Adrienne Asch, bioethicist, scholar, and disability rights activist, died Wednesday morning at her home in New York City. Online tributes from her colleagues, students, and friends attest to the wide and deep impact she had on those who knew her work, and especially on those who were fortunate enough to know her personally.
Adrienne’s work and thinking about prenatal selection technologies and practices, a perspective on them grounded in both disability rights and reproductive rights, and what she termed markets in “genes and gestation” exerted a strong influence here at the Center for Genetics and Society. As one colleague put it, “Adrienne challenged our misconceptions, deepened our understanding, and inspired us to more inclusive perspectives.”
Two especially influential books that Adrienne co-edited are Prenatal Testing and Disability Rights (Georgetown University Press, 2000) and The Double-Edged Helix: Social Implications of Genetics in a Diverse Society (Johns Hopkins University Press 2002).
Adrienne was an opening plenary speaker at CGS’s 2010 Tarrytown Meeting. Her brief comments there, available on YouTube and below, showcase both her keen insight and the graciousness that she always tried – and often managed – to bring to discussions of intellectually and emotionally challenging issues. Here are a few roughly transcribed excerpts:
I don’t want to assume that all of us share everything I’m going to say. I hope part of what we’ll do is figure out what we share and what we don’t, and how to work with what we do share and how to deal with our differences.
Many of us here have spent considerable time trying to argue against what we see as dangers of extreme parental selectivity, or of markets in reproductive labor and genetic materials. Here I want to suggest three concerns for group discussion: a concern about selection [in which I include adoption, gamete selection and prenatal testing], a concern about markets – even if those markets don’t include selection – and a concern about the frequent dismissal of what are termed “symbolic harms.”
We have a difficult task: how to find the shared values and language to reach our philosophical opponents, and the millions of people in this country and worldwide who haven’t considered these questions at all. Why do we, and why should the rest of society, care about symbolic harms – and why are they more than symbolic?
Adrienne Asch at The Tarrytown Meeting, July 2012
Thanks to former CGS program associate Brendan Parent for sending a list of organizations to which you can donate in Adrienne's honor:
Disability Rights Education and Defense Fund, Berkeley CA
Lisa Jardine, the chair of the Human Fertilisation and Embryology Authority (HFEA), has announced that she will be stepping down from her position as head of the United Kingdom’s regulatory agency for assisted reproduction in January 2014. Since the announcement, she has been vocal about a number of important points.
In an interview with The Independent, Jardine argued that some IVF clinics have been over-using intracytoplasmic sperm injection (ICSI), a technique involving the insertion of sperm into eggs with micro-manipulation devices. She points out that although ICSI makes in vitro fertilization procedurally easier, it has limited utility and carries documented risks to resulting children.
In a commentary she wrote for the BBC, Jardine also warned that IVF still has a very high failure rate. “The world of IVF is a market, a market in hope,” she said. “Those who enter it deserve to be fully informed of its potential to deliver grief and a sense of failure, as well as success.”
However, for some reason, Jardine seems to be actively propagating highly dubious hope around extremely controversial and unverified mitochondrial replacement techniques. These would create an embryo through a biologically radical process that would combine genetic material from three people. The procedure has received extensive regulatory guidance from the HFEA. If the UK decides to carve out an exception to an existing law in order to allow clinical trials of mitochondrial replacement, it would become the first approved form of inheritable human genetic modification anywhere in the world.
While many people are alarmed and disturbed by that prospect, Jardine seems proud of her personal involvement with the issue. In a short press statement on her departure, she noted,
I am particularly honoured to have overseen the ‘Medical Frontiers: debating mitochondria replacement’ public consultation. It clearly demonstrated the specialised ability the HFEA has to engage, educate and communicate complex science and public opinion.
Jardine is disappointed she will not be able to see through the HFEA’s consultation on mitochondrial replacement – the so-called “three-parent” IVF babies who will receive their mitochondrial DNA from a donor egg.
Jardine apparently sees her work on this technique as a high point of her six years at the HFEA. Under her guidance, the HFEA certainly has played a critical role in advancing the potential change to UK law that could allow scientists to attempt human clinical trials as early as next year.
The trouble is that there are many reasons to believe that mitochondria replacement poses profound safety, social and ethical concerns, and there are a growing number of people, from scientists, to activists, to politicians, who have spoken up about them. But for some reason, Jardine has been extremely reluctant to accept these varied and widespread critiques. In an article she wrote for the BBC, she stated,
Over the past two years, the HFEA has carried out a consultation process with clinicians, scientists and the public in order to advise the present government on whether this technique - which has up to now only been allowed in the research laboratory - should be introduced into clinical practice. Perhaps surprisingly, the public supported the new technique, if it could prevent serious illness. They had little objection to its being approved for clinical use, as long as it was scrupulously overseen by an appropriate regulatory body.
Pete Shanks and I wrote a blog about the HFEA’s claim of "public support" shortly after its report came out. We were surprised to read – in the agency’s own report –that in what was by far the largest strand of the public consultation, and the only one open to everyone, the majority of people were against the introduction of any form of this technique, for a broad array of reasons.
We weren’t the only ones who noticed the discrepancy between the consultation’s data and what the HFEA reported to the public. But the HFEA responded defensively to the claim that they misrepresented their data, saying, “Our consultation was a more nuanced exercise than simply counting up votes for and against the techniques.”
I’m not sure what “nuanced” could mean other than that they seem to have considered the voices that agreed with them and disregarded the rest. I truly don’t understand why Jardine is comfortable saying that “the public supported the new technique.” At best, this is an over-simplification of an extremely socially and historically important moment. At worst, it is an example of exactly what she has decried: pandering to the market of hope, at the expense of desperate patients.
In early November there was what GenomeWeb accurately called "a media swoon" about one particular gene editing technology, and "in particular the question of whether this method may be used to improve people at the germ line level." Less than two weeks later, the brouhaha seems to have evaporated, but it's worth examining because it shows how media manipulation can distort scientific reality.
The story was launched (5 pages/month free; text also here) in London by The Independent, a roughly center-left newspaper that is by some distance the lowest-selling British national daily. Doubtless this explains why the editors keep fiddling with the paper's design. Originally a broadsheet, it switched to a smaller format in 2003-4, redesigned in 2005, with tweaks in the next few years before a major revamp in 2010, adjusted again in 2011 … and still the sales continued to fall. So on November 7, 2013, it changed again.
But even the greatest design needs content to sell. And what did they choose? The front page (pictured; larger here) featured a large picture of Yasser Arafat, separated by a modest horizontal line from the main headline:
The next genetic revolution
(Seriously, did no one notice this juxtaposition?) Arafat has been dead for 9 years, and the rumors about his poisoning had been floating around for weeks. The top of the page pushes a speculative piece about President Kennedy, the anniversary of whose death was still two weeks away. The other teasers discuss a Russell Brand interview that was already two weeks old, a TV show hooked to twerking (the October sensation), and two political thumb-suckers that could have run in any month this year or last.
In other words, they were not news. Nor is the so-called "genetic revolution," notwithstanding the Independent's headline:
Exclusive: 'Jaw-dropping' breakthrough hailed as landmark in fight against hereditary diseases as Crispr technique heralds genetic revolution
This front-page story by Science Editor Steve Connor was supported by a separate interview (also here) with Jennifer Doudna of UC Berkeley, a video explanation of the science, and an op-ed by Nobel laureate Craig Mello ("a triumph of basic science with huge implications"). The day after, the Independent featured a round-up of quotes ("Scientists call for more public debate") and the initial coverage was topped off with an editorial:
March of science: The 21st century will be the age of genetics. It is time to put our fears about 'designer babies' into perspective.
That's a lot of "exclusive" discussion. The development that underlies it all is a gene-editing technique that was hailed as "a Swiss army knife" — in August of 2012. Its cute acronym, Crispr (Clustered regularly interspaced short palindromic repeats), helps its media appeal, but the work is real and important.
Doudna, Emmanuelle Charpentier of Umea University in Sweden, and their colleagues identified an enzyme, CAS9, that could cut both strands of DNA at a specified location. From the interview:
"You can actually introduce new genetic information at the site of cleavage. So it has become a powerful way of doing genetic engineering. It's a fundamentally different way of recognising DNA target sites," Professor Doudna said.
Could this be done in human cells? Yes, that has subsequently been demonstrated by several teams, including Doudna et al. (pdf here) and — slightly earlier to press — in two papers published online in Science on January 3, 2013, by Feng Zhang et al. and by George Church et al., who note that:
Our results establish an RNA-guided editing tool for facile, robust, and multiplexable human genome engineering.
Cheap and Easy Technique to Snip DNA Could Revolutionize Gene Therapy
And does anyone have scientific doubts about the technique? Why, yes they do. In June, this letter was published in Nature Biotechnology:
High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells
In other words, the accuracy of the technique may have been overstated, leading to unexpected genetic alterations.
The Independent's recent series lacked any such context. It is, essentially, a magazine-style puff piece and that's all. It's admittedly based on genuine science, but that is still evolving, and subject to an entirely normal process of professional criticism. Moreover, Connor just had to add the designer-baby twist to his interview:
But perhaps the most intriguing and controversial application of Crispr-CAS9 will be the possibility of altering the genes of IVF embryos. Studies on mouse embryos show it is incredibly effective, and some IVF doctors may want to see if it can work on human embryos — which is illegal in Britain at present because it amounts to "germline" gene therapy.
Doudna, responding, downplayed this:
"Certainly, at this stage, I don't think we understand it well enough. Would you be correcting one problem but introducing others?"
But Connor had his story. Which caught the interest of the Daily Mail (circulation about 25 times larger than the Independent's) and Newstrack India, among others. Kate Henderson of the Las Vegas Guardian Express put together a pretty good selection of the notably enthusiastic quotes from the various articles. And thus talk of human germline intervention pings around the globe.
Fortunately, there was some pushback. BioNews ran a piece that included some mildly moderating comments, some of which seem to have been provided by the Science Media Centre (itself the subject of controversy for pro-GM publicity). The consensus was that there remains "a long way to go," the technology requires "a significant amount of work" and "the hype needs to be tempered with a little caution." Church, with his usual knack for the media-friendly quote, commented:
"Talking about the future is better than letting it sneak up on us. We need to do more of this or we will be left with very limited vocabulary in the space between positive and negative hype."
According to the Guardian (admittedly, an interested party), the Independent's re-launch boosted the its national circulation on day one by only 3,000, most of which evaporated the next day. But the hype may linger on.
Posted by Miriam Zoll, Biopolitical Times guest contributor on November 15th, 2013
Recently the American Society for Reproductive Medicine (ASRM) asserted that “60 percent of women who go through [fertility] treatments eventually end up with a baby.”
Those just entering the often-confusing and misleading world of assisted reproductive technology (ART) statistics, may mistakenly assume that out of 100 women randomly walking into a clinic, 60 will emerge with a baby in their arms.
Prospective patients deciding whether to invest precious time and resources toward reproductive medical services, or pursue adoption or foster care, need to understand what the ASRM’s statistic actually means and how it differs from, and is similar, to information provided by the Centers for Disease Control (CDC). That agency’s 2010 statistics found that, overall, 70 percent of cycles result in childlessness.
The two data sets are, to quote an old adage, apples and oranges. The difference between them has to do with how and what is being counted.
Analyzing data about pregnancies per cycle, a careful review of CDC statistics based on age found a 58 percent failure rate in women 35 and younger; 78 percent failure rate women 37-39; an 88 percent failure rate in women 40-42; and a 95 percent failure rate in women 43-44. The data cited by the ASRM is pulled from one study published in 2012 in the New England Journal of Medicine, “Cumulative Birth Rates with Linked Assisted Reproductive Technology (ART) Cycles.” It also confirms a 70 percent failure rate per cycle.
The study’s ‘best possible’ numbers scenario of 60 percent rests on pregnancy outcomes for 247,000 women who underwent no more than seven linked cycles over a four-year period. Approximately 25 percent of the women dropped out after the first cycle failed, and 33 percent after subsequent failed cycles. Roughly 50 percent of the women were younger than age 35—the age group consistently known to experience the highest ART success rates. Indeed, of the women in the study who were younger than 31 years of age, 63 percent experienced live birth. Among women 40 and older, there was an 81 to 93 percent failure rate––a failure rate consistent with the CDC data reported by age. Had half the study group been older than 40, the live birth outcomes would have been significantly lower.
Many women choosing fertility services never reach the IVF “cycle” phase. Some succeed with less invasive procedures while many others cannot afford to pay for multiple cycles. In addition, a ”live birth” does not necessarily mean couples bring home a healthy baby; multiple embryo transfers can often lead to premature births and expensive, prolonged stays in neonatal intensive care units.
When we think about how best to educate prospective patients/consumers, the NEJM study is important for a host of reasons. First, it confirms that those buying these services should plan for multiple cycles and all that they entail––including drug side effects, miscarriages, strained relationships, depleted bank accounts––and the debilitating grief that goes along with all of it. As someone who has run the gamut of IVF procedures without conceiving, I can attest that the psychological costs are immeasurable, while the long-term health risks remain largely unknown. Additionally, with so few insurance policies in the U.S. providing coverage for more than one or two cycles, the study’s findings reinforce the need for customers to budget anywhere from $40,000 for two cycles, all the way up to $200,000 for ten or more.
The study also verifies that older women using their own eggs experience the least success with IVF, signaling a greater demand for controversial egg donation. Infertility specialists obtain third-party eggs by injecting so-called “donors” with potent drugs that can cause serious side effects, ranging from dangerous swelling of the ovaries to infertility, stroke, and in rare cases, death.
ART services are packaged in hope, and can be very difficult to walk away from. There are serious emotional and physical risks involved––for women, their partners, donors and surrogates, and any potential offspring. This is all the more reason why those contemplating treatments should think very carefully about the notion of self protection, and determine ahead of time how many and what kind of interventions they plan to pursue before they begin.
Miriam Zoll is the author of the new memoir-expose, Cracked Open: Liberty, Fertility and the Pursuit of High-Tech Babies (Interlink-June 2013). She is a member of the boards of the global women's health and human rights organization, Our Bodies Ourselves, and Voice Male Magazine.