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CRISPR Embryos at Karolinska: Controversies Demand Oversight

Posted by Elliot Hosman on October 7th, 2016

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Rumors have been circulating since 2014 about various research teams around the world applying the genetic engineering tool CRISPR-Cas9 in human embryos. Surprisingly, only two experiments have been officially reported in scientific journals—both of them in nonviable embryos incapable of being used for reproduction, and both out of Guangzhou, China.

CRISPR in viable human embryos

On September 22, NPR’s Rob Stein reported an exclusive look inside the Karolinska Institute in Sweden at ongoing but previously undisclosed work using CRISPR in viable human embryos. Stein had traveled to Stockholm to interview researcher Fredrik Lanner and his colleagues about their program of injecting CRISPR into viable human embryos to “knock out” genes potentially linked to early development. NPR quoted CGS executive director Marcy Darnovsky who cautioned:

It's a step toward attempts to produce genetically modified human beings. This would be reason for grave concern. … If we're going to be producing genetically modified babies, we are all too likely to find ourselves in a world where those babies are perceived to be biologically superior. And then we're in a world of genetic haves and have-nots...

The next day, Hank Greely, director of the Center for Law and the Biosciences at Stanford University, told Eric Niiler in Seeker that there is “good valid medical use” for basic scientific research using CRISPR in embryos, but followed that with a warning:

Still, Greely acknowledges that some scientists or the public might say that the Swedish experiment could be an ethical "slippery slope" toward a gene-edited human. “Even if you don't intend to, it makes it easier for someone else to do it,” Greely said.

Rogue actors: “Bioethics, get out of the way”

While many scientists, scholars, legal experts, and public interest advocates oppose using human gene editing for reproductive purposes, others question why anyone would dare stand in the way. There are longer and shorter answers. Our knowledge of both CRISPR and genetics/genomics is poor—not  just on its own terms, but also in relation to other spheres of knowledge, particularly the ways in which they each interact with evolution, environments, public health, and social justice. For the foreseeable future, it would be reckless for a scientist to implant CRISPR-injected embryos for pregnancy not only because of serious safety concerns, but also in terms of democratic governance—especially given the select echelons to which most of the debate is currently restricted, and the range of social and political threats that genome editing poses to the human species.

In Seeker, legal scholar Rosario Isasi of the University of Miami voiced concern about edited human embryos being misused to produce genetically modified humans.

What are the oversight and controls to prevent this technology from being misused and go to a stage that, for now, the scientific community has agreed is a no-go?

In the italics (added) above, Isasi refers to the concluding statement from the International Summit on Human Gene Editing in D.C. in December 2015, in which the organizing committee argued:

It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved…and (ii) there is broad societal consensus about the appropriateness of the proposed application.…any clinical use should proceed only under appropriate regulatory oversight.

Ensuring that researchers work within the bounds of existing national and international prohibitions against heritable genetic modifications in early human cells can be difficult when: (1) commercial and reputational incentives interfere, and (2) rogue scientists exploit basic research for socially and scientifically unsafe ends. Isasi noted in Seeker that the Karolinska Institute has been the venue of an ongoing controversy involving Paolo Macchiarini, a stem cell researcher whose implants of artificial trachea into people led to deaths between 2012 and 2014. Isasi asked:

How did they supervise that [artificial trachea] research, which makes me wonder, what mechanisms were in place to oversee this (gene-editing) proposal [?]

Concerns about end runs or misbehavior by individual scientists have recently grown. On September 27, the news heard ‘round the world was that a fertility doctor based in New York City went to Mexico to use scientifically controversial mitochondrial manipulation techniques to produce a child from an embryo engineered from the DNA of three people. New Hope Fertility Clinic’s John Zhang will take the stage and present the methods used to produce this “three-parent baby” at the upcoming conference of the American Society for Reproductive Medicine, the trade organization for fertility practitioners. The scientific portion of the annual meeting this year is aptly titled: "Scaling New Heights in Reproductive Medicine". It will be instructive to see whether Zhang is met with applause for his “disruptive” and “innovative” foray, or whether his colleagues will criticize the ways he short-circuited public policy and democratic discussions of emerging biotechnology regulations.

Clear boundaries - for some

In an interview with Paul Knoepfler, Lanner noted the existing Swedish policy against using modified embryos for pregnancy:

Swedish law is clear that genome editing is only allowed within the first 14 day[s] as long as the embryo is not transferred back for a continued pregnancy. This means that heritable genome editing for clinical purposes would not be allowed in Sweden. The clear legislation has been key in us moving ahead with these plans…. I’m actually pretty skeptical that the technology will be used for genome editing in the early embryo anytime soon.

The situation in China is different. While that country has regulations that would technically ban gene-edited embryos being used for pregnancy, it is unclear whether these regulations are enforced. On September 24, news emerged out of China that a CRISPR testing facility for genetically modified animals was under scrutiny for “faking inspection records and using students instead of certified technicians to conduct tests.” The testing center was established by the Chinese Academy of Agricultural Science, whose website lists partners including the Gates Foundation and UC Davis. It is a subsidiary of the Chinese Academy of Science which co-sponsored last December’s International Summit on Human Gene Editing with the U.S. National Academies and the UK’s Royal Society. Chief researcher Huang Dafang noted:

The incident has exposed management problems of some similar institutes, and serves as a warning…

Where does that leave the U.S.?

Many across the spectrum of opinion have noted the alarming speed with which CRISPR is being applied in research labs, including to human embryos, outside public scrutiny. Absent consistent laws or guidelines, many are concerned that rogue researchers may conclude that it is “safe enough” to implant edited embryos for pregnancy.

Given the competitive pressures in the world of science, the commercial incentives to be “first to market,” and the forum-shopping inherent to today’s biomedical enterprise, the “three-person IVF” child born in Mexico is a cautionary tale. Someone, somewhere could soon decide to try for a CRISPR baby. We should aim to protect future children from being born stripped of their privacy and guaranteed a life of medical display and tracking that was justified on their behalf to service goals like parental genetic connection.

We need a federal ban on any private or publically funded research aimed at clinical tests of human germline interventions and specifically against the use of gene-edited human germ cells in assisted reproduction. We also need an international conversation on how to pressure the biomedical sector in a range of political contexts to stay away from the human germline.

Previously on Biopolitical Times:

Composite image via Pixabay (lungs), Pixabay (baby silhouette), and Flickr/Lisa Camper (DNA)

Collaborative Science on Historically Burdened Concepts: Intelligence, Genetics, Race & Socio-economic Status

Posted by Daphne Martschenko, Biopolitical Times guest contributor on October 6th, 2016

Image via Wikimedia: "Lithograph of a North American skull from Samuel Morton's Crania Americana, 1839. Morton believed that intelligence was correlated with brain size and varied between racial groups".

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Charged Words

Intelligence is a highly charged word with ties to racist, classist, and eugenic narratives. In the United States, it has been used historically to assert and establish racial and class hierarchies, especially those between Blacks and Whites, and has long been linked to notions of biological difference.

In the early twentieth century, these notions were frequently explicit. As one example among many, Princeton psychologist Carl Campbell Brigham, creator of the SAT and member of the Advisory Council of the American Eugenics Society, wrote in 1922:

According to all evidence available…American intelligence is declining, and will proceed with an accelerating rate as the racial admixture becomes more and more extensive…There is no reason why legal steps should not be taken which would insure a continuously progressive upward evolution… The steps that should be taken to preserve or increase our present intellectual capacity must of course be dictated by science. (Brigham, 1922: 210)

Even in the years following World War Two, when overt claims of racial differences in intelligence were often muted, Nobel Laureate (in physics) William Shockley could openly argue:

I sincerely and thoughtfully believe that attempts to demonstrate that American Negro shortcomings are preponderantly hereditary is the action most likely to reduce Negro agony in the future… I propose a serious scientific effort to establish by how much the distribution of hereditary potential for intelligence of our black citizens falls below whites…If those Negroes with the fewest Caucasian genes are in fact the most prolific and also the least intelligent, then genetic enslavement will be the destiny of their next generation. (Shockley, 1971: 244)

In June 2000, when the completion of a preliminary sequence of the human genome was announced at the White House, President Bill Clinton famously said,

One of the great truths to emerge from this triumphant expedition inside the human genome is that in genetic terms, all human beings, regardless of race, are more than 99.9 percent the same. (GenomeTV, 2012)

But this did not end debate about race, genes, and intelligence. In fact, many observers have noted that the years following this announcement saw an uptick in claims that race is a biologically meaningful system of classification. In 2005, Francis Collins himself suggested that “we now need to study how genetic variation and disease risk are correlated with self-identified race” (Krimsky, 2011: 25).

Among those who study genetics and intelligence today, the discourse about race is couched in more subtle and humanitarian terms than it was in the twentieth century. Take for example G is for Genes, published in 2013 by behavioral psychologist Kathryn Asbury and behavioral geneticist Robert Plomin. The book advocates for “genetically sensitive” schools that use genetic information to maximize a child’s abilities through a system of personalized learning. In a chapter titled “Mind the Gap: Social Status and School Quality,” the authors discuss the impacts of low-income status, poor parenting, and teacher quality on a child’s success in the classroom. Race is remarkably absent from the picture.

Of course, conscious and unconscious assumptions about links between race and cognitive ability haven’t simply disappeared. Although race is not valid as a biological system of categorization (Cooper et al, 2003), it remains an important causal social factor. Any research that has a history of marginalizing certain groups needs to address race explicitly—both as an inherited colonial system of classification and as a form of social inequality.

Recognizing the detrimental impact of race on an individual’s life circumstances is important for creating meaningful and effective improvements and change. Talking about race as a social factor that shapes an individual’s everyday experiences is a way of challenging vast and recurring misapprehensions that locate race in notions of the biological. Failing to talk about it makes that challenge far less likely to succeed.

Heated Debate

Both in the social sciences and hard sciences, discomfort, confusion, and even denial often accompany conversations about intelligence. Each side habitually questions the rigor, benefit, and legitimacy of the other’s work. My own research as a PhD candidate sits between these fields, where the tensions between the two are inescapably clear.

My work focuses on four terms with burdened histories: intelligence, genetics, race, and socio-economic status. I examine how genetics research into intelligence and educational attainment affects the United States education system, where documented racial and socioeconomic disparities prevail and where teacher perceptions of student ability are known to affect student performance and referrals for gifted education programs (Elhoweris et al, 2005; Gillborn et al, 2012; Grissom, 2016; Slate et al, 1990).

On the one hand this means that I’m reading Genome-Wide Association Studies on educational attainment or intelligence, and engaging with geneticists who produce a form of scientific knowledge (Davies et al, 2011; Plomin et al, 2013; Rietveld et al, 2013; Selzam et al, 2016). On the other hand, I’m working with teachers in the classroom who are trying to make sense of why some bodies are less visible in gifted education programs than others (though gaining access in schools has been remarkably difficult, highlighting the charged and controversial nature of this project).

This is terrain on which it should be possible to connect the social sciences to hard sciences. But it is a landscape fraught with competing and underlying political debate. Two of the key questions: Are hard scientists socially responsible for how their work is interpreted and disseminated? Are social scientists truly informed about the science behind the work they often critique?

As an anthropologist, I am aware of the murky origins of my field as a whole—its expansion to legitimize Western colonialism, its use of scientific language and eugenics to validate social hierarchy as naturally occurring and biologically based. Anthropology, like other disciplines, has mobilized the concept of intelligence to maintain racialized matrices of power and hierarchies of inequality.

Scientists, on the other hand, often see their work as separate from social structures and narratives, rather than embedded in them. But insisting on the inherent objectivity of science is dangerous. In the case of genetics research on intelligence, its social impact on the US education system is potentially vast. Those who choose to research the biological basis for intelligence or educational attainment have a special responsibility to recognize this, and to understand its historical and foreseeable pitfalls. Collaborating with social scientists can help to make social implications more clear. While socially neutral research might not exist, socially responsible research certainly should.

Social scientists also have a responsibility. They can understand the methods and techniques of scientific research. And they can engage with geneticists in an open and inquiring manner. Intelligence researchers see legitimate benefits for individuals and society in their work. The social sciences can understand what the argued benefits are and why they are deemed valuable. Having a background in basic genetics and understanding the methodological practices at work in the field can strengthen critiques of the risky assumptions built into the methods and techniques of genetics research or highlight weaknesses in findings.

Scholars working in the hard sciences have faulted the media for misinterpretation, oversimplification, or sensationalism of their work (Asbury and Plomin, 2013: 96). Those in both social and hard sciences have noted that misleading hype often emerges in university press releases associated with the research (Evans, 2016: 11-13).  Understanding the conditions and constraints of research, and what published academic journal findings can actually demonstrate, might test whether this is, in fact, the case and keep researchers and public media in check.

Prospects for Reconciliation

So how do we collaborate across the social and hard sciences? And how do we as researchers make our ways through our work detached from personal lived experiences, appearances, and backgrounds that might inform how we look at another discipline? How might we try and set apart our work from the history that precedes it? Is it too dangerous to even try? Would doing so perpetuate systems that marginalize or make peripheral certain groups? I know my experiences as an ethnic minority and my work in the education system with underrepresented groups certainly inform my approach to research; denying this would ignore potential biases I carry.

Whatever collaboration might look like, finding a common language for discussion is paramount. Part of the disconnect between the soft and hard sciences stems from different academic vocabularies and expressions, making one field at times seem like a foreign language to the other. I think, for instance, that hard scientists might have trouble reading this piece, filled as it is with an anthropologist’s lexicon.  Creating a shared language centered on the pursuit of knowledge could be one good starting point, since both sides already seem invested in this area in their own way. Shared language that acknowledges the social consequences and historical context of knowledge production would also be enormously beneficial. Together, these sets of common concepts and vocabulary might help bridge the existing divide between the social and hard scientists.

Intelligence. Genetics. Race. Socio-economic status. Using these four words in the same sentence has closed doors for me as a researcher. Each is difficult to talk about on its own—and they’re almost explosive when joined together. Despite this, I strongly believe in combining these concepts through a full range of biological and social science methodologies—and in the value of picking up some diplomacy skills along the way.

Image via Wikimedia

Works Cited

Asbury, K., & Plomin, R. (2013). G is for genes : the impact of genetics on education and achievement, xii, 197 pages.

Brigham, C. C. (1922). A study of American intelligence. Princeton: Princeton university Press.

Cooper, R. S., Kaufman J. S., & Ward, R. (2003). Race and Genomics. New England Journal of Medicine, 348(12), 1166-1170.

Davies, G., Tenesa, A., Payton, A., Yang, J., Harris, S. E., Liewald, D.(2011).
Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Molecular Psychiatry, 16(10), 996–1005.

Elhoweris, H., Mutua, K., Alsheikh, N., & Holloway, P. (2005). Effect of Children’s Ethnicity on Teachers’ Referral and Recommendation Decisions in Gifted and Talented Programs. Remedial and Special Education, 26(1), 25–31.

Evans, J. P. (2016). (Mis)understanding Science: The Problem with Scientific Breakthroughs. Hastings Center Report, 46(5), 11–13.

GenomeTV. (2012). Human Genome Announcement at the White House (2000). Retrieved from

Gillborn, D., Rollock, N., Vincent, C., & Ball, S. J. (2012). “You got a pass, so what more do you want?”: race, class and gender intersections in the educational experiences of the Black middle class. Race Ethnicity and Education, 15(1), 121–139.

Grissom, J. A., & Redding, C. (2016). Discretion and Disproportionality: Explaining the Underrepresentation of High-Achieving Students of Color in Gifted Programs. AERA Open, 2(1).

Krimsky, S., Sloan, K., & Council for Responsible Genetics (Eds.). (2011). Race and the genetic revolution: science, myth, and culture. New York: Columbia University Press.

Plomin, R., Haworth, C. M. A., Meaburn, E. L., Price, T. S., & Davis, O. S. P. (2013).
Common DNA Markers Can Account for More Than Half of the Genetic Influence on Cognitive Abilities. Psychological Science, 24(4), 562–568.

Rietveld, C. A., Medland, S. E., Derringer, J., Yang, J., Esko, T., Martin, N. W., Koellinger, P. D. (2013). GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment. Science, 340(6139), 1467–1471.

Selzam, S., Krapohl, E., von Stumm, S., O’Reilly, P. F., Rimfeld, K., Kovas, Y., Plomin, R. (2016). Predicting educational achievement from DNA. Molecular Psychiatry.

Shockley, W. (1971). Negro IQ Deficit: Failure of a “Malicious Coincidence” Model Warrants New Research Proposals. Review of Educational Research, 41(3), 227–248.

Slate, J. R., Jones, C. H., & Charlesworth, J. R. (1990).Relationship of Conceptions of Intelligence to Preferred Teaching Behaviors. Action in Teacher Education, 12(1), 25–30.

Don’t Miss This: The Story of CRISPR Told in a Comic

Posted by Kayla Tolentino on October 6th, 2016

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The billion-dollar patent battle over CRISPR/Cas-9 “gene editing” technology is layered with blockbuster scientific papers, media storms, superstar researchers, and legal drama, which are all the right elements to make up a thrilling graphic novel. Illustrator Andy Warner helps to break down the complexities of the still unraveling CRISPR story through a recent comic strip, “Bad Blood: Who gets credit for the technology to cut-and-paste the human genome?”

Two opposing hands tug on DNA strands as if in competition. Text reads: "One of the biggest discoveries in biotech has the potential to radically alter our lives... and nobody knows who owns it."

A baby's eye pupils reflect DNA strands, as if looking into future. Text reads: "This system could be theoretically used to edit the genome of any organism, from wheat to mosquitoes... to human."

“Bad Blood” animates the key players in the ongoing legal fight between the Broad Institute and UC Berkeley, focusing on the increasingly recognizable trio of CRISPR co-discoverers Jennifer Doudna, Emmanuelle Charpentier, and Feng Zhang. The strip also illustrates journalists Antonio Regalado (MIT Tech Review) and Sharon Begley (currently STAT) who have been closely following the patent case and technical developments, and cites their thoughts on the ambiguities of credit for CRISPR and its potential social conseqeunces. 

Strikingly, after explaining the nitty-gritties of the science and patent law underlying gene editing technologies, Warner leaves readers with a thought-provoking parallel: the historic development of the nuclear bomb, and the anguishing dilemma it posed for the scientists involved with the effort. His portrayal of Albert Einstein invokes the volatile political climate during which the atomic bomb was developed, and suggests the current need to question the social and political context of CRISPR and how this will shape the potential outcomes of its uses.

Albert Einstein contemplates. Text reads: "In the spring of 1939, Albert Einstein realized that every step required for the creation of an unfathomable powerful weapon had been individually comlpeted."A cloud of nuclear wastes is illustrated with red colors. Text reads: "All that was required was sequence. If you strung these reactions together in order, you obtained an atomic bomb."

We are in a critical moment to make decisions that would safeguard future generations. And we are in a critical moment for artists, cultural groups, and various non-scientific communities to actively come together to interpret the present debates about gene editing technologies, creatively examine their unknowns, and engage in conversations about how to shape our future. 

In the last panel of “Bad Blood,” Warner recognizes the urgency of an ongoing discussion to discuss the potential impacts of gene editing on our humanity:

Text reads: "It is fitting then, that the responsibility for ushering in this brave new world is as undecided as the ethical and existential questions it raises." Bordering the text are strands of DNA. A hand is snipping parts of it, and a glue bottle is featured at the top left corner of the border.

For more information on CRISPR, you can visit CGS’ resources:

Previously on Biopolitical Times:

Images via Andy Warner/The Nib

Presidential Candidates on Science

Posted by Pete Shanks on September 16th, 2016 was launched in 2007 with a goal of promoting a Presidential debate entirely on scientific topics. That hasn't happened yet, but the organization, which includes a broad selection of establishment figures and is co-organized by the National Academies, AAAS, and the Council on Competitiveness, is still trying.

Meanwhile, they set a perhaps more realistic goal of agreeing on 20 science-related questions and getting written answers from the candidates. The answers from Hillary Clinton, Donald Trump and Jill Stein are now online. Libertarian Gary Johnson has not yet responded.

Here’s what you get from the candidates for each question (illustrated with extracts from responses to the opioid problem):

  • From Clinton, three or four paragraphs that read as though they were drafted by a competent policy analyst and edited, or at least approved, by the candidate.
    • Sample:  "We must work with medical doctors and nurses across the country to treat this issue on the ground, from how patients are accessing these medications to how we are supporting them in recovery."

  • From Trump, one paragraph that might have been extemporized by himself and then translated into a form of English.
    • Sample: "As this is a national problem that costs America billions of dollars in productivity, we should apply the resources necessary to mitigate this problem."

  • From Stein, short paragraphs (often several) that frequently make a lot of utopian sense.
    • Sample: "We will end the 'war on drugs' and redirect funds presently budgeted for the 'war on drugs' toward expanded research, education, counseling and treatment."

The Center for Genetics and Society’s core concerns about human biotechnologies are not explicitly covered. There are no references in either the questions or the answers to germline or other gene editing, or to genomics, stem cells, eugenics or precision medicine, to name but a few. Privacy is mentioned only in the context of the Internet in general.

Press reactions are listed on-site. Science had an anodyne but reasonably accurate summary. Lawrence M. Krauss in the New Yorker took a wry approach. Trump’s contributions were dissected at length by Martin Longman at Washington Monthly, who calls them variously “straight unresponsive pablum,” “almost unbelievable,” showing “no clue” and, on nuclear power, “positively Palinesque.” (Read the whole thing!) Michael Schulman at The Cubit blog (part of Religion Dispatches) has an entertaining summary that accurately concludes: asked questions about forces that will affect the basic well-being and survival of the United States’ citizenry. In theory, that’s the stuff of democracy. Not one of them, though, felt like something that will even remotely sway the election.

At almost the same time, Neal Lane and colleagues at Rice University issued a report arguing strongly that the White House Office of Science and Technology Policy (OSTP) and the position of science adviser should be retained by the next president, who should, as Science notes, "lay out priorities for science and innovation within the first 100 days of taking office.” The report is not specific on issues, but very strong on process.

On the lighter side, there are reports that Trump intends to nominate Peter Thiel, the notorious billionaire transhumanist, to the Supreme Court. Everyone involved denies this on the record, but the rumor is said to derive from sources close to Mr. Thiel. Someone allegedly close to the candidate confirms (on background) that there has been discussion but cautions:

Trump’s offers often fail to materialize in real life.

Previously on Biopolitical Times:

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