CRISPR-Cpf1: Hype by Association
Posted by Elliot Hosman on October 2nd, 2015
Another week, a fresh slew of CRISPR gene editing news and developments.
On September 24 Thomson Reuters predicted that Jennifer Doudna and Emmanuelle Charpentier would earn a Nobel Prize in chemistry for their widely celebrated 2012 research on the gene editing complex, CRISPR and associated protein Cas9. We could know as early as October 7 whether the Nobel committee will cut the wait time between publishing and laurels for a chemistry award from its 20-year average since 1985 to just three years.
The same day that the annual Nobel predictions hit the wire, Doudna, Charpentier, and a number of other researchers were gathered at Cold Spring Harbor Laboratory (CSHL) in New York for the first day of a conference called Genome Engineering: The CRISPR/Cas Revolution. That evening, Charpentier co-chaired a session with Feng Zhang, a co-discoverer of CRISPR’s gene editing capabilities and currently a rival of Charpentier’s and Doudna’s in a patent fight about the discovery. When Zhang took the stage after Charpentier, he pivoted away from CRISPR-Cas9 and, in the words of one participant, “blew us all out of the water.”
Zhang’s talk described a new CRISPR discovery that would be published the next day in Cell: an alternative CRISPR-associated protein called Cpf1. According to a Broad Institute press release,
“Zhang and his collaborators searched through hundreds of CRISPR systems in different types of bacteria, searching for enzymes with useful properties that could be engineered for use in human cells.”
The statement goes on to quote Broad Director Eric Lander asserting that the “Cpf1 system represents a new generation of genome editing technology…with the potential for even simpler and more precise genome engineering.”
Nature’s and Science’s headlines echoed this assessment, celebrating the discovery as an improvement on Cas9 and a sharper pair of molecular scissors, respectively.
But coverage in MIT Technology Review included some additional views. Science writer Antonio Regalado quotes University of Minnesota researcher Dan Boytas, who notes that the “greatest value may be more in terms of the patent landscape than a scientific advancement,” and George Church, who describes a coming “niche market for a collection of different proteins so that cuts can be placed anywhere in the genome.” Regalado also reports that researchers outside the Cpf1 research team “said the new system was likely to fill a limited role in what is a growing toolbox of DNA-editing techniques.”
Writing in Wired—a publication not averse to CRISPR hype—Sarah Zhang reinforced the idea that Cpf1 is not a Cas9 “rival so much as a complementary tool,” not so much an improvement as a method with slightly different capabilities. Wired quotes Feng Zhang’s research colleague John van der Oost: “We have the feeling it’s just the tip of the iceberg.” Doudna herself, in an October 1 interview on the Nobel Prize rumors, said that the research “underscores the wonderful diversity of these CRISPR systems” but that it was “unclear” whether Cpf1 will be “useful for genome editing.”
So for some, Cpf1 signals CRISPR 2.0, a “better way to edit the genome” or an “outsnip” of CRISPR/Cas9 potentially undercutting Doudna and Charpentier’s predicted grasp on a #NobelPrize. A different take is that we are still in the earliest stages of understanding the scientific, let alone the social, legal, and ethical, implications of CRISPR genome editing.
Previously on Biopolitical Times:
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Considering CRISPR: Putting a thumb on the scale?
Posted by Pete Shanks on September 24th, 2015
The National Academies of Sciences and of Medicine have announced the date for their closely watched and long-awaited International Summit on Human Gene Editing: December 1–3, in Washington, DC.
Officially co-hosting will be the Chinese Academy of Sciences and the UK Royal Society. No other European organization is included as a partner, despite (or perhaps because of) the region’s explicit policies on human germline modification as set forth by the Council of Europe’s Convention on Human Rights and Biomedicine, which proscribes it.
A German scientist is, however, a member of the planning committee. The UK and China each have two representatives on the committee.
The explicit goal of the "international summit" is "to discuss the scientific, medical, ethical, and governance issues associated with human gene-editing research." Though the meeting is only ten weeks away, the details of the agenda and the invited speakers have not been announced. CGS’s Marcy Darnovsky has been invited to speak, and has accepted.
It is perhaps interesting that the word "medical" has been added to the list of issues since the original announcement. It's not inappropriate, but the addition would seem to skew the discussion in the direction of implementation. Also, what will be the scope of the "ethical issues" discussed? Worryingly, a recent Institute of Medicine committee considering a related technique seemed to limit them to narrowly defined research ethics, and not to consider broader social issues.
Naturally, people with varying views are staking out positions and trying to persuade others. George Church is campaigning in New Scientist; and others on all sides of the issue are, quite rightly, putting their views forward.
On September 1, the Wellcome Trust, Medical Research Council, and three other leading British research organizations put out a statement supporting preclinical use of gene editing in human embryos and affirming
that there may be future potential to apply genome editing in a clinical context using human germ cells or embryos, though this is prohibited by law in the UK and unlikely to be permissible in other European jurisdictions at present.
Then the Hinxton Group, an international consortium of stem cell researchers, essentially agreed. Its statement stressed [pdf] that
Policymakers should refrain from constraining scientific inquiry unless there is substantial justification for doing so that reaches beyond disagreements based solely on divergent moral convictions.
Critics called this increasing the pressure for genetically modified embryos. It certainly seems close to "get out of the way."
So far, so normal in the politics of science. But the next step was
unusual: Kathy Niakan, a researcher at the Francis Crick Institute in London, applied to the UK
authorities for a license to edit the genes of human embryos.
But why now? Arthur Caplan made the relevant point that:
not sure the case has been made that you need to go and study human
embryos right now. It does seem to me that before you make the case that
you want to try this in human embryos, you ought to explain why you
don't need to do more animal work with this brand-new technology.
going to be true for quite a while yet. So with the discussion of germline gene editing just getting underway, why the rush?
Robin Lovell-Badge, one of the two British representatives on the National Academies' summit organizing committee, seems to have been involved in all three of these efforts. He's Naikan's boss, and advocate in the press; he's on the steering committee of the group that drafted the Hinxton statement; and his connections with the Wellcome Trust are long-standing and deep. Certainly all three initiatives match his opinion, expressed in April, that:
I disagree with such a moratorium [on embryo editing], which is in any case unlikely to be
effective. I am fully supportive of research being carried out on early
human embryos in vitro…The arguments become even more contentious when
dealing with 'enhancement'. However, while we work towards using the
methods to make disease-resistant crops and animals, should we deny this
possibility for humans?
He is of course entitled to express that opinion, as he surely will in December. But does it begin to look as though there is
an effort to put a thumb on the scale?
Previously on Biopolitical Times:
Original composite image via Pixabay
Ohio Abortion Bill Stokes Old Tensions between Disability and Abortion Rights Advocates
Posted by Emma Maniere on September 24th, 2015
The recent Ohio bill that would ban abortion based on a fetal diagnosis of Down syndrome has triggered widespread comment. In a state where 23 of 33 senators, 65 of 99 representatives, and the governor oppose abortion rights, and half of abortion clinics have closed in the past four years, it is likely to pass.
The bill also raises longstanding tensions between perspectives based in disability rights versus reproductive rights. As Sujatha Jesudason and Julia Epstein explain:
The disability rights movement is concerned about the number of pregnancies terminated solely because an expectant mother receives a diagnosis of a potential fetal disability. And the reproductive rights movement worries that any line of questioning concerning a woman’s prerogative to terminate her pregnancy will inevitably lead to undermining her decision-making autonomy.
Here, we examine how a selection of news articles and commentaries address – or ignore – this tension.
News coverage in The Economist is explicit on the point, arguing that “the bill scrambles some familiar positions.”
Abortion advocates are almost uniformly proponents of robust state funding for social services, including for the disabled. The anti-abortion lobby is generally staunchly conservative and opposed to anything that looks like a new entitlement. If the law goes through, as seems likely, women will be required by the state to give birth to their disabled child, but will not be able to count on much help from the state to raise it.
An article in The New York Times also mentions strains between advocates of disability rights and abortion rights, and notes in passing that the bill has the effect of “driv[ing] a wedge” between them. But the article mainly focuses on the fact that “some parents of children with Down syndrome [who] are strong proponents” of the bill, giving no indication that many disability rights advocates support abortion rights, and that many reproductive rights advocates are sympathetic to the disability rights perspective.
Several op-eds and commentaries explore these matters with far greater nuance and sensitivity. In a New York Times op-ed, Mark Lawrence Schrad presents his and his wife’s decision to have a daughter with Down syndrome as just that: a choice, despite medical and societal assumptions that they would opt to terminate the pregnancy. “[W]hen it comes to abortion and special needs,” he writes, “there is no easy answer – and the idea that these deeply personal ethical and social decisions could simply be legislated away is ridiculous.” Like The Economist piece, Schrad highlights the hypocrisy of abortion rights opponents who would both force women to have children for whom they may be unprepared and slash state support for those same families. Personal experience has driven Schrad to value reproductive choice, but he that believes for any choice to be meaningful, the necessary support systems must first be in place.
Writing in Bioethics Forum, philosophy and bioethics professor Bonnie Steinbeck stresses that the Ohio bill is unconstitutional and unenforceable, much like the authors above, but she also grapples with disability rights advocates’ concerns “that the choice of abortion in such cases is often based on ignorance about the kind of life the child could lead and discriminatory attitudes toward people with disabilities.” In addition, she notes, these attitudes may extend to people already living with disabilities, or even to the belief that because abortion is an option there is no need for the state to provide resources for people with Down syndrome and other disabilities. Steinbeck concludes with a call for Ohio legislators to direct their attention to “ensuring that all people with disabilities, Down syndrome or otherwise, get the resources and services they need.”
Judith Levine’s “Disability and the Politics of Abortion” in Seven Days explores more deeply the “tension between the ideals of the two movements” and the “ambivalence in the hearts of any of the people who hold those ideals.” As she points out, “many people straddle the two communities — pro-choice feminists who also fight for respect and rights for the disabled, and disability-rights activists who believe in unqualified reproductive freedom.” Levine quotes the late disability scholar Adrienne Asch, who was simultaneously fully committed to the right to choose abortion for any reason, and profoundly troubled by termination of pregnancies with particular children. “My moral opposition to prenatal testing and selective abortion flows from the conviction that life with disability is worth living,” Asch wrote. In a phone conversation, disability rights scholar and advocate Martha Saxton explained to Levine the “bind” that feminists with disabilities encounter: constant confrontation with their own mortality, when they wonder – in a “ridiculous hypothetical” – whether their mother would have chosen to abort them had testing been available. Saxton remains politically pro-choice and personally conflicted. "The challenge for reproductive-rights activists,” she said, “is not to identify with the fetus but to identify with women and with disabled people who are alive now — to fight for people living under this oppression, this idea that we would be better off being dead."
Levine notes that anti-choice activists have long portrayed the fetus as the ultimate innocent victim, and that adding disability to the imagery only completes this picture of perfect vulnerability. Their objective, she says, is not good policy, but “to gain strategic – and emotional – advantage. By portraying themselves as friends of the disabled unborn, they're vying for the sympathies of the already born disabled.” Levine argues that rather than allowing legislation to save fetuses with disabilities at the expense of their mother’s freedom, we should develop policies and technologies that make lives in all bodies – no matter what their abilities – worthwhile.
In January of this year, before the Ohio bill had been introduced, a similar legislative initiative in Indiana prompted David Perry, the father of a son with Down syndrome, to write a commentary in RH Reality Check entitled “Anti-Choice Legislators Try to Force Wedge between Reproductive, Disability Rights Activists.” Perry takes issue with the “faux advocacy for disability right” in which anti-choicers and the “disability hierarchies” they invoke one-dimensionally label children with Down syndrome as “cute” “blessings” and “angels.” He supports what he calls the pro-information movement, which seeks to equip potential parents with accurate information free of bias. He furthermore advocates for an intersectional approach to movement-building that would connect disability and reproductive rights activists. Perry endorses a coalition that acknowledges “a woman’s right to choose is inviolate” but warns that “before that choice, let’s make sure that it’s based on reality, not fear-mongering or misinformation.”
The tension between reproductive rights and disability rights activists stoked by Ohio legislators is not new. One effort to address it was a series of cross-movement roundtable discussions sponsored by Generations Ahead, a public interest organization in existence from 2007 to 2012 that grew out of a Center for Genetics and Society program. Bridging the Divide, a report on the roundtable series, articulated a series of shared principles and values that, it concluded:
suggest a need to reframe the issues—a framing away from the right not to have children to a right to have children, and a framing away from creating a self-sufficient, productive individual to re-shaping society to provide for the needs of all people, regardless of gender, race, ability, sexual orientation, citizenship status and class. In pivoting away from more narrow agendas and principles to broader, more inclusive values, new political opportunities and new alliances are possible.
These recommendations have not yet been fully embraced by reproductive rights and disability rights advocates. But the legislators in Ohio would do well to remember the call for basic human dignity that inspires both the movements they seek to divide.
Previously on Biopolitical Times:
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Forgotten Stories of the Eugenic Age #4, Part 1: The Short Life and Eugenic Death of Baby John Bollinger
Posted by Natalie Oveyssi on September 24th, 2015
|Book on eugenics, 1916 edition|
[Forgotten Stories of the Eugenic Age is a blog series exploring the lesser-known ways that eugenics affected and engaged American lives during the first half of the twentieth century.]
In November 1915, Chicago physician Harry Haiselden decided to let newborn John Bollinger die.
Baby Bollinger, as he was called in the many press reports of the time, was born paralyzed on the left side of his body, missing his left ear altogether and the ear drum of his right ear. His right cheek was connected to his shoulder, and he had a curved spine and closure of the intestinal tract. His only chance of survival was immediate surgery.
Obstetrician Climena Serviss called in the hospital’s chief surgeon, Dr. Haiselden, to consult. A firm believer in the doctrine of eugenics, he examined Baby Bollinger and arrived at the conclusion that even if surgery was successful, the child would grow up to be a mental and moral “defective” who would burden his family and society and taint the human race. Indeed, Haiselden believed that it would be morally wrong to allow the baby to live. As he later recounted, he wondered, “Would his mind be clear? Would his soul be normally alive? That I do not know, but the chances are against it.” Haiselden informed the baby’s parents that, in his estimation, the child would be better off dead. In due course, Mr. and Mrs. Bollinger came to agree.
Having made this decision, Haiselden contacted a reporter to share the story, believing that shedding light on such practices would make the case for the betterment of society through eugenics. Journalists from other newspapers latched onto the story, reporting it as one of the first cannon shots of the eugenic movement.
Haiselden was not the first prominent figure to voice the belief that certain children’s lives should not be preserved. In 1912, D. H. H. Goddard—respected eugenist, author of The Kallikak Family: A Study in the Heredity of Feeble-Mindedness, and coiner of the term “moron”—argued, ironically at a Philadelphia “baby saving show,” for the extermination of children with intellectual and physical disabilities who are “calculated to grow up to increase the race of thieves and paupers.” But Haiselden's decision in the case of Baby Bollinger pushed this concept from the hypothetical realm into reality.
As newspapers printed the story, a firestorm erupted. While the baby lay in the hospital dying of starvation, calls poured in, with some people begging Haiselden to reconsider, and others urging him to remain steadfast in the course he had chosen. Threats to kidnap the child and take him elsewhere for care led the hospital to station a guard at his bedside.
When the baby finally died on November 18 at five days old, the controversy intensified. Members of the public thirsted to hear Haiselden's reasons for refusing to operate so they could decide whether to praise his ideals or excoriate his callousness. Some took to the papers to demand that the state open an inquest to formally settle the matters of whether Baby Bollinger would have lived with operation, whether the baby was truly mental or morally “damaged,” and whether a doctor had the right to determine “defectiveness” in an infant, and, once done, decide if that baby should live or die. They wanted, too, to pass their own judgments on Baby Bollinger’s fitness to live.
Coroner Peter Hoffman had initially believed that an inquest was unlikely, since “the case is not different from many others” and “the physician knows the cause of death,” but the extensive public attention prompted police to open an official investigation. Hoffman's office was asked to perform an autopsy, and a coroner's jury was to determine whether Haiselden would be charged with any crime.
Six prominent Chicago-area physicians were selected for the jury and held a hearing in which they called witnesses and peppered Haiselden with questions about the baby's health and his reasons for inaction. Haiselden explained his choices in a signed statement issued before the Coroner’s jury took up its inquiry:
I say again that it is our duty to defend ourselves and the future generations against the mentally defective we allow to grow and suffer among us, and add to our burden and our problem. . . . So let us be sensible. Let us approve of the sterilization of the insane and the defective, and of the children of habitual drunkards, when both father and mother are so. Let us reproduce ourselves in 100 per cent fashion, so that by weeding out of our undesirables we decrease their burden and ours and lay the foundation for a normal race, which would result four generations from now. Let us venerate a standard with soul and sense, instead of desecrating it with crumbling tradition and mindless sentimentality. At the hearing, Haiselden testified that he had consulted with fifteen other physicians over the fate of Baby Bollinger, fourteen of whom had agreed with his decision. However, when pressed to give names, he could only provide two: Dr. Climena Serviss, who had initially called him for consultation, and Chicago Health Commissioner Dr. John Dill Robertson, who had publicly denounced Haiselden's actions and who testified against him at the hearing.
Haiselden further stated that he had told these fifteen physicians that if any wished to operate, he would not prevent them from doing so. They all declined his offer, he said, until one asked for permission about two hours before the baby died. Haiselden denied the request on the grounds that it was “against [his] ethics to operate on a dying person.”
Haiselden’s testimony included a series of contradictory statements. “I did not believe the life prospects of the child were good.” “He might have lived for a number of years." "A dangerous surgical operation would have gained nothing for the child.” “Without [an operation], the baby could not live.” “I did not wish to operate lest, if it should die on the table, I should be accused of killing the baby.”
He argued that the parents had been fully informed about their baby's health problems and had not been pressured to accept his decision. He recounted telling the father that, in his professional estimation, the baby would be disturbingly deformed, mentally and morally defective, a burden to himself and society, and doomed to a life of pain and suffering. The mother had never seen the child, and the parents had not been informed that Dr. Robertson supported an operation. Mr. and Mrs. Bollinger had agreed to allow the doctor to treat their baby as he thought best.
He protested in his defense that it was common practice among Chicago doctors—and indeed doctors everywhere—to allow “hopelessly defective” babies to die. In fact, he said, at least one baby a day in Chicago is secretly left to die, a statement that no one at the hearing contradicted. He concluded, “If I am to be jailed, I am ready to take my medicine. My conscience is clear.”
John Dill Robertson was Haiselden's strongest critic at the hearing. He testified that he had examined the baby, and had expected his problems to be worse than they were. Robertson thought that if the infant had received a timely operation, he would have had a chance of survival. He expressed concern about the dangerous precedent of not working to the fullest extent to save a life, and of relegating to a single doctor judgment over worthiness to live. “If our civilization has reached a stage where the life or death of infants is to be determined on the grounds of fitness,” he said, “then, like the ancient Spartans, we should establish a legal tribunal to pass upon the babies that are to live and those that are to be exposed to death.”
After the autopsy and hearing, the jury declared in a statement, “We find no evidence from the physical defects in the child that it would have become mentally or morally defective. Several of the physical defects might have been improved by plastic operations.” The jury also expressed the belief that a “prompt operation would have prolonged and perhaps saved the life of the child.”
The jury agreed that “morally and ethically, a surgeon is fully within his rights in refusing to perform any operation which his conscience will not sanction.” However, it hinted that it was uncomfortable with the idea of any one doctor making a decision to withhold a potentially lifesaving operation. It recommended that at least two doctors be consulted in such matters. In its strongest criticism of Haiselden, the jury concluded, “We believe that the physician’s highest duty is to relieve suffering and to save or prolong life.”
This was indeed the strongest formal censure Haiselden would receive; the coroner’s jury decided not to charge him.
Even after the verdict, the state of Illinois considered indicting Haiselden for criminal carelessness due to a faulty diagnosis in the Baby Bollinger case. In December, the Illinois Board of Health pursued an inquiry and examined the testimony from the inquest, but chose not to pursue further action. Haiselden had been the consulting and not the attending physician in the Bollinger case, they reasoned, and so could not be held responsible for the baby’s death.
Professional organizations issued a range of responses to the Baby Bollinger case. Before the child's death, the Medico-Legal Society of New York passed a resolution commending Haiselden for allowing the baby to die, thus “not only saving the child misery, but saving society the responsibility of caring for it.”
On the other hand, after long deliberation, the Chicago Medical Society expelled Haiselden on March 14, 1916. Even so, the society sidestepped addressing the morality of Haiselden's actions, and explained that their decision was based not on the doctor’s actions in the Bollinger case, but for “seeking newspaper notoriety and gaining financially” from it. As Independent magazine later observed, Haiselden’s offense, then, “at the worst is not a question of ethics at all, but merely a violation of trade union rules.”
Other organizations deliberately ignored the case. The New York Academy of Medicine held its regular meeting on the evening of December 2, two weeks after the baby’s death. Earlier that same day, another baby had died due to similar inaction from her doctors, whom some maintained had been emboldened by Haiselden’s precedent. However, the president of the organization said that it would be against the association’s rules to discuss the two cases at the meeting.
In spite of his expulsion from the Chicago Medical Society, Haiselden continued to practice at the German-American Hospital where Baby Bollinger had been born and died, and the case continued to bring him his notoriety and financial benefits in the following months and years. In fact, debate raged long after the legal and professional consequences were put to rest. And the public was soon to receive more fodder, as Haiselden’s eugenic legacy was not yet complete.
[To be continued with Part 2.]
1. “Baby a Day Allowed to Die.” Washington Post, Nov. 21, 1915.
2. “Bollinger Baby Inquiry: Illinois Authorities May Prosecute Doctor Who Refused to Operate.” New York Times, Dec. 10, 1915.
3. “Chicago Medical Society Drops Dr. H. J. Haiselden.” Chicago Daily Tribune, Mar. 15, 1916.
4. “Clear Baby’s Doctor: Six Physicians on Coroner’s Jury Make Report.” Washington Post, Nov. 20, 1915.
5. “Clears Dr. Haiselden: Health Board Drops Charges in Baby Bollinger Case.” New York Times, Feb. 7, 1916.
6. “Death for Weak Babies Is Opposed by Medical Men of the Capital.” Washington Post, Jun. 3, 1912.
7. “Defective Babe Dies as Decreed.” New York Times, Nov. 18, 1915.
8. “Dispute Doctor Who Let Baby Die.” New York Times, Nov. 20, 1915.
9. “Dr. Haiselden Called Before Medical Body.” Chicago Daily Tribune, Dec. 14, 1915
10. “Dr. Haiselden Expelled: Bollinger Baby’s Doctor Dropped by Chicago Medical Society.” Washington Post, Mar. 15, 1916
11. “Dr. Haiselden Is Expelled.” New York Times, Mar. 15, 1916.
12. “Dr. Haiselden to Face State Board Inquiry.” Chicago Daily Tribune, Nov. 24, 1915.
13. “Hurrah for Dr. Holt: Dr. Haiselden Endorses Action of New York Specialist.” New York Times, Nov. 25, 1915.
14. “Jury Clears, Yet Condemns, Dr. Haiselden” Chicago Daily Tribune, Nov. 20, 1915.
15. “Jury of Surgeons Studies Babe’s Case.” New York Times, Nov. 19, 1915.
16. “Justify Doctor’s Act: Chicago Officials Hold Autopsy Over Bollinger Baby.” Washington Post, Nov. 19, 1915.
17. “May Prosecute Doctor: Movement in Chicago to Accuse Haiselden Because of Baby’s Death.” Washington Post, Nov. 24, 1915.
18. “Medico-Legal Society of New York Commends Dr. Haiselden’s Stand.” Washington Post, Nov. 18, 1915.
19. “Might Kill Baby to Use the Knife.” New York Times, Nov. 26, 1915.
20. “New-Born Cripple to Be Left to Die.” New York Times, Nov. 25, 1915.
21. “Physician Is Sustained in Baby’s Death.” San Francisco Chronicle, Nov. 20, 1915.
22. “Roberts Baby Dies Without Operation.” New York Times, Dec. 3, 1915.
23. “State Opens Inquiry: Illinois Officials Takes Up Bollinger Baby’s Case.” New York Times, Nov. 25, 1915.
24. “Surgeon Lets Little Child Die When Knife Could Have Saved It.” Washington Post, Nov. 18, 1915.
25. “Won’t Let Malformed Baby Die Despite the Wish of Its Parents.” Washington Post, Nov. 25, 1915.
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