopsies on the brains of 59 women. They found neurons with Y chromosomes in 63 percent of them. The neurons likely developed from cells originating in their sons.”

What about blood type? Is it possible to have not one but two different blood types? Indeed it is. Mothers and fetuses can intermingle red blood cells during and after gestation. That means if you’re a mother you may have some Type A cells and some Type O cells, for example. While women who carry fetuses with incongruous blood types normally develop antibodies to suppress them, the mismatched type often lingers in the blood stream long after the baby is born.1

Challenges Ahead

Our newfound view of cellular nonconformity is certain to have rippling import for everyone from geneticists and oncologists to forensic investigators. To be sure, multiple DNA sequences deflate some of the confidence services like 23andMe and other genetic counseling and personal genomics services can provide. Sequencing the genome of a single group of cells with one suite of medical predispositions and physiological baselines doesn’t tell you anything about cells with a different genetic manual.

Medical practitioners will need to work out how the presence of multiple genomes impacts the host. Specifically, we need a better understanding of how isolated blotches of a “foreign” or mutant genome fit into the overall genetic canvas. Is genetic diversity spread across different sites of the body something that promotes proper health, or is this cause for concern?

As you can imagine, such a situation can also create headaches for forensic scientists working to establish identity of victims and criminals.

“Last year, for example, forensic scientists at the Washington State Patrol Crime Laboratory Division described how a saliva sample and a sperm sample from the same suspect in a sexual assault case didn’t match.”

With this and other research into the microbiome, it’s clear that speaking of our genome in the singular is no longer tenable. We are curator to a mosaic of genetic programming, and the implications and links to medical science will take time to fully dissect. If this latest research has shown us anything, it’s that no neat and tidy schema for reality is immune to being ruptured by new evidence.

External link: DNA Double Take

Further reading: You can actually have two sets of DNA

1. In rare cases, it is even possible for your blood type to change. As mentioned, an organ transplant can alter the genetic makeup of the recipient, but certain kinds of transplantation can even overwrite the patient’s blood type over time, such as bone marrow transplants. To prevent body-wide rejection, doctors will ideally use a donor that is a match in blood type and other biomarkers, especially human leukocyte antigens (HLA), but once the recipient’s marrow is replaced, it will begin pumping out the donor’s blood cells. It may take several weeks or months for the original blood type to be replaced entirely, but eventually it will.

 
 
In 1951 doctors at Johns Hopkins in Baltimore diagnosed an unusually extreme case of cervical cancer. The breakneck growth rate and resistance to common remedies were unlike anything previously seen. Without informed consent, the doctor scraped a clump of cells from the cancerous tumor during one of the 30 year-old woman’s visits and deposited them with a nearby cell culture lab operated by George Gey. There, in the air-controlled space of Gey’s facility, something happened that researchers had long suspected out of reach.

Where countless other cells before them had died, hers survived, and multiplied indefinitely. The immortality of this one cell line would prove instrumental in treating a number of the world’s most heavy-hitting diseases and set the stage for an all new era in cell research, medical diagnosis, drug development, and bioethics. But this is a story not just about bundles of cells, but about the humanity behind them, and in particular the family to which they will forever be tied.

That woman was Henrietta Lacks. Henrietta passed away just nine months after her diagnosis, but it would be more than two decades before her family received word of the namesake cell line which survived her — HeLa. Its value as a scientific and commercial commodity was paramount, getting bogged down in the thicket of rights and privacy less so. Once researchers discovered that Henrietta’s cells did not die but instead bred a new generation every twenty-four hours, HeLa quickly became the tireless workhorse of the culture community. Vials were trucked to research facilities around the world, where they were regularly exposed to a pavilion of infectious diseases, merged with non-human DNA, and even shot into space in an effort to study the influence of zero gravity.

Over time, details about the parent of the eponymous cells funneled out of view. Henrietta’s own kin were oblivious to the fact that her cells still lived, were being actively studied and tested in dozens of countries, and were even being exchanged at great profit.1 Once the unwitting donor’s official name was released, journalists descended in full fervor, leading to a lifetime of turmoil and unrest for the Lacks household. Set against the rich legacy of the family’s cells, their life of poverty and unpaid medical bills seemed untoward, and this sense of injustice only mounted as more details filtered in from the press.

Rebecca Skloot’s segue into this lush narrative was by and large a product of serendipitous circumstance, having first heard of HeLa in an intro to biology course at her local community college. After learning that these cells had lived outside of their host’s body for the better part of a century, and about the remarkable advances they have gifted to science, Skloot shot up her hand and innocently asked, “Who was she?” The professor’s reply proved unsatisfying: “An African American woman.” The seed of curiosity had been planted. By the time Skloot graduated she’d decided to write a book to recover this disremembered woman whose cells had won so many posthumous victories for science and society.

Who Was Henrietta Lacks?

For more than a decade, Skloot layered herself into the Lacks’ story, befriending and forming deep bonds with Henrietta’s children and cousinry. She forges an especially strong connection with Deborah Lacks, Henrietta’s youngest daughter, who was unfortunately too young to remember much about her mother. With a mix of patience and persistence the two work together to dig up Henrietta’s heritage and bring to light her hitherto uncelebrated legacy. It is Skloot’s at times unstable relationship and camaraderie with Deborah that gives the narrative its steam, as the two probe ever deeper into the mystery surrounding her mother.

Tracing the family’s roots fixes Henrietta’s childhood at the tail end of the Jim Crow era, a time when segregation meant a great deal more than which bathroom and water fountain one was required to use. Rampant legal disadvantages in the South bred systemic, institutionalized deprivations for Blacks, and this included limited access to medical care. Having spent her youth on a slave plantation in Clover, Virginia, Henrietta joined in the Great Migration at the ripened age of twenty-one, exchanging her familiarity with tobacco fields for a new life in Baltimore. Nine years later, she would be diagnosed with the malignancy that led to her iconic cell line. And it would be another fifty years before Deborah, with the help of Skloot, laid eyes on her mother’s original medical records.

Johns Hopkins Hospital was founded for the express purpose of treating Baltimore’s poor and, unlike today, informed consent upon providing blood or tissue samples was neither required by law nor common practice (the term did not even appear in a court document until 1957). Like everyone at the time, Henrietta hadn’t a clue about what would become of her excised genetic material and the boons it would — or could — lavish upon the scientific community. This became a flashpoint issue in the years that followed as the occasional patient attempted to turn a gray area into a lucrative venture. While we learned more about DNA and transmissible disease, Henrietta’s resilient cells inaugurated an international conversation on the commercialization of biological materials and where exactly donors fit within that ecosystem. In many ways, the conversation is ongoing.2

The HeLa Legacy

To properly gauge the vastitude of the legacy tied up in Henrietta’s cells, it’s important to understand twentieth century cell culture. Until Henrietta came along, cell immortality was a pipe dream. While standard, non-cancerous cells had been grown in vitro since 1907, none of them survived long enough to endure important testing, petering out after 50 divisions on average.3 Even cancer cells, like those common to cervical cancers, died shortly after relocation to the culture environment. This meant not only was there a brief window for experimentation but that a continuous supply of fresh cells was needed to sustain research. Many in the field yearned for a better way.

HeLa keynoted a paradigm shift. They were robust enough to survive in the bricolage of materials used in Dr. Gey’s culture medium, and they were susceptible to the same range of infectious diseases as were normal cells. This allowed researchers to inject the lively DNA with diseases as well as cures. Much more than a newfound convenience, this revolutionized the medical and biological sciences, so much so that one of the researchers Skloot interviews in the book, when asked what would happen if HeLa was pulled from research use, replied, “Restricting HeLa cell use would be disastrous. The impact that would have on science is inconceivable.” (p. 328)

Thanks to Dr. Gey’s partnering efforts with labs around the globe, the benefits of HeLa manifested seemingly overnight. One year after HeLa’s discovery, Jonas Salk and his team were able to derive a vaccine for polio by infecting HeLa cells, followed shortly by drug treatments for HPV, herpes, leukemia, influenza, hemophilia, and Parkinson’s disease. In 1953 HeLa became the first cells to be cloned successfully. In total, some 60,000 papers have been published on HeLa, and cell culturists still use her cancer cells as a model for human biology.

Just what was it that gave HeLa cells their added dose of moxie? Even today, we can only speculate. We now know that Henrietta was infected with both HPV and syphilis, so one theory is that this virulent combination may have helped suppress PCD. A rival theory suggests she had highly atypical genes to begin with, perhaps a rare mutation, that enabled the cancer to spiral in unspecified directions. A good deal of uncertainty remains. HeLa has also been a source of much frustration over the years from regularly contaminating other cell lines, often halting research until the botch-up is sorted.

Closing Thoughts

Rebecca Skloot’s ten-year effort is a literary and cultural marvel balanced between unsheathing the humanity behind one of the richest stories in all of science and laying bare the bioethical implications to which it is attached. It succeeds on both fronts. Skloot is at her most exhilarating when channeling the lens of Deborah Lacks as they band together to reach some much-needed closure to the saga thrust upon the Lacks family. With her first book, Skloot has demonstrated in equal measure her facility for conveying scientific nuance while weaving meaning and poetic force into a cohesive whole. While this is first and foremost a work of nonfiction, its pages are emblazoned with enough touches of novel-like charisma to beckon both crowds. The Immortal Life of Henrietta Lacks is a timeless narrative delivered by a gifted writer and the definitive presentation of the legacy Henrietta never lived to see. Highly recommended.

Skloot also founded The Henrietta Lacks Foundation – click here for more – to provide support for the Lacks as well as assistance to African Americans pursuing education in science and medicine. A portion of her book’s proceeds are donated to the Foundation.

Note: This review is mirrored over at Goodreads and at Amazon.

Further reading: 5 important ways Henrietta Lacks changed medical science

1. The biotech outfit Microbiological Associates began selling HeLa for profit as early as 1952.

2. Skloot includes a superb summary in the afterword which draws together the various threads of this nuanced debate. The clinic-patient relationship is somewhat different today, though still more opaque than some regulators call for. As of this writing, there is no law requiring informed consent (i.e., signed permission) before submitting to any DNA sample. Nor is there any law stipulating that patients be informed of their tissue’s commercial potential. There have been a few high profile court cases, but “no law enacted to enforce the ruling, so it remains only case law.” (p. 326) Most medical institutions today do provide consent forms, but the loose regulation means the language employed is inconsistent and often vague.

3. Otherwise known as the Hayflick limit.

 
 
Life on earth is symbiotic. We are deeply interconnected with and inseparable from the rest of the biosphere. This deep alliance manifests in our genetic distance from other animals and plants, and by the vast array of microbes for which we serve as worthy hosts.

As many as 1¹² microbes are at this very moment foraging and scuttling about inside each and every one of us, some providing beneficial aid, some promoting harm, and some just along for the ride. Our ties run deeper, however. Advanced sequencing methods show that a whopping 8% of our genome is inherited viral DNA. Moreover, 37% of human genes have homologs in bacteria and 28% are traceable to unicellular eukaryotes.

This tangled web of co-dependency suggests that studying humans and other animals in isolation no longer makes sense. Instead of viewing ourselves as freestanding individuals, we are perhaps best thought of as integrated biological ecosystems. Bacterial colonies with legs.

A recent piece on i09 probes this connectedness by asking a question indissociable from Darwin’s great theory: is every living thing on earth related? After all, to talk about Darwinian evolution is to talk about universal common ancestry (UCA), the idea that all of life on earth is genetically linked to a single progenitive forerunner. Dogs, corvids, cetaceans, worms – if you follow the chain far enough back in time, you’d eventually converge upon a primordial bundle of life which gave rise to the biodiversity witnessed today.

We still can only speculate on the specific characteristics of this last universal ancestor (LUA), but recent statistical analysis provides further support for this key pillar of Darwin’s theory. Douglas Theobald, a research professor at Brandeis University in Massachusetts, now lends compelling mathematical evidence toward UCA and against multiple ancestry.

Theobald and his team started with twenty-three proteins common to twelve different organisms alive today. The twelve chosen are distributed evenly (four a piece) among the three basic domains of life: Archaea, Bacteria and Eukarya. Using model selection theory, the team then ran the genetic sequences to determine whether single or multiple ancestry was more likely.
 

Various patterns of descent can be grouped according to how much commonality organisms share in terms of their DNA. This can easily be done for specific phyla, but the statistical work done at Brandeis integrates all three of life’s branches, concluding that the overlap in gene relationships points to a genetic center, existing most likely 3.5 to 3.8 billion years ago. A number of variables were fed into their model, choosing to rely on more than just sequence similarity. The results strongly favor single ancestry over a multiply threaded origin scenario.

Various attempts have been made to distill and visualize earth’s great chain of being. The collaborative, peer-reviewed Tree of Life Web Project, which began back in 1995, is a superb rendering of relatedness and perhaps the best source freely available. Go ahead. Meet the family below.

Courtesy of the Tree of Life Web Project

The image (click here for a larger view) collates all major phyla and locates them according to the best available molecular and cladistic data. It’s a tidy picture of the history of life on earth.

While we have much to learn about the details, the results are in: we are intertwined with an imponderably vast chain of life reaching back to precellular material and to the interstellar maelstroms from whence it derived. We share kinship, however distant, with every form of life on earth – with those that once paced and stalked the steppes of Europe, with those that paddle and float in the chemosynthetic depths of the Pacific, with those that soar, swoop and sail the skies above us, and with those that have yet to come.
 

External link: Is every living thing on Earth related?

Feature image: “Redwood Extreme” by colindub.com

 
 
Over at his blog, Jerry Coyne silences the recent hype over intimations of another “humanness” gene. It’s an idea frequently propagated by the hinterlands of irresponsible journalism. In an effort to explain the looming question of just what it is that accounts for the vast phenotypic difference, albeit minor genetic difference, between humans and our closely linked mammalian cousins (e.g., chimpanzees, bonobos), overzealous journalists tend to seize upon each new gene as representing the essence of Homo sapiensness. We saw it with the FOXP2 gene, and here again with miR-941, a short sequence of microRNA.
 

What, then, can account for our oversized brains, advanced vocal tract allowing for speech development and our seemingly more complex neural outputs in contrast with other primates and mammals? One question we might consider is whether it is possible that a single genetic change (such as the appearance of miR-941) could have altered the primate brain in such a way that it set off the rapid growth of brain size and functional complexity reified in the human species?

We know, for example, how primate brains have been shown to enlarge in certain cortical regions once new information or actions are learned. Is it possible that miR-941 enabled specific cortical areas of the brain to respond more readily to previously non-integrated cortical inputs and thus create neural networks that led to both larger brains and more advanced cognitive capacities, and that the skulls of such primates were concomitantly able to enlarge in order to house them?

Or is hedging all of our bets on a single, omnipotent gene an absurd form of Panglossianism, or “a mug’s game,” as Coyne suggests? The solution to such a complex question is likely to involve a mixture of genes and interrelated factors. The large proportion of unexplored “junk” DNA resting in our genome is one potential hiding place for a forthcoming solution. We still have an imperfect understanding of the roles noncoding DNA and RNA play in the overall function of an organism. As we dig deeper into this repository, we may find the answer is much knottier than any one gene can untangle.

External link: Popular press wildly overblows “gene for humanity”

Feature image: “Ape” by kalmichael

 
 
How much different would life be were we to add millions of more colors to our visual palette? A tetrochromat may be able to answer that question. A tetrochromat is an individual with an additional photoreceptor in their retina, allowing that person to perceive a more gradated spectrum of colors compared with the conventional trichromat. Thanks to the female’s dual X chromosome carried on each cell, this phenomenon is believed to occur only in women and not in men.

Four-coned women are not typically aware of their superior color acuity. This makes sense given that everything we see is created, produced and marketed by three-coned individuals. Indeed, human handiwork operates predominantly in a trichromatic space. Not only is it difficult to self-identify as tetrachromatic, it is just as challenging to craft experiments to ferret out these supervisual prodigies. The very nature of the phenomenon that makes it tricky to test for, a bit like someone trapped in a two-dimensional world checking for extra dimensions.

One explanation of the anomaly is that the neural connections required to bear witness to a more subtle kaleidoscope of shades may lie dormant, waiting to be activated. Perhaps it is only after focused training that women can make use of their additional sensory feedback. This hypothesis would be consistent with several studies showing that individuals who work in highly color-sensitive environments, such as textile and manufacturing, have greater color discrimination. Activation by immersion may be the best way to identify tetrachromacy.

A new piece in Discover Magazine chronicles one British scientist’s attempt to track down some of these women and untap their full visual potential.

Excerpts:

External link: The Humans With Super Human Vision

Further reading: Some women may perceive millions more colors than the rest of us. Are you one of them?

Feature image via i09

 
 
Geneticists now believe blue eyes are a relatively recent physical trait. While the earth was once filled entirely with brown-eyed people, a genetic mutation occurring within the last 10,000 years resulted in a single, blue-eyed ancestor. Every blue-eyed person since, including femme fatale Reese Witherspoon, is believed to be genetically linked to that common ancestor.

For those unfamiliar with genetics, your physical appearance is a reflection of your genes, which are inherited from your biological parents. Small genomic differences can disproportionately translate to large physiological differences. Gene expression and regulation go a long way toward explaining why we drastically differ in appearance from apes despite sharing around 98%+ of their DNA makeup. Changes in a genomic sequence, known as mutations, can lead to new physical traits.

The mutation resulting in blue-eyed humans occurred in a gene dubbed OCA2, which regulates the level of melanin in your iris. This alteration reduces melanin levels substantially, shifting iris pigmentation from brown to blue. By sampling DNA from 800 living, blue-eyed individuals and tracing maternal lineages back to older and older DNA data, geneticists were able to conclude that all blue-eyed humans descend from a single, maternal ancestor who lived somewhere between 6 and 10,000 years ago. A larger population of ancient DNA samples would shrink the estimate’s range substantially, but DNA is unfortunately hard to come by from that long ago due to organic decomposition.

Are men or women more likely to have blue eyes?

The answer to this is mostly indeterminable because first, iris color is an autosomal physical trait. It is not sex-linked to an X or Y chromosome like color blindness or male pattern baldness, which are primarily X-linked traits. Thus, both sexes have roughly the same probability of inheritance. Secondly, iris color is regulated by more than just the OCA2 gene, and we currently do not know how many or which genes contribute to iris color. This is also the case for many other inherited traits, such as male pattern baldness listed above. Few traits are exclusively sex-linked; often, other genes are involved but are simply less contributive. It’s possible to estimate probabilities of blue-eyed children given a specific set of genes, but as gene variation grows, the accuracy of these estimates diminish.

What’s surprising to geneticists is the abundance of this mutation in present day. An estimated 20-40% of modern Europeans have blue eyes, a surprisingly high figure for a relatively brief period of time.

My take? Blue-eyed people get laid more easily! Unfair? It’s science.

External Link: Genetic mutation makes those brown eyes blue