Wednesday, October 27, 2021

Spectrum 10K and Cognitive Dissonance in Autism Research

The Thinker, Rodin
 Photo by AndrewHorne, Public domain, via Wikimedia Commons
[image: A photo of Rodin's sculpture The Thinker, which is a naked
man sitting on a rock, hunched over with his head resting on his encurled fist.]

Mary Doherty
twitter.com/AutisticDoctor
www.linkedin.com/in/mary-doherty-5b84b186/

Spectrum 10K, the largest study of autism in the UK, was launched on August 24, 2021 amid a flurry of media attention—only to be paused less than three weeks later following an outcry from the autistic community (of which I am a member.) Concerns were raised around ethics and data management, but the primary issue is the potential use of such research for eugenic purposes.

I am peripherally associated with the biomedical autism research community, as a member of the AIMS-2-Trials Autism Representatives Steering Committee, and ECRAN, the associated early career researcher network. My involvement in such a controversial project stems from my desire to potentially influence the research agenda for the benefit of the autistic community: Many autism researchers have never known an autistic person, except as a research subject, and interacting as professional peers has been illuminating for many. (My perspective is outlined in a talk given at an ECRAN workshop in 2020 entitled Stigma and Unconscious Bias.)

As a medical doctor—a consultant anaesthetist—my knowledge of autism genetics and genomics research is basic. I mix up the terminology, and watch colleagues wince when I say genetics instead of genomics, although I know the difference. (I experience the same automatic wince when researchers use person-first language or misuse the term 'neurodiverse.')

My own research interests focus on healthcare access for autistic adults and issues facing autistic medical professionals, therefore I bring a range of perspectives as I consider my response to Spectrum 10K. I have sufficient knowledge of the current autism research agenda, the history of autism, and current advances in reproductive medicine to be seriously concerned about this project and similar research underway worldwide.

On the one hand the Spectrum 10K team states their values on their website, including a clear anti-eugenics stance:

“Spectrum 10K is anti-eugenics. To be precise, we do not work towards or advocate for termination of pregnancy in relation to a foetus who may later be diagnosed as autistic. We are aware of and abhor the awful history of eugenics, including how science has been used to justify many atrocities globally.”
On the other, this project is basic science dressed up as helping autistic people with co-occurring medical conditions. But ultimately it is a genomics project which will add to the evidence base around polygenic scores (PGS) for autism. These polygenic risk scores for medical conditions are already being used to select embryos during in vitro fertilization (IVF). There are already toddlers in this world who were selected as embryos based on polygenic scores for various medical conditions; the implications of this new direction in reproductive medicine were recently discussed in a leading medical journal. Such a test is not available for autism yet, but we have to ask if this is where the research is leading?

As for the AIMS-2-Trials, it is an international consortium of research teams and industry partners who are “exploring the biology of autism to tailor treatments and develop new medicines” and who also claim to oppose eugenics: “AIMS-2-TRIALS is not developing a genetic test and is ethically opposed to eugenics. It is also unlikely that a genetic test will ever be specific or accurate enough to predict whether a person will develop autism.”

While Spectrum 10K and AIMS-2-Trials are separate projects, there are researchers common to both. And both stake their anti-eugenics positioning on the expectation that a genetic test “specific or accurate enough to predict whether a person will develop autism” is unlikely. But are such claims disingenuous, given the current move towards using polygenic risk scores in reproductive medicine?

While such possibilities are denied, a preprint from a Spectrum 10K research team suggests otherwise. This study, not yet peer reviewed, suggests that polygenic scores (PGS) correlate with clinical profiles, and appear to show an apparent protective effect of autism PGS on co-occurring developmental disabilities. (This means that common genetic variants associated with autism are less likely to be associated with co-occurring intellectual disability, but ‘de novo’ or rare high impact genetic variants are more likely to be associated with intellectual disability.)

Recent and related discussions with leaders in the biomedical autism research field has led me to the astounding realisation: The possibility of paving pathways for eugenics may not be simply inadequately considered, but not considered at all. There is no attempt to hide the search for stratification biomarkers (biological features which can be used to group autistic people into subtypes), and it is unclear what the research community expects to be the outcome of such work. 

I have no doubt that the individual researchers I have encountered are well-meaning and sincere in their desire to positively impact the world. However, there appears to be a total lack of awareness of current reproductive medicine practices' bias against neurodivergent people, never mind the implications. For example, autistic people or even those with a family history of autism are currently prohibited from acting as sperm donors for IVF, with sperm banks subject to legal action for failing to prevent autistic children being born. Since 2013, it is accepted practice in Western Australia to use sex selection during IVF to reduce the likelihood of an autistic child (sex selection is not allowed in general, except where there is a history of autism).

Additionally, there is the ever-growing list of conditions that can be detected by preimplantation genetic diagnosis (PGD) and therefore prevented. Given the stigma associated with autism, and the focus on costs attributed to potentially life long care needs, the desire to add autism to that list seems to be driving much of the current research agenda. 

Also, a recent, questionable paper by Blaxil et al claims that the increasing costs of autism poses a “serious threat to the economic future of the U.S,” and the authors propose a prevention strategy, citing a lack of evidence for reduced costs using an intervention strategy. Their “prevention” scenario assumes that strategies and opportunities are already “used by wealthy parents to lower their children’s risk of ASD” and suggest these “can be identified and made available rapidly to lower income children and ethnic minorities.” Criticisms of the paper are currently under consideration, but nonetheless, it was peer reviewed and published in Journal of Autism and Developmental Disorders.

So we know that society, if given a chance, will prevent us autistic people from existing. We know it is happening already, as detailed above. Is it possible, is it credible that biomedical autism researchers at the cutting edge of autism genetics research are genuinely unaware of developments in allied fields? Is this a result of working in silos, in which scientists are so isolated from those in other disciplines that they have no idea of how their works might intersect or overlap?  

Spectrum 10K and similar projects will inevitably lead to polygenic scores being used to select for or against autistic people, particularly as data sharing alliances increase across the world. Therefore, as work on differentiating between groups of autistic people using polygenic scores and stratification biomarkers is ongoing, the obvious question arises: Is this an attempt to select for those who may be deemed useful, while preventing others with more complex needs from existing? 

This is the essential question, the proverbial elephant in the room, as stratification is the subject of much current autism research. Yet this is not a straightforward quest. While on a superficial level the challenges associated with autism may appear to be split into separate "functioning" categories, the reality for autistic people is much more complex and fluid. Those who are familiar with the autistic world know this, yet the search for a genetic basis on which to segment our population continues.

Many autism researchers, however, are unfamiliar with the autistic world, and seem to assume that autism is to be avoided or prevented, even if it’s no longer considered acceptable to use the word “cure.” Or do researchers only avoid using that term in autistic company? What about in labs where autistic people are excluded, or forced to remain incognito? I hear valiant efforts to use appropriate terminology in spaces where we are known to be present, only to hear the same professionals revert to person-first language and functioning labels once back in the apparent security of their professional sphere. Are the considerations being shown to autistic concerns in Spectrum 10K and other autism research realms merely performative? 

There is a cognitive dissonance that arises from the contradictions inherent in stating “we do not want a prenatal test for autism to be developed," while simultaneously producing basic science which will inevitably lead to that outcome. As an anaesthetist, that is akin to saying I don’t want patients to be aware during surgery, while failing to administer anaesthesia. The inherent contradictions in this positioning are baffling. How is it credible that scientists working in this field are unaware of these developments in the wider field of reproductive medicine, as appears to be the case? 

The alternative is that they are aware but are being disingenuous, and I don’t know if that is worse. I also have no clue whether individual scientists are being honest or not. It’s likely that there are some in either group. Is it possible that some within the biomedical research community are well-meaning but na├»ve, and also being manipulated by those with darker motives or commercially driven intent? Or are they so compartmentalized in their thinking that they see no inherent conflict in pursuing autism genetics research while espousing an anti-eugenics stance? 

While ethical issues in genomics research are common across all specialties, medical conditions are generally acknowledged to be worth preventing. Curing cancer is in no way akin to eugenics, but autism is different. Autism is not an illness, and autistic people have the right to exist. Our community has already been the target of eugenics, such as Aktion T4 in Nazi Germany and the paediatric euthanasia programme at Am Spiegelgrund. Hans Asperger, once lauded as a hero, is now hated by many, following revelations he condemned to death those children considered to be unbearable burdens to their families. Yet how can those who exhort us to “learn from history and not repeat its terrifying mistakes” fail to appreciate that their current work may lead to similar outcomes? Do they genuinely differentiate between active killing of those autistic people deemed unworthy of life, and prenatal prevention? 

Or is this the hidden agenda? Is there a tacit understanding among scientists that the actual goal is in fact to prevent the births of those deemed "undesirable," while keeping those who might contribute to society? My heart breaks at this thought. Is there societal support for this potential outcome, driven by the cost of care needs?

Scientists being unaware of the potential for harm unleashed by their work being used in unanticipated ways is not new. Scientific regret is well documented, as exemplified by Oppenheimer, Einstein, and even Nobel, as regret was the catalyst for establishment of the Nobel Peace Prize. But the scientists involved in Spectrum 10K cannot claim ignorance. They have been told, loud and clear by the autistic community, from the earliest days of EU AIMS, Aims-2-Trials and since, culminating in the outcry over and boycott of Spectrum 10K.

Spectrum 10K is currently paused to “co-design and conduct a meaningful consultation.” The approach of setting a research agenda, then including autistic people in a tokenistic manner—as with AIMS-2-Trials A-Reps—is no longer sufficient. The autistic community, including autistic researchers and scientists, must be involved at the highest levels when decisions are made regarding the autism research agenda. We cannot be kept busy with token consultations while the real decisions are made elsewhere.

The gulf between the biomedical research and the autistic communities is far deeper than realised by the research community. An apology is needed for past harms to our community by biomedical research, but perhaps this needs to start with exploring what those harms have been. As we see in non-pharmacological autism interventions, the harms may not be obvious to non-autistic people. For example, alongside financial costs, mental health issues for autistic people are often suggested as a target of biomedical autism research, without any appreciation that the current intervention and research agenda may in fact be exacerbating mental ill-health

As a community, autistic people have documented our research priorities, and causes of autism or “cures” do not feature prominently. We want research that will directly and positively affect our lives. We recognise that biomedical researchers generally do not have the skills to conduct the type of research we want, but the skills they do have can potentially be used for our benefit. Genomics offers enormous potential for improving human health. Knowledge in this area is accelerating at an astonishing rate, with debates raging around the ethics of genome editing, and regulation urgently required to avoid discrimination against vulnerable groups

Autistic people are a vulnerable community, and as stakeholders in this debate, we deserve full and transparent engagement. We cannot allow the scientific process to continue in a direction that results in elimination of other autistic people, only for researchers to express regret when the inevitable outcomes occur. Scientists may claim that regulation is the role of society, not science. Yet who guides society on such matters, if not scientists with knowledge of the field? 

These are difficult issues. If the obvious conclusion is valid; that PGS or other interventions may be used either to avoid autistic babies, or to avoid those deemed to have a higher likelihood of complex needs, then this must be openly acknowledged. If the biomedical research community is blindly forging ahead with lack of awareness or insight, this is an altogether different—but no less pressing—problem. In either case, the only way forward is absolute transparency, open debate, and a truly participatory approach to future research.

Friday, October 22, 2021

About That Study on "Preventing" Autism Diagnoses, and How Autism Researchers Can Do Better

Source: Wikimedia Commons
[image: Photo of a smiling Black toddler with curly black hair up in puffs, sitting in a 
Black adult's lap, while a smiling medical professional interacts with them.]

Patrick Dwyer, MA
Lucas Harrington, PsyD
Ava Gurba, BS
 

Last month, researchers in Australia led by Andrew Whitehouse published a new study: a trial of a “pre-emptive” intervention for infants assessed to have an elevated likelihood of later developing autism.  Internet furor immediately ensued, with some headlines proclaiming that the new intervention could prevent as many as two-thirds of autism diagnoses. Many neurodiversity advocates were naturally horrified by these ominous headlines, but was the media portrayal accurate?

What were the researchers trying to do?

The researchers who conducted the study claimed that it “chershes neurodiversity”: that instead of being about suppressing autism, the intervention aimed to help the caregivers of these possibly-neurodivergent babies better understand their children and adapt the environment to be more supportive of the infants’ needs.  The researchers said that the “inaccurate” media headlines “misrepresented” what they were trying to do.

If the study really was about helping caregivers understand neurodivergent children, it could be very much in line with the neurodiversity movement’s goals. Damian Milton’s concept of the “double empathy problem”—which is supported by empirical research—highlights that it is not only autistic people who struggle to understand neurotypicals, but also neurotypicals who struggle to understand autistics.

So if the goal of this controversial study was really trying to address the double empathy problem for caregivers of young children, in a manner aligned with the neurodiversity movement and with autistic people’s priorities, did the researchers succeed?

How close did the researchers come?

Although the researchers did come quite a bit closer to succeeding in this than many of the headlines about their work would suggest, in many ways their study also illuminates just how far autism research still has to go, in order to reach the standards the community can trust. Nevertheless, the intervention itself was probably the area in which the researchers’ study came closest to meeting the community’s standards and expectations.

The intervention—which is summarized in one of the paper’s supplements—does indeed explicitly aim to help parents understand and have empathy for the child’s point of view. In particular, it aims to promote parental attunement to the child’s unique, individual way of socially connecting with the caregiver, making sure that the child does not become discouraged or disinterested after efforts to connect are overlooked or misunderstood. This is very well-aligned with the goals and objectives of the neurodiversity movement.

The researchers also tried to keep track of whether the intervention caused adverse events (they reported it didn’t), which is something that autism intervention research has historically tended to ignore. Thus, although it’s not quite clear how the researchers judged whether adverse events were caused by the intervention, their work made progress over prior research by simply considering the possibility the intervention could cause harm.

Furthermore, the intervention involved weekly sessions with parents that were only about two hours long each.  A lot of pressure gets placed on parents of young neurodivergent children.  While this intervention did recruit parents to drive its effects, it doesn’t seem like this time commitment would cut into other important parent-child activities.

One potentially concerning part of the intervention protocol says that it includes “reinforcement” of interpersonal interactions between babies and caregivers. That word often conjures up images of artificial manipulation, as in the case of children being rewarded with food and praise for doing things they would not otherwise be willing to do. This can often encourage the child to “mask” their autistic traits, hiding their true feelings and needs in order to receive approval or tangible rewards from others. Pressure to mask is a common concern among autistic advocates and masking is associated with a number of negative mental health outcomes.

However, reinforcement also occurs naturally, when the natural outcome of a behavior encourages the person to repeat their behavior in the future. For example, if a baby points at something and receives it, they are naturally reinforced for pointing, meaning that they are encouraged to continue doing so because it helped adults accurately understand and meet their needs. 

We emailed the authors of the study to learn more about their intent, and they clarified that parents were encouraged to respond naturally to baby-initiated interactions: if the baby’s behaviour suggests that they are trying to communicate or request something, the caregiver should respond accordingly. This teaches the baby that reaching out to others can be a positive and worthwhile experience. Thus, the “reinforcement” in the protocol seems to be nothing more than good, empathetic parenting.

Where did they fall short?

Although the intervention itself may have been consistent with the community’s expectations and goals, the researchers probably did fall short by failing to make this clear in the main body of the paper, or even the supplement. Ideally, community members shouldn’t have to send follow-up emails to reassure themselves of key details about research studies.

Moreover, although the authors of the paper were careful to frame their work in a neurodiversity-aligned way when they responded to backlash from the autistic community, their original paper is written in a very traditional, medical model-aligned manner. The first sentence describes autism as a “disorder” characterized by “impairments,” and much of the rest of the paper is devoted towards explaining how the intervention may have reduced autism “symptom severity” and made children less likely to receive an autism diagnosis. This is, of course, totally inconsistent with the goals of the neurodiversity movement. It might even risk resurrecting the spectre of the “refrigerator mother” by implying that parents, as the deliverers of the intervention, can control whether their children become autistic or not.

Why are the authors saying one thing in their paper, while talking about how the intervention “cherishes neurodiversity” elsewhere?  They probably weren’t trying to be duplicitous, especially since the intervention itself seems inoffensive, but many of the institutions of academia do tend to encourage orthodoxy—one might even say rigidity and insistence on sameness!—in academic papers. For example, the authors may have decided to write their paper the traditional way in order to get it through peer review more quickly; one of the downsides of academic peer review is that any departure from convention tends to elicit knee-jerk criticism. Moreover, researchers unfamiliar with the neurodiversity movement would have needed a neurodiversity framing to be justified and explained, lengthening the paper, and medical journals (such as the one the authors published in) tend to require short, simple papers.

Unfortunately, the authors made a choice to focus on how their intervention affected “autism symptoms” and autism diagnosis. Admittedly, studies take time to run—they chose their outcome measures more than five years ago, and they may well have regretted the choice later—but it was clearly not a choice in line with the priorities of neurodiversity advocates.

Did the study actually reduce autism diagnoses?

One important question is whether the media hype was justified: Did the study actually reduce the odds of autism diagnosis?  Statistically, it’s quite a bit more complicated than some of the simplistic media headlines suggest.

Crucially, the claim that “two thirds” of autism diagnoses were prevented is based on a tiny number of children. Of the 89 children that were examined by the researchers when they reached the age of three years old, only 12 children could clearly be diagnosed with autism.  Three of the diagnosed children had received the intervention, and nine were controls. These are extremely small numbers!

Could it have been a fluke?  If you repeatedly toss twelve coins, chance alone will sometimes give you more heads than tails, or more tails than heads...

Indeed, fewer children who received the intervention were indubitably neurotypical—only five—than children in the control group, eight of whom were assessed as clearly neurotypical.  Does this mean the intervention, while reducing the odds of autism, also reduced the odds of being neurotypical?

The researchers used a statistical test (i.e. a “Fisher exact test”) to determine whether children’s likelihood of being clearly autistic, clearly neurotypical, or potentially neurodivergent differed between intervention and control groups more than would be expected by chance. The result did not quite achieve statistical significance, meaning that the intervention group wasn’t necessarily either less autistic or less neurotypical than the control group: both trends might well have been flukes. As such, the media headlines about two-thirds of autism diagnoses being “prevented” were very premature!

It’s also worth noting—as the researchers did—that not all children can be reliably diagnosed as autistic when they are three years old. It’s possible that some children in the very large potentially-neurodivergent group, who fell short of meeting the formal autism diagnostic criteria, will still receive an autism diagnosis later in life. The intervention might have reduced autistic traits enough to delay diagnosis, but not prevent it.

Unfortunately, news media that need to sell headlines don’t always closely scrutinize research papers for these sorts of caveats. Moreover, sometimes it’s hard to spot the caveats unless you have the specialized training and knowledge that comes from being a researcher. Since plenty of people in the autism world who aren’t researchers are very interested in—and very affected by—autism research, we as a field need to do a better job clearly and transparently communicating the limitations of our work.

Did the study actually reduce autism traits?

Only follow-up monitoring will tell whether more study participants will come to meet autism diagnostic criteria as they grow older, but the researchers did say that they already have evidence showing that so-called “autism symptoms” were lower in the intervention group than the control group.

But what does it actually mean to have fewer “autism symptoms”? The main measure used by the researchers—the Autism Diagnostic Observation Schedule-2 (ADOS-2)—assesses a wide variety of autism-related traits, ranging from functional skills (e.g., pointing to communicate) to harmless differences (e.g., unusual phrasing), to possible stress responses (e.g., repetitive movements). On a positive front, a child could look “less autistic” because they are more skilled or less stressed, while still maintaining a fundamentally autistic neurology. Alternatively, a child could look “less autistic” because they have learned to suppress unusual behaviors, (i.e., mask their autism), without improving—and perhaps even hurting—their quality of life. ADOS-2 scores alone do not give us enough information to assess whether the outcome is desirable.

What do researchers need to do better?

Too often, neurodiversity and community perspectives are treated as an afterthought or a distraction, rather than a scientific priority. The aftermath of this study poignantly illustrates the need for widespread change. No matter how well-designed an intervention is in the laboratory, stigmatizing messages of “disorder” and “prevention” will damage the public’s trust in its potential. How can the field of autism research begin healing the rift with the autistic community?

On an individual level:

The authors of this study did many things right that should be repeated by future work. In addition to directly addressing the double empathy problem, they reportedly partnered with autistic people, and they investigated whether the intervention caused harm. One area of improvement would be being more transparent about these efforts so that the community can know how thoroughly their concerns were addressed. Researchers should also take care to communicate clearly, so that their work cannot easily be distorted or misrepresented in the news media.

More broadly, researchers need to fundamentally shift how they think about autism. Researchers often continue to conceptualize the neurotype solely in terms of deficits, despite ample evidence of associated strengths as well as harmless/neutral differences. A neurodiversity-informed framework would not ignore the challenges associated with autism, but rather balance that perspective with acknowledgement of valued aspects. A neurodiversity-informed researcher would select or develop outcome measures that reflect the autistic community’s goals for themselves, such as quality of life and mental health, rather than assuming that fewer “autism symptoms” or lack of an autism diagnosis is inherently good. Indeed, a neurodiversity-informed researcher might worry about whether falling short of diagnostic criteria could leave people without necessary supports.

Partnering with the community

It is very difficult to achieve the competence to navigate these complex issues without direct community voices. Although the researchers said their study emerged out of ongoing community partnerships, it’s unclear what this entailed. For researchers to secure community trust and establish genuine collaborations, autistic partners must represent a range of perspectives (e.g., race, gender, level of support need), and have meaningful power to challenge traditional researchers’ biases. If community collaborators are meaningfully included in the research team, community collaborators could, to name just a few examples:

  • Ensure that outcome measures and intervention goals reflect community priorities;
  • Ensure that intervention methods are likely to be helpful, not harmful; and
  • Anticipate how community members will engage with and respond to research papers, and revise the framing to be respectful and sensitive.

Perspectives of autistic parents may be particularly valuable and insightful regarding how to create supportive environments for autistic children.

Systemic changes needed in our field

Researchers may be frustrated by the slower pace of community collaboration. This is understandable, because many researchers face intense career pressure to publish lots of papers quickly (“publish or perish,” some say). However, this systemic issue merely emphasizes how our field must change. Partnering with the community should not be seen as “slowing down progress” any more than a thorough literature review is “slowing down progress.” Research results cannot be considered meaningful if important context has been excluded in the name of saving time. 

Unfortunately, there is no shortage of systemic barriers facing those idealistic researchers who are already attempting to partner with the community or re-evaluate traditional assumptions. It can be difficult to secure funding or publication for efforts that require readers to rethink their assumptions. Journal editors often require tight word counts, leaving little room for nuance.

It will be hard for the community to trust research until the autistic perspective is meaningfully represented at every level, from grant funding to ethics approval to journal peer review. Some of these changes are beginning to occur, with autistic researchers and other community members reviewing grant applications at the AIR-P Network, journal submissions at Autism in Adulthood, and to some extent NIMH grant applications, but much more needs to be done. This will require not only greater inclusion of community members in these processes, but also proactive support for developing autistic autism experts, who are often excluded from education and employment by lack of accommodation or even direct stigma. These sorts of large-scale systemic changes would help researchers, autistic laypeople, and parents gain confidence that research is truly working towards the best interests of the people it aspires to help.

In summary, it appears that many concerns about this infant intervention were misplaced. The core message of Whitehouse et al. is no different than what neurodiversity advocates have been saying all along: neurodivergent children, like their neurotypical peers, will be more socially engaged when they are treated as human beings with meaningful perspectives and intentions.

At the same time, we do not intend to say that the outcry from the autistic community was unreasonable. This incident has highlighted much deeper issues in the field of autism research. Why did the authors feel the need to dress up their message in the language of pathology and prevention? What if the headlines had read, “Autism doesn’t have to be a problem if children are understood and supported”? Exciting new visions are emerging for research that can be easily embraced by the neurodiversity movement. We must all do our part to further these efforts and help create a future where new generations of neurodivergent children are accepted, understood, and able to thrive.