To Err is Biotechnological: Reflections on Pew’s Human Enhancement Survey

Posted by Gina Maranto, Biopolitical Times guest contributor on August 9th, 2016

Deep brain stimulation, image via Wikimedia.

Untitled Document

Permit me a brief digression before I comment on the latest Pew Research Center survey of Americans’ attitudes toward biomedical technologies meant to “enhance” human performance.

I am married to a bioengineered man.  Almost three years ago, after having been steadily eroded by Parkinson’s disease for over a decade, my husband Mark Derr braved deep brain stimulation (DBS) surgery.  His incredible surgical team at Johns Hopkins implanted electrodes into his brain and a battery-driven stimulus device in his upper left pectoral, and the results seemed, at the time, nothing short of miraculous.  With a mere incremental upping of the voltage during an initial adjustment session, the DBS instantaneously stilled Mark’s tremulous hand and foot, giving him relief that the standard drugs had only intermittently provided.

Much as DBS has improved his quality of life, Mark is far from cured.  DBS cannot address the muscle stiffness, balance problems, and neurological pain he experiences daily.  And the instrument requires constant attention.  Mark’s days consist of frequent monitoring of his device; his weeks, of periodic adjustments of the voltage; his months, of consultation with his medical minders in Baltimore, where he travels every five months or so for “tweaking.”  His latest technician there told him, “You are your own experiment.” 

Based on direct experience, then, I would advise that heady promises regarding biotechnology should be viewed with a high degree of skepticism. DBS, for example, may eventually get better at addressing Parkinson’s symptoms, but cannot reverse the neuronal damage that lies at the base of the disease.  Many other biotechnological interventions also carry with them an almost guaranteed set of deficits, inadequacies, inconveniences, and risks that are conveniently ignored in the valedictory narratives woven around them. 

More profoundly, Mark both is and is not the Mark he was before DBS, and questions of how identity or even soul are altered by such technologies are only rarely addressed. (For excellent examples where they are, check out Françoise Baylis’s, “'I Am Who I Am’: On the Perceived Threats to Personal Identity from Deep Brain Stimulation” and Sherry Turkle’s edited volume, The Inner History of Devices.)

In some ways, the Pew survey, which looked at attitudes toward three hypothetical “enhancements” (although one, which would involve genetic enhancement of future children, is presented as a preventative medical measure), suggests that Americans get that biotech interventions raise profound social and ethical questions.  In the chart below, more respondents said they were concerned rather than enthused about fiddling with babies’ genomes, following in the footsteps of Johnny Mnemonic, or engaging in blood doping squared.  Not only did most of those surveyed expect that the cons would outweigh the pros of such interventions, a majority believed such interventions “could exacerbate the divide between the haves and have-nots in society…[and that] inequality would increase because only the wealthy could afford these enhancements.”

[Figure via Pew Research Center]

But Pew itself seems oddly disposed to undercut its own findings in the large accompanying piece probing “expert” opinion on enhancement in general. David Masci, in “Human Enhancement: The Scientific and Ethical Dimensions of Striving for Perfection,” seems to take the side of the pro-enhancement champions, giving ample play to the “sky’s the limit” point of view of self-avowed transhumanists and giving the final world to a futurist who says, “We’ll probably start by taking a human version of nirvana and creating it in some sort of virtual reality,” and then “we’ll transition to realms of bliss that we can’t conceive of at this time because we’re incapable of conceiving it.”   Masci also strives to normalize enhancement, starting his piece with the claim that, “Human enhancement is at least as old as civilization.”

This claim, often advanced in pro-enhancement camps, suggests that education and exercise are equivalent to chips in the brain or performance enhancement through genetic alterations that would increase, say, fast twitch muscles.  Call it argument by sleight of hand or by failure to make proper category distinctions.  If we really want an accurate analogy, we should think about phase changes: water becomes colder and colder, and then becomes ice.  A quantitative change leads to a qualitative change.  Step by step, biotechnologists alter us; at a certain point, a qualitative change ensues.  We cannot perfect the human; we can only push genes and protoplasm past a certain point—and no one quite knows where it lies, but many have agreed that the germline is certainly one clear and present possibility—and we will have crafted a new entity. But to what purpose is questionable.

Masci writes

Instead of leaving a person’s physical well-being to the vagaries of nature, supporters of these technologies contend, science will allow us to take control of our species’ development, making ourselves and future generations stronger, smarter, healthier and happier.

To this I say hooey and hooey again.  Even the most exquisitely engineered of artifacts—take the Large Hadron Collider for example—are prone to error and screw ups.  Surprise, chance, and unpredictability are hard wired into our universe.  Whether breakdowns come from passing birds or wayward weasels, breakdowns will come.  Even when our biomedical and bioengineering prowess achieves its best, there will always be downsides.


Gina Maranto is a fellow at the Center for Genetics and Society. She is Professor and Director of Ecosystem Science and Policy and Coordinator of the Environmental Science and Policy program at the University of Miami's Leonard and Jayne Abess Center. Her articles, opinion pieces, and reviews have appeared in Discover, The Atlantic Monthly, Scientific American, The New York Times, and other publications. She is the author of Quest for Perfection: The Drive to Breed Better Human Beings.


Previously on Biopolitical Times:

Image via Wikimedia

Questions about Deaths in Cancer Trials using Gene-Altered Cells

Posted by Katherine Drabiak on August 5th, 2016

Untitled Document

In the past month, the media has reported seven patient deaths of subjects enrolled in separate gene therapy clinical trials being conducted by Juno Therapeutics and by Ziopharm Oncology, Inc., both aimed at immunotherapy-based cancer treatments that have sparked widespread hope. Despite these deaths, the trials continue to move forward.

Media coverage of trials related to gene therapy has portrayed the clinical research rollercoaster.  Just this past week, The New York Times ran an unusually lengthy and high-profile series of articles in the Sunday paper about immunotherapy treatments for cancer, some involving genetic modification of immune cells. The articles describe the promising aspects of engineering one’s own immune system to fight cancer, including dramatic stories of tumors “melting away” and promises of complete remission.  

Yet commentary on the ethical implications of these events has been scant, and these events raise a number of concerns about what bioethicists call “therapeutic misconception” – vulnerable patients seeking enrollment in a clinical trial with the mistaken belief that the gene therapy is approved by the FDA to be safe and effective. The clinical trial deaths also highlight lingering questions about transparent reporting of adverse events to the FDA and appropriately navigating financial conflicts of interest.  Instead, numerous articles have focused on how these deaths impact the bottom line: corporate stock prices

The excitement has been building for some time. In June 2015, MIT Technology Review described Juno’s experimental T-cell immunotherapy for leukemia as “Biotech’s Coming Cancer Cure” and profiled the “miracle” recovery of 20-year old leukemia patient Milton Wright III. Wright signed up for the clinical trial because “they hyped it up, like it was going to be amazing” and MIT Technology Review has characterized Juno’s immunotherapy trials as “remarkable.”

Some scientists are hopeful for a breakthrough, particularly for patients whose cancer has returned after multiple rounds of traditional chemotherapy. For vulnerable patients seeking a “miracle cure,” such characterizations blur the distinction between approved therapy and clinical research that may or may not produce a viable therapy. As a disclaimer, I have not seen any of the informed consent documents from Juno or Ziopharm. But whatever these documents say, media descriptions of a “coming cancer cure” make it challenging to fully convey the risks to sick people with few other options who are considering enrolling in clinical trials as a last-ditch treatment effort. This is precisely the kind of situation that the term “therapeutic misconception” addresses.  

We must cautiously tread when describing Phase I and Phase II clinical trials to patients who are simultaneously acting as research subjects, and take care not to inflate our words when we discuss this research in the media. Despite the misleading name, these early gene therapy trials are not approved therapies, but experiments to assess safety, dosing tolerability, and effectiveness. The goal for this stage of research is not to provide a treatment for this specific person, but rather to contribute to generalized knowledge. It focuses on asking: Will this method of gene therapy work? Is it safe? Are there adverse risks so severe or frequent which constitute an unacceptable level of risk? 

It is not clear whether the patients recognize the uncertainty of benefit, especially when measured against the magnitude of risk. Gene therapy poses a distinct, and an arguably riskier, profile of possible adverse effects compared to drugs alone because it can permanently alter the recipient’s cells and holds the potential for severe latent adverse effects such as cancer, immunologic, neurologic, and autoimmune complications. 

When unexpected serious adverse reactions do occur that are related to the trial, the sponsor must report these to the FDA. Several months ago in May 2016, Juno reported one death to the FDA of a subject who was enrolled in one of its CAR-T protocols for leukemia, asserting: “It is not clear what caused the death, and a change at this time is not warranted.” In July, Juno reported two more deaths, this time stating that they resulted from compounding factors (a chemotherapy drug Fludarabine used in conjunction with the CAR-T protocol). Juno subsequently updated its statement, disclosing there have been four total deaths from its CAR-T protocols. 

In response, the FDA temporarily (and very briefly) suspended the clinical trial, causing a fleeting plummet in Juno’s stock prices. Juno quickly submitted a modified protocol that removed Fludarabine, updated the trial brochure, and amended the patient consent form to the FDA. The FDA deemed these modifications acceptable and expediently lifted the hold within days, despite the alarming disclosure. Juno’s trial – and stock prices  – were back in business.  Articles (here and here) characterized these deaths and the corresponding swift response as a “bump in the road,” myopically questioning how it would impact the clinical trial progression and corporate financial outlook. Minimizing patient deaths that may have resulted from the gene therapy rather than their underlying illness is dehumanizing and ethically inappropriate, even if we reason that these patients were near the end of life.     

One biotech analyst questioned FDA’s decision to quickly lift the clinical trial hold, observing, “They are trying to referee a game while the rules are still being written. And it appears to be causing some deaths that should have been avoided.”

Ziopharm made similar headlines in the past few months relating to its Phase I clinical trials designed for glioblastoma patients. Ziopharm partnered with the synthetic biology company Intrexon, and has been studying a gene therapy technique using a genetically engineered virus that is directly injected into the subject’s tumor. According to Ziopharm, the third subject died 15 days after beginning the trial of an intracranial hemorrhage. Prior to this report, two other enrolled subjects also died, albeit months after the initiation of one of the trials. According to a press release, Ziopharm maintains the intracranial hemorrhage death “is an isolated case” and the other patient deaths were unrelated, and attributed those outcomes to pre-existing illness, stating, “these patients are all, unfortunately, medically fragile.”
The problem with reporting adverse events, including deaths, to the FDA resides in a substantial loophole that awards discretion to the investigator to decide whether the adverse event is serious and whether it reasonably resulted from the gene therapy. Although the investigator theoretically stands in the best position to sort through the noise of the confounding variables of underlying illness or other drugs the subject may be taking, this nonetheless creates a troublesome reliance upon the corporation whose stock price and profitability are tenuously tied to clinical trial performance. This creates an undeniably powerful motivation to shift the blame of any adverse outcomes.

As Professor Osagie K. Obasogie has noted, profit motives remain entrenched in medical research, which can further complicate relationships where industry and medical care become intertwined. The arrangement between Ziopharm and MD Anderson Cancer Center exemplifies such enmeshment: Ziopharm and Intrexon executed a deal with MD Anderson to provide $100 million in stock, and recently appointed MD Anderson physician Dr. Laurence Cooper as Ziopharm’s newly minted CEO.  Similarly, Science’s recent profile of competitor Dr. Carl June’s work at the University of Pennsylvania also flagged the potential conflict of interest arising from its partnership with Novartis to develop gene therapies for which June would hold a financial stake arising from related patents.

Despite assertions that these relationships will be managed according to institutional conflict of interest policies, such heavy financial ties heighten the stakes and necessarily raise concerns about independent judgment and transparency. The call to uphold ethical tenets of research is nothing new, particularly when there is a frantic competition to bring an FDA-approved product to market. Back in 2007, Obasogie raised similar concerns after a patient death in a gene therapy trial for arthritis: “Time is money; in the rush to get products to market, patient safety can inadvertently take a backseat.”

These vulnerable patients have a stake, too. We must ask the right questions to see whether they appreciate the risks they decide to undertake. We must stop blindly accepting these dismissals of deaths and assurances that conflicts of interests are mitigated, especially when there is so much riding on clinical trials’ success.

Katherine Drabiak, JD is an Assistant Professor at USF Health in the College of the Public Health.  You can follow her updates here:

Previously on Biopolitical Times:

Image via Pixabay

The Case Against Public Investment in Reproductive Genetic Modification

Posted by Jessica Cussins, Biopolitical Times guest contributor on August 3rd, 2016

Untitled Document Philosopher Tina Rulli argues that three-person IVF is not a “life-saving therapy” or even a medical treatment at all. Rulli explains why the technology does not meet a plausible social value standard that would justify public research investment, and why other germline modification techniques may not either.

UC Davis Assistant Professor of Philosophy Tina Rulli published a report titled "What is the Value of Three-Parent IVF?" in the July-August 2016 Hastings Center Report.

If you have seen any of the countless descriptions of three-parent or three-person IVF, also called mitochondrial replacement, as a “life-saving treatment,” you might find the question in the title confusing. How could any life-saving treatment not be of value?

As Rulli explains, the claim that this technology would save lives is “inaccurate and exaggerated.” Three-person IVF would not cure, treat, or save anyone. At best, it would allow women affected by a particular kind of mitochondrial disease to have an unaffected child who is mostly genetically related to her.  

The experimental procedure works by genetically engineering an embryo to combine the intending mother’s nuclear DNA with another woman’s mitochondrial DNA. The choice a woman would make is not “do I save my child?” but “do I want to have a child in this way?” Rulli makes a strong argument that these are not morally equivalent, and that it is irresponsible to act as though they are.

How one thinks about this distinction between creating an unaffected genetically related child and saving lives may have implications well beyond three-person IVF. As Rulli points out, the creating-saving distinction probably holds for any form of germline genetic modification:  

The argument here might provide a template for objections to other germline modifications or gene therapies that are valuable solely or primarily because they may enable prospective parents to have healthy genetically related children who would not otherwise exist.

For example, it would probably mean that the experiment carried out in April using CRISPR to introduce an HIV-resistant mutation into the DNA of embryos could also not be called a life-saving treatment, even if it worked well (it didn’t) and even if it was going to be used to generate a person with altered risk factors (it wasn’t).

Rulli further undermines the medical relevance of three-person IVF by pointing out that it isn’t the most effective way to reduce the transmission of mitochondrial disease. Only a small subset of mitochondrial disease could even hypothetically be addressed by this technology, since most cases involve mutations in nuclear DNA (instead of or in addition to mutations in mitochondrial DNA). And the procedure would only be accessible to women with far more financial resources than most have.

The alternative to three-person IVF – using an entire egg (rather than an egg that has had its nucleus removed) provided by another woman – would completely eliminate the risk of transmitting mitochondrial disease. In other words, the real value of the experimental procedure is not about health at all, but about the personal preference to have a genetic connection to one’s child. Rulli refers to this as “medicalization of a social preference” that works by “preserving the dominance of the bionormative family schema.”

Based on these points, Rulli asserts that three-person IVF lacks the social value that proponents have claimed for it, and that would be a necessary precondition of ethical clinical research, both in order to use limited health resources responsibly and to avoid human exploitation. She therefore concludes, despite the Institute of Medicine’s report endorsing the potential of “clinical trials,” that any public research investment in three-person IVF would be unethical.

Rulli reaches this conclusion even without addressing the multiple safety and efficacy concerns that have cropped up regarding three-person IVF. She takes it for granted that the technology will do what it says it will do. But she does note:

If the concerns about the safety of three-parent IVF for children and future generations are legitimate, then these considerations are not over-ridden by proponents’ claims about the great, life-saving potential of this technology. We know those claims to be fictional.

Throughout the push for legalization of these three-person IVF techniques, some advocates have painted any concern raised as anti-science or anti-technology. Rulli takes pains to point out that she is neither. Her argument is not against the technology per se, but whether to invest public resources in its development when the opportunity cost of that research includes, among other things, diminishing resources for investigating treatments for people suffering from mitochondrial diseases today.

Given the firestorm of attention to CRISPR, and the relative ease of genetically modifying an embryo versus an adult, we may well see arguments about germline gene editing as a “life-saving treatment.” Proponents are already pointing to three-person IVF as a pioneer technology that is paving the way for other forms of germline modification, so it is critical to set the record straight. Rulli’s report will be a useful framework to have on hand.

Previously on Biopolitical Times:

Image via Pixabay

Editorial Precision? Snapshot of CRISPR germline in the news

Posted by Hasmik Djoulakian on August 1st, 2016

Two colorful balls representing genes are in focus while the rest in the background are out of focus.

It’s been less than a year and a half since researchers at Sun Yat-sen University reported their first-of-its-kind experiment using CRISPR/Cas-9 to genetically modify nonviable human embryos. Since then, controversy about the prospect of using CRISPR for human reproduction – to alter the traits passed down to future generations – has been covered in hundreds of news articles, editorials, and commentaries. But how well has this media spotlight illuminated the key points of the debate?

Nearly every article that discusses CRISPR uses the term “gene editing,” and many say explicitly that it is a “precise” tool just like a “cut-and-paste” word processing program. A recent paper co-authored by CGS fellow Lisa Ikemoto notes that metaphors used to inform public policy addressing emerging biotechnologies should encompass: (1) the ethical complexity of the technology, (2) an accurate description of how it works, and (3) the known and unknown consequences of various applications.  Does the “gene editing” metaphor give us any of that in contemplating the idea of genetically modified babies?

Along with many others, the Center for Genetics and Society is deeply concerned about using CRISPR to modify the human germline, for both safety and societal reasons. First, as nearly all agree, it would be way too risky; among other problems, it could result in off-target effects that would be passed down to future generations. Second, it’s not medically necessary – there are much better and safer ways for people at risk of transmitting inherited diseases to ensure their children are unaffected. Beyond the technical risks of CRISPR are the likely social consequences of allowing human germline interventions, including its use to “enhance” the children of the already affluent, thus reinforcing existing inequalities and creating opportunities for new ones.

Curious about the extent to which these concerns were being fairly represented in the media, we decided to take a closer look. We selected 40 news articles and commentaries covering the potential uses of CRISPR in humans over the last year and a half in three media outlets: The Washington Post, The Guardian, and The New York Times. We then examined each article to see how it handled five specific points that we see as critical to a full understanding of the global, political, and technical aspects of human germline gene editing:

  • The first was whether the article notes the difference between somatic gene editing – that is, using CRISPR as a gene therapy to treat affected patients – and germline gene editing – modifying the genes in human embryos or reproductive cells.
  • Second, we asked whether the article mentions social and political concerns as well as technical and safety questions.
  • The third point we looked for was some acknowledgement that many countries have already established legal prohibitions on human germline modification.
  • Fourth, we determined whether the article takes stock of available alternatives to germline gene editing, such as embryo screening (pre-implantation genetic diagnosis or PGD, used with IVF).
  • Finally, we asked whether the article accurately represents the potential scope and type of illnesses that germline editing would theoretically be used to address.

Initial Observations

This project is a preliminary one, our sample was small, and our results should be seen as tentative. With those caveats in mind, here’s what we found.

Perhaps most surprising and unsettling is that very few articles (only 6 out of 40) mention PGD as an alternative to germline editing that, in nearly every case, would allow people to prevent the transmission of inherited conditions to a fully genetically related child. This omission could mislead readers into believing that germline editing is needed and desired by large numbers of people with genetic conditions, which it is not.

Similarly, only 7 of the 40 articles clearly specify that CRISPR technology would be technically relevant for diseases that have clear genetic determinants, but not for health conditions that are significantly determined either by social and environmental factors, or by so many genetic interactions and trade-offs that choosing which to “edit” could be a fool’s errand.

On the other hand, the majority of articles do distinguish in some way between somatic and germline modification, discuss social and political concerns along the lines of “ethics” and “unequal access,” and touch on other countries’ policies regarding human germline modification. Of the 40 articles in our sample, 28, 31, and 26, respectively, make these points.

It seems reasonable that readers should be able to rely on newspapers like The Washington Post, The Guardian, and The New York Times to make all of the key distinctions and provide key information about recent developments in biotechnology. Proposals to use powerful new technologies to create genetically modified human beings are highly controversial, and we will be ill-equipped to address them with only patchwork understandings of their significance and consequences. 

A spreadsheet showing the 40 articles in our sample, and our coding on each of the five points examined can be found here.

Previously on Biopolitical Times:

  • Public Opposes Human Germline “Enhancement” by Overwhelming Majority

  • Stopping or Selling Human Germline Modification?
  • "Moonshot Medicine": Putative Precision vs. Messy Genomes
  • False Inevitabilities and Irrational Exuberance
  • Image via Flickr/Tom Woodward

    Displaying 1-4 of 1334  
    Next >> 
    Last Page » 
    « Show Complete List » 



    home | overview | blog | publications | about us | donate | newsletter | press room | privacy policy

    CGS • 1120 University Ave, Suite 100, Berkeley, CA 94702 USA • • (p) 1.510.625.0819 • (F) 1.510.665.8760