The Proxy Consent Loophole: Part 2 of The Rise and Fall of “Stem Cells for autism” at Duke University
This is the second in a series about Duke University’s experiments on autistic children, in which young children, including those with IQs below 70, were injected with stem cells to see if it would stop them from being autistic. This series looks at the 9 years from first FDA approval in 2014, to the addition of Expanded Access (EAP) “pay to play” clinical trials in 2019, to pushback from experts and finally the cancellation of the EAP in 2023.
Stem cell hype and the proxy consent loophole
“Love. It is something you express to your children,” read the first line of Cryo-Cell’s main page on autism. “Displays of affection can do wonders to how you feel, but for the mother and father of an autistic child, it may seem like they can never give that gift to their child—or receive it in return.”
In 2020, Cryo-Cell was marketing its stem cells[1] as an autism treatment, with the promise that infusing autistic children with stem cells from cord blood might transform them into more expressive, loving children. Cryo-Cell’s online testimonials claimed parents could see changes in their children following infusion with Cryo-Cell products. One story described a dad being able to share a hug with his child, supposedly as a result of stem cell infusion. For another family, Cryo-Cell claimed:
“Gracie’s parents says her autism now affects only 10 per cent of their day.”
The company pitched stem cells as a potential treatment for many conditions, including autism, diabetes, eczema, “signs of aging” and, in a 2021 investor pitch, potentially to treat COVID-19. While stem cells are only proven to treat a few specific conditions (not autism), Cryo-Cell leveraged public interest and media hype around stem cells to market it for autism.
Cryo-Cell had an interesting relationship with a team of researchers at Duke University who, as I referenced in the previous post, had been running clinical trials to see if stem cell infusions would cure children of autistic traits, since 2014. (These were called the IMPACT trials.) As of 2019, the Duke team had gotten Expanded Access Project (EAP) approval from the US Food and Drug Administration (FDA) to charge parents a whopping $15,000 to have their children enrolled in the trials for this unproven and risky treatment.
This approval from FDA was odd, to say the least, since EAP guidelines specify there should be no existing standard of care for the condition treated and/or that it be life threatening. But autism is not life-threatening and there are standards of care for autism.
Cryo-Cell had aligned with the Duke team to have exclusive patent rights to Duke’s biologics procedure if researchers could provide proof of concept. (Spoiler alert: They did not.) The agreement would have granted the company the “rights to proprietary processes and regulatory data related to cord blood and cord tissue developed at Duke, [making] Cryo-Cell the only cord blood bank with the right to offer treatments to [autistic] children at its own infusion clinic under Duke’s FDA-approved Investigational New Drug Application.”
Interestingly, Duke’s project lead, Dr. Joanna Kurtzberg, was the Medical Director for Cryo-Cell International and Director of the Carolinas Cord Blood Bank, which dealt in stem cells. Prior to the project’s cancellation, Cryo-Cell had been breaking ground on clinics that promised to deliver stem cell “therapy” for autism for a fee, building on the EAP fee that Duke researchers had charged families for partaking in some of the clinical trials, which was $15,000 per family per infusion.
The company had initially announced in 2021 that it would open its first dedicated clinic in 2022 and, in its pitch deck to investors, projected annual revenue per clinic to be $24 million. Frances Verter, Director of the website Parents Guide to Cord Blood (PGCB), which promoted the EAP, positioned Duke’s IMPACT trials this way:
“When children have profound autism,” wrote Verter, “their parents worry if they will ever master enough skills to live independently once their parents are gone. Will their extended family take care of them? Will society take care of them? What is the harm in letting these families try a wide range of therapeutic options?”
In her support, Verter --whose background is in computer programming and astrophysics-- left out a few crucial facts. One is that stem cells are a highly-regulated medical product because they carry significant risks. The FDA has documented risks associated with stem cell treatments that include allergic reactions; the ability of cells to move from placement sites and change into inappropriate cell types or multiply; failure of cells to work as expected; and the growth of tumors. The use of unlicensed stem cell hospitalized 17 people in the US from 2018 to 2019, The Washington Post reported.
As bioethicist Leigh Turner points out, risks include a person receiving cells that haven’t been properly manufactured and processed or contaminated products. “This isn’t just a hypothetical, theoretical possibility. This has happened already,” he told me.[2] Use in children should be undertaken with special care, as they can face barriers later in life such as not being able to safely receive stem cells again for diseases like bone cancer. There is also a trauma risk to children undergoing a procedure that’s known to be uncomfortable and difficult during the infusions and in the following weeks.
In the US, experiments with stem cells are regulated. The FDA typically sets a high bar in assessing the risks versus the potential benefits, echoing the International Society for Stem Cell Research’s guidelines for undertaking stem cell research on humans which states:
“Before launching high-risk trials…researchers should establish the safety and optimality of other intervention components.”
The guideline points to a core aspect of stem cell therapy: because of its risk, it’s often turned to only when there is no other standard of care. But there are reasonable standards of care for autism, so how did it come to be that Duke’s project was approved by its Institutional Review Board (IRB), the university reviewers who determine whether a project is ethical? Why did the FDA approve an EAP “pay-to-play” study, where children’s parents parted with $15,000 for the experiment?
Was everybody taken in by stem cell hype?
There certainly was enough of it at the time. The Duke’s team’s first study of 25 children in 2014, which failed to show any evidence of benefit, had been hyped in a CNN feature co-authored by Dr Sanjay Gupta, which described the unproven treatments as potentially “promising”. It featured a personal story about Gracie, a young autistic girl and her family. In the vague style that seems a hallmark of the project’s media coverage, Gupta’s team stated that the family may or may not have benefitted from the clinical trial, but Gracie’s mother told CNN: “She got better, and we’re just thankful for that – whether it be the stem cells or not. We’re just thankful for what changes have happened.”
Acknowledging that the study was open label (meaning families knew that their child had received stem cells and could thus have a confirmation bias), team member Geraldine Dawson told CNN that they needed to do more thorough testing in a second trial before coming to any conclusions. Kurtzberg echoed this, but with a twist of positivity:
“We’ll be extraordinarily encouraged if the second trial shows that the cells benefit children when the placebo does not. We will consider that a breakthrough.”
While CNN covered the initial hopes of the Duke project participants, the news station didn’t follow up on the results of the second trials, which ended up to be disappointing. Families and stem cell companies continue to share the clip and parents in the support groups thrive off the hint of possibility in it. Some parents whose children were in the IMPACT trial even expressed their belief that Dr. Kurtzberg knew the treatments did work and that the trials were more of a formality than an actual test. As bioethicist Jeremy Snyder told me:
“In a piece like that, the language about ‘this is all very early days,’ gets sandwiched around these emotional, highly compelling [personal] stories. …And, there is no correction and these stories get shared online; they get shared in the crowdfunding campaigns; they get shared in patient groups. Even if more recent data doesn’t support that kind of story, the article is still there. You can look at it today and I think that’s hugely problematic.”
Like other stem cell ventures, there appears to have been a “political economy of hope” at play, a term that Alan Petersen and Katie Seear identified in Technologies of Hope, their 2011 advertising study focused on stem cell hype. “Hope is characterized by the view that new and better treatments are imminent, being tested and in the pipeline,” they wrote. “Thus, it can be viewed as a form of capital whose reproduction demands continuing belief in the future rather than resignation and accommodation to the present.” Within the context of autism, this marketing of hope may distract parents from investing energy into existing standards of care if the majority of their energy is focused on an imagined future miracle.
Stem cell hype had been running high for years—so high that, in 2014, the Duke team had been able to get FDA approval to run trials on children as young as two years old and experimentation on children with IQs under 70 was permitted. By choosing the most vulnerable children for these studies, Duke defied an ethical principle of research: that risky studies should be performed on informed, competent, consenting adults.
The team faced a dilemma, of course, because there are no informed, competent, consenting autistic adults who would agree to the level of risk and the dehumanization of the study.
Thus, the Duke team’s only way to gather study subjects was via what I have labeled the “proxy consent loophole”. The proxy consent loophole builds off legitimate uses of proxy consent (such as a parent consenting to emergency surgery for their baby) and expands it to justify parents proxy consenting to have their children enrolled in non-essential, experimental scenarios that no child would ever choose to endure. I
In this case, parents were convinced to consent on their children’s behalf, in part, by the rhetoric of hope that the Duke and Cryo-Cell team were spreading through media and the Cryo-Cell website.
But the children did not consent.
Coming Saturday: A brief history of the funding FOR Duke University’s autism stem cell trials: the big donors, the media hype and the results of the early clinical trials (no evidence of benefit and clear evidence of harm).
[1] Stem cells (blood stem cells) are immature cells in the blood that can develop into mature cells in the body. Autologous stem cells come from the patient themselves, taken from bone marrow or cord blood banked at birth and allogeneic stem cells are from stem cells of other people (donors). Embryonic stem cells come from embryos.
[2] For example, one clinic in Florida used fat cells from the patients’ abdomens in a procedure they were misled into thinking was part of a federally-regulated clinical trial. The patients experienced bilateral retinal detachments, eye hemorrhages and other devastating injuries.