Category Archives: Religion

Editing the Human Germline: Groundbreaking Science and Mind-numbing Sentiment.

by Kenneth W. Krause.

Kenneth W. Krause is a contributing editor and “Science Watch” columnist for the Skeptical Inquirer.  Formerly a contributing editor and books columnist for the Humanist, Kenneth contributes frequently to Skeptic as well. He can be contracted at krausekc@msn.com.

The CRISPR Complex at work.

Should biologists use new gene-editing technology to modify or “correct” the human germline? Will our methods soon prove sufficiently safe and efficient and, if so, for what purposes?  Much-celebrated CRISPR pioneer, Jennifer Doudna, recently recalled her initial trepidations over that very prospect:

Humans had never before had a tool like CRISPR, and it had the potential to turn not only living people’s genomes but also all future genomes into a collective palimpsest upon which any bit of genetic code could be erased and overwritten depending on the whims of the generation doing the writing…. Somebody was inevitably going to use CRISPR in a human embryo … and it might well change the course of our species’ history in the long run, in ways that were impossible to foretell.

(Doudna and Sternberg 2017). And it didn’t take long.  Just one month after Doudna and others called for a moratorium on human germline editing in the clinical setting, scientists in Junjiu Huang’s lab at Sun Yat-sen University in Guangzhou, China published a paper describing their exclusively in vitro use of CRISPR on eighty-six human embryos (Liang et al. 2015).  Huang’s goal was to edit mutated beta-globin genes that would otherwise trigger a debilitating blood disorder called beta-thalassemia.

But the outcomes were mixed, at best.  After injecting each embryo with a CRISPR complex composed of a guide RNA molecule, a gene-slicing Cas-9 enzyme, a synthetic repair DNA template, and a “glow-in-the-dark” jellyfish gene that allows investigators to track their results as cells continue to divide, Huang’s team delivered a paltry five percent efficiency rate.  Some embryos displayed unintended, “off-target” editing.  In others, cells ignored the repair template and used the related delta-globin gene as a model instead.  A third group of embryos turned mosaic, containing cells with an untidy jumble of editions.  Part of the problem was that CRISPR had initiated only after the fertilized egg had begun to divide.

By using non-viable triploid embryos containing three sets of chromosomes, instead of the usual two, Huang avoided objections that he had destroyed potential human lives.  Nevertheless, both Science and Nature rejected his manuscript based in part on ethical concerns.  Several scientific agencies also promptly reemphasized their stances against human germline modification in viable embryos, and, in the US, the Obama Administration announced its position that the human germline should not be altered at that time for clinical purposes.  Francis Collins, director of the National Institutes of Health, emphasized that the US government would not fund any experiments involving the editing of human embryos.  And finally, earlier this year, a committee of the US National Academies of Sciences and Medicine decreed that clinical use of germline editing would be allowed only when prospective parents had no other opportunities to birth healthy children.

Meanwhile, experimentation continued in China, with similarly grim results. But this past August, an international team based in the US—this time led by embryologist Shoukhrat Mitalipov at the Oregon Health and Science University in Portland—demonstrated that, under certain circumstances, genetic defects in human embryos can, in fact, be efficiently and safely repaired (Ma et al. 2017).

Embyologist Shoukhrat Mitalipov.

Mitalipov’s group attempted to correct an autosomal dominant mutation—where a single copy of a mutated gene results in disease symptoms—of the MYBPC3 gene.  Crucially, such mutations are responsible for an estimated forty percent of all genetic defects causing hypertrophic cardiomyopathy (HCM), along with ample portions of other inherited cardiomyopathies.  Afflicting one in every 500 adults, HCM cannot be cured, and remains the most common cause of heart failure and sudden death among otherwise healthy young athletes.  These mutations have escaped the pressures of natural selection, unfortunately, due to the disorder’s typically late onset—that is, following reproductive maturity.

Prospective parents can, however, prevent HCM in their children during the in vitro fertilization/preimplantation genetic diagnosis (IVF/PGD) process.  Where only one parent carries a heterozygous mutation, fifty percent of the resulting embryos can be diagnosed as healthy contenders for implantation.  The remaining unhealthy fifty percent will be discarded.  As such, correction of mutated MYBPC3 alleles would not only rescue the latter group of embryos, but improve pregnancy rates and save prospective mothers—especially older women with high aneuploidy rates and fewer viable eggs—from risks associated with increasing numbers of IVF/PGD cycles as well

With these critical facts in mind, Mitalipov and colleagues employed a CRISPR complex generally similar to that used by Huang.  It included a guide RNA sequence, a Cas-9 endonuclease, and a synthetic repair template.  In one phase of their investigation, the team fertilized fifty-four human oocytes (from twelve healthy donors) with unhealthy sperm carrying the MYBPC3 mutation (from a single donor), and injected the resulting embryos eighteen hours later with the CRISPR complex.  The result? Thirteen treated embryos became jumbled mosaics.

Mitalipov changed things up considerably, however, in the study’s second phase by delivering the complex much earlier than he and others had done in previous experiments—indeed, at the very brink fertilization. More precisely, his colleagues injected the CRISPR components along with the mutated sperm cells into fifty-eight healthy, “wild-type” oocytes during metaphase of the second meiotic division.  Here, the results were impressive, to say the least.  Forty-two treated embryos were normalized, carrying two copies of the healthy MYBPC3 allele—a seventy-two percent rate of efficiency, no “off-target effects” were detected, and only one embryo turned mosaic.

Mosaicism and Off-target Effects.

Mitalipov’s team achieved a genuine breakthrough in terms of both efficacy and safety.  Perhaps nearly as interesting—and, in fact, the study’s primary finding, according to the authors—is that, in both experimental phases, the embryos consistently ignored Mitalipov’s synthetic repair template and turned instead to the healthy maternal allele as their model.  Such is not the case when CRISPR is used to edit somatic (body) cells, for example.  Apparently, the team surmised, human embryos evolved an alternative, germline-specific DNA repair mechanism, perhaps to afford the germline special protection.

The clinical implications of this repair preference are profound and, at least arguably, very unfortunate.  First, with present methods, it now appears unlikely that scientists could engineer so-called “designer babies” endowed with trait enhancements.  Second, it seems nearly as doubtful that CRISPR can be used to repair homozygous disease mutations where both alleles are mutant.  Nevertheless, Mitalipov’s method could be applied to more than 10,000 diseases, including breast and ovarian cancers linked to BRCA gene mutations, Huntington’s, cystic fibrosis, Tay-Sachs, and even some cases of early-onset Alzheimer’s.

At least in theory.  As of this writing, Mitalipov’s results have yet to be replicated, and even he warns that, despite the new safety assurances and the remarkable targeting efficiencies furnished by his most recent work, gene-editing techniques must be “further optimized before clinical application of germline correction can be considered.” According to stem-cell biologist George Daley of Boston Children’s Hospital, Mitalipov’s experiments have proven that CRISPR is “likely to be operative,” but “still very premature” (Ledford 2017).  And while Doudna characterized the results as “one giant leap for (hu)mankind,” she also expressed discomfort with the new research’s unmistakable inclination toward clinical applications (Belluck 2017).

Indeed, within a single day of Mitalipov’s report, eleven scientific and medical organizations, including the American Society of Human Genetics, published a position statement outlining their recommendations regarding the human germline (Ormond et al. 2017).  Therein, the authors appeared to encourage not only in vitro research but public funding as well.  Although they advised against any contemporary gene-editing process intended to culminate in human pregnancy, but also suggested that clinical applications might proceed in the future subject to a compelling medical rationale, a sufficient evidence base, an ethical justification, and a transparent and public process to solicit input.

And of course researchers like Mitalipov will be forced to contend with those who claim that, regardless of purpose, the creation and destruction of human embryos is always ethically akin to murder (Mitalipov destroyed his embryos within days of their creation).  But others have lately expressed even less forward-thinking and, frankly, even more irrational and dangerous sentiments.

For example, a thoroughly galling article I can describe further only as “pro-disability” (In stark contrast to “pro-disabled”) was recently published, surprisingly to me, in one of the world’s most prestigious science publications (Hayden 2017).  It begins by describing a basketball game in which a nine-year-old girl, legally blind due to genetic albinism, scored not only the winning basket, but, evidently—through sheer determination—all of her team’s points.  Odd, perhaps, but great!  So far.

But the story quickly turns sour, to the girl’s father who apparently had asked the child, first, whether she wished she would have been born with normal sight, and, second (excruciatingly), whether she would ever help her own children achieve normal sight through genetic correction. Unsurprisingly, the nine-year-old is said to have echoed what we then learn to be her father’s heartfelt but nonetheless bizarre conviction: “Changing her disability … would have made us and her different in a way we would have regretted,” which to him, would be “scary.”

To be fair, the article very briefly appends counsel from a man with Huntington’s, for instance, who suggests that “[a]nyone who has to actually face the reality … is not going to have a remote compunction about thinking there is any moral issue at all.”  But the narrative quickly circles back to a linguist, for example, who describes deaf parents who deny both their and their children’s disabilities and have even selected for deafness in their children through IVF/PGD, and a literary scholar who believes that disabilities have brought people closer together to create a more inclusive world (much as some claim Western terrorism has).  The author then laments the fact that, due to modern reproductive technology, fewer children are being born with Down’s syndrome.

To summarize, according to one disabilities historian, “There are some good things that come from having a genetic illness.”  Uh-huh.  In other words, disabilities are actually beneficial because they provide people with challenges to overcome—as if relatively healthy people are incapable of voluntarily and thoughtfully designing both mental and physical challenges for themselves and their kids.

I think not. Disabilities, by definition, are bad.  And, as even a minimally compassionate people, if we possess a safe and efficient technological means of preventing blindness, deafness, or any other debilitating disease in any child or in any child’s progeny, we also necessarily have an urgent ethical obligation to use them.

 

References:

Belluck, P. 2017. In breakthrough, scientists edit a dangerous mutation from genes in human embryos. Available online at https://nyti.ms/2hnZ9ey; accessed August 9, 2017.

Doudna, J.A., and S.H. Sternberg. 2017. A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution. Boston: Houghton Mifflin Harcourt.

Hayden, E.C. 2017. Tomorrow’s children. Nature 530:402-05.

Ledford, H. 2017. CRISPR fixes embryo error. Science 548:13-14.

Liang, P., Y. Xu, X. Zhang, et al. 2015. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein and Cell 6(5):363-72.

Ma, H., N. Marti-Gutierrez, S. Park, et al. 2017. Correction of a pathogenic gene mutation in human embryos. Nature DOI:10.1038/nature23305.

Ormond, K.E., D.P. Mortlock, D.T. Scholes, et al. 2017. Human germline genome editing. The American Journal of Human Genetics 101:167-76.

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CRISPR-Cas9: Not Just Another Scientific Revolution (Special Report).

by Kenneth W. Krause.

Kenneth W. Krause is a contributing editor and “Science Watch” columnist for the Skeptical Inquirer.  Formerly a contributing editor and books columnist for the Humanist, he writes regularly for Skeptic magazine as well.  He may be contacted at krausekc@msn.com.

Poised to transform the world as we know it, a new gene-editing system has bioethicists wringing their hands, physicians champing at the bit, and researchers dueling with demons.

CRISPR6

Is it possible to overstate the potential of a new technology that efficiently and cheaply permits deliberate, specific, and multiple genomic modifications to almost anything biological? What if that technology was also capable of altering untold future generations of nearly any given species—including the one responsible for creating it?  And what if it could be used, for better or worse, to rapidly exterminate entire species?

Certain experts have no intention of veiling their enthusiasm, or their unease. Consider, for example, biologist David Baltimore, who recently chaired an international summit dedicated primarily to the technology’s much-disputed ethical implications.  “The unthinkable has become conceivable,” he warned his audience in early December.  Powerful new gene-editing techniques, he added, have placed us “on the cusp of a new era in human history.”

If so, it might seem somewhat anticlimactic to note that Science magazine has dubbed this technology its “Breakthrough of the Year” for 2015, or that its primary developers are widely considered shoo-ins for a Nobel Prize—in addition, that is, to the US$3 million Breakthrough Prize in Life Sciences already earned by two such researchers.  All of which might sound trifling compared to the billions up for grabs following imminent resolution of a now-vicious patent dispute.

Although no gene-editing tool has ever inspired so much drama, the new technology’s promise as a practical remedy for a host of dreadful diseases, including cancer, remains foremost in researchers’ minds. Eager to move beyond in vitro and animal model applications to the clinical setting, geneticists across the globe are quickly developing improved molecular components and methods to increase the technology’s accuracy.  In case you haven’t heard, a truly profound scientific insurrection is well underway.

Adapting CRISPR-Cas9.

Think about a film strip. You see a particular segment of the film that you want to replace.  And if you had a film splicer, you would go in and literally cut it out and piece it back together—maybe with a new clip.  Imagine being able to do that in the genetic code, the code of life.—biochemist Jennifer Doudna (CBS News 2015).

Genetic manipulation is nothing new, of course. Classic gene therapy, for example, typically employs a vector, often a virus, to somewhat haphazardly deliver a healthy allele somewhere in the patient’s genome, hopefully to perform its desired function wherever it settles.  Alternatively, RNA interference selects specific messenger RNA molecules for destruction, thus changing the way one’s DNA is transcribed.  Interference occurs, however, only so long as the damaging agent remains within the cell.

Contemporary editing techniques, on the other hand, allow biologists to actually alter DNA—the “code of life,” as Doudna suggests—and to do so with specific target sequences in mind.  The three major techniques have much in common.  Each involves an enzyme called a programmable nuclease, for example, which is guided to a particular nucleotide sequence to cleave it.

Then, in each case, the cell’s machinery quickly repairs the double-stranded break in one of two ways. Non-homologous end joining for gene “knock out” results when reconstruction, usually involving small, random nucleotide deletions or insertions, is performed only by the cell.  Here, the gene’s function is typically undermined.  By contrast, homology-directed repair for gene “knock in” occurs when the cell copies a researcher’s DNA repair template delivered along with the nuclease.  In this case, the cleaved gene can be corrected or a new gene or genes can be inserted (Corbyn 2015).

But in other ways, the three editing techniques are very distinct. Developed in the late 1990s and first used in human cells in 2005, zinc-finger nucleases (ZFN) attach cutting domains derived from the prokaryote Flavobacterium okeanokoites to proteins called zinc fingers that can be customized to recognize certain three-base-pair DNA codes.  Devised in 2010, transcription activator-like effector nucleases (TALENs) fuse the same cutting domains to different proteins called TAL effectors.  For both ZFN and TALENs, two cutting domains are necessary to cleave double-stranded DNA (Maxmen 2015).

The third and most revolutionary editing technique, and subject of this paper, consists of clustered regularly interspaced short palindromic repeats (CRISPR) and a CRISPR-associated protein-9 nuclease (Cas9). Introduced as an exceptionally precise editing technique in 2012 by Doudna at the University of California, Berkeley, and microbiologist Emmanuelle Charpentier at the Max Planck Institute for Infection Biology in Berlin, CRISPR-Cas9 is actually the bacterium Streptococcus pyogenes’ adaptive immune system that confers resistance to foreign elements, like phages and plasmids.

CRISPR3

CRISPR thus refers to short bits of DNA seized from invading viruses and stored in the bacterium’s own genome for future reference, and Cas9 is the enzyme S. pyogenes uses to cleave a subsequent invader’s double helix.  In other words, in its native setting, CRISPR-Cas9 is the system a certain bacterium uses to recognize and disable common biological threats.  Unlike ZFN and TALENs, CRISPR-Cas9 does not rely on the F. okeanoites cutting domain and, as such, can cleave both strands of an interloper’s double helix simultaneously with a single Cas9 enzyme.

But what makes the CRISPR system so special, in part, and so adaptable to the important task of gene-editing, is its relative simplicity. Only three components are required to achieve site-specific DNA recognition and cleavage.  Both a CRISPR RNA (crRNA) and a trans-activating crRNA (tracrRNA) are needed to guide the Cas9 enzyme to its target sequence.  What Doudna and Charpentier revealed six years ago, however, were the seminal facts that an even simpler, two-component system could be developed by combining the crRNA and tracrRNA into a synthetic single guide RNA (sgRNA), and that researchers could readily modify a sgRNA’s code to redirect the Cas9 enzyme to almost any preferred sequence (Jinek et al. 2012).  Today, a biologist wanting to edit a specific sequence in an organism’s genome can quickly and cheaply design a sgRNA to match that sequence, order it from a competitive manufacturer for US$65 or less, and have it delivered in the mail (Petherick 2015).

None of which is to suggest that a CRISPR system is always the best tool for the gene-editing job, at least not yet. Critically, CRISPR-Cas9 is relatively easy to program and remains the only technique allowing researchers to “multiplex,” or edit several genomic sites simultaneously.  But TALENs have the longest DNA recognition domains and, thus, tend so far to result in the fewest “off-target effects,” which occur when nucleotide sequences identical or similar to the target are cut unintentionally.  And ZFNs are much smaller than either TALENs or CRISPR-Cas9, especially the most popular version derived from S. pyogenes, and are therefore more likely to fit into the tight confines of an adeno-associated virus (AAV)—currently the most promising vector for the delivery of gene-editing therapies.

Even so, CRISPR research continues to progress at breakneck speed. In 2014, the number of gene-editing kits ordered from Addgene, a supplier based in Cambridge, Massachusetts, for research using ZFN and TALENs totaled less than 1000 and less than 2000, respectively.  During that same year—only two years after the new technology was introduced, the number of kits ordered for CRISPR research totaled almost 20,000 (Corbyn 2015).  More importantly, rapidly increasing orders seem to have translated into significant results.  As 2015 ended and a new year began, new studies announcing the creation of smaller guide RNAs and, especially, the reduction of off-target effects began to dominate science headlines.

Building a Better Mousetrap.

At some point everyone needs to decide how specific is specific enough. The idea that you would make a tool that has absolutely no off-target effects is a little too utopian.—bioengineer Charles Gersbach (Ledford 2016).

It’s cheap, easy to use, and remarkably efficient, but CRISPR-Cas9 is not perfect. In early experiments, in fact, pathologist Keith Joung at the Massachusetts General Hospital in Boston, discovered that his enzymes were cutting unintended as often as targeted sequences (Servick 2016).  The U.S. Food and Drug Administration has yet to announce requirements for clinical use of the new technology.  But to help future clinicians safely repair defective, disease-causing genes, for example, researchers are exploring various means of reducing off-target effects that could harm patients in any number of ways, including through uncontrolled cellular growth and cancer.

A CRISPR-Cas9 system “licenses” a DNA sequence for cleavage through a two-stage recognition process (Bolukbasi et al. 2016). Even the most basic details are somewhat technical, of course, but very illuminating.  First, a Cas9-sgRNA complex will attach and remain attached to a DNA sequence only if an appropriate protospacer-adjacent motif (PAM) is nearby.  PAM sequences are very short, often only a few base-pairs long.  In the case of an S. pyogenes Cas9, an NGG PAM is much-preferred, but NAG and NGA PAMs are sometimes inefficiently recognized (“N” represents any nucleobase followed by two guanine, or “G” nucleobases).

CRISPR2

Second, and only if an appropriate PAM is recognized, the sgRNA will interrogate the neighboring DNA sequence through Watson-Crick base pairing in a 3′-to-5′ direction. For an S. pyogenes Cas9, the guide sequence will measure twenty nucleotides long.  If the 3′ end of the programmed guide sequence is complementary to the DNA sequence near the PAM element, “R-loop” formation is initiated.  In zipper-like fashion, further complementarity of the DNA is assessed through extension of the R-loop.  If a complete target sequence is confirmed, allosteric activation of the Cas9 enzyme—actually, activation of Cas9’s two nuclease domains, RuvC and HNH—will result in dual cleavage and, accordingly, a complete double-stranded break in the target sequence.

Unsurprisingly, then, the specificity of a CRISPR-Cas9 system is determined in two ways. In large part, off-target effects are managed through careful design of the sgRNA.  Ideally, the guide sequence would match the target sequence perfectly, and show no homology elsewhere in the genome.  More realistically, however, at least partial homology will often occur at other genomic sites where, unfortunately, off-target cleavage could ensue.  Researchers have developed algorithms that help predict sufficient homology, but have yet to clearly and comprehensively define how closely guide and DNA sequences must harmonize before licensing occurs.  Nevertheless, nuclease activity has been observed at off-target sites displaying up to four or five nucleotide mismatches.

So, careful design of the sgRNA is critical. But one team of researchers, including Joung, recently confirmed that truncating the guide sequence can also help (Fu et al. 2014).  Shortening their guides to as few as seventeen nucleotides, instead of the usual twenty, Joung’s group was able to not only decrease nuclease activity at many off-target sites, but to preserve nearly thorough activity at the majority of intended sites as well.

Other groups have achieved similar success by inactivating one of the two nuclease domains, thus creating a “nickase” that cleaves only one strand of the target sequence (Ran et al. 2013). Here, a double-stranded break can still be achieved by joining two Cas9 nickases with two different sgRNAs targeting adjacent sites on opposing DNA strands.  Importantly, the obligatory use of two active nickases decreases the likelihood of off-target cleavage.

Perhaps the latest and most significant progress in this area, however, has been achieved through modification of the unaltered, or “wild-type,” Cas9 nuclease. Last December, for example, synthetic biologist Feng Zhang at the Broad Institute of MIT and Harvard University announced that he and his colleagues had engineered the Cas9 to render it less likely to act at genomic sites presenting mismatches between RNA guides and DNA targets (Slaymaker et al. 2015).  Appropriately, Zhang dubbed his new enzyme an “enhanced specificity” S. pyogenes Cas9, or eSpCas9 for short.

Feng Zhang

Feng Zhang

Knowing that negatively charged DNA binds to a positively charged groove in the Cas9 enzyme, Zhang’s team predicted that by replacing only a few among the 1400 or so positively charged amino acids with neutral equivalents they could temper the wild-type Cas9’s enthusiasm for binding to and cutting off-target sites. They created and tested several new versions of enzyme that reportedly reduced unintended activity at least tenfold, while maintaining robust on-target cleavage.

Earlier this year, however, Joung and colleagues claimed to have bested Zhang’s results by bringing “off-target-effects to levels where we can no longer detect them, even with the most sensitive methods” (McGreevey 2016). Like Zhang, Joung focused on points of interaction between Cas9 and DNA sequences.  His team created fifteen new enzyme variants by replacing up to four long amino acid side-chains that bind to DNA with shorter chains that do not (Kleinstiver et al. 2016).

Joung then tested each of his Cas9 variants in human cells, and found that one three-substitution and one four-substitution version rejected mismatched sites while maintaining full on-target activity. The latter variant, subsequently named SpCas9-HF1—“HF” denoting “high-fidelity,” induced targeted activity as reliably as a wild-type Cas9 when deployed with eighty-five percent of the thirty-seven different guide RNAs tested.  Similarly, SpCas9-HF1 generated no detectable off-target mutations with six of seven guide RNAs (and only one mutation with the seventh) compared to twenty-five such effects produced by the wild-type Cas9.

Keith Joung

Keith Joung

Joung’s group also tested their hi-fi creations at less typical genomic locations that are particularly difficult to control for off-target effects due to the inclusion of repeat sequences. But even there, his supplemental variants, since designated HF2, HF3, and HF4, appeared to eliminate off-target activity that tended to persist following use of the HF1 version.

It’s too early to judge which of these innovations will prove most valuable or, in fact, whether all of them will soon be superseded by modifications or entirely different systems yet to be introduced. But much progress has already been made and, importantly, at this point, many of the foregoing strategies and designs can be used in concert to bring us closer yet to the day when CRISPR gene-editing becomes a clinical convention.

Breaking Barriers.

This is now the most powerful system we have in biology. Any biological process we care about now, we can get the comprehensive set of genes that underlie that process. That was just not possible before.—biochemist David Sabatini (Yong 2015).

CRISPR-Cas9, of course, is only one among many prokaryotic CRISPR systems that could, at some point, prove useful for any number of human purposes. Use of Cas9 variations, however, has already resulted in successes far too numerous to review liberally here.  Even so, two recent applications in particular reveal the extraordinary, yet strikingly simple, means by which researchers have achieved previously unattainable outcomes.

In the first, three different teams confronted Duchenne muscular dystrophy (DMD), a terrifying disease that affects about one in every 3500 boys in the U.S. alone (Long et al. 2015, Nelson et al. 2015, and Tabebordbar et al. 2015). DMD typically stems from defects in a gene containing seventy-nine protein-coding exons.  If even a single exon suffers a debilitating mutation, the gene can be rendered incapable of producing dystrophin, a vital protein that protects muscle fibers.  Absent sufficient dystrophin, both skeletal and heart muscle will deteriorate.  Patients usually end up confined to wheelchairs and dead before the age of thirty.

CRISPR12

Traditional gene therapy, stem cell treatments, and drugs have proven mostly ineffective against DMD. Scientists have corrected diseased cells in vitro, or in a single organ—the liver.  But treating muscle cells throughout the body, including the heart, is a far more daunting task, because they can’t all be removed, treated in isolation, and then replaced.  And given current ethical concerns, most researchers are prohibited from even considering the possibility of editing human embryos for clinical purposes.

As such, researchers here decided to employ CRISPR-Cas9 technology to excise faulty dystrophin gene exons in both adult and neonatal mice by delivering it directly into their muscles and bloodstreams using non-pathogenic adeno-associated viruses. AAVs, however, are too small to accommodate the relatively large S. pyogenes Cas9, so each team opted instead to deploy a more petite Cas9 enzyme found in Staphylococcus aureus.

Neither group’s interventions resulted in complete cures. But dystrophin production and muscle strength was restored, and little evidence of off-target effects was observed, in treated mice.  One lead researcher later suggested that, although clinical trials could be years away, up to eighty percent of human DMD victims could benefit from defective exon removal (Kaiser 2015).

Remarkably, each of the three teams obtained results comparable to those of the others. Perhaps most impressively, however, these experiments marked the very first instances of using CRISPR to successfully treat genetic disorders in fully-developed living mammals.

But an ever-growing population needs to protect its agricultural products too. Plant DNA viruses, for example, can cause devastating crop damage and economic crises worldwide, but especially in underdeveloped regions including sub-Saharan Africa.  More specifically, the tomato yellow leaf curl virus (tomato virus) is known to ravage a variety of tomato breeds, causing stunted growth, abnormal leaf development, and fruit death.

CRISPR11

Like DMD, the tomato virus has proven an especially intractable problem. Despite previous efforts to control it through breeding, insecticides targeting the vector, and other engineering techniques, we currently know of no effective means of managing the virus.  Undeterred, another group of biologists decided to give CRISPR-Cas9-mediated viral interference a try (Ali et al. 2015).

In this study, the investigators chose to manipulate a species of tobacco plant, well-understood as a model organism, which is similarly vulnerable to tomato virus infection. The experiment was completed in two fairly predictable stages.  First, the group designed sgRNAs to target certain tomato virus coding and non-coding sequences and inserted them into different, harmless viruses of the tobacco rattle variety.  Second, they delivered the newly loaded rattle viruses into their tobacco plants.  After seven days, the plants were exposed to the tomato virus and, after ten more days, they were analyzed for symptoms of infection.

The group agreed that the CRISPR-Cas9 system had reliably cleaved and introduced mutations to the tomato viruses’ genomes. Fortuitously, every plant expressing the system had either abolished or significantly attenuated all symptoms of infection.  The investigators concluded further that the technique was capable of simultaneously targeting multiple DNA viruses with a lone sgRNA, and that other transformable plant species, including tomatoes, of course, would be similarly affected.

One can only guess, at this point, how certain interests might receive these and other types of genome-edited crops. Will nations eventually classify them as GMO or, alternatively, as organisms capable of developing in nature?  Will applicable regulations focus on the processes or products of modification?  Regardless, one can hardly ignore these commodities’ potential windfalls, especially for those in dire need.

Given recent innovations in specificity, for example, CRISPR-based disease research will likely continue to advance quickly toward clinical and other more practical applications. So long as it affects only non-reproductive somatic cells, such interventions should remain largely uncontroversial.  Human gametes and embryos, on the other hand, have once again inspired abundant debate and bitter division among experts.

Moralizing Over Science.

Genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable.—Edward Lanphier et al. (2015).

To intentionally refrain from engaging in life-saving research is to be morally responsible for the foreseeable, avoidable deaths of those who could have benefitted.—bioethicist Julian Savulescu et al. (2015).

The results of the first and, so far, last attempt to edit human embryos using CRISPR-Cas9 was published by a team of Chinese scientists on April 18 of last year (Liang et al. 2015). Led by Junjiu Huang, the group chose to experiment on donated tripronuclear zygotes—non-viable early embryos containing one egg and two sperm nuclei—neither intended nor suitable for clinical use.  Their goal was to successfully edit endogenous β-globin genes that, when mutated, can cause a fatal blood disorder known as β-thalassemia.

Junjiu Huang

Junjiu Huang

By his own admission, Huang’s outcomes were less than spectacular. Eighty-six embryos were injected with the Cas9 system and a molecular template designed to affect the insertion of new DNA.  Of the seventy-one that survived, fifty-four embryos were tested.  A mere twenty-eight were successfully spliced and, of those, only four exhibited the desired additions.  Rates of off-target mutations were much higher than expected too, and the group would likely have discovered additional unintended cuts had they examined more than the protein-coding exome, which represents less than two percent of the entire human genome.

In all fairness, however, the embryos’ abnormality might have been responsible for much of the total off-target effect. And, of course, Huang was unable to take advantage of many specificity-enhancing upgrades to the CRISPR system yet to be designed at the time of his investigations.  In any case, his team acknowledged that their results “highlight the pressing need to further improve the fidelity and specificity” of the new technology, which in their opinions remained immature and unready for clinical applications.

Nevertheless, the Chinese experiment ignited a brawl among both scientists and bioethicists over the prospect of human germline modification with the most powerful and accessible editing machinery ever conceived. Similar quarrels had accompanied the proliferation of technologies involving recombinant DNA, in vitro fertilization, gene therapy, and stem cells, for example.  But never had the need to address our capacity to reroute the evolution of societies—indeed, of the entire species—seemed so real and immediate.

Leading experts, including Baltimore and Doudna, had previously met in Napa, California, on January 24, 2015 to discuss the bioethical implications of rapidly emerging technologies. In the end, they “strongly discouraged … any attempts at germline genome modification for clinical application in humans,” urged informed discussion and transparent research, and called for a prompt global summit to recommend international policies (Baltimore et al. 2015).  A surge of impassioned literature ensued.

A small group led by Sangamo BioSciences president, Edward Lanphier, was one of the first to weigh in (Lanphier et al. 2015). Calling for a “voluntary moratorium” on all human germline research, Lanphier first expressed concerns over potential off-target effects and the genetic mosaicism that could result, for instance, if a fertilized egg began dividing before all intended corrections had occurred.  He also found it difficult to “imagine a situation in which use of human embryos would offer therapeutic benefits over existing and developing methods,” suggesting as well that pre-implantation genetic diagnosis (PGD) and in vitro fertilization (IVF) were far better options than CRISPR for parents carrying the same mutation for a genetic disease.  In any case, he continued, with so many unanswered questions, clinicians remained unable to obtain truly risk-informed consent from either parents looking to modify their germlines or from affected future generations.  Finally, Lanphier implied that even the best intentions could eventually lead societies down a “slippery slope” toward non-therapeutic genetic enhancement and so-called “designer babies.”

Edward Lanphier

Edward Lanphier

Francis Collins, evangelical Christian and director of the National Institutes of Health (which currently refuses to fund human germline research), expressed similar views regarding the sufficiency of PGD and IVF, the impossibility of informed consent, and non-therapeutic enhancement (Skerrett 2015). Additionally, Collins worries that access to the technology would be denied to the economically disadvantaged and that parents might begin to conceive of their children “more like commodities than precious gifts.”  For the director, given the “paucity of compelling cases” in favor of such research, and the significance of the ethical counterarguments, “the balance of the debate leans overwhelmingly against human germline engineering.”

On the other hand, Harvard Medical School geneticist, George Church, urges us to ignore pleas for artificially imposed bans, “encourage the innovators,” and focus more on what he deems the obvious benefits of germline research (Church 2015). Responding to Lanphier and Collins, he argues as well that, without obtaining consent, parents have long exposed future generations to mutagenic forces—through chemotherapy, residence in high-altitudes, and alcohol intake, for example.  We have also consistently chosen to enhance our offspring and future generations through mate choice, among many other things.  Church also points out that PGD during the IVF procedure is incapable of offering solutions to individuals possessing two copies of a detrimental, dominant allele, or to prospective parents who both carry two copies of a harmful, recessive allele.  Moreover, in most instances, PGD cannot be used to avoid more complex polygenic diseases, including schizophrenia.   Nor can we presume that new technology costs will always create treatment or enhancement inequities.  In fact, according to Church, the price of DNA sequencing, for example, has already plummeted more than three million fold.  Finally, germline editing is probably not irreversible, Church contends, and certainly not as error-prone at this point as many have suggested.  “Senseless” bans, he concludes, would only “put a damper on the best medical research and instead drive the practice underground to black markets and uncontrolled medical tourism.”

George Church

George Church

Taking a slightly different tack, Harvard cognitive scientist, Steven Pinker, censures bioethicists generally for getting bogged down in “red-tape, moratoria, or threats of prosecution based on nebulous but sweeping principles such as ‘dignity,’ ‘sacredness,’ or ‘social justice’” (Pinker 2015a). Imploring the bioethical community to “get out of the way” of CRISPR, Pinker reminds them that, once decried as morally unacceptable, vaccinations, transfusions, artificial insemination, organ transplants, and IVF have all proven “unexceptional boons to human well-being.”  Further, the specific harms of which moratorium proponents warn, including cancer, mutations, and birth defects, “are already ruled out by a plethora of existing regulations and norms” (Pinker 2015b).  In the end, he advises, both scientists and everyday people need and deserve a well-diversified research portfolio.  “If you ban something, the probability that people will benefit is zero.  If you don’t ban it, the probability is greater than zero.”

Such were among the arguments considered by a committee of twelve biologists, physicians, and ethicists during the December, 2015 International Summit on Human Genome Editing, organized by the U.S. National Academies of Science and Medicine, the Royal Society in London, and the Chinese Academy of Sciences. The Summit was chaired by David Baltimore.  Doudna and Charpentier, winners of the US$3 million Breakthrough Prize in Life Sciences, attended with Zhang—a now much-celebrated trio considered front runners for a Nobel Prize, though also entangled through their institutions in a CRISPR patent dispute potentially worth billions of dollars.

Doudna, Charpentier, and Zhang

Doudna, Charpentier, and Zhang

After three days of discussion, the Summit’s organizing committee issued a general statement rejecting calls for a comprehensive moratorium on germline research (NAS 2015). The members did, however, advise without exception against the use of edited embryos to establish pregnancy.  “It would be irresponsible to proceed,” they added, “with any clinical use of germline editing” until safety and efficacy issues are resolved and there exists “a broad societal consensus about the appropriateness of the proposed application.”  In conclusion, the committee called for an “ongoing forum” to harmonize the current global patchwork of relevant regulations and guidelines and to “discourage unacceptable activities.”  This forum, the members judged, should consist not only of experts and policymakers, but of “faith leaders,” “public interest advocates,” and “members of the general public” as well.

Wasting little time, the UK’s Human Fertilization and Embryology Authority approved on February 1, 2016, the first attempt to edit healthy human embryos with the CRISPR-Cas9 system.  The application was filed last September by developmental biologist, Kathy Niakan, of the Francis Crick Institute in London.  Niakan intends to use CRISPR to knock out one of four different genes in a total of 120 day-old, IVF-donated embryos to investigate the roles such genes play in early development.

Kathy Niakan

Kathy Niakan

Her research could help identify genes crucial to early human growth and cell differentiation and, thus, lead to more productive IVF cultures and more informed selection practices. It could also reveal mutations that lead to miscarriages and, one day, allow parents to correct these problems through gene therapy.  Following careful observation, Niakan intends to destroy her embryos by the time they reach the blastocyst stage on the seventh day.  Under British law, experimental embryos cannot be used to establish pregnancy.

But the human germline is not the only, or even most pressing, subject of CRISPR controversy. Some, for example, warn of the creation of dangerous pathogens and biological warfare (Greely 2016).  But many others, including Doudna, urge that we quickly address “other potentially harmful applications … in non-human systems, such as the alteration of insect DNA to ‘drive’ certain genes into a population” (Doudna 2015).

Driving DNA.

Clearly, the technology described here is not to be used lightly. Given the suffering caused by some species, neither is it obviously one to be ignored.—evolutionary geneticist Austin Burt (2003).

In broad terms, a “gene drive” can be characterized as a targeted contagion intended to spread through a population with exceptional haste. Burt pioneered the technology through his study of transposable elements—“selfish” and often parasitic DNA sequences that exist merely to propagate themselves.  Importantly, transposons can circumvent the normal Mendelian rules of inheritance dictating that any given gene has a fifty percent chance of being passed from parent to offspring.

Thirteen years ago, Burt envisioned the use of a microbial transposon-like element called a “homing endonuclease” for humanity’s benefit. When inserted into one chromosome, the endonuclease would cut the matching chromosome inherited from the other parent.  The cell would then quickly repair the cut, often using the first chromosome as a template.  As such, the assailed sequence in the second chromosome would be converted to the sequence of the selfish element.  In a newly fertilized egg, the endonuclease would likewise convert the other parent’s DNA and, eventually, drive itself into the genomes of nearly one-hundred percent of the population.

CRISPR1

 

Burt believes we can use gene drives to weaken or even eradicate mosquito transmitted diseases like malaria and dengue fever. If scientists engineered just one percent of a mosquito population to carry such a drive, he calculates, about ninety-nine percent would possess it in only twenty generations.  In fact, Burt announced five years ago that he had created a homing endonuclease capable of locating and cutting a mosquito gene (Windbichler 2011).  But his elements were difficult to program for precise application.

Enter CRISPR-Cas9. As we’ve seen, Cas9 is an eager endonuclease and guide RNAs are easy to program and can be quickly synthesized.  In April of last year, biologists Valentonio Gantz and Ethan Bier revealed that they had used CRISPR-Cas9 to drive color variation into Drosophila fruit flies (Gantz and Bier 2015).  Though they labeled it a “mutagenic chain reaction” at the time, it was the first gene drive ever deployed in a multicellular organism.

Today, researchers sort potential gene drives into two major groups. Replacement drives seek only to displace natural with modified populations.  Suppression drives, by contrast, attempt to reduce or even eradicate populations.  At this point, no drives have been released into the wild.  Nevertheless, researchers have lately designed one of each type to affect mosquitos carrying the deadly human malaria parasite, Plasmodium falciparum.

The first study was led by microbiologist Anthony James, who collaborated on the project with Gantz and Bier (James et al. 2015). Focusing on the prevention of disease transmission, this group engineered Anopheles stephensi mosquitos, highly active in urban India, to carry two transgenes producing antibodies against the malaria parasite, a CRISPR-Cas9-mediated gene drive, and a marker gene.  Because the very lengthy payload rendered insertion a challenging process, James was able to isolate only two drive-bearing males among 25,000 larvae.  But when mated with wild-type females, these and subsequent transgenic males spread their anti-malaria genes at an impressive rate of 99.5 percent.  Transgenic females, on the other hand, processed the drive quite differently and passed it on at near-normal Mendelian ratios.

Despite its overall success, James doesn’t imagine that his team’s replacement drive could eliminate the malaria parasite independently. Instead, he envisions its use to reduce the risk of infection and to compliment other strategies already being employed.  Even so, because such drives would not exterminate P. falciparum or its mosquito vector, they would potentially allow the parasite to one day evolve resistance to their transgene components.

mosquito-anopheles

The second study’s goal was quite different. Here, molecular biologist, Tony Nolan, along with Burt and others, first identified three genes in the Anopheles gambiae mosquito, active in sub-Saharan Africa, that when mutated cause recessive infertility in females (Hammond et al. 2016).  Second, they designed a CRISPR-Cas9 gene drive to target and edit each gene.  Following insertion, they bred their transgenic mosquitos with wild-types and found that nearly all female offspring were born infertile.  In a subsequent experiment, Nolan released 600 vectors—half transgenic, half wild-type—into a cage.  After only four generations, seventy-five percent of the population carried the mutations, exactly what one would expect from an effective gene drive.

A suppression drive like Hammond’s could, in theory, eliminate a parasite’s primary vector. In such a scenario, the parasite might find another means of conveying the disease to humans—more than 800 species of mosquito inhabit Africa alone, for example.  But it might not.  The loss would also substantially alter the relevant ecosystem.  But despite other methods of controlling the disease, malaria still claims more than a half million lives every year, mostly among children under five.

Even in theory, no gene drive is a panacea. They function only in sexually reproducing species, and best in species that reproduce very rapidly.  Nor would their effects be permanent—most transgenes would prove especially vulnerable to evolutionary deselection, for example.   But neither would they turn out as problematic as some might imagine. They can be easily detected through genome sequencing, for instance, and are unlikely to spread accidentally into domesticated species.  And if scientists sought for whatever reason to reverse the effects of a previously released drive, they could probably do so with the release of a subsequent drive.

As Church and others have recently suggested, it “doesn’t really make sense to ask whether we should use gene drives. Rather, we’ll need to ask whether it’s a good idea to consider driving this particular change through this particular population”  (Esvelt et al. 2014).

References:

Ali, Z., A. Abulfaraj, Ali Idris, et al. 2015. CRISPR/Cas9-mediated viral interference in plants. Genome Biology 16:238 DOI:10.1186/s13059-015-0799-6.

Baltimore, D., P. Berg, M. Botcham, et al. 2015. A prudent path forward for genomic engineering and germline gene modification. Science 348(6230):36-38.

Bolukbasi, M.F., A. Gupta, and S.A. Wolf. 2016. Creating and evaluating accurate CRISPR-Cas9 scalpels for genomic surgery. Nature Methods 13(1):41-50.

Burt, A. 2003. Site-specific selfish genes as tools for the control and genetic engineering of natural populations. Proceedings of the Royal Society B 270:921-928.

CBS News. 2015. Could Revolutionary Gene-editing Technology End Cancer? Available online at http://www.cbsnews.com/news/crispr-jennifer-doudna-gene-editing-technology-diseases-dangers-ethics/; accessed January 25, 2016.

Church, G., 2015. Encourage the innovators. Nature 528:S7.

Corbyn, Z. 2015. Biology’s big hit. Nature 528:S4-S5.

Doudna, J. 2015. Embryo editing needs scrutiny. Nature 528:S6.

Esvelt, K., G. Church, and J. Lunshof. 2014. “Gene Drives” and CRISPR Could Revolutionize Ecosystem Management. Available online at http://blogs.scientificamerican.com/guest-blog/gene-drives-and-crispr-could-revolutionize-ecosystem-management/; accessed February 6, 2016.

Fu, Y., J.D. Sander, D. Reyon, et al. 2014. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nature Biotechnology 32:279-284.

Gantz, V.M., and E. Bier. 2015a. The mutagenic chain reaction: A method for converting heterozygous to homozygous mutations. Science 348(6233):442-444.

Gantz, V.M., N. Jasinskiene, O. Tatarenkova, et al. 2015. Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1521077112.

Greely, H.T. 2016. Are We Ready for Genetically Modified Animals? Available online at http://www.weforum.org/agenda/2016/01/are-we-ready-for-genetically-modified-animals; accessed February 3, 2016.

Hammond, A. R. Galizi, K. Kyrou, et al. 2016. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nature Biotechnology DOI: 10.1038/nbt.3439.

Jinek, M., K. Chylinski, I. Fonfara, et al. 2012. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816-821.

Kaiser, J. 2015. CRISPR Helps Heal Mice With Muscular Dystrophy. Available online at http://www.sciencemag.org/news/2015/12/crispr-helps-heal-mice-muscular-dystrophy; accessed January 30, 2015.

Kleinstiver, B.P., V. Pattanayak, M.S. Prew, et al. 2016. High-fidelity CRISPR-Cas9 nuclease with no detectable genome-wide off-target effects. Nature 529:490-495.

Lanphier, E., F. Urnov, S.E. Ehlen, et al. 2015. Don’t edit the human germline. Nature 519:410-411.

Ledford, H. 2016. Enzyme Tweak Boosts Precision of CRISPR Genome Edits. Available online at http://www.nature.com/news/enzyme-tweak-boosts-precision-of-crispr-genome-edits-1.19114; accessed January 28, 2016.

Liang, P., Y. Xu, X. Zhang, et al. 2015. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 6(5):363-372.

Long, C., L. Amoasii, A.A. Mireault, et al. 2015. Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science DOI: 10.1126/science.aad5725.

Maxmen, A. 2015. Three technologies that changed genetics. Nature 528:S2-S3.

McGreevey, S. 2016. High-fidelity CRISPR. Available online at https://hms.harvard.edu/news/high-fidelity-crispr; accessed January 29, 2016.

National Academies of Science. 2015. International Summit Statement. Available at http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12032015a; accessed January 2, 2016.

Nelson, C.E., C.H. Hakim, D.G. Ousterout, et al. 2015. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science DOI: 10.1126/science.aad5143.

Petherick, A. 2015. Nature outlook genome editing. Nature 528:S1.

Pinker, S. 2015a. The Moral Imperative for Bioethics. Available online at https://www.bostonglobe.com/opinion/2015/07/31/the-moral-imperative-for-bioethics/JmEkoyzlTAu9oQV76JrK9N/story.html; accessed February 2, 2016.

Pinker, S. 2015b. Steven Pinker Interview. Available online at https://www.ipscell.com/2015/08/stevenpinker/; accessed February 2, 2016.

Ran, F.A., P.D. Hsu, C. Lin, et al. 2013. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 154:1380-1389.

Savulescu, J., J. Pugh, T. Douglas, et al. 2015. The moral imperative to continue gene editing research on human embryos. Protein Cell 6(7):476-479.

Servick, K. 2016. Researchers Rein In Slice-happy Gene Editor, CRISPR. Available online at http://www.sciencemag.org/news/2016/01/researchers-rein-slice-happy-gene-editor-crispr; accessed January 28, 2016.

Sherkow, J.S. 2015. The CRISPR Patent Interference Showdown Is On. Available online at https://law.stanford.edu/2015/12/29/the-crispr-patent-interference-showdown-is-on-how-did-we-get-here-and-what-comes-next/; accessed January 29, 2016.

Skerrett, P., 2015. First Opinion. A Debate: Should We Edit the Human Genome? Available online at http://www.statnews.com/2015/11/30/gene-editing-crispr-germline/; accessed February 2, 2016.

Slaymaker, I. M., L. Gao, B. Zetsche, et al. 2015. Rationally engineered Cas9 nucleases with improved specificity. Science 351(6268):84-88.

Tabebordbar, M., K. Zhu, J.K.W. Cheng, et al. 2015. In vivo gene editing in dystrophic mouse and muscle stem cells. Science DOI: 10.1126/science.aad5177.

Windbichler, N., M. Menichelli, P.A. Papathanos, et al. 2011. A synthetic homing endonuclease-based gene drive system in the human malaria mosquito. Nature 473:212-215.

Yong, E. 2015. The New Gene-editing Technique that Reveals Cancer’s Weaknesses. Available online at http://www.theatlantic.com/science/archive/2015/11/a-revolutionary-gene-editing-technique-reveals-cancers-weaknesses/417495/; accessed on January 30, 2016.

Undeniably Nye.

[Notable New Media]

by Kenneth W. Krause.

Kenneth W. Krause is a contributing editor and “Science Watch” columnist for the Skeptical Inquirer.  Formerly a contributing editor and books columnist for the Humanist, Kenneth contributes regularly to Skeptic as well.  He may be contacted at krausekc@msn.com.

In Undeniable: Evolution and the Science of Creation (St. Martin’s 2014), recently-celebrated creationist debater, Bill Nye (“the Science Guy”), has collected a few dozen frustratingly brief essays on a wide variety of scientific topics with special emphasis, of course, on evolution.  Undeniable could inspire very casual readers of full-length non-fiction–if such creatures really exist.  But it might disappoint certain others.

I can’t help but conclude that Nye’s primary motive was to cash in quickly on his recent popularity among science literates and left-leaning political ideologues.  Which is absolutely fine–better him than Oprah’s spawn, for example.  First, he includes precious few references that discriminating and truly curious readers not only crave, but require.  Second, Nye’s opinions on GMOs, for example, were apparently premature.  Indeed, he changed his mind around February of this year, shortly after his visit to Monsanto’s headquarters.  “GMOs are not inherently bad,” he finally concluded in an interview with HuffPost Live. “We are able to feed 7.2 billion people, which a century and a half ago you could barely feed 1 and a half billion people and [it’s] largely because of the success of modern farming.”  True, but why would that fact surprise anyone, let alone Bill Nye?

In any case, Nye remains an exceptional science communicator, perhaps because of his wonderfully geeky bow-tie, or maybe because he claims to empathize with the many religiously-abused deniers of evolution–including his debate opponent, Ken Ham, who still insists that the Earth is no more than 6000 years old.  Nye understands “the troubling nature of the shortness of our lives,” for instance.  But human mortality can either “make you want to listen to old country western songs about how miserable life can be,” he says, “or it can fill you with joy.”

I don’t know about any of that–mortality is a pretty tough nut to crack, regardless of one’s musical tastes.  But Nye’s certainly correct that humans as a species–most individuals excluded, of course–have made great strides in comprehending the objective truths of our existence in just the last 150 of our 100,000 total years on planet Earth–thanks to the methods of science.  “Think what lies ahead for our species,” he prescribes hopefully, “if we preserve biodiversity and raise the standard of living for everyone.”  That could be great, I suppose–depending.  But maybe a great deal to ask of a species whose adult members continue to think of “science” as merely a subject they studied (or not so much) in school.

An Evolutionary Perspective on Religious Violence.

Kenneth W. Krause is a contributing editor and “Science Watch” columnist for the Skeptical Inquirer.  Formerly a contributing editor and books columnist for the Humanist, Kenneth contributes regularly to Skeptic as well.  He may be contacted at krausekc@msn.com.

Following several recent episodes of well-publicized Islamic violence, I’m reminded of an old and, for many, uncomfortable question.  Among ideologies, is monotheism—its Abrahamic forms in particular—especially or even uniquely capable of inspiring hostility?   Was Sigmund Freud, for example, justified in 1939 to insist that “religious intolerance was inevitably born with the belief in one God” (Freud 1967)?  And was his Jungian counterpart, James Hillman, correct to later suggest that “because a monotheistic psychology must be dedicated to unity, its psychopathology is intolerance of difference” (Hillman 2005)?

Anthropologist David Eller characterizes monotheism as a dualistic, good versus evil attitude that not only “builds conflict into the very fabric of the cosmic system” by crafting two “irrevocably antagonistic” domains “with the ever-present potential for actual conflict and violence,” but also “breeds and demands a fervor of belief that makes persecution seem necessary and valuable” (Eller 2010).  Rodney Stark, co-director at Baylor University’s Institute for Studies of Religion, agrees.  Committed to a “doctrine of exclusive religious truth,” he argues, particularistic traditions “always contain the potential for dangerous conflicts because theological disagreements seem inevitable.”  Innovative heresy naturally arises from the religious person’s desire to comprehend scripture thought to be inspired by the all-powerful and “one true god.”  As such, Stark finds, “the decisive factor governing religious hatred and conflict is whether, and to what degree, religious disagreement—pluralism, if you will—is tolerated” (Stark 2014).

Those who judge these commentators correct might wonder as well how deeply monotheism and its violent tendencies are rooted in the human psyche.  Can the relationship between man, the Abrahamic religions, and conflict be explained, or at least more fully illuminated, by evolutionary science?  Author and psychiatrist Hector Garcia seems to think so.

The God of Abraham was created not only in the image of man, says Garcia, but far more revealingly in the images of alpha-male humans and their non-human primate forebears.  It is no accident, he continues, that the majority of all religionists worship a god who is “fearsome and male,” who “demands reckoning” and “rains fury upon His enemies and slaughters the unfaithful,” and who is portrayed in the holy texts as “policing the sex lives of His subordinates and obsessing over sexual infidelity” (Garcia 2015).

No more an accident than the evolutionary processes of natural selection and differential reproduction.  Why would an eternal, non-material, and all-powerful divinity like Yahweh, Allah, or Christ, Garcia asks, preoccupy himself with “what are ultimately very human, and very apelike” concerns?  That such a god would ever need to assert and maintain dominance by threat or physical aggression, for example, or to use violence “to obtain evolutionary rewards such as food, territory, and sex,” seems incomprehensible.

That is, until one recognizes the Abrahamic gods as the highest-ranking alpha-male apes of all time.  In that light, these divinities “reflect the essential concerns of our primate evolutionary past—namely, securing and maintaining power, and using that power to exercise control over material and reproductive resources.”  In other words, to help them cope during a particularly brutal era, the male authors of the Abrahamic texts fashioned a god “intuitive to their evolved psychology,” and, as history tends to demonstrate, “with devastating consequences.”

Rules of reciprocity govern the social lives of non-human primates (which scientists routinely study as surrogates for the ancestors of modern humans).  When fights break out among chimpanzees, for instance, those who have previously received help from the victim are much more likely than others to answer his calls.  And apes that are called but fail to respond are far more likely to be ignored or even attacked rather than helped if and when they plead for assistance during future altercations.  Dominant males also rely on alliances to maintain rank and will punish subordinates that so much as groom or share food with their rivals.  In fact, many researchers calculate that the most common intra-society cause of ape aggression is the perceived infraction of social rules—many of which administer reciprocity and maintain alliances.

Similar to their primate ancestors, men have long sought alliances with their dominant alpha-gods.  Extreme examples abound in our sacred texts.  In Genesis 22:1-19, Abraham’s willingness to sacrifice Isaac, his own son, demonstrates his unflinching submissiveness to God, who “reciprocates in decidedly evolutionary terms,” according to Garcia, by offering Abraham and his descendants the ultimate ally in war.  Similarly, In Judges 11:30-56, Jephthah sacrifices his daughter as “burnt offering” to Yahweh for help in battle against the Ammonites.

But gods have rivals too; and strangely—except from an evolutionary perspective—so do supposedly omnipotent gods.  Created by dominant men, these divinities are expressly jealous.  And like their primate forebears, such gods build and enforce alliances with their followers against all divine rivals.  As Exodus 22.20 warns, “He who sacrifices to any god, except to the LORD only, he shall be utterly destroyed.”  But as an earthly extension of loyalty, God requires more practical action as well.  Muslims, for example, are expected to “fight those of the unbelievers who are near to you and let them find in you hardness.” (Sura 9:123).

Thus, monotheism not only establishes in- and out-groups with evolutionary efficiency, it also intensifies and legitimizes them.  The foundational texts are capable of removing all compassion from the equation (“thine eye shall have no pity on them” [Deut. 7:16]), thus leaving all manner of brutality permissible (“strike off their heads and strike off every fingertip of them” [Sura 8:12]).  The first Crusade illustrates one bloody case in point.  Accounts of the Christian attack on Jerusalem in 1099 document the slaughter of nearly 70,000 Muslims.  The faithful reportedly burned the Jews, raped the women, and dashing their babies’ wailing heads against posts.  As a campaign waged against a religiously-defined “other,” this assault was then considered unequivocally righteous.

As a more sexually-oriented demonstration of the alpha-God parable, Garcia offers Catholic Spain’s late sixteenth- and early seventeenth-century conquest of the Pueblo Indians in New Mexico.  Here, the incursion didn’t end with the violent acquisition of territory.  In striking resemblance to the belligerent behaviors of dominant male non-human primates, Christian occupiers emasculated their native male rivals, cloistered their women, and appropriated their mating opportunities.

The Spaniards began, of course, by claiming the natives’ territory in the name of Christ and God.  They destroyed their prisoners’ religious buildings and icons and, as many male animals do, marked their newly usurped grounds.  Catholic iconography was erected while the most powerful “medicine men” were persecuted and killed.  Conquistador and governor of the New Mexico province, Juan de Onate, neutralized all capable men over the age of twenty-five by hacking away one of their feet (Guitierrez 1991).

Meanwhile, the Franciscan friars were tasked with their captives’ spiritual conquest.  To install themselves as earthly dominant males, the friars undermined the existing male rank structure through public humiliation.  Native sons were forced to watch helplessly as the Franciscans literally seized, twisted, and in some cases tore away their fathers’ penises and testicles, rendering them both socially submissive and sexually impotent.  “Indian men were to sexually acquiesce to Christ, the dominant male archetype,” says Garcia, “and the Franciscans exercised extreme brutality to accomplish such subservience, to include attacking genitalia in the style of male apes and monkeys.”

The friars hoarded the native women into cloisters, thus acquiring exclusive sexual access—which was sometimes but not always voluntary.  Inquisitorial court logs documented numerous incidences of violence which were seldom if ever prosecuted.  One example involved Fray Nicolas Hidalgo of the Taos Pueblo who fathered a native woman’s child after strangling her husband and violating her.  Another friar, Luis Martinez, was accused of raping a native girl, cutting her throat, and burying her body under his cell.  In these brutal but, to primatologists, eerily familiar cases, Garcia writes, “we can easily spy male evolutionary paradigms grinding their way across the Conquista—the sexual domination of men, the sexual acquisition of females, and differential reproduction among despotic men—all strongly within a religious context.”

But the most unnerving evolutionary strategy among male animals—especially apes and monkeys, is infanticide.  Typically, only males attempt it, and often after toppling other males from power.  The reproductive advantage is unmistakable.  Killing another male’s offspring eliminates the killer’s (and his male progeny’s) future competition for females.  In many species, the practice also sends the offended mother immediately into estrus, providing the killer with additional reproductive access.  Perhaps counterintuitively, the mothers may also have something to gain by mating with their infants’ slayers, because infanticidal males are somewhat more likely to produce infanticidal, and thus more evolutionarily fit, offspring.

Unfortunately, this disturbing pattern is replicated in modern humans.  As Garcia notes, the number of child homicides committed by stepfathers and boyfriends is substantially higher—in some instances, up to one-hundred times higher—than those committed by biological fathers.  And we suspect that genetics are involved because the pattern occurs across cultures and geographic regions, including the United States, Canada, and Great Britain.

Perhaps unsurprisingly at this point, the evolutionary strategy of infanticide is also reflected in religion.  In the Bible, for example, God orders his followers to “kill every male among the little ones” along with “every woman who has known man lying with him.” (Numbers 31:17-18)  The virgins, of course, are to be enslaved for sexual amusement.  Also, in his prophesy against Babylon, God declares that the doomed city’s “infants will be dashed to pieces” as their parents look on. (Isaiah 13-16)  This time, the hapless infants’ mothers will be “violated” as well.

It is no mere coincidence, Garcia argues, that mostly men have claimed to know what God wants.  Dominant human males have inherited their most basic desires from our primate ancestors.  Interestingly, their omnipotent and immortal gods are frequently portrayed as possessing identical earthly cravings.  The monotheistic God demands territory and access to women, for example.  And from an objective perspective, this God’s desires serve only to justify the ambitions of the most powerful men.

As natural history would predict, human males have relentlessly pursued—and continue to pursue—the monopolization of territorial and sexual resources through “fear, submission, and unquestioning obeisance.”  Garcia’s alpha-God expects and accepts no less.  Most regrettably, however, “men have claimed this dominant male God’s backing while perpetrating unspeakable cruelties—including rape, homicide, infanticide, and even genocide.”

Can natural history help explain monotheism’s extraordinary record of belligerence?  Perhaps only in a generalized and highly speculative way.  But one might reasonably contend that the documented persistence and ferocity of religious violence seems almost unimaginable absent devotion to an allegedly all-powerful, ultra-dominant god.

 

References:

Eller, Jack David. 2010. Cruel Creeds, Virtuous Violence: Religious Violence across Culture and History. NY: Prometheus.

Freud, S. 1967. Moses and Monotheism. NY: Vintage.

Garcia, H. 2015. Alpha God: The Psychology of Religious Violence and Oppression. Amherst, NY: Prometheus.

Guitierrez, R. 1991. When Jesus Came the Corn Mothers Went Away: Marriage, Sexuality and Power in Mexico, 1500-1846. Stanford: Stanford University Press.

Hillman, J. 2005. A Terrible Love of War. NY: Penguin.

Stark, R. and K. Corcoran. 2014. Religious Hostility: A Global Assessment of Hatred and Terror. Waco, TX: ISR Books.

Religion and Violence: A Conceptual, Evolutionary, and Data-Driven Approach (Cover Article).

by Kenneth W. Krause.

Kenneth W. Krause is a contributing editor and “Science Watch” columnist for the Skeptical Inquirer.  Formerly a contributing editor and books columnist for the Humanist, Kenneth contributes regularly to Skeptic as well.  He may be contacted at krausekc@msn.com.

For a recent broadcast of Real Time with Bill Maher, the impish host arranged a brief “debate” between neuroscientist and popular religion critic, Sam Harris, and movie actor Ben Affleck(1).  The timely topic for consideration, of course, was Muslim violence.  The exchange warmed up quickly.  Harris pronounced Islam “the mother-lode of bad ideas” and Affleck scorned his opponent’s attitude as “gross” and “racist.”  Sound-bites duly served, the discussion ended almost as soon as it began.

But the Harris-Affleck affair wasn’t a complete waste of electricity.  If nothing else, it exposed a gaping intellectual void in the dialogue over the relationship between religion and hostility.  Unfortunately, this debate has been long-dominated by extreme or undisciplined claims on both sides.  Some suggest, for example, that all organized violence is religiously inspired at some level, while others insist that all religion is entirely benevolent when practiced “correctly.”  These arguments are plainly meritless and compel no response.

Nor can I credit the proposition that religion is often or ever the sole cause of violence.  Organized aggression—whether war, Crusade, Inquisition, lesser jihad, slavery, or terrorism, for instance—typically derives in some measure from greed or political machination.  Similarly, individual violence—honor killing, suicide bombing, genital mutilation, and faith healing, to name a few—usually results from jealousy, bigotry, ideology, or psychopathology in addition to religion.

Some social scientists have argued that religious belligerence ensues from simple prejudice, defined as judgment in the absence of accurate information.  Here, the customary prescription includes education and exposure to a broader diversity of religious tradition.  But as Rodney Stark, co-director at Baylor University’s Institute for Studies of Religion, recently observed, “it is mostly true beliefs about one another’s religion that separates the major faiths.”(2)  Muslims deny Christ’s divinity, for example, and Christians reject Muhammad’s claim as successor to Moses and Jesus.  As such, Stark reasons, education is unnecessary and “increased contact might well result in increased hostility.”

religious violence

Religion Misunderstood?

More interesting, on the other hand, are a collection of perspectives that both diminish and subordinate the role of religion in violent contexts to that of mere pretense or veneer.  In other words, these writers contend that religion is seldom, if ever, the original or primary cause of aggression.  Rather, they suggest, the sacred serves only as an efficient means of either motivating or justifying what should otherwise be recognized as purely secular violence.

Such is the latest appraisal of Karen Armstrong, ex-Catholic nun and easily the twenty-first century’s most prolific popular historian of religion.  In rapid response to Harris’s televised vilification of Islam, Armstrong enlisted the popular press.  During an inexplicable interview with Salon, she echoed Affleck’s hyperbole, equating Harris’s criticism of Islam to Nazi anti-Semitism.(3)  Such comparisons are absurd, of course, because condemnation of an idea is categorically different from denigration of an entire population, or any member thereof.

But more to the point, Armstrong argued that the very idea of “religious violence” is flawed for two reasons.  First, ancient religion was inseparable from the state and, as such, no aspect of pre-modern life—including organized violence—could have been divided from either the state or religion.  Second, she continued, “all our motivation is always mixed.”  Thus, modern suicide bombing and Muslim terrorism, for example, are more personal and political, according to Armstrong, than religious.

The point was developed further in Fields of Blood, Armstrong’s new history of religious violence:

Until the modern period, religion permeated all aspects of life, including politics and warfare … because people wanted to endow everything with significance. Every state ideology was religious … [and thus every] successful empire has claimed that it had a divine mission; that its enemies were evil …. And because these states and empires were all created and maintained by force, religion has been [wrongly] implicated in their violence.(4)

To the contrary, says the author, religion has consistently stood against aggression.  The Priestly authors of the Hebrew Bible, for instance, believed that warriors were contaminated by violence, “even if the campaign had been endorsed by God.”  Similarly, the medieval Peace and Truce of God graciously “outlawed violence from Wednesday to Sunday.”  And in the past, Sunni Muslims were “loath to call their coreligionists ‘apostates,’ because they believed that God alone knew … a person’s heart.”

So both the ancient and modern problems, Armstrong contends, are not in religion per se, “but in the violence embedded in our human nature and the nature of the state.”  Thus, the “xenophobic theology of the Deuteronomists developed when the Kingdom of Judah faced political annihilation,” and the Muslim practices of al-jihad al-asghar and takfir (the process of declaring someone an apostate or unbeliever) were resuscitated “largely as a result of political tension arising from Western imperialism (associated with Christianity) and the Palestinian problem.”

Some of Armstrong’s claims are no doubt true, but far less relevant than she apparently imagines.  For example, that religion was conjoined with the state did not render it ineffectual in terms of bellicosity—perhaps quite the opposite, as we will soon see.  In other cases, the author’s claims are logically flawed.  For instance, an older version of a tradition is not more “authentic” than its successors simply by virtue of its age.  Also, that violence results from manifold causes does not negate or even diminish the accountability of any contributing influence, including religion.

Ultimately, Armstrong misrepresents the issue entirely by setting up her true intellectual adversaries as conveniently feeble straw men.  “It is simply not true,” she postures, “that ‘religion’ is always aggressive.”  Agreed, but no serious person has ever made that accusation.  If the author’s primary argument is that every (or any) religion isn’t always violent, I can’t help but conclude she wasted a great deal of time and energy supporting it.

Nevertheless, Armstrong’s most recent commentary reminds us that religion generally, and all major religious traditions collectively, are a well-mixed bag.  Indeed, both Buddhism and Jainism were at least founded on the principle of ahimsa, or non-violence.  And, yes, the sacred regularly intertwines with politics and government, sometimes to a degree rendering it indistinguishable from the state itself.  Finally, hostility in the name of religion, whether perpetrated by a state, group, or individual, is frequently motivated by a host of factors in addition to faith.  However, that religion is so often employed as a pretense or veneer to inspire people to violence only tends to confirm its hazardous nature.

A More Methodical Approach.

To more astutely characterize the relationship between religion and violence, and to distinguish between differentially aggressive traditions, we need to apply a more disciplined and less biased method.  Cultural anthropologist David Eller proposes a comprehensive model of violence consisting of five contributing dimensions or conditions that, together, predict the source’s propensity to expand both the scope and scale of hostility(5).  These dimensions include group integration, identity, institutions, interests, and ideology.

Eller applies his model to religion as follows: First, religion is clearly a group venture featuring “exclusionary membership,”  “collective ideas,” and “the leadership principle, with attendant expectations of conformity if not strict obedience”—often to superhuman authorities deserving of special deference.  Second, sacred traditions offer both personal and collective identities to their adherents that stimulate moods, motivations, and “most critically, actions.”

Next, most faiths provide institutions, perhaps involving creeds, codes of conduct, rituals, and hierarchical offices which at some point, according to Eller, can render the religion indistinguishable from government.  Fourth, all religions aspire to fulfill certain interests.  Most crucially, they seek to preserve and perpetuate the group along with its doctrines and behavioral norms.  The attainment of ultimate good or evil (heaven or hell, for example), the discouragement or punishment of “dissent or deviance,” proselytization and conversion, and opposition to non-believers might be included as well.

Finally, “religion may be the ultimate ideology,” the author avers, “since its framework is so totally external (i.e., supernaturally ordained or given), its rules and standards so obligatory, its bonds so unbreakable, and its legitimation so absolute.”  For Eller, the “supernatural premise” is critical:

This provides the most effective possible legitimation for what we are ordered or ordained to do: it makes the group, its identity, its institutions, its interests, and its particular ideology good and right … by definition. Therefore, if it is in the identity or the institutions or the interests or the ideology of a religion to be violent, that too is good and right, even righteous.

Arguably, the author surmises, “no other social force observed in history can meet those conditions as well as religion.”  And when a given tradition satisfies multiple conditions, “violence becomes not only likely but comparatively minor in the light of greater religious truths.”

Confronting the question at hand, then, and with Armstrong’s historical observations and Eller’s generalized model of violence in mind, I propose a somewhat familiar, though perhaps distinctively limited two-part hypothesis describing potential relationships between religion and aggression.

First, I do not contend that religion is ever the sole, original, or even primary cause of bellicosity.  Such might be the case in any given instance, but for the purpose of determining generally whether faith plays a meaningful role in violence, we need only ask whether the religion is a sine qua non (without which not), or “cause-in-fact,” of the conflict.  Second, although all religions can and often do stimulate a variety of both positive and negative behaviors, clearly not all faiths are identical in their inherent inclination toward hostility.  Indeed, there should be little question that the traditions of Judaism, Christianity, and Islam have all satisfied each of Eller’s conditions with exceptional profusion.  Accordingly, I propose that the Abrahamic monotheisms are either uniquely adapted to the task or otherwise especially capable of inspiring violence from both their followers and non-followers.

Causation, Briefly.

Determining whether a violent act would have occurred absent religious belief can be difficult, to say the least.  Even so, it is insufficient to simply note, as some critics of religion often do, that the Bible prescribes death for a variety of objectively mundane offenses, including adultery (Leviticus 20:10) and taking the Lord’s name in vain (Leviticus 24:16).  And to merely remind us, for example, that Deuteronomy 13:7-11 commands the devoted to stone to death all who attempt to “divert you from Yahweh your God,” or that Qur’an 9:73 instructs prophets of Islam to “make war” on unbelievers, provides precious little evidence upon which to base an indictment of religious conviction.

Sam Harris’s vague declaration, “As man believes, so will he act,” seems entirely plausible, of course, but is also highly presumptive given the fact that humans are known to frequently hold two or more conflicting beliefs simultaneously.(6)  Nor can we casually assume that every suicide bomber or terrorist has taken inspiration from holy authority—even if he or she is a religious extremist.

On the other hand, there is substantial merit in Harris’s criticism of those faithful who, regardless of the circumstances, “tend to argue that it is not faith itself but man’s baser nature that inspires such violence.”  Again, there can be more than one cause-in-fact for any outcome, especially in the psychologically knotty context of human aggression.  Further, when an aggressor confesses religious inspiration, we should accept him at his word.

So when we are made aware, for example, that one of Francisco Pizarro’s companions, whose fellow soldiers brutalized the Peruvian town of Cajamarca in 1532, had written back to the Holy Roman Emperor Charles V (a.k.a. King Charles I of Spain), recounting that “for the glory of God … they have conquered and brought to our holy Catholic Faith so vast a number of heathens, aided by His holy guidance,” we should concede the rather evident possibility that the Spaniards slaughtered or forcibly converted these natives at least in part because of their religion.(7)

Monotheism Conceptually.

Eller denies that all religion is “inherently” violent.  Nonetheless, he recognizes monotheism’s tendency toward a dualistic, good versus evil, attitude that not only “builds conflict into the very fabric of the cosmic system” by crafting two “irrevocably antagonistic” domains “with the ever-present potential for actual conflict and violence,” but also “breeds and demands a fervor of belief that makes persecution seem necessary and valuable.”

Stark agrees.  Committed to a “doctrine of exclusive religious truth,” he writes, particularistic traditions “always contain the potential for dangerous conflicts because theological disagreements seem inevitable.”  Innovative heresy naturally arises from the religious person’s desire to comprehend scripture thought to be inspired by the all-powerful and “one true god.”  As such, Stark finds, “the decisive factor governing religious hatred and conflict is whether, and to what degree, religious disagreement—pluralism, if you will—is tolerated.”(8)

Indeed, many modern-era writers before me have distinguished monotheism as an exceptionally belligerent force.  Sigmund Freud, for example, argued in 1939 that “religious intolerance was inevitably born with the belief in one God.”(9)  More recently, Jungian psychologist, James Hillman, concurred: “Because a monotheistic psychology must be dedicated to unity, its psychopathology is intolerance of difference.”(10)  Even Karen Armstrong agreed when writing in her late fifties.  Of the faiths of Abraham, she reflected, “all three have developed a pattern of holy war and violence that is remarkably similar and which seems to surface from some deep compulsion inherent in this tradition of monotheism, the worship of only one God.”(11)

Author Jonathan Kirsch, however, addressed the issue directly in 2004, comparing the relative bellicosity of polytheistic and monotheistic traditions.  Noting the early dominance of the former over the latter, Kirsch described their most profound dissimilarity:

[F]atefully, monotheism turned out to inspire a ferocity and even a fanaticism that are mostly absent from polytheism. At the heart of polytheism is an open-minded and easygoing approach to religious belief and practice, a willingness to entertain the idea that there are many gods and many ways to worship them. At the heart of monotheism, by contrast, is the sure conviction that only a single god exists, a tendency to regard one’s own rituals and practices as the only proper way to worship the one true god.(12)

Former professor of religion, Edward Meltzer, adds that for the monotheist, “all divine volition must have one source, and this entails the attribution of violent and vengeful actions to one and the same deity and makes them an indelible part of the divine persona.”  Meanwhile, polytheists “have the flexibility of compartmentalizing the divine” and to “place responsibility for … repugnant actions on certain deities, and thus to marginalize them.”(13)

For Kirsch, the Biblical tale of the golden calf reveals an exceptional belligerence in the faiths of Abraham.  After convincing a pitiless and indiscriminate Yahweh not to obliterate every Israelite for worshiping the false idol, Moses nonetheless organizes a “death squad” to murder the 3000 men and women (to “slay brother, neighbor, and kin,” according to Exodus 32:27) who actually betrayed their strangely jealous god.

In the Pentateuch and elsewhere, Kirsch elaborates, “the Bible can be read as a bitter song of despair as sung by the disappointed prophets of Yahweh who tried but failed to call their fellow Israelites to worship of the True God.”  “Fatefully,” the author continues, the prophets—like their wrathful deity—“are roused to a fierce, relentless and punishing anger toward any man or woman who they find to be insufficiently faithful.”

This ultimate and non-negotiable “exclusivism” of worship and belief, Kirsch concludes, comprises the “core value of monotheism.”  And “the most militant monotheists—Jews, Christians and Muslims alike—embrace the belief that God demands the blood of the nonbeliever” because the foulest of sins is not lust, greed, rape, or even murder, but “rather the offering of worship to gods and goddesses other than the True God.”

Indeed, the historical plight of these faiths’ Holy City seems to bear credible testimony to Kirsch’s rendering.  As Biblical archeologist Eric Cline observed a decade ago, Jerusalem has suffered 118 separate conflicts in the past four millennia.  It has been “completely destroyed twice, besieged twenty-three times, attacked an additional fifty-two times, and captured and recaptured forty-four times.”  The city has endured twenty revolts and “at least five separate periods of violent terrorist attacks during the past century.”  Ironically, the “Holy Sanctuary” has changed hands peacefully only twice during the last four thousand years.(14)

For anthropologist Hector Avalos, Jerusalem figures prominently in this discussion as a religiously-defined “scarce resource.”  Of course many social scientists have attributed hostility to competition over limited resources.  Avalos, however, argues that the Abrahamic faiths have created from whole cloth four categories of scarce resource that render them especially prone to the inducement of recurrent and often shocking acts of violence.(15)

Sacred spaces and divinely inspired or otherwise authoritative scriptures comprise the author’s first and second categories.  Such spaces and scriptures are scarce because only certain people will ever receive access to or be ordained with the power to control or interpret them.  Group privilege and salvation constitute Avalos’ third and fourth categories, neither of which will be conferred on a person, consistent with religious tradition, except under extraordinary circumstances.  Obviously, all such resources are related and, in many ways, interdependent.

To emphasize the point, Regina Schwartz, director of the Chicago Institute for Religion, Ethics, and Violence, employs the Biblical story of Cain and Abel.  In the book of Genesis, the first brothers offer dissimilar sacrifices to God, who favors Abel’s offering, but not Cain’s.  And so the gifting is transformed into a competition for God’s blessing, apparently a commodity in very limited supply.  Denied God’s approval—and now God’s preference—Cain murders Abel in a jealous rage.  Here, Schwartz finds, “monotheism is depicted as endorsing exclusion and intolerance,” and the scarce resource of “divine favor” as “inspiring deadly rivalries.”(16)

In the religious milieu, Avalos argues, scarcity is markedly more tragic and immoral because the alleged existence of these resources is ultimately unverifiable and, according to empirical standards, not scarce at all.  Even so, for religionists the stakes are not only real, but as high as one could possibly imagine.  Control over such resources, after all, determines everlasting bliss or torment for both one’s self and all others.  Assuming belief, at least in the context of scarce resource theory, indeed—what’s not to fight, perhaps even kill or die for?

The Evolution of Monotheism.

The God of Abraham was created not only in the image of man, says professor of psychiatry, Hector Garcia, but far more revealingly in the images of alpha-male humans and their non-human primate forebears.  It is no accident (and certainly no indication of credibility), Garcia continues, that the majority of all religionists worship a god who is “fearsome and male,” who “demands reckoning” and “rains fury upon His enemies and slaughters the unfaithful,” and who is portrayed in the holy texts as “policing the sex lives of His subordinates and obsessing over sexual infidelity.”(17)

No more an accident, that is, than the evolutionary process of natural selection and differential reproduction.  Why would an eternal, non-material, and all-powerful divinity like Yahweh, Allah, or Christ, Garcia asks, preoccupy himself with “what are ultimately very human, and very apelike” concerns?  That such a god would need to assert and maintain dominance by threat or physical aggression, for example, or to use violence “to obtain evolutionary rewards such as food, territory, and sex,” seems unfathomable.

Until, that is, one comes to recognize the Abrahamic gods as the highest-ranking alpha-male apes of all time.  In that light, these divinities “reflect the essential concerns of our primate evolutionary past—namely, securing and maintaining power, and using that power to exercise control over material and reproductive resources.”  In other words, to help them cope during a particularly brutal era, the male authors of the Abrahamic texts fashioned a god “intuitive to their evolved psychology,” and, as history demonstrates, “with devastating consequences.”

Rules of reciprocity govern the social lives of non-human primates (which scientists routinely study as surrogates for the ancestors of modern humans).  When fights break out among chimpanzees, for instance, those who have previously received help from the victim are much more likely than others to answer his calls.  And apes that are called but fail to respond are far more likely to be ignored or even attacked rather than helped if and when they plead for assistance during future altercations.  Dominant males also rely on alliances to maintain rank and will punish subordinates that so much as groom or share food with their rivals.  In fact, many researchers calculate that the most common intra-society cause of ape aggression is the perceived infraction of social rules—many of which administer reciprocity and maintain alliances.

Like their primate ancestors, men have long sought alliances with their dominant alpha-gods.  Extreme examples abound in our sacred texts.  In Genesis 22:1-19, Abraham’s willingness to sacrifice Isaac, his own son, demonstrates his unflinching submissiveness to God, who “reciprocates in decidedly evolutionary terms,” according to Garcia, by offering Abraham and his descendants the ultimate ally in war.  Similarly, In Judges 11:30-56, Jephthah sacrifices his daughter as “burnt offering” to Yahweh for help in battle against the Ammonites.

But gods have rivals too; and strangely—except from an evolutionary perspective—so do omnipotent gods.  Created by dominant men, these divinities are expressly jealous.  And like their primate forebears, they build and enforce alliances with their followers against all divine rivals.  As Exodus 22.20 warns, “He who sacrifices to any god, except to the LORD only, he shall be utterly destroyed.”  But as an earthly extension of loyalty, God requires action as well.  Muslims, for example, are expected to “fight those of the unbelievers who are near to you and let them find in you hardness.” (Sura 9:123).

Thus, monotheism not only establishes in- and out-groups with evolutionary efficiency, it also intensifies and legitimizes them.  The founding texts are capable of removing all compassion from the equation (“thine eye shall have no pity on them” [Deut. 7:16]), thus leaving all manner of brutality permissible (“strike off their heads and strike off every fingertip of them” [Sura 8:12]).  The first Crusade offers just one bloody case in point.  Accounts of the Christian attack on Jerusalem in 1099 document the slaughter of nearly 70,000 Muslims.  The faithful reportedly burned the Jews, raped the women, and dashing their babies’ wailing heads against posts.  As a campaign waged against a religiously-defined “other,” this assault was considered unequivocally righteous.

As a second, more sexually-oriented, illustration of the alpha-God parable, Garcia offers Catholic Spain’s late sixteenth- and early seventeenth-century conquest of the Pueblo Indians in New Mexico.  Here, the incursion didn’t end with the violent acquisition of territory.  In striking resemblance to the behaviors of dominant male non-human primates, Christian occupiers emasculated their native male rivals, cloistered their women, and appropriated their mating opportunities.

The Spaniards began, of course, by claiming the natives’ territory in the name of Christ and God.  They destroyed their prisoners’ religious buildings and icons and, as many male animals do, marked their newly pilfered grounds.  Catholic iconography was erected while the most powerful medicine men were persecuted and killed.  Conquistador and governor of the New Mexico province, Juan de Onate, neutralized all capable men over the age of twenty-five by hacking away one of their feet.(18)

Meanwhile, the Franciscan friars were tasked with their captives’ spiritual conquest.  To install themselves as earthly dominant males, the friars undermined the existing male rank structure through public humiliation.  Native sons were forced to watch helplessly as the Franciscans literally seized, twisted, and in some cases tore away their fathers’ penises and testicles, rendering them both socially submissive and sexually impotent.  “Indian men were to sexually acquiesce to Christ, the dominant male archetype,” says Garcia, “and the Franciscans exercised extreme brutality to accomplish such subservience, to include attacking genitalia in the style of male apes and monkeys.”

The friars hoarded the native women in cloisters, thus acquiring exclusive sexual access—which was sometimes but not always voluntary.  Inquisitorial court logs documented numerous incidences of violence which were seldom if ever prosecuted.  One example involved Fray Nicolas Hidalgo of the Taos Pueblo who fathered a native woman’s child after strangling her husband and violating her.  Another friar, Luis Martinez, was accused of raping a native girl, cutting her throat, and burying her body under his cell.  In these brutal but, to primatologists, eerily familiar cases, Garcia writes, “we can easily spy male evolutionary paradigms grinding their way across the Conquista—the sexual domination of men, the sexual acquisition of females, and differential reproduction among despotic men—all strongly within a religious context.”

But the most unnerving evolutionary strategy among male animals—especially apes and monkeys, is infanticide.  Typically only males attempt it, and often after toppling other males from power.  The reproductive advantage is unmistakable.  Killing another male’s offspring eliminates the killer’s (and his male progeny’s) future competition for females.  In many species, the practice also sends the offended mother immediately into estrus, providing the killer with additional reproductive access.  Perhaps counterintuitively, the mothers also have much to gain by mating with their infants’ slayers because infanticidal males are genetically more likely to produce infanticidal, and thus more evolutionarily fit offspring.

Unfortunately, this disturbing pattern is replicated in modern humans.  As Garcia notes, the number of child homicides committed by stepfathers and boyfriends is substantially higher—in some instances, up to one-hundred times higher—than those committed by biological fathers.  And we know that genetics are involved in this pattern because it occurs across cultures and geographic regions, including the United States, Canada, and Great Britain.

Perhaps unsurprisingly at this point, the evolutionary strategy of infanticide is also reflected in religion.  In the Bible, for example, God orders his followers to “kill every male among the little ones” along with “every woman who has known man lying with him.” (Numbers 31:17-18)  The virgins, of course, are to be enslaved for sexual amusement.  Also, in his prophesy against Babylon, God declares that the doomed city’s “infants will be dashed to pieces” as their parents look on. (Isaiah 13-16)  This time, the hapless infants’ mothers will be “violated” as well.

It is no mere coincidence, Garcia argues, that mostly men have claimed to know what God wants.  Dominant human males have inherited their most basic desires from our primate ancestors.  Interestingly, their omnipotent and immortal God is frequently portrayed as possessing identical earthly cravings.  He demands territory and access to women, for example.  And from an objective perspective, this God’s desires serve only to justify the ambitions of the most powerful men.

As natural history would predict, human males have relentlessly pursued—and continue to pursue—the monopolization of territorial and sexual resources through “fear, submission, and unquestioning obeisance.”  The alpha-God expects and accepts no less.  Most regrettably, however, “men have claimed this dominant male god’s backing while perpetrating unspeakable cruelties—including rape, homicide, infanticide, and even genocide.”

Modern Islam.

Sam Harris believes we are at war with Islam.  “It is not merely that we are at war with an otherwise peaceful religion that has been ‘hijacked’ by extremists,” he argues.  “We are at war with precisely the vision of life that is prescribed to all Muslims in the Koran, and further elaborated in the literature of the hadith.”  “A future in which Islam and the West do not stand on the brink of mutual annihilation,” Harris portends, “is a future in which most Muslims have learned to ignore most of their canon, just as most Christians have learned to do.”(19)

Incendiary rhetoric aside, and given what we know about monotheism generally, is Harris naïve to emphasize Islamic violence?  After all, Western history is saturated with exclusively Christian bloodshed.  Pope Innocent III’s thirteenth-century crusade against the French Cathars, for example, may have ended a million lives.  The French Religious Wars of the sixteenth-century between Catholics and Protestant Huguenots left around three million slain, and the seventeenth-century Thirty Years War waged by French and Spanish Catholics against Protestant Germans and Scandinavians annihilated perhaps 7.5 million.

Islamic scholar and apostate, Ibn Warraq, doesn’t think so.  Westerners tend to mistakenly differentiate between Islam and “Islamic fundamentalism,” he explains.  The two are actually one in the same, he says, because Islamic cultures continue to receive their Qur’an and hadith literally.  Such societies will remain hostile to democratic ideals, Warraq advises, until they permit a “rigorous self-criticism that eschews comforting delusions of a … Golden Age of total Muslim victory in all spheres; the separation of religion and state; and secularism.”(20)

Likely entailed in this hypothetical transformation would be a religious schism the magnitude of which would resemble the Christian Reformation in its tendency to wrest scriptural control and interpretation from the clutch of religious and political elites and into the hands of commoners.  Only then can a meaningful Enlightenment toward secularism follow.  And as author Lee Harris has opined, “with the advent of universal secular education, undertaken by the state, the goal was to create whole populations that refrained from solving their conflicts through an appeal to violence.”(21)

In the contemporary West, Rodney Stark concurs, “religious wars seldom involve bloodshed, being primarily conducted in the courts and legislative bodies.”(22)  In the United States, for example, anti-abortion terrorism might be the only exception.  But such is clearly not the case in many Muslim nations, where religious battles continue and are now “mainly fought by civilian volunteers.”  In fact, data recently collected by Stark appears to support Sam Harris’s critique rather robustly.

Consulting a variety of worldwide sources, Stark assembled a list of all religious atrocities that occurred during 2012.(23)  In order to qualify, each attack had to be religiously motivated and result in at least one fatality.  Attacks committed by government forces were excluded.  In the process, Stark’s team “became deeply concerned that nearly all of the cases we were finding involved Muslim attackers, and the rest were Buddhists.”  In the end, they discovered only three Christian assaults—all “reprisals for Muslim attacks on Christians.”

808 religiously motivated homicides were found in the reports.  A total of 5026 persons died—3774 Muslims, 1045 Christians, 110 Buddhists, 23 Jews, 21 Hindus, and 53 seculars.  Most were killed with explosives or firearms but, disturbingly, twenty-four percent died from beatings or torture perpetrated not by deranged individuals, but rather by “organized groups.”  In fact, Stark details, many reports “tell of gouged out eyes, of tongues torn out and testicles crushed, of rapes and beatings, all done prior to victims being burned to death, stoned, or slowly cut to pieces.”

Table 1:  Incidents of Religious Atrocities by Nation (2012).

Nation Number of Incidents
Pakistan 267
Iraq 119
Nigeria 106
Thailand 52
Syria 44
Afghanistan 27
Yemen 22
India 20
Lebanon 20
Egypt 15
Somalia 14
Myanmar 11
Kenya 9
Russia 7
Sudan 7
Iran 6
Israel 6
Mali 6
Indonesia 5
Philippines 5
China 4
France 4
Libya 4
Palestinian 4
Algeria 2
Bangladesh 2
Belgium 2
Germany 2
Jordan 2
Macedonia 2
Saudi Arabia 2
Bahrain 1
Bulgaria 1
Kosovo 1
South Africa 1
Sri Lanka 1
Sweden 1
Tajikistan 1
Tanzania 1
Turkey 1
Uganda 1
TOTAL 808

As Table 1 shows, present-day religious terrorism almost always occurs within Islam.  Seventy percent of the atrocities took place in Muslim countries, and seventy-five percent of the victims were Muslims slaughtered by other Muslims, often the result of majority Sunni killing Shi’ah (the majority only in Iran and Iraq).  Pakistan (80 percent Sunni) ranked first in 2012, likely due to its chronically weak central government and the contributions of al-Qaeda and the Taliban.

Christians accounted for twenty percent (159) of all documented victims.  Eleven percent of those (17) were killed in Pakistan, but nearly half (79) were slain in Nigeria, often by Muslim members of Boko Haram, often translated from the Hausa language as “Western education is forbidden.”  Formally known as the Congregation and People of Tradition for Proselytism and Jihad, Boko Haram was founded in 2002 to impose Muslim rule on 170 million Nigerians, nearly half of which are Christian.  Some estimate that Boko Haram jihadists—funded in part by Saudi Arabia—have slaughtered more than 10,000 people in the last decade.

Such attacks are indisputably perpetrated by few among many Muslims.  But whether the Muslim world condemns religious extremism, even religious violence, is another question.  According to Stark, “it is incorrect to claim that the support of religious terrorism in the Islamic world is only among small, unrepresentative cells of extremists.”  In fact, recent polling data tends to demonstrate “more widespread public support than many have believed.”

Shari’a, the religious law and moral code of Islam, is considered infallible because it derives from the Qur’an, tracks the examples of Muhammad, and is thought to have been given by Allah.  It controls everything from politics and economics to prayer, sex, hygiene, and diet.  The expressed goal of all militant Muslim groups, Stark argues, is to establish Shari’a everywhere in the world.

Table 2:  Percent of Muslims Who Think . . .

  Shari’a must be the ONLY source of legislation Shari’a must be a source of legislation Total
Saudi Arabia 72% 27% 99%
Qatar 70% 29% 99%
Yemen 67% 31% 98%
Egypt 67% 31% 98%
Afghanistan 67% 28% 95%
Pakistan 65% 28% 93%
Jordan 64% 35% 99%
Bangladesh 61% 33% 94%
United Arab Emirates 57% 40% 97%
Palestinian Territories 52% 44% 96%
Iraq 49% 45% 94%
Libya 49% 44% 93%
Kuwait 46% 52% 98%
Morocco 41% 55% 96%
Algeria 37% 52% 89%
Syria 29% 57% 86%
Tunisia 24% 67% 91%
Iran 14% 70% 84%

Gallup World Polls from 2007 and 2008 show that nearly all Muslims in Muslim countries want Shari’a to play some role in government.(24)  As Table 2 illustrates, the degree of desired implementation varies from nation to nation.  Strikingly, however, a clear majority in ten Muslim countries—and a two-thirds supermajority in five—want Shari’a to be the exclusive source of legislation.

In 2013, an Egyptian criminal court sentenced Nadia Mohamed Ali and her seven children to fifteen years imprisonment for apostasy.  One could argue, however, that Nadia got off easy because in Egypt the decision to leave Islam is punishable by death.  In fact, death is the mandatory sentence for apostasy in both Afghanistan and Saudi Arabia.  But do such laws garner support from Muslims in general?

That same year, the Pew Forum on Religion and Public Life asked citizens in twelve Islamic nations whether they supported the death penalty for apostasy.(25)  Their responses are reflected in Table 3.  In Egypt, eighty-eight percent of Nadia’s fellow residents would have approved of her and her children’s executions, as would a majority of Jordanians, Afghans, Pakistanis, Palestinians, Dijboutians, and Malaysians.

Table 3:  Death Penalty for People Who Leave the Muslim Religion?

Percent of Muslims Who Favor the Death Penalty for Apostasy
Egypt 88%
Jordan 83%
Afghanistan 79%
Pakistan 75%
Palestinian Territories 62%
Djibouti 62%
Malaysia 58%
Bangladesh 43%
Iraq 41%
Tunisia 18%
Lebanon 17%
Turkey 8%

But from a western perspective, so-called “honor” killing ranks among the most incomprehensible of Muslim customs.  Stark details four truly mindboggling cases:  In one, a young lady was strangled by her own family for the “offense” of being raped by her cousins.  In the other three, girls who eloped, acquired a cell phone, or merely wore slacks that day were hung or beaten to death.  From 2012 alone, Stark isolated seventy-eight reported honor killings, forty-five of which were committed in Pakistan.

Many protest that simple domestic violence is often misclassified as honor killing.  But, again, Pew survey data seems to suggest otherwise.(25)  Table 4 shows the percentage of Muslims in eleven countries who believe it is often or sometimes justified to kill a woman for adultery or premarital sex in order to protect her family’s honor.  Thankfully, only in Pakistan and Iraq do a majority (sixty percent) agree.  But in all other Muslim nations polled, a substantial minority—including forty-one percent in Jordan, Lebanon, and Pakistan—appear to approve of these horrific murders as well as their governments’ documented reluctance to prosecute them.

Table 4:  Is it justified for family members to end a woman’s life who engages in premarital sex or adultery in order to protect the family’s honor?

Percent of Muslims Who Responded Sometimes/Often Justified
Afghanistan* 60%
Iraq* 60%
Jordan 41%
Lebanon 41%
Pakistan 41%
Egypt 38%
Palestinian Territories 37%
Bangladesh 36%
Tunisia 28%
Turkey 18%
Morocco 11%

*In these countries, the question was modified to: “Some people think that if a woman brings dishonor to her family it is justified for family members to end her life in order to protect the family’s honor . . .”

Stark also cites a report from the Human Rights Commission of Pakistan.(27)  In 2012 alone, according to that organization, 913 Pakistani females were honor killed—604 following accusations of illicit sexual affairs, and 191 after marriages unapproved by their families.  Six Christian and seven Hindu women were included.

Monotheism Tamed?

Islam is not universally violent, of course.  The same polls, for example, show that few if any British and German Muslims and only five percent of French Muslims agree that honor killing is morally acceptable.  But the data from Islamic nations tend first, to support the proposition that Abrahamic monotheism is uniquely adapted to inspire violence, and second, to demonstrate that the belief in one god continues to fulfill this exceptionally vicious legacy.  It is no accident, for example, that nearly all Muslims in these countries are particularists, believing that “Islam is the one true faith leading to eternal life.”(28)

On the other hand, Westerners ought not to conclude from these polls that the perils of monotheism are confined to the geographic regions surrounding North Africa and the Middle East.  Even in the distant United States, for example, children continue to die needlessly because their Christian parents reject science-based medicine in favor of “prayer healing.”(29)  Enduring tragedies of this ilk would seem unimaginable in the absence of religious devotion to an allegedly all-powerful, ultra-dominant god.

References: 

(1)  Real Time with Bill Maher: Ben Affleck, Sam Harris and Bill Maher Debate Radical Islam (HBO). 2014. http://www.youtube.com/watch?v=vln9D81eO60 (posted October 6, 2014).

(2)  Stark, R. and K. Corcoran. 2014. Religious Hostility: A Global Assessment of Hatred and Terror. Waco, TX: ISR Books.

(3)  Schulson, M. 2014. Karen Armstrong on Sam Harris and Bill Maher. http://www.salon.com/2014/11/23/karen_armstrong_sam_harris_anti_islam_talk_fills_me_with_despair/ (posted November 23, 2014).

(4)  Armstrong, Karen. 2014. Fields of Blood: Religion and the History of Violence. NY: Knopf.

(5)  Eller, Jack David. 2010. Cruel Creeds, Virtuous Violence: Religious Violence across Culture and History. NY: Prometheus.

(6)  Harris, S. 2005. The End of Faith: Religion, Terror, and the Future of Reason. NY: W.W. Norton.

(7)  Diamond, J. 1997. Guns, Germs, and Steel: The Fates of Human Societies. NY: W.W. Norton.

(8)  Stark, R., and K. Corcoran. 2014. Religious Hostility.

(9)  Freud, S. 1967. Moses and Monotheism. NY: Vintage.

(10)  Hillman, J. 2005. A Terrible Love of War. NY: Penguin.

(11)  Armstrong, Karen. 2001. Holy War: The Crusades and Their Impact on Today’s World. NY: Anchor Books.

(12)  Kirsch, J. 2004. God Against the Gods: The History of the War Between Monotheism and Polytheism. NY: Viking Compass.

(13) Meltzer, E. 2004. “Violence, Prejudice, and Religion: A Reflection on the Ancient Near East,” in The Destructive Power of Religion: Violence in Judaism, Christianity, and Islam (Volume 2: Religion, Psychology, and Violence), ed. J. Harold Ellens. Westport, CT: Praeger.

(14)  Cline, E.H. 2004. Jerusalem Besieged: From Ancient Canaan to Modern Israel. U. of Mich. Press 2004.

(15)  Avalos, H. 2005. Fighting Words: The Origins of Religious Violence. Amherst, NY: Prometheus.

(16)  Schwartz, R. 2006. “Holy Terror,” in The Just War and Jihad: Violence in Judaism, Christianity, & Islam, ed. R.J. Hoffman. Amherst, NY: Prometheus.

(17)  Garcia, H. 2015. Alpha God: The Psychology of Religious Violence and Oppression. Amherst, NY: Prometheus.

(18)  Guitierrez, R. 1991. When Jesus Came the Corn Mothers Went Away: Marriage, Sexuality and Power in Mexico, 1500-1846. Stanford: Stanford University Press.

(19)  Harris, S. The End of Faith.

(20)  Warraq, Ibn. 2003. Why I Am Not a Muslim. Amherst, NY: Prometheus.

(21)  Harris, L. 2007. The Suicide of Reason: Radical Islam’s Threat to the West. NY: Basic Books.

(22)  Stark, R., and K. Corcoran. 2014. Religious Hostility.

(23)  Stark’s sources included thereligionofpeace.com, the Political Instability Task Force Worldwide Atrocities Data Set, Tel Aviv University’s annual report on worldwide anti-Semitic incidents, the U.S. Commission on International Religious Freedom’s annual report for 2013, and the U.S. State Department’s International Freedom Report, 2013.

(24)  The Gallup World Poll studies have surveyed at least one thousand adults in each of 160 countries (having about 97 percent of the world’s population) every year since 2005.

(25)   The World’s Muslims: Religion, Politics and Society. 2013. http://www.pewforum.org/2013/04/30/the-worlds-muslims-religion-politics-society-overview/ (posted April 30, 2013) and http://www.pewforum.org/files/2013/04/worlds-muslims-religion-politics-society-topline1.pdf

(26)  Ibid.

(27)  State of Human Rights in Pakistan in 2012. Islamabad, Pakistan, May 4, 2013.

(28)  Pew Forum on Religion and Public Life, The World’s Muslims: Religion Politics and Society. (Washington, DC, 2013).

(29)  Hall, H. 2013. Faith Healing: Religious Freedom vs. Child Protection. http://www.sciencebasedmedicine.org/faith-healing-religious-freedom-vs-child-protection/ (posted November 19, 2013).

Why Gay and Lesbian: A New Epigenetic Proposal.

by Kenneth W. Krause.

Kenneth W. Krause is a contributing editor and “Science Watch” columnist for the Skeptical Inquirer.  Formerly a contributing editor and books columnist for the Humanist, Kenneth contributes regularly to Skeptic as well.  He may be contacted at krausekc@msn.com.

The persistence of homosexuality among certain animal species, including humans, has bewildered scientists at least since the time of Darwin.  Why should same-sex attraction persist when evolution assumes reproductive success?  Does homosexuality—especially among humans—facilitate the intergenerational transfer of genetic material in some other way?  Or perhaps it advances an entirely different objective that justifies it’s more obvious procreative disadvantage.  Such questions have long attracted gene-based explanations for homosexuality.

Consider “kin selection,” for example.  As E.O. Wilson first suggested in 1975, maybe human homosexuals are like sterile female worker bees that assist the queen in reproduction.  One study of homosexual men, known in Independent Samoa as fa’afafine, revealed that gays are significantly more likely than straight men to help their siblings raise children.

But to satisfy the kin selection hypothesis, each gay must account for the survival of at least two sibling-born children for every one he fails to reproduce—a difficult standard to attain accomplish.  In any case, relevant studies in the U.S. and U.K. have failed to provide such evidence.

As a possible explanation for male homosexuality, other researchers have offered the “fertile female” hypothesis.  Here, a genetic tendency toward androphilia, or attraction to males—though problematic for men from an evolutionary perspective—is thought to enhance the reproductive success of their straight, opposite-sex relatives by rendering them hyper-sexual.

At least two studies have claimed results in support of the fertile female model.  Notably, this hypothesis is also capable of explaining why gayness persists at a constant but low frequency of about eight percent in the general global population.

A former faculty member at Harvard Medical School and the Salk Institute, neuroscientist Simon LeVay favors evidence suggesting a suite of several “feminizing” genes (LeVay 2011).  The inheritance of a limited number of these genes, LeVay proposes, will make males, for instance, more attractive to females—and thus presumably more successful in terms of reproduction—by rendering them less aggressive and more empathetic, for example.

But a few men in the family tree will receive “too many” feminizing genes and, as a result, be born gay.  Indeed, one Australian study has discovered that gender-atypical traits do enhance reproduction, and that heterosexuals with homosexual twins achieved more opposite-sex partnerships than heterosexuals without homosexual twins—though statistical significance was observed only among females.

Even so, most explanations are not based solely in genetics.  Evidence suggests as well, for example, that a variety of mental gender traits are shaped during fetal life by varying levels of circulating sex hormones.  Especially during certain critical periods of development, testosterone (T) levels in particular are thought to cause the brain to organize in a more masculine or feminine direction and, later in life, to influence a broad spectrum of gender traits including sexual preference.

For instance, women suffering from congenital adrenal hyperplasia due to elevated levels of prenatal T and other androgens are known to possess gender traits significantly shifted toward masculinity and lesbianism.  Importantly, female fetuses most severely affected by CAH and, thus, most heavily exposed to prenatal androgens are the most likely to experience same-sex attraction later in life.

Similarly, the bodies of male fetuses afflicted with androgen insensitivity syndrome—a condition in which the gene coding for the androgen receptor has mutated—will fail to react normally to circulating T.  As a result, these XY fetuses will later appear as girls and, as adults, share an attraction to men.  In sum, although a number of other factors could be, and likely are, at play, it is now fairly well established that prenatal androgen levels have a substantial impact on sexual orientation in both men and women.

But three researchers working through the National Institute for Mathematical and Biological Synthesis have recently combined evolutionary theory with the rapidly advancing science of both androgen-dependent sexual development and molecular regulation of gene expression to propose a new and provocative epigenetic model to explain both male and female homosexuality (Rice, et. al. 2012).

According to lead author William Rice at the university of California, Santa Barbara, his group’s hypothesis succeeds not only in squaring homosexuality with natural selection—it also explains why same-sex attraction has been proven substantially heritable even though, one, numerous molecular studies have so far failed to locate associated DNA markers and, two, concordance between identical twins—about twenty percent—is far lower than genetic causation might predict.

At the model’s heart are sex-specific epigenetic modifications, or epi-marks.  Generally speaking, epi-marks can be characterized as molecular regulatory switches attached to genes’ backbones that direct how, when, and to what degree genetic instructions are carried out during an organism’s development.  They are created anew during each generation and are usually “erased” between generations.

But because epi-marks are produced at the embryonic stem cell stage of development—prior to division between soma and germline—they can in theory be transmitted across generations.  Indeed, some evidence does suggest that on rare occasions (though not at scientifically trivial rates) they will carry over, and thus mimic the hereditary effect of genes.

Under typical circumstances, Rice instructs, sex-specific epi-marks serve our species’ evolutionary objectives well by canalizing subsequent sexual development.  In other words, they protect sexually essential developmental endpoints by buffering XX fetuses from the masculinizing effects and XY fetuses from the feminizing effects of fluctuating in utero androgen levels.  Significantly, each epi-mark will influence some sexually dimorphic traits—sexual orientation, for example—but not others.

According to the new model, however, when sex-specific epi-marks manage to escape intergenerational erasure and transfer to opposite-sex offspring, they become sexually antagonistic (SA) and thus capable of guiding the development of sexual phenotypes in a gonad-discordant direction.  As such, Rice hypothesizes, “homosexuality occurs when stonger-than-average SA-epi-marks (influencing sexual preference) from an opposite-sex parent escape erasure and are then paired with weaker-than-average de novo sex-specific epi-marks produced in opposite-sex offspring.”

To summarize, Rice’s team argues that differences in the sensitivity of XY and XX fetuses to the same levels of T might be caused by epigenetic mechanisms.  Normally, such mechanisms would render male fetuses comparatively more sensitive and female fetuses relatively less sensitive to exposure.  But if such epigenetic labels pass between generations, they can influence sexual development.  And if they pass from mother to son or from father to daughter, sexual development can proceed in a manner that is abnormal (or “atypical,” if you prefer).  In those very exceptional cases, offspring brain development can progress in a fashion more likely to result in homosexuality.

Rice’s observations and insights are fascinating, to say the least.  Indeed, popular news reports describe a scientific community highly appreciative of the new model’s theoretical power.   Nevertheless, a great deal of criticism has been tendered as well.

LeVay, for example, describes the authors’ hypothesis generally as “a reasonable one that deserves to be tested—for example by actual measurement of the epigenetic labeling of relevant genes in gay people and their parents.”  He reminded me, however, that Rice hasn’t actually discovered anything.  The new model is in fact pure speculation, says LeVay, and it never should have been reported—as some media have done—as “the cause” (or even as “a cause”) of homosexuality.

More specifically, LeVay offers three points of caution.  First, he warns that an epigenetic explanation is not to any degree implied from the current data on fetal T levels.  When based on single measurements, he concedes, male and female fetuses may indeed show some overlap.  But because T levels fluctuate in both males and females throughout development, allegedly anomalous individuals might easily average completely sex-typical T levels over time.  Second, LeVay sees “little or no evidence” that epi-marks ever escape erasure in humans.

Finally, LeVay continues to favor genetic explanations.  The incidence of homosexuality in some family trees, he says, is more consistent with DNA inheritance than with any known epigenetic mechanism.  Moreover, he warns, we should never underestimate the difficulty of identifying genetic influences—especially with regard to mental traits.  In such cases, complex polygenic origins are far more likely to be at play than single, magic genetic bullets.

Other neuroscientists have posed equally important questions.  How can we test whether the appropriate epi-marks—probably situated in the brain—have been erased?  Is it too simplistic to suggest identical or even similar mechanisms for both male and female homosexuality?  Why is it important to isolate the specific biological causes of same-sex attraction?  By doing so, do we run the risk of further stigmatizing an already beleaguered population?

Rice doesn’t deny his new model’s data deficit.  Nor does he portray the epigenetic influence on same-sex attraction as an exclusive one.  His team does, however, insist that epigenetics is “a probable agent contributing to homosexuality.”  We now have “clear evidence,” they maintain, that “epigenetic changes to gene promoters … can be transmitted across generations and … can strongly influence, in the next generation, both sex-specific behavior and gene expression in the brain.”

The authors contend as well that their hypothesis can be rapidly falsified because it makes “two unambiguous predictions that are testable with current technology.”  First, future large-scale association studies will not identify genetic markers correlated with most homosexuality.  Any such associations found, they say, will be weak.

Second, future genome-wide epigenetic profiles will distinguish differences between homosexuals and non-homosexuals, but only at genes associated with androgen signaling or in brain regions controlling sexual orientation.  Testing this second prediction, they admit, may proceed only with regard to lesbianism by comparing profiles of sperm from fathers with and without homosexual daughters.

To my knowledge, Rice and his colleagues have never squarely addressed the question of whether, for philosophical or sociological reasons, we should refrain from delving further into the dicey subject of same-sex attraction.  Such questions do, however, expose a tendency toward communal repression and a general lack of respect for the scientific enterprise.  These decisions should be left to the scientists and those who fund them.

References:

LeVay, Simon. 2011. Gay, Straight, and the Reason Why: The Science of Sexual Orientation. NY: Oxford University Press.

Rice, W., Friberg, U., and Gavrilets, S. 2012. Homosexuality as a consequence of epigenetically canalized sexual development.  The Quarterly Review of Biology 87(4): 343-368.

What Next for Gay Marriage?

by Kenneth W. Krause.

Kenneth W. Krause is a contributing editor and “Science Watch” columnist for the Skeptical Inquirer.  Formerly a contributing editor and books columnist for the Humanist, Kenneth contributes regularly to Skeptic as well.  He may be contacted at krausekc@msn.com.

(The US Supreme Court may very well rule on the legality of same-sex marriage bans in 2015.  Originally published in 2011, this article remains informative.)

Voters here in Wisconsin passed a ban on same-sex marriage in the fall of 2006. The following morning, I thoughtlessly tried to console a lesbian coworker by predicting a universal right to marry within a decade. “That’s fine,” she replied blankly, “but that doesn’t help us now.” For me, the gay marriage issue was and will always be no more than a legal and moral abstraction. For my coworker and her long-time partner, on the other hand, the marriage ban was a personal tragedy and a cold, hard slap in the face from their most trusted friends and neighbors.

In November 2008, the citizens of California passed Proposition 8, amending that state’s constitution to ban recognition of same-sex marriages performed thereafter. The initiative passed with 52 percent of the vote. Another lesbian, Kristen Perry, brought suit against California’s then governor, Arnold Schwarzenegger, and then Attorney General, Jerry Brown, asking the court to strike the law as unconstitutional.

On August 4, 2010, U.S. District Judge Vaughn Walker, a republican appointed by George H. W. Bush, ruled that Proposition 8 had created an “irrational classification” and “unconstitutionally burden[ed] the exercise of the fundamental right to marry.” Thus, according to the federal court, voters in California had violated the Equal Protection and Due Process clauses of the Fourteenth Amendment. On August 16, the Ninth Circuit Court of Appeals ordered Walker’s judgment stayed pending the state’s appeal. One way or another, Perry v. Schwarzeneggar is widely expected to reach the United States Supreme Court.

My prediction in 2006 may have been insensitively timed. But it was firmly based on clear trends toward public and legal acceptance of homosexuals in America. In the 2003, for example, the Supreme Court overturned Bowers v. Hardwick—precedent from seventeen years past—to strike down a state law criminalizing gay sex. “[A]dults may choose to enter upon this relationship in the confines … of their own private lives and still retain their dignity,” Justice Anthony Kennedy wrote for the majority in Lawrence v. Texas, and “[p]ersons in a homosexual relationship may seek autonomy for these purposes, just as heterosexuals do.”

In isolation those words appear to bode well indeed for homosexuals. But other scraps of Lawrence muddy the jurisprudential waters considerably. First, although the Texas statute discriminated against gay sex on its face, the Court’s ruling was based only on due process but not on equal protection grounds. Second, and more importantly, Kennedy’s opinion explicitly warned that his ruling did “not involve … formal recognition to any relationship that homosexual persons seek to enter.”

But Justice Antonin Scalia wasn’t convinced. In his dissent, Scalia protested that the majority’s opinion “dismantles the structure of constitutional law that has permitted a distinction to be made between heterosexual and homosexual unions, insofar as formal recognition in marriage is concerned.” Lawrence “‘does not involve’ the issue of homosexual marriage,” he carped, “only if one entertains the belief that principle and logic have nothing to do with the decision of this Court.”

So, assuming that a legislative ban on gay marriage like Proposition 8 will soon reach the Supreme Court, what’s the likely outcome? For Martha Nussbaum, University of Chicago professor of law and ethics, and author of From Disgust to Humanity: Sexual Orientation & Constitutional Law (Oxford, 2010), the answer depends upon the relative influence of two competing philosophical paradigms.

Based partially in right-wing collectivism, the “politics of disgust” defer to the group and sustain democratic domination of disfavored minorities. Perhaps epitomized by Englishman Lord Devlin’s and American Leon Kass’s views that the average person’s deep-seated aversion toward a given practice is reason enough to make it illegal, disgust cares not whether the practice is actually harmful.

gay haters

The “politics of humanity,” by contrast, is founded in the tenets of classical liberalism and is categorically anti-collectivist. Exemplified by John Stuart Mill’s libertarian principle that individual freedoms should remain unrestricted except to avoid injury to others, humanity relies upon the imaginative skills inherent in compassion and sympathy and emphasizes equal respect for the dignity of all persons.

According to Nussbaum, the politics of disgust are slowly yielding to the politics of humanity in the U.S. And “[e]ven those who believe that disgust still provides a sufficient reason for rendering certain practices illegal,” she vies, “should agree … that disgust provides no good reason for limiting liberties or compromising equalities that are constitutionally protected.” But constitutional interpretation, of course, is precisely where the ethical rubber hits the political road.

One can certainly argue, as Nussbaum does, that American constitutional jurisprudence has already displayed an increasingly enthusiastic tendency to reject disgust in favor of humanity. In recent decades—especially during times of peace, the Court has afforded equal protection or substantive due process rights to a wide variety of disfavored minorities, including women, blacks, the mentally retarded, members of non-traditional families, and even prisoners.

Indeed, seven years prior to Lawrence, the Court granted a mammoth victory to homosexuals too. In 1992, Colorado passed Amendment 2, a ballot measure disqualifying gays from the benefits of antidiscrimination laws. Proponents justified the ban contending that homosexuals shouldn’t be afforded “special rights.” Penning the majority opinion in Romer v. Evans as well, Justice Kennedy rejected that characterization of the ban’s effect. “This Colorado cannot do,” he ruled on equal protection grounds: “A state cannot so deem a class of persons a stranger to its laws.”

So, in light of Romer, are states precluded from deeming gay persons strangers to their laws of marriage? Nussbaum remains skeptical. In that case, she explains, “illegitimate intent was written all over the law and its defense.” Romer was “a very narrow holding,” she cautions, offering “little guidance for future antidiscrimination cases involving sexual orientation.” Importantly, Kennedy had subjected Colorado’s law to mere rational basis review as opposed to intermediate or strict scrutiny, meaning that he did not, in Romer, identify homosexuals as a suspect class deserving maximum protection. Which is not to suggest that he couldn’t or wouldn’t do so in a future case, but rather only to point out that other discriminatory state laws, if more shrewdly crafted, might survive the less demanding standard of review.

Thus, Nussbaum reasons, “The secure protection of gays … would seem to require a holding that laws involving that classification, like laws involving race or gender, warrant some form of heightened scrutiny.” In order to induce such a holding, a plaintiff would generally need to convince a court that homosexuality is an immutable characteristic (a contentious proposition nevertheless consistent with available scientific evidence), that homosexuals have suffered a long history of discrimination, and that they remain politically vulnerable.

Somewhat surprisingly, however, Nussbaum argues that state rather than federal courts should manage the issue of gay marriage until democratic majorities can be trusted to support inclusion. Local adjudication, she argues, would shield the U.S. Supreme Court from this particularly hazardous battle in the culture wars, and encourage the kind of robust experimentation inherent in federalism that, hopefully, will result in a more educated polity.

And certain states have already taken that initiative. Nussbaum offers Varnum v. Brien, a 2009 decision delivered by the Supreme Court of Iowa, as ample grounds for optimism. Although only 44 percent of Iowans presently support same-sex marriage, the seven-member court in Varnum struck the local Defense of Marriage Act, and, applying intermediate scrutiny, unanimously ruled that the state had no important interest in denying marriage licenses to its citizens based on sexual orientation.

What Nussbaum could not have known when writing From Disgust to Humanity was that on November 2, 2010, Iowa voters would oust each of the three Varnum justices who were up for retention. The facts surrounding the election make it clear that Iowans were reacting to the previous year’s ruling on gay marriage. The high court justices faced no opponents and needed only 50 percent of the vote to retain their seats. By contrast, each of the 71 lower court judges on the ballot were easily reelected. Incidentally, the anti-retention campaign was heavily financed by out-of-state special-interest groups, including the National Organization for Marriage and the American Family Association.

So, with Iowa in mind, might judges subject to reelection in other states be less inclined to stand up for homosexuals in defiance of local majorities? Gays might be forced to look to the U.S. Supreme Court once again, and to Justice Kennedy, who is likely to cast the deciding vote on a panel equally divided over several social issues. Would Kennedy extend his reasoning in Lawrence and Romer to cover same-sex marriage rights? Or would the committed Catholic Justice, appointed by Ronald Reagan in 1988, draw the line at marriage, a term still rife with religious connotations? Would he defer to democratic majorities, perhaps siding with Scalia the constitutional originalist?

In Justice Kennedy’s Jurisprudence: The Full and Necessary Meaning of Liberty (Kansas, 2009), Frank Colucci, political scientist at Purdue University—Calumet, dispels popular reports of Kennedy’s alleged inconsistency, dissecting the Justice’s public declarations to expose an underlying jurisprudential philosophy of individual rights. Kennedy “employs a moral reading of the Constitution,” Colucci finds, “to enforce individual liberty, [but] not equality, as the moral idea he finds central” to the document. Although he often sides with judicial minimalists and originalists, he does so for different reasons. In fact, Kennedy favors an expansive role for the Court and remains the justice most likely to strike legislation he deems contrary to the Constitution.

Much to Scalia’s irritation, Kennedy’s search for liberty’s parameters ends not in the Constitution’s text or tradition. Rather, his overriding concern seems to be whether government intrusion prevents the individual “from developing his or her distinctive personality or acting according to conscience,” according to Colucci, or demeans a person’s community standing and denigrates his or her “human dignity.” To provide “objective referents” for his constitutional interpretations, the Justice cites sociological research, international law, and emerging political consensus. His moral precepts, the author says, “have clear rhetorical roots in post-Vatican II Catholic social thought.”

In cases dealing with religion specifically, Kennedy has supported “noncoercive” government action, opining in Allegheny County v. Greater Pittsburgh ACLU, for example, that states should be given “some latitude in recognizing and accommodating the central role religion plays in our society.” Then again, in Lawrence, the Justice clearly emphasized a religiously denounced individual right, professing the founders’ insight that “later generations [would] see that laws once thought necessary and proper in fact serve only to oppress.” Similarly, Kennedy was swayed in Roper v. Simmons by recent trends among a very few states and in the world at large before concluding that death was a cruel and unusual punishment for minors.

Although he recognizes Kennedy’s potentially decisive impact on such questions, Colucci does not directly address the prospects for same-sex marriage. Nevertheless, his conclusions seem to portend well for gays. In Kennedy’s constitutional jurisprudence, personal autonomy has trumped democracy. Tradition and precedent are crucial, yes, but do not entirely define the Court’s dynamic and continuing role to “discover” the meaning of individual liberty, perhaps through recent expressions of moral advances made both at home and abroad.

All of which leads me briefly to Proud To Be Right: Voices of the Next Conservative Generation (Harper, 2010), a title unlikely to be cited, one might hastily presume, in support of any article predicting the relatively imminent legalization of homosexual marriage. Here, Jonah Goldberg—founding editor of the National Review Online, contributor to Fox News, and best-selling author of Liberal Fascism—has assembled an impressive band of young and unapologetically conservative writers—some religious, some secular—“who do not yet have a megaphone, but might deserve one.”

In the ironically titled “Liberals Are Dumb,” for example, evangelical Christian blogger Rachel Motte touts the value of a rigorous liberal arts education for every conservative activist who wants to be taken seriously. And in “The Politics of Authenticity,” social conservative Matthew Lee Anderson warns politicians that his peers are considerably less obsessed over sexual mores, but much more concerned about the ethics of conducting business and war than their older, value-voting predecessors. A more intellectual and less personally intrusive conservatism focused on economics and foreign policy? One can only hope.

But particularly relevant to the issue at hand is a refreshingly candid piece from James Kirchik, contributing editor to the New Republic, called “The Consistency of Gay Conservatives.” Though the GOP’s base—presently empowered by the religious Right—remains opposed to gay marriage, Kirchik portends, support will likely increase as the Republican pool grows younger. Why? Because “the ‘gay agenda’ today,” he says, “is fundamentally conservative.”

Gay activists in California, after all, protest not for “free love,” but only for the right to marry their committed partners. “They want to join this bedrock institution,” Kirchik reminds us, “not tear it apart.” In fact, the prevailing scientific explanation for homosexuality—unmistakably deterministic—is repudiated not so much by conservatism, the author contends, but instead by “Left-wing ‘queer’ theorists, who argue that binary sexuality is a social construct.” A little more food, perhaps, for feminist thought.

Living in the largely rural Midwest, even the least bigoted person is tempted to write off homosexuals for inspiring too few vocal allies and entirely too many powerful foes. Gay marriage remains one of those annoying, distracting, “hot button” political skirmishes in a larger culture war that, quite frankly, never deserved Americans’ precious time and energy in the first place. But the forces of religious bigotry will soon lose this battle, as they have so many others in recent centuries.

Whether the courts recognize and respect it or not, public opinion from nearly every perspective appears to be converging on at least quiet support for same-sex marriage. Thus, the Earth continues to grow a little rounder, the solar system more heliocentric, and the universe ever more capacious. Meanwhile, humanity grows less childlike. As we continue to discover and realize our vast potential, we find less and less occasion for odium and pettiness.

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