Dr. Fleck presents on public funding for whole genome sequencing at International Bioethics Retreat

Leonard Fleck photo

Dr. Leonard Fleck, professor in the Center for Ethics, participated in a keynote debate this month as part of the 24th annual International Bioethics Retreat that was presented virtually from Paris. Each year, “experts in medicine, philosophy, law, and health policy are invited from around the world to present their current research projects.”

Within the debate format, Dr. Fleck addressed the question: “Whole Genome Sequencing: Should It Be Publicly Funded?” Dr. Fleck defended the affirmative in this debate, while Dr. Leslie Francis of the University of Utah defended the negative. Continue reading below for Dr. Fleck’s summary of the debate.

Whole Genome Sequencing: Should It Be Publicly Funded?

Below are the key elements in the affirmative side of that debate, as well as acknowledgment of legitimate points made by Dr. Francis.

We can start with the question of what Whole Genome Sequencing [WGS] is. It refers to creating a complete map of all three billion base pairs of DNA in an individual. Next, how might WGS be used? It can be used for preventive, diagnostic, therapeutic, reproductive, and public health purposes? It can be used by adults as part of a preventive strategy, i.e., identifying genetic vulnerabilities to disorders that might be managed or prevented through behavioral change. WGS can be used diagnostically to correctly identify very rare disorders that otherwise will require a costly and painful diagnostic odyssey. This is most often true in the case of infants.

WGS is used therapeutically in the case of metastatic cancer. Both the patient and cancer tumors would be mapped in order to find a genetic driver of the cancer that could then be attacked with a targeted cancer therapy, such as trastuzumab to attack a HER2+ breast cancer. WGS can be used in a reproductive context to do non-invasive prenatal assessment of a fetus. Likewise, some advocate using WGS to do neonatal genetic screening in place of the heel stick and blood draw that will test for 56 childhood genetic disorders. WGS could test for hundreds of very rare genetic disorders that can affect children. The public health context is very visible right now as we do WGS of the COVID variants now emerging.

Why public funding? The key argument is that it is a matter of health care justice. WGS costs about $1000 for the sequencing itself, and another $2000 for the analysis, interpretation, and counseling. Insurers will generally not pay for WGS. Roughly, only the top quintile in the U.S. economic spectrum can afford to pay for WGS out of pocket. This can yield significant health advantages for them, most especially avoiding various sorts of genetic harms. More precisely, the relatively wealthy might learn of one or more health risks through WGS that would suggest the need for additional testing and therapeutic interventions, all of which would be paid for by their insurance. The less financially well off may have good health insurance but be unaware of the need to use it in a timely way without the advantage of WGS. One possible result is that a curable disease becomes incurable when symptoms are clinically evident. This is an injustice that can be avoided if access to WGS is publicly funded.

My esteemed debate partner Dr. Francis emphasized that the ethics issues are much more complex than simply matters of health care justice. The distinctive feature of any form of genetic testing is that it yields considerable information about any number of first-degree relatives who may or may not want an individual to know that information. If we do WGS on a neonate, for example, we might discover that neonate has an APOE 4/4 variant for early dementia. That means at least one parent has that vulnerability, which they might not wish to know. In addition, do those parents have any obligation to notify any other relatives of their potential vulnerability? What if, instead, it was a BRCA1 mutation for breast or ovarian cancer? More problematic still, what if WGS is used at public expense in prenatal screening with the result that some parents choose to have an abortion. Would advocates for a Right to Life view have a right to object to their tax dollars being used to facilitate access to a procedure to which they conscientiously object? This is why we have debates.

CRISPR Dangers Highlight the Need for Continued Research on Human Gene Editing

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This post is a part of our Bioethics in the News series

By Jennifer Carter-Johnson, PhD, JD

The excitement and potential of CRISPR to treat severe genetic conditions by editing disease-causing DNA has taken an unexpected hit. A recent Wall Street Journal article highlighted the unexpected results from a CRISPR study in which attempts to edit a human gene responsible for blindness resulted in the loss of the entire chromosome from the cells in the embryos. These results echo another study conducted in human cell lines published earlier in 2019.

CRISPR is a targeted gene editing process that allows scientists to direct genetic modifications with far more precision than prior procedures. CRISPR has been touted as a gigantic leap in the ability to modify DNA by creating or repairing pinpoint DNA mutations without affecting other areas of the chromosome on which the gene resides. The recent study indicates that the technique might not be as straightforward in humans – and thus neither will be its use to fight disease.

Blue DNA double helix puzzle with missing pieces
Image description: A partially assembled puzzle that is an image of blue double helix DNA molecule structures. Image source: Arek Socha/Pixabay

CRISPR Technology – Promise and Problems

The value in CRISPR mediated genetic modification can be seen in a wide variety of biotechnology products, such as genetically modified crops and new biologics. But perhaps the most exciting and most controversial potential for CRISPR can be found in the desire to modify embryonic genomes to remove genetic abnormalities for which we currently have no cure.

This promise of embryonic gene editing is appealing not only because it would remove the condition from the child born from the gene-edited embryo, but also because the offspring of that child would also be free of the condition. CRISPR gene editing – because it is done at the embryonic stage – creates germline mutations that are passed to future generations. In a therapeutic use of CRISPR, those mutations would be cures for often untreatable diseases.

However, it is this very promise that raises many of the problems with CRISPR embryonic gene editing. Much debate has surrounded embryonic gene editing. Until this recent news, there were fears that CRISPR may make gene editing too easy. The technological development of CRISPR in embryonic gene editing is moving at a breakneck pace as scientists around the world are working on procedures. Biohackers work in their garages and livestream the use of CRISPR to edit their own genomes.

Many are debating which genes should be targeted and how fast the research into actual trials should proceed. Most agree that severe diseases would be the best place to start, but should the technology be deployed for cosmetic benefits such as eye color, or diseases for which a treatment exists? The dangers of CRISPR editing are unclear, and there has been an informal moratorium on the use of the technology to create children. Despite that, there has been at least one rogue scientist who has created genetically modified embryos and brought them to full term birth.

International Policy on Human Gene Editing

The scientific research is not occurring in a vacuum. Each country decides how CRISPR can be used in its medical system – both when the technique is safe enough and on which diseases it should be used.

An international commission recently pronounced that the technology is not ready for clinic implementation because scientists don’t understand the full safety issues surrounding its use in human embryos. The commission described some of the potential clinical uses in the future and outlined a basic safety protocol for approval.

One of the creators of CRISPR, Jennifer Doudna, has also spoken out against applying CRISPR too hastily to embryonic gene editing. 

Based on the recent studies showing loss of chromosomes, the international commission and other scientists are correct to call for a moratorium on clinical embryonic gene editing.

Blue and green DNA double helixes and binary code
Image description: An abstract image of blue and green double helix structures and binary code (zeros and ones) against a black background. Image source: Gerd Altmann/Pixabay

CRISPR – The Path Forward

The setback in CRISPR gene editing does not mean that the technology and research should be discarded. The potential to change lives is too great; however, the dangers of use with our current understanding are even greater. So how do we move forward with CRISPR in embryonic gene editing? The answer must include balance – in research strategies and in voices.

While the technology is not ready for clinical use, and we have not yet determined which uses would be appropriate if it were available, the science should not stand still. The research surrounding CRISPR gene editing will yield insights into human biology that we cannot predict. For example, the loss of chromosome length in human embryonic cells undergoing CRISPR treatment seems to be different than the response of other species of embryonic cells. And debates about the appropriate use of the technology will allow us to discover more about ourselves as humans. 

As we debate the best way to develop and deploy CRISPR technology, we should look to a variety of stakeholders. Scientists have a solid track record in understanding when recombinant DNA technology has potentially hazardous implications. In the 1970s, the Asilomar Conference allowed scientists to put together research guidelines that allowed the technology to be developed without harming public health. In fact, the international scientific consensus not to use the technology such as described above indicates that scientists are beginning that work. Such a moratorium on clinical uses gives us time to understand how to deploy the technology in the safest manner.

Additionally, there is a role for the voices of the patients whose lives could be changed by the technology. Patients may not be in the best place to judge when the technology should be deemed safe enough to deploy, but they certainly will have input about which mutations cause hardships that merit the risk of germline editing. Many of these patients already work with scientists on potential treatments for their diseases. CRISPR discussions may open another avenue for many.

Finally, there is a role for legal regulation of the use of CRISPR. Governments should listen to the voices of scientists and potential patients in drafting these regulations. But as shown by the example of at least one rogue scientist, there needs to be teeth to the moratorium on CRISPR clinical use at this time. CRISPR and its use in human gene editing raise complicated issues and hold great promise as a powerful tool to defeat genetic diseases. The development of those technologies will not be straightforward or without risk and will require more basic science research to achieve clinical efficacy. But with proper planning, we may learn more about ourselves as humans on the path to a cure.

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Jennifer Carter-Johnson, PhD, JD, is Associate Dean for Academic Affairs and Associate Professor of Law in the Michigan State University College of Law. Dr. Carter-Johnson is a member of the Michigan State Bar. She is registered to practice before the U.S. Patent and Trademark Office.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Tuesday, December 15, 2020. With your participation, we hope to create discussions rich with insights from diverse perspectives.

You must provide your name and email address to leave a comment. Your email address will not be made public.

More Bioethics in the News from Dr. Carter-Johnson: Biohacking: How a DIY Approach to Biology Can Shape Our FutureWeb of Interests Surrounding Medicines Makes Patient Access Increasingly DifficultHumanity in the Age of Genetic ModificationDefining The Spectrum of “Normal”: What is a Disease?Dawn of False Hope: Spread of “Right To Try” Laws across the U.S.

Continue reading “CRISPR Dangers Highlight the Need for Continued Research on Human Gene Editing”

Biohacking: How a DIY Approach to Biology Can Shape Our Future

Bioethics in the News logoThis post is a part of our Bioethics in the News series

By Jennifer Carter-Johnson, PhD, JD

In 2017, Josiah Zayner live-streamed himself injecting a gene therapy construct designed to edit the DNA in his muscle cells to give him bigger muscles. This moment was noteworthy because the gene therapy construct had been created entirely by Zayner in his garage laboratory. Such work is called biohacking or DIY biology.

These actions do not come without consequences. He has recently been investigated for practicing medicine without a license, and the state of California recently passed a law to require all such kits to include a notice “stating that the kit is not for self-administration.”

What is Biohacking?
Zayner is not alone; in fact, the biohacking movement is growing across the country. Zayner also sells kits that allow other biohackers to experiment with DNA and gene editing from his website, The Odin. There are also laboratories across the country that allow interested people to have space to conduct biology experiments without having to build a home laboratory.

Biohacking at its core is bringing science out of the laboratories of academia and industry and into grasp of citizen scientists. But the exact definition of what is included in biohacking differs among people. Biohacking includes a diverse variety of science experiments such as tracking of sleep and diet, under-skin implantation of computer chips and other technology, ingestion of “smart drugs” and sub-clinical levels of LSD, transplantation of gut and skin microbiomes, infusion of “young blood” to reverse aging, and genetic modification of bacteria, yeast and human cells.

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Image description: an equipment setup called a “makerbay” in a Hong Kong biohacking makerspace. Image source: Athena Lam/Flickr Creative Commons.

Each type of biohacking brings its own risks and rewards. This blog post will focus on genetic modification of cells using new gene editing techniques such as CRISPR. Advances in gene editing technology over the past five years have made accessible science that was once confined to expensive, high-technology laboratories. For a broader look at CRISPR and gene editing by researchers and bio-hackers, Netflix has a new documentary series, Unnatural Selection.

Benefits of Biohacking
First and foremost, the benefit of biohacking is access to science. Not everyone can afford an advanced degree biology or wants to work full time in a laboratory. Biohacking democratizes science for people who have a passion for learning about the world and how it works. It also has the potential to increase access to medicine. One endeavor, the Open Insulin Project, attempts to find a cheaper and intellectual property-free way to produce and distribute insulin to make it available to people who have a hard time affording the drug.

In addition to access, biohacking communities are also hubs of outreach and education. The laboratory spaces often hold classes and meeting spaces for like-minded individuals to network. There are competitions that bring together student and citizen scientist teams who work on using synthetic biology to create biological solutions to local and international problems.

Biohackers are taking these responsibilities seriously as a whole. The community has even developed its own code of ethics emphasizing open access, transparency, education, safety, environment, and peaceful purposes.

Risks of Biohacking
Although biohacking has many benefits, there are risks of which the world and individual citizen scientists should be aware. Perhaps the largest potential threats are the lack of education and regulation within the biohacking community.

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Image description: two people are gathered at a table containing various types of scientific equipment. Image source: Martin Dittus/Flickr Creative Commons.

While Josiah Zaynor holds a PhD in biopohysics, not all biohackers are so well educated. Community laboratories help with classes and mutual support, but home-based biohackers must rely on their own knowledge and understanding, though websites are available for questions and discussions. Education and outreach to biohackers is also the strategy of the FBI in recent years, though many biohackers are reticent to accept its help. Additionally, while the community does have a code of ethics, there is little formal ethics training in concepts such as informed consent or using animals in research.

Due to the open definition and decentralized structure of biohacking, regulation is almost impossible. Lack of regulation leaves laboratory safety in the hands of the biohackers. As with any scientific endeavor involving genetic engineering, accidents can occur that could lead to the release of environmentally destructive organisms. Biohackers injecting themselves or others could cause any number of infections or adverse reactions. Additionally, the risk of the development of dangerous or ineffective gene therapies and other products by biohackers has led the Food and Drug Administration to issue warnings to the public about untested products. This risk is especially relevant in an era of rising drug costs.

Other dangers, such as specific threats to biosecurity, are real but attenuated. While it is possible biohackers could genetically engineer a bacteria or virus, there are far easier ways for a small-scale terrorist group to attack.

Future of Biohacking
Highly technical equipment and processes are becoming more accessible. People are looking for ways to take control of their health and provide access to medicines. Curiosity about the natural world should be encouraged.

The risks are real, but we can deal with them by working together. By having community leaders willing to confront the risks and help develop community norms, we can shape the application of biohacker energies. Zayner himself has realized that other biohackers may seek to emulate his self-experimentation and get hurt.

In the end, biohacking is here to stay.

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Jennifer Carter-Johnson, PhD, JD, is an Associate Professor of Law in the College of Law at Michigan State University. Dr. Carter-Johnson is a member of the Michigan State Bar. She is registered to practice before the U.S. Patent and Trademark Office.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, November 14, 2019. With your participation, we hope to create discussions rich with insights from diverse perspectives.

You must provide your name and email address to leave a comment. Your email address will not be made public.

More Bioethics in the News from Dr. Carter-Johnson: Web of Interests Surrounding Medicines Makes Patient Access Increasingly DifficultHumanity in the Age of Genetic ModificationDefining The Spectrum of “Normal”: What is a Disease?Dawn of False Hope: Spread of “Right To Try” Laws across the U.S.

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Worried about your privacy? Your genome isn’t the biggest threat.

Bioethics in the News logoThis post is a part of our Bioethics in the News series

By Tom Tomlinson, PhD

It was good news to learn last month that the “Golden State Killer” had at last been identified and apprehended. A very evil man gets what he deserves, and his victims and their families get some justice.

The story of how he was found, however, raised concerns in some quarters. The police had a good DNA sample from the crime scenes, which with other evidence supported the conclusion that the crimes were committed by the same person. But whose DNA was that? Answering that question took some clever detective work. Police uploaded the DNA files to a public genealogy website, GEDmatch, which soon reported other users of GEDmatch who were probably related to the killer. More ordinary police work did the rest.

Most of the concern was over the fact that the police submitted the DNA under a pseudonym, in order to make investigative use of a database whose members had signed up and provided their DNA only for genealogical purposes.

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Image description: a black and white photo of the panopticon inside of Kilmainham Gaol in Dublin, Ireland. Image source: Craig Sefton/Flickr Creative Commons.

My interest in this story, however, is the way it both feeds and undermines a common narrative about our DNA—that it is uniquely identifying, and that therefore any uses of our DNA pose special threats to our privacy. As The New York Times expressed this idea, “it is beginning to dawn on consumers that even their most intimate digital data—their genetic profiles—may be passed around in ways they never intended.”

It’s true that a sample of DNA belongs uniquely to a particular individual. But the same is true of a fingerprint, a Social Security number, or an iris. More importantly, by themselves none of these pieces of information reveals who that unique individual is.

As the Golden State Killer story illustrates, it’s only when put in the context of other information that any of these admittedly unique markers becomes identifying. If the GEDmatch database contained nothing but genetic profiles, you could determine which genomes the killer was related to. But you’d have no idea who those genomes belonged to, and you’d be no closer to finding the killer.

Although an individual genome can’t by itself be identifying, it can provide a link that ties together different information sources which include that genome. It can then be that collection that points to an individual, or narrows the list of possibilities to increase the odds of identification, and the threats to privacy. Imagine the state police maintains a database of forensic DNA linked to records of criminal convictions, and provides that database to criminologists, stripped of any names or other direct identifiers. Imagine as well that one of the hospitals provides researchers with DNA from their patients along with their de-identified medical records (which can include patients’ age, race, first 3 ZIP numbers, and other demographic information).

If we put those together we can do some interesting research: use the DNA link to identify those who both committed various crimes and had a psychiatric history, so we can compare them to convicted felons without a psychiatric history.

But now it may take very little additional information to identify someone in that combined database and invade their privacy. If I’m a researcher (or hacker) who knows that my 56-year-old neighbor was convicted of assault, I can now also find out whether he has a record of psychiatric illness—and a lot more besides. What he had thought private, is no longer so.

The point of this somewhat fanciful example is that as more information is collected about us, from more sources, the threats to our privacy will increase, even if what’s contained in individual sources offers little or no chance of identification.

For this reason, the prospect of merging various data sources for “big data” health research will challenge the current research regulatory framework. Under both the current and the new rules (which haven’t yet gone into effect), the distinction between identifiable and non-identifiable research subjects is critical. Research using information that can be linked to an individual’s identity requires that person’s consent. To avoid this requirement, research data must be “de-identified”. De-identification is the regulatory backbone on which much of the current “big data” research relies, allowing the appropriation of patient medical records and specimens for use in research without consent; and it provides the regulatory basis for uploading the data collected in NIH-supported research into a large NIH-sponsored database, the database of Genotypes and Phenotypes (dbGaP), which most NIH-supported genomic studies are required to do. Data from dbGaP can then be used by other researchers to address other research questions.

The possibilities of merging such “de-identified” databases together for research purposes will only increase, including facial recognition databases being collected online and on the street. As the mergers increase, it will become more difficult to claim that the people represented in those databases remain non-identifiable. As Lynch and Meyer point out in the Hastings Center Report, at this point there will be two choices. We can require that all such research will need at least broad consent, which will have to be reaffirmed every time a person’s data is used in new contexts that make identification possible. Or we will have to fundamentally reassess whether privacy can play any role at all in our research ethics, as the very idea of “privacy” evaporates in the panopticon of everyday surveillance.

Tom Tomlinson photoTom Tomlinson, PhD, is Director and Professor in the Center for Ethics and Humanities in the Life Sciences in the College of Human Medicine, and Professor in the Department of Philosophy at Michigan State University.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, July 12, 2018. With your participation, we hope to create discussions rich with insights from diverse perspectives.

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Gene Editing: God’s Will or God’s Won’t

Bioethics in the News logoThis post is a part of our Bioethics in the News series

By Leonard M. Fleck, PhD

Give God a rest; do your own gene editing (and thinking). On August 2, 2017 the New York Times headline read, “In Breakthrough, Scientists Edit a Dangerous Mutation from Genes in a Human Embryo.” The mutation was of a gene called MYBPC3, and the result of that mutation is a disease called hypertrophic cardiomyopathy. This disease affects 1 in 500 people. Its victims are typically young athletes. CRISPR-cas9 is the technology used to accomplish the gene editing. More precisely, a synthetic healthy DNA sequence was injected into an egg cell fertilized by a sperm cell with the mutated gene. This healthy DNA sequence was supposed to be copied into the newly created embryo. In fact, however, the maternal DNA was copied, thereby correcting the paternal mutation in 72% of the resulting embryos. A total of 54 embryos were created, later destroyed, after genetic analysis had been done. The remaining embryos were genetically mosaic. This research received worldwide attention.

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Image description: a black and white image of an 8-cell human embryo, day 3. Image source: Wikimedia Commons.

I want to raise two questions. How should we assess this research and its future possible uses from an ethical perspective? How should we assess public policies designed to regulate this research now and in the future? I am going to give more attention to this latter question in the context of a liberal, pluralistic, democratic political culture because many people would demand that the research itself be outlawed, not just regulated. The relevant question to ask is this: What sort of justification must be given for regulating or banning gene-editing technologies used to create or modify human embryos? The short answer I will defend in response to that question is that regulations must satisfy public reason and public interest requirements (as explained below).

From an ethical perspective, gene-editing technology represents considerable potential benefit, as the example of hypertrophic cardiomyopathy above suggests. At least 200 single-gene disorders could be corrected at the embryonic or pre-embryonic level, thereby preventing premature death or substantial diminishment of quality of life in these future possible children (as well as potential descendants of those children). To be clear, no gene-editing technology is ready for clinical application. Off-target effects remain a problem. From an ethical perspective, the risk-benefit ratio of such interventions today weighs too heavily on the risk side. Researchers, however, are confident that these risks can be overcome.

Assuming that the safety issues can be effectively managed, another ethical objection is that these future possible children (maybe for several generations) would not have consented to such fundamental interventions. I do not see this as a compelling objection. Parents today must consent to very risky surgery or other medical interventions in a two-year old child that could result in the death of that child or substantial lifelong impairment. We have to trust the judgment of parents and physicians in such circumstances. We have to believe they are all acting in the best interests of that child (absent compelling evidence to the contrary). This seems perfectly analogous to what would be occurring with gene-editing of an embryo. (For a broad overview of relevant ethical principles, see Wolpe et al., 2017.)

I now want to switch to concerns in the context of public policy. What sort of political justification would be needed to legitimize the complete banning of gene-editing research on human embryos? Here are two answers that are entirely “out of bounds” in a liberal, pluralistic society: (1) doing gene-editing of embryos is “playing God,” and (2) destroying embryos should never be regarded as an acceptable part of medical research.

The phrase “playing God” invokes amorphous religious associations, deliberately and arrogantly engaging in some life-or-death activity that is the exclusive prerogative of God. However, if this is supposed to be a compelling argument for public policy purposes, then large areas of medical practice would have to be outlawed as well. It might well be the will of God that I die from my heart attack, but I still want my surgeon to be agnostic and do the bypass surgery needed to save my life. God is typically described as being omnipotent, though millions of embryos are created annually with thousands of serious genetic disorders. Allowing those future possible children to suffer the awful consequences of those disorders by forbidding the development of the technology that could correct those disorders looks like willful social negligence, not impiety.

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Image description: a bone cancer cell (nucleus in light blue) at the microscopic level. Image source: ZEISS Microscopy/Flickr Creative Commons.

Critics of gene-editing rail against the possible, speculative harms this technology could unleash on future generations of children, all the while ignoring the very real harms current actual children are having to suffer as a consequence of these genetic disorders. This is not just shortsighted; it is ethically and politically perverse. Virtually everyone agrees that it would be premature today to do embryonic gene-editing with the intent of bringing that future possible child to birth. However, nothing would justify laws that would forbid going forward with the research until such time as it would be safe to introduce into the clinic.

Some religious critics will object to the destruction of embryos that will be integral to the development of this technology. We noted above that 54 embryos were created and destroyed in connection with the hypertrophic cardiomyopathy research. Some religious critics will see those embryos as having the moral status of persons with the same rights as you and I. However, this is where public reason must be invoked as the appropriate basis for formulating policy in a liberal, pluralistic society.

Public reason (Rawls, 1996) must be neutral or agnostic with respect to all religious belief systems or other comprehensive worldviews. From an objective, scientific perspective embryos have no capacity to feel pain, no consciousness, no interests, and no personal identity. Embryos are not mini-persons. Some religious adherents may believe otherwise. They are free to affirm that belief in the private social space of their religious community. However, they may not seek to create laws that would effectively impose that belief on citizens who did not share that belief. This would be an illegitimate, illiberal use of the coercive powers of government unless they were able to justify such laws through an appeal to public reasons and related public interests.

Public reasons are reasons that all free and equal reasonable citizens as citizens can accept as reasonable, as consistent with the best science and fair terms of cooperation in a just society. Public reasons are the currency of rational democratic deliberation. Public interests are interests that all citizens have, and that could not be adequately protected or enhanced without the use of the coercive powers of government to control those who would threaten those interests. Protecting air and water quality would be a clear example of a public interest.

A liberal, pluralistic society recognizes and respects many reasonable ways of living a good life. Individuals are free to order their lives in accord with many different reasonable values that do not represent a threat to the rights of others or to various public interests. Consequently, such a society will accept that some people will refuse to use gene-editing technology in the future to alter the genetic endowment of their future possible children. This is political respect for procreative liberty.

It would be illiberal and illegitimate for some political group to use the coercive powers of the state to force religious individuals to use gene-editing technology, contrary to their religious beliefs. Likewise, these religious individuals must be mutually respectful of the procreative liberty rights of others to use gene-editing technology to alter the genetic endowments of their future possible children. This would include paying taxes to support the medical and scientific research needed to develop safe and effective versions of embryonic gene-editing, keeping in mind the taxes needed to pay for the health care needs of children born with cystic fibrosis or muscular dystrophy or any number of other medical problems that could have been avoided with judicious gene-editing.

In conclusion, there can be reasonable disagreement regarding various uses of embryonic gene-editing technology. However, that disagreement will have to invoke public reasons and public interests. God’s will and God’s won’t are not public interests.

Fleck smallLeonard M. Fleck, PhD, is a Professor in the Center for Ethics and Humanities in the Life Sciences and the Department of Philosophy at Michigan State University.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, December 14, 2017. With your participation, we hope to create discussions rich with insights from diverse perspectives.

You must provide your name and email address to leave a comment. Your email address will not be made public.

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Designing Children: Patents and the Market are not Sufficient Regulation

Bioethics-in-the-News-logoThis post is a part of our Bioethics in the News series. For more information, click here.

By Jennifer Carter-Johnson, PhD, JD

In an October report entitled “Breeding Out Disease,” 60 MINUTES correspondent Nora O’Donnell reported on the use of pre-implantation genetic diagnosis (PGD) to screen embryos produced during in vitro fertilization (IVF) procedures.i PGD allows doctors to determine if an embryo contains a gene that will lead to disease or increased risk of disease after birth. PGD currently can be used to screen for diseases caused by a single defective gene. Examples of such diseases include cystic fibrosis, Tay-Sachs, muscular dystrophy, sickle-cell anemia, hemophilia, and Huntington’s disease as well as certain types of cancer and some types of early onset Alzheimer’s. For parents who know that they carry a family risk of these diseases, PGD can relieve fear about some of the diseases that their child will face.

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Source: Flickr Creative Commons

The report also described a relatively newly developed patented process that can be used in concert with PGD. The process, and the company that sells the service, is called GenePeeks. GenePeeks uses DNA profiles from a potential set of parents to determine the likely genetic profiles of children from that couple. Couples can then use that information to determine the diseases towards which to direct any PGD screening. However, the patent for the GenePeeks process is written quite broadly and contemplates screening for not only diseases but also over 500 other traits such as eye shape and color, sex, the ability to roll one’s tongue, social intelligence and cognitive abilities.ii While prospective parents don’t quite have the technology to specifically pick and choose the traits, à la the movie Gattaca,iii they would be able to predict and select either for, or against, genetic traits that the child might possibly naturally inherit.

In spite of the peace of mind many prospective parents receive from using these two technologies, a host of ethical and regulatory issues surround them. For instance, the extent to which parents should have the ability to tailor the genetic traits of their children is completely unregulated. Additionally, the disposition of unused embryos is controversial; embryos with disease-causing mutations are usually discarded, and excess embryos are often frozen indefinitely. Other uses for excess embryos, such as stem cell research, are equally fraught with controversy. Beyond such embryonic issues, a cycle of IVF and PGD will cost around 20,000 dollars, making access to this aspect of reproductive technology and disease-screened offspring a luxury. Also, once the DNA of a parent or child is sequenced, the potential exists for insurance companies and employers to discriminate based on genetic profile, and databases of DNA profiles could additionally be matched against forensic data from crime scenes.

In light of these potential problems, Nora O’Donnell interviewed two of the developers and patent owners related to the technology. She independently asked each one what regulations should be in place to keep PGD and GenePeeks limited to disease testing. The responses of the two men interviewed were essentially the same – and essentially wrong. Each explained that due to patent exclusivity few can practice the technology. Both doctors promised to act as gatekeepers for the technology and use it exclusively for screening for disease in embryos and conducting related disease research, rather than crafting designer children – even though such designer activities were explicitly described in the GenePeeks patent. “Trust us,” seemed to be the echoing cry.

However, the number of people who can sell a technology at a given moment has little bearing on whether a technology will need to be regulated. The number of patients GenePeeks and the PGD firm see each year number in thousands. Moreover, patents can be licensed broadly fairly quickly, increasing the reach of the technology even further. Once the patents expire, twenty years after filing, everyone will be free to offer the service for sale. More importantly, and problematically, the issuance of a patent does not indicate that a technology is being used ethically.

Patent law is technologically neutral. In 1980, in the case of Diamond v. Chakrabarty, the Supreme Court determined that “anything under the sun that is made by man” can be patented so long as the new technology is useful, novel and non-obvious. The Chakrabarty case dealt with the patentability of genetically modified bacteria and is credited with ushering in the biotechnology industry.

Furthermore, the same Chakrabarty Court recognized that patents may incentivize technology that needs regulation. In the discussion of the technology underlying genetically modified bacteria, the Chakrabarty Court contemplated a “parade of horribles” that could result if this underlying genetic technology were patented and encouraged. Among the potential problems discussed were the spread of pollution and disease, loss of genetic diversity and a devaluation of human life. The Chakrabarty Court then invited legislatures to pass any laws to regulate this new biotechnology by a “balancing of competing values and interests.”

Congress and various administrative agencies have answered that invitation in a myriad of circumstances and in as many distinct ways. Concerns over cloning and human ownership led Congress to forbid any patents directed toward a human organism.v The development of genetically modified crops and animals resulted in a multi-agency co-operative regulatory regime encompassing the Food and Drug Administration (FDA), the US Department of Agriculture and the Environmental Protection Agency.vi The Genetic Information Nondiscrimination Act (GINA) of 2008 prohibited discrimination in health coverage and employment based on genetic information.vii The FDA has promulgated rules for DNA research and the safety and efficacy of the resulting new biologics as well as the informed consent of volunteers for related clinical trials.  This oversight has not been limited to Federal laws and regulations as state legislatures have dealt with family law issues such as surrogacy agreementsviii and ownership of frozen embryos.ix

As the PGD and GenePeeks technologies develop, so too must the laws and regulations surrounding their use. Recently, the FDA announced new guidelines for proving the safety and accuracy of genetic tests. However, testing accuracy does not address whether the tests should be used in a capacity beyond disease diagnosis. As these technologies demonstrate, inventors and patent owners may be smart, and ethical, but they do not necessarily speak for all segments of society and they are at least in part generally profit-driven. Society needs to consider precisely potential problems beyond technical ability and rather than waiting to react, judiciously guide a growing industry.

References:

Breeding Out Disease, 60 MINUTES. Last accessed at http://www.cbsnews.com/news/breeding-out-disease-with-reproductive-genetics/.

ii  Method and system for generating a virtual progeny genome, Patent #8620594 (filed Aug 22, 2012).

iii Gattaca, Sony Pictures Entertainment (1997).

iv  Diamond v. Chakrabarty, 447 U.S. 303 (1980).

America Invents Act of 2011 (Pub. L. 112–29, § 33,Sept. 16, 2011, 125 Stat. 340(enacted September 22, 2011).

vi Emily Marden, Risk and Regulation: U.S. Regulatory Policy on Genetically Modified Food and Agriculture, 44 B.C.L. Rev. 733 (2003).

vii Genetic Information Nondiscrimination Act of 2008 Pub.L. 110–233, 122 Stat. 881 (enacted May 21, 2008).

viii Guide to State Surrogacy Laws. Last accessed at https://www.americanprogress.org/issues/women/news/2007/12/17/3758/guide-to-state-surrogacy-laws/.

ix  See, e.g., Szafranski v. Dunston, 993 N.E.2d 502 (2013).

Jennifer Carter-Johnson, PhD, Jj-carter-johnsonD, is an Associate Professor of Law in the College of Law at Michigan State University. Dr. Carter-Johnson is a member of the Michigan State Bar and the Washington State Bar. She is registered to practice before the U.S. Patent and Trademark Office.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, December 4, 2014. With your participation, we hope to create discussions rich with insights from diverse perspectives.

You must provide your name and email address to leave a comment. Your email address will not be made public.

Mighty mitochondria: a tiny organelle that can, and should, save lives

Bioethics-in-the-News-logoThis post is a part of our Bioethics in the News series. For more information, click here.

By Monica List, DVM, MA

A June 3rd headline from The Guardian reads: “Genetic treatment using three-parent embryos may be ready in two years.” This provocative headline surely raised many hackles. The thought of genetically modifying humans commonly produces a visceral reaction, even in those who in principle are not opposed to genetic modification. Perhaps this visceral reaction is well founded; after all, it is one thing to tinker with the genome of a corn plant to make it more resistant to pests or drought, but to modify the genetic code of human beings may change what it means to be human.

This deeply ingrained fear of genetic modification in humans may be responsible in part for negative reactions to proposals to conduct Phase 1 clinical research trials for mitochondrial replacement, the novel procedure that this Guardian article refers to. Mitochondrial replacement involves the replacement of defective maternal mitochondria with mitochondria from a healthy female donor.

DNAMitochondria, the cellular organelles that act as tiny powerhouses, are always inherited from the mother. An interesting feature of mitochondria is that they have their own form of DNA, mtDNA, which consists of 37 genes, an insignificant amount relative to the estimated 25,000 genes that make up the human genome. However in some women mitochondria carry mutations that may result in severe and often fatal disease in their children. (Callaway, 2014)

While maternal carriers can appear to be perfectly healthy, mtDNA is much more susceptible to mutation – it mutates about 1000 times faster than chromosomal DNA – so when defective mtDNA is passed on to the offspring the effects of those mutations can manifest as mitochondrial disease. Among other conditions, mitochondrial disease, for which currently there is no treatment, can result in kidney disease, blindness, deafness, neurological problems, and dementia. (Nuffield Council on Bioethics, 2012)

Two mitochondrial replacement techniques, maternal spindle transfer and pronuclear transfer, have been developed but the idea behind mitochondrial replacement is far from new. Researchers started performing pronuclear transfers in mice back in the 1980s. More recently, research has been conducted on maternal spindle transfer in rhesus macaques, producing five healthy monkeys. Currently, a research team at Newcastle University has been performing pronuclear transfers on healthy, fertilized human eggs. To date they have performed around 100 successful transfers. (Callaway, 2014)

While experimental treatment could offer those mothers who are carriers of abnormal mitochondria the possibility of having a healthy child, ethical and legal controversy could prevent this procedure from moving forward to the clinical trial phase. In the UK, the law prohibits any procedure involving the modification of a person’s DNA. This means that although the described procedure could be ready to go to clinical trial in 18-24 months, the law first would have to be modified for this to occur. According to an article published in The Washington Post, in February of this year a US FDA expert advisory panel held a two-day meeting to discuss the issue. Although the FDA has not yet released official comments, the advisory panel recommended that a public hearing be held.

Most of the arguments against the use of this procedure in humans involve some sort of slippery slope scenario: allowing mitochondrial replacement will inevitably lead to cloning, designer babies, and other horrors worthy of a dystopian fiction novel. These arguments easily can be countered by referring to the scientific facts underlying mitochondrial replacement. First, as previously pointed out, mtDNA is distinct from chromosomal DNA, and as such mtDNA is not responsible for a person’s genotypic or phenotypic characteristics. Second, mitochondrial replacement does not involve genetic modification. No individual genes are being altered or replaced. What are being transferred from donor to recipient are cellular organelles. So in a way, it is a form of micro-organ donation, and not genetic modification.

A more interesting set of arguments against mitochondrial replacement raises questions pertinent to research ethics, for example, those related to risk/benefit ratio, and boundaries between research and clinical practice. On the surface the risk/benefit analysis does not seem too problematic. To begin with, extensive preliminary research has been conducted successfully on animal models; moreover, no other treatment options are currently available for mitochondrial disease patients. The next logical step would be to conduct Phase 1 clinical trials. A report from the Nuffield Council on Bioethics seems to agree with this approach, stating: “subject to appropriate oversight, it is ethical to gather further information about these techniques, in order that they can be considered for treatment use.” (Nuffield Council on Bioethics, 2012) However, the risk/benefit analysis may not be so simple, considering that the procedure being tested not only will affect the involved subject, but also potentially the subject’s future offspring. We may be facing a whole new set of ethical questions related to intergenerational risk/benefit analysis.

Even more ethically problematic than the risk/benefit issue is the matter of establishing effective boundaries between research and clinical practice. In this case there is little distinction to be made; consenting subjects would be enrolling in a trial that offers them the only option to bear a healthy child. While it may be clear to those subjects that they are in fact participating in research, due to the nature of the procedure as well as to the desired outcome (a healthy baby) it is plausible to think that researchers and clinicians will work together very closely to monitor the process, thereby blurring, more than usual, accepted boundaries between research and practice.

These and other important ethical questions should be seriously considered, but in and of themselves they should not prevent mitochondrial replacement research from moving forward, especially when serious suffering and untimely death can be prevented. What is unnecessarily distracting is the moral panic related to the possibility of this research leading to genetic modification of chromosomal DNA. Hopefully, for now that panic will remain confined to the pages of science fiction novels.

References:

Callaway, E. Reproductive medicine: the power of three. Nature 509 (7501). May 21, 2014. http://www.nature.com/news/reproductive-medicine-the-power-of-three-1.15253#/video

Clark, Stuart. Genetic treatment using three-parent embryo may be ready in two years. The Guardian. Published online June 3, 2014.
http://www.theguardian.com/science/2014/jun/03/genetic-treatment-mitochondrial-replacement-three-parent-embryo-dna-law

Eunjung Cha, Ariana and Sandhya Somashekhar. FDA panel debates technique that would create embryos with three genetic parents. The Washington Post. Online, February 25, 2014. http://www.washingtonpost.com/national/health-science/fda-panel-debates-technique-that-would-create-embryos-with-three-genetic-parents/2014/02/25/60371c58-9e4d-11e3-b8d8-94577ff66b28_story.html

Mitalipov, S. et al. Limitations of Preimplantation Genetic Diagnosis for Mitochondrial DNA Diseases. Cell Reports, 7 (4): 935 – 937. May 22, 2014.

Nuffield Council on Bioethics. Summary of report. Novel techniques for the prevention of mitochondrial DNA disorders: an ethical review. June 12, 2012. Available online: http://nuffieldbioethics.org/sites/default/files/Mitochondrial_DNA_disorders_summary_web.pdf

list-cropMonica List, DVM, MA, is a doctoral student in the Department of Philosophy at Michigan State University. She earned a veterinary medicine degree from the National University of Costa Rica in 2002, and an MA degree in bioethics, also from the National University, in 2011.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, July 10, 2014. With your participation, we hope to create discussions rich with insights from diverse perspectives. You must provide your name and email address to leave a comment. Your email address will not be made public.

Welcome to FDA Enforcement

Bioethics-in-the-News-logoThis post is a part of our Bioethics in the News series. For more information, click here.

By Kayte Spector-Bagdady, J.D., M.Bioethics

 “This is me, my DNA. It helps make me who I am…I might have an increased risk of heart disease, arthritis, gallstones, hemochromatosis…hundreds of things about my health. Getting my 23andMe results, it really opened my eyes. The more you know about your DNA, the more you know about yourself. I do things a little differently now…”

On November 22, 2013, 23andMe (the leading direct-to-consumer (DTC) genetic testing company), received a “Warning Letter” from FDA—a first for the DTC genetic testing industry. In this letter, FDA requested that 23andMe discontinue marketing its personal genome service until further authorization and end its TV campaign excerpted above (now the YouTube video is marked “private”). 23andMe’s official FDA response might not be public, but on December 5, 2013, 23andMe did announce publicly that it was going to stop selling new customers its DTC health-related genetic test. Unlike, for example, an X-ray, “DTC” tests are those available directly to purchasers, like a pregnancy test. While there are many benefits to having certain diagnostic tests available directly to consumers without a trained intermediary, there are also concerns about giving laypersons medical information without specific guidance from a healthcare practitioner.

This is not the DTC genetic testing industry’s first tango with the U.S. federal government. In 2006 the Government Accountability Office (GAO) released a report on nutrigenetic testing which found that companies were selling $1,200/year vitamins (actually worth $35/year in a local drug store) to “fix” DNA. In 2010 a GAO investigator was advised by an industry representative that her BRCA mutation, associated with an increased risk of breast cancer, meant that she was “in the high risk of pretty much getting” the disease (GAO did not reveal company identities for either of its reports).

In fact, just a few years ago, nearly thirty DTC companies offered 400 discrete genetic tests—until Pathway Genomics announced in 2010 that it was going to start offering its previously web-based product in Walgreens across the country. This got the attention of FDA, which eventually sent 23 “Untitled Letters” (for a violation not quite as significant as those triggering a “Warning Letter”) stating that these products were in fact medical devices and had to receive FDA clearance or approval. Soon thereafter many DTC genetic testing companies either altered their model by requiring a physician order or collapsed entirely—leaving 23andMe to dominate the industry.

In 2007, 23andMe offered thirteen health reports for $999. As of December 2, 2013, 23andMe offered over 250 health reports for $99—including reports regarding a higher risk for Alzheimer’s Disease to whether your cilantro will taste soapy—all in a colorful box promising “Welcome to you.”

As of today, for the same $99, 23andMe is selling an analysis of your ancestral origins and lineage  and “raw genetic data” “without 23andMe’s interpretation” but have suspended their health-related genetic information service “to comply with [FDA’s] directive to discontinue new consumer access during our regulatory review process.”

FDA’s jurisdiction hinges on whether the 23andMe’s product can appropriately be considered a medical device under the Food, Drug, and Cosmetic Act. There has been a lot of interesting debate in the tweetisblogosphere regarding whether 23andMe is marketing their test as their terms of service state, for “research and educational use only,” or, as the TV adds promised, to tell you “hundreds of things about your health” so you can do things “a little differently.” But another possible consequence of 23andMe canceling their health analysis is the unintended encouragement of a new DTC genetic industry—one providing genetic medical information only.

Last year, Gene By Gene started the trend by offering consumers genomic sequencing only: a raw data file of As, Ts, Cs, and Gs without any interpretation. Think this. But, for the majority of consumers, raw sequence data services require a parallel offering of interpretation-only services to provide a marketable product.

FDA has stated that it’s not interested in regulating raw genomic data as a medical device, but entities that provide genomic interpretation (see, e.g., openSNP) can reveal more sensitive medical information about an individual’s propensity to develop disease and pharmacogenomic information about the efficacy of particular drugs given a particular genetic makeup—which places these services squarely within FDA’s area of interest. 23andMe has always offered customers their raw data as part of its package, but it’s the genetic risk and drug responses (i.e., analyzed information) that FDA cited as concerning in its letter.

But just as FDA begins to seriously grapple with the DTC genetic testing industry, open-source, web-based platforms that interpret genomic data free of charge are going to pose further challenges to the limits of FDA’s ability to regulate (potentially non-commercial) speech, and effectively utilize enforcement mechanisms made for tangible money-making products on information and open-sourced platforms.

The interpretation of FDA’s Warning Letter may be clear, but the future of DTC genetic testing might instead lie in how you interpret the letters “A, T, C, and G.”

(Still interested? Read more on the topic from me and my co-author Lizzy Pike here).

References:

Letter from Alberto Gutierrez, Dir., Office of In vitro Diagnostics and Radiological Health, Ctr. for Devices & Radiological Health, Food & Drug Admin., U.S. Dep’t of Health & Human Services, to Ann[e] Wojcicki, C.E.O., 23andMe, Inc. (Nov. 22, 2013).

U.S. Gov’t Accountability Office, GAO-06-977T, Nutrigenic Testing: Tests Purchased from Four Web Sites Misled Consumers, Testimony Before the S. Special Comm. on Aging (July 27, 2006).

U.S. Gov’t Accountability Office, Highlights of GAO-10-847T, Direct-to-Consumer Genetic Tests: Misleading Results are Further Complicated by Deceptive Marketing and Other Questionable Practices (July 22, 2010).

kayte-spector-bagdadyKayte Spector-Bagdady, J.D., M.Bioethics, is Associate Director at the Presidential Commission for the Study of Bioethical Issues where she managed the Commission’s reports on Privacy and Progress in Whole Genome Sequencing and Anticipate and Communicate: Ethical Management of Incidental and Secondary Findings in the Clinical, Research, and Direct-to-Consumer Contexts.*

Join the discussion! Your comments and responses to this commentary are welcomed. The author will not, unfortunately be able to respond to all comments, but will read input with interest. With your participation, we hope to create discussions rich with insights from diverse perspectives. You must provide your name and email address to leave a comment. Your email address will not be made public.

* The findings and conclusions in this blog are those of the author and do not necessarily represent the official position of the Presidential Commission for the Study of Bioethical Issues or the Department of Health and Human Services. Use of official trade names does not mean or imply official support or endorsement by the author.