Tag: dna

Bioethics Blogs

Transferring Embryos with Genetic Anomalies

Jackie Leach Scully argues that respect for equality and diversity, and not just respect for the parental autonomy and the welfare of the future child, should inform policies governing the use of preimplantation genetic diagnosis.

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The Ethics Committee of the American Society for Reproductive Medicine recently published an Opinion on “Transferring embryos with genetic anomalies detected in preimplantation testing.” The Opinion aims to help providers deal with the rare but ethically difficult situation when prospective parents want to transfer embryos with a known genetic anomaly that is linked to a serious health-affecting disorder.

Preimplantation genetic diagnosis (PGD) is typically used by couples to avoid transferring a genetic anomaly to their children. Using PGD to ensure the transfer of a genetic anomaly, rather than avoid it, seems deeply counter-intuitive. Yet, there are several scenarios where this might happen. For example, this might be a reasonable option when the only transferable embryos carry the genetic anomaly, or when the embryos carry a different, but potentially just as serious, genetic variation.

The most problematic cases, however, occur when prospective parents express an actual preference for children with ‘their’ genetic condition – an anomalous condition that others perceive in negative terms. It’s an uncommon situation, but despite its rarity steps have been taken to block attempts by prospective parents to ‘choose disability’, such as the UK’s legislation on reproductive medicine. The legislation prohibits the use of an embryo (or gamete, in the case of egg and sperm donation) that has a genetic anomaly “involving a significant risk” of “a serious physical or mental disability, serious illness, or a serious medical condition” unless there are no other unaffected embryos or gametes that could be used instead.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Medical Decision-Making In the Tragic Life of Charlie Gard

by Craig Klugman, Ph.D.

On Friday, Charlie Gard is scheduled to have his life support discontinued. Charlie Gard is an 11-month-old baby born with RRM2B encephalomyopathic mitochondrial DNA depletion syndrome—a rare genetic disorder with no cure. Those with the mutation live at most into early childhood with a multitude of life threatening conditions (lactic acidosis, ammonia build up, heart abnormalities). Charlie suffers from seizures, cannot independently breathe. He is also blind and deaf. Great Ormond Street Hospital (London) and Charlie’s doctors believe there is nothing more medically that can be done to benefit him and requested to remove his life sustaining treatment. Connie Yates and Chris Gard, his parents, believe that there is a chance of a miraculous cure in an experimental nucleoside treatment in the United States, even though the technique has never been tried for this condition. In the words of the unnamed U.S. specialist, nucleoside treatment would provide a “small hope” for helping

The case has gone through the British courts and the European Court of Human Rights, all of which agreed with the hospital. They declared that prolonging Charlie’s life would be “inhumane and unreasonable.” The courts believed that the experimental treatment in the US would be futile and could cause Charlie much suffering. The European Court ruled on July 4 that life support can be removed on Friday.

Under British law, when parents and physicians disagree on treatment, the courts normally intervene and are the final decision-makers. Unlike in the US, the highest value is the best interest (benefit) to the child rather than parental rights to make decisions for their child.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

Legal status of human-animal chimeras – hybrid embryos

In addition to the biomedical problems raised by human-animal hybridization, there are also objective legal problems.

A recent article in the Journal of Medical Ethics (2014; 40, 284-285) reviewed this topic following a debate in the United Kingdom (UK) House of Lords in December 2012. The underlying problem is to determine whether hybrids containing human biological material, mainly DNA, should be considered partially human and if so, what their legal status should be.

See our Special Report New advances and challenges in the production of human-animal chimeras

The Human Fertilisation and Embryology Act 2008 (HFE Act 2008) regulates the legal aspects of human-animal hybrids. These hybrids refer to any embryo containing human nuclear or mitochondrial DNA as well as animal nuclear or mitochondrial DNA, but in which the animal DNA is not predominant. Other categories of hybrids can be legally regulated by the “Animal Act 1986”.

However, deciding which of the two categories into which hybrid embryos should fall is not that easy.

The English Health Minister, Lord Darzi of Denham, stated that hybrid embryos should be regulated by human statutes when they are considered to be “predominantly” human, which is not easy to determine. In fact, a chimeric embryo in which non-human cells were initially predominant could continue to develop into a hybrid in which human cells predominate.

Lord Darzi also stated that chimeric embryos that are “functionally” predominantly human should also be considered as human. However, the term “functionally human” is ambiguous, which complicates the issue of its legal status.

It was therefore concluded that the UK parliament needs to more definitively determine the legal status of embryos containing human and animal genetic material, following an extensive, in-depth debate that must take into account public opinion on this matter.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

The amazing finding of senescent cells in embryos. Until now, these cells had been found only in aging tissue

The discovery raises the possibility that the start and end of life are intimately connected

The process by which cells cease multiplying is known as senescence. In 1961, biologists Hayflick and Moorehead cryoconserved human fetal cells and found that these divide around 50 times and then simply stop doing so, as occurs in the human body (see recent article, AGING CELLS ARE KEY TO FINDING FOUNTAIN OF YOUTH)

In fact, senescent cells are involved in many of the signs of aging: wrinkled skin, cataracts, and arthritic joints, which are produced by the effect of an increase in these cells. On the contrary, it has been found that by decreasing senescent cells in mice, signs of rejuvenation can be detected in these animals.

Considering that in all research, senescent cells have been found only in old or damaged tissues, the last place one would expect to find them would be at the very beginning of life, in the embryo. Now, however, three scientific teams have reported that they have observed the same phenomenon at this point.

Senescent cells in embryos

For the first time, senescent cells have been found in embryos, and scientists have presented proof that senescence is crucial for their proper development.

This discovery raises the possibility that the start and end of life are intimately connected. In order for life to have a good start, senescent cells are needed, i.e. youth needs a little bit of old age.

Scott Lowe, an expert in senescence at Memorial Sloan-Kettering Cancer Center, who did not participate in the research, has lauded the studies, which point to the unexpected role of old age, and predicted that it would provoke a spirited debate between developmental biologists, who study how embryos are formed.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

In the Journals – June 2017, part two by Aaron Seaman

The first part of the In the Journals post for June 2017 can be found here. And now, for part two…

 

Medical Humanities

SPECIAL ISSUE: Communicating Mental Health

Introduction: historical contexts to communicating mental health

Rebecca Wynter and Leonard Smith

Contemporary discussions around language, stigma and care in mental health, the messages these elements transmit, and the means through which they have been conveyed, have a long and deep lineage. Recognition and exploration of this lineage can inform how we communicate about mental health going forward, as reflected by the 9 papers which make up this special issue. Our introduction provides some framework for the history of communicating mental health over the past 300 years. We will show that there have been diverse ways and means of describing, disseminating and discussing mental health, in relation both to therapeutic practices and between practitioners, patients and the public. Communicating about mental health, we argue, has been informed by the desire for positive change, as much as by developments in reporting, legislation and technology. However, while the modes of communication have developed, the issues involved remain essentially the same. Most practitioners have sought to understand and to innovate, though not always with positive results. Some lost sight of patients as people; patients have felt and have been ignored or silenced by doctors and carers. Money has always talked, for without adequate investment services and care have suffered, contributing to the stigma surrounding mental illness. While it is certainly ‘time to talk’ to improve experiences, it is also time to change the language that underpins cultural attitudes towards mental illness, time to listen to people with mental health issues and, crucially, time to hear.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

The Moral Question That Stanford Asks Its Bioengineering Students

June 28, 2017

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When students in Stanford University’s Introduction to Bioengineering course sit for their final exams, the first question that they have to answer is about our ability to write DNA.

Scientists have fully sequenced the genomes of humans, trees, octopuses, bacteria, and thousands of other species. But it may soon become possible to not just readlarge genomes but also to write them—synthesizing them from scratch. “Imagine a music synthesizer with only four keys,” said Stanford professor Drew Endy to the audience at the Aspen Ideas Festival, which is co-hosted by the Aspen Institute and The Atlantic. Each represents one of the four building blocks of DNA—A, C, G, and T. Press the keys in sequence and you can print out whatever stretch of DNA you like.

In 2010, one group did this for a bacterium with an exceptionally tiny genome, crafting all million or so letters of its DNA and implanting it into a hollow cell. Another team is part-way through writing the more complex genome of baker’s yeast, with 12 million letters. The human genome is 300 times bigger, and as I reported last month, others are trying to build the technology that will allow them to create genomes of this size.

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The Atlantic

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Huntington’s Disease: Gene Editing Shows Promise in Mouse Studies

My father was a folk song collector, and I grew up listening to the music of Woody Guthrie. On July 14th, folk music enthusiasts will be celebrating the 105th anniversary of Guthrie’s birth in his hometown of Okemah, OK. Besides being renowned for writing “This Land is Your Land” and other folk classics, Guthrie has another more tragic claim to fame: he provided the world with a glimpse at the devastation caused by a rare, inherited neurological disorder called Huntington’s disease.

When Guthrie died from complications of Huntington’s a half-century ago, the disease was untreatable. Sadly, it still is. But years of basic science advances, combined with the promise of innovative gene editing systems such as CRISPR/Cas9, are providing renewed hope that we will someday be able to treat or even cure Huntington’s disease, along with many other inherited disorders.

My own lab was part of a collaboration of seven groups that identified the Huntington’s disease gene back in 1993. Huntington’s disease occurs when a person inherits from one parent a mutant copy of the huntingtin (HTT) gene that contains extra repetitions, or a “stutter,” of three letters (CAG) in DNA’s four-letter code. This stutter leads to production of a misfolded protein that is toxic to the brain’s neurons, triggering a degenerative process that, over time, leads to mood swings, slurred speech, uncontrolled movements, and, eventually, death. In a new study involving a mouse model of Huntington’s disease, researchers were able to stop the production of the abnormal protein by using CRISPR tools to cut the stutter out of the mutant gene.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Responsibility in the age of precision genomics

by Alexa Woodward

Alexa is a fellow in the Precision Medicine: Ethics, Policy, and Culture project through Columbia University’s Center for the Study of Social Difference. The following is her reflection on the ongoing discussion around the Precision Medicine Initiative that has been the subject of recent political, social, and popular media attention. A recent presentation by Sandra Soo-Jin Lee, PhD, from the Center for Biomedical Ethics at Stanford University spurred our multi-disciplinary discussion of some of the following themes.

What is normal, anyway?

Genetically speaking, that’s precisely the question that the Obama administration’s Precision Medicine Initiative (PMI) seeks to answer. In recruiting and collecting comprehensive genetic, medical, behavioral, and lifestyle data from one million Americans, the scientific and medical communities will be better able to understand what constitutes normal genetic variation within the population, and in turn, what amount of variation causes or contributes to disease or disease risk.[1] Using this data, researchers could potentially create tailored approaches for intervention and treatment of an incredible range of diseases.

The PMI has a secondary aim: to increase the representation of previously underrepresented populations in research – primarily African Americans and Hispanics/Latinos. Inclusion of these groups in research has been a challenge for decades, with lack of access, distrust in the medical and research systems, and institutionalized racism all playing exclusionary roles. More broadly, outside of the government initiative, the promise of precision medicine ultimately seeks to alleviate disparities by finding and addressing supposed genetic differences, and empowering people with information to take responsibility for their health.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

New Concerns Raised Over Value of Genome-Wide Disease Studies

June 21, 2017

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Compare the genomes of enough people with and without a disease, and genetic variants linked to the malady should pop out. So runs the philosophy behind genome-wide association studies (GWAS), which researchers have used for more than a decade to find genetic ties to diseases such as schizophrenia and rheumatoid arthritis. But a provocative analysis now calls the future of that strategy into question — and raises doubts about whether funders should pour more money into these experiments.

GWAS are fast expanding to encompass hundreds of thousands, even millions, of patients (see ‘The genome-wide tide’). But biologists are likely to find that larger studies turn up more and more genetic variants — or ‘hits’ — that have minuscule influences on disease, says Jonathan Pritchard, a geneticist at Stanford University in California. It seems likely, he argues, that common illnesses could be linked by GWAS to hundreds of thousands of DNA variants: potentially, to every single DNA region that happens to be active in a tissue involved in a disease.

In a paper published in Cell on 15 June1, Pritchard and two other geneticists suggest that many GWAS hits have no specific biological relevance to disease and wouldn’t serve as good drug targets. Rather, these ‘peripheral’ variants probably act through complex biochemical regulatory networks to influence the activity of a few ‘core’ genes that are more directly connected to an illness.

… Read More

Image via Flickr Attribution Some rights reserved by The Moonstone Archive

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The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Precision Oncology: Gene Changes Predict Immunotherapy Response

Caption: Adapted from scanning electron micrograph of cytotoxic T cells (red) attacking a cancer cell (white).
Credits: Rita Elena Serda, Baylor College of Medicine; Jill George, NIH

There’s been tremendous excitement in the cancer community recently about the life-saving potential of immunotherapy. In this treatment strategy, a patient’s own immune system is enlisted to control and, in some cases, even cure the cancer. But despite many dramatic stories of response, immunotherapy doesn’t work for everyone. A major challenge has been figuring out how to identify with greater precision which patients are most likely to benefit from this new approach, and how to use that information to develop strategies to expand immunotherapy’s potential.

A couple of years ago, I wrote about early progress on this front, highlighting a small study in which NIH-funded researchers were able to predict which people with colorectal and other types of cancer would benefit from an immunotherapy drug called pembrolizumab (Keytruda®). The key seemed to be that tumors with defects affecting the “mismatch repair” pathway were more likely to benefit. Mismatch repair is involved in fixing small glitches that occur when DNA is copied during cell division. If a tumor is deficient in mismatch repair, it contains many more DNA mutations than other tumors—and, as it turns out, immunotherapy appears to be most effective against tumors with many mutations.

Now, I’m pleased to report more promising news from that clinical trial of pembrolizumab, which was expanded to include 86 adults with 12 different types of mismatch repair-deficient cancers that had been previously treated with at least one type of standard therapy [1].

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.