Tag: genotype

Bioethics Blogs

Snapshots of Life: Muscling in on Development

Credit: Gabrielle Kardon, University of Utah, Salt Lake City

Twice a week, I do an hour of weight training to maintain muscle strength and tone. Millions of Americans do the same, and there’s always a lot of attention paid to those upper arm muscles—the biceps and triceps. Less appreciated is another arm muscle that pumps right along during workouts: the brachialis. This muscle—located under the biceps—helps your elbow flex when you are doing all kinds of things, whether curling a 50-pound barbell or just grabbing a bag of groceries or your luggage out of the car.

Now, scientific studies of the triceps and brachialis are providing important clues about how the body’s 40 different types of limb muscles assume their distinct identities during development [1]. In these images from the NIH-supported lab of Gabrielle Kardon at the University of Utah, Salt Lake City, you see the developing forelimb of a healthy mouse strain (top) compared to that of a mutant mouse strain with a stiff, abnormal gait (bottom).

In each strain, you see the lateral triceps and brachialis muscles (purple), other types of muscle (red) and tendons (green). However, in the healthy mouse, the lateral triceps and brachialis muscles are distinct, which gives the forelimb its flexibility; while in the mutant mouse, the two muscles are fused and indistinct, limiting the forelimb’s function.

The mice with the abnormal lateral triceps and brachialis have a mutation in a gene called Tbx3, which codes for a transcription factor that switches other genes off and on. If you follow this blog, you know that a lot of exciting research is currently focused on transcription factors, including how precise combinations of transcription factors can turn skin cells into blood stem cells or be used to make neurons.

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

DNA papers, please

Kuwait is planning to build a complete DNA database of not just citizens but all other residents and temporary visitorsThe motivation is claimed to be antiterrorism (the universal motivation!) and fighting crime. Many are outraged, from local lawyers over a UN human rights committee to the European Society of Human Genetics, and think that it will not be very helpful against terrorism (how does having the DNA of a suicide bomber help after the fact?) Rather, there are reasons to worry about misuse in paternity testing (Kuwait has strict adultery laws),  and in the politics of citizenship (which provides many benefits): it is strictly circumscribed to paternal descendants of the original Kuwaiti settlers, and there is significant discrimination against people with no recognized paternity such as the Bidun minority. Plus, and this might be another strong motivation for many of the scientists protesting against the law, it might put off public willingness to donate their genomes into research databases where they actually do some good. Obviously it might also put visitors off visiting – would, for example, foreign heads of state accept leaving their genome in the hands of another state? Not to mention the discovery of adultery in ruling families – there is a certain gamble in doing this.

Overall, it seems few outside the Kuwaiti government are cheering for the law. When I recently participated in a panel discussion organised by the BSA at the Wellcome Collection about genetic privacy, at the question “Would anybody here accept mandatory genetic collection?” only one or two hands rose in the large audience. When

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

FDA OKs Epclusa, First Drug for All Major Forms of HCV

June 28, 2016

(Medscape) – The US Food and Drug Administration (FDA) has approved the combination drug of sofosbuvir and velpatasvir (Epclusa, Gilead Sciences) for adults with chronic hepatitis C virus (HCV) infection, the first one to treat all six major genotypes of the infection, the agency announced today. The new drug’s broad coverage could make it a one-size-fits-all therapy suitable for primary care. Gilead Sciences President and CEO John Gilliland said in a news release that sofosbuvir/velpatasvir could eliminate the need for genotype testing, “which can be a barrier to treatment in certain resource-constrained settings.”

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

Storage and stockpiling as techniques of preparedness: Managing the bottlenecks of flu pandemics by Frédéric Keck

In the last twenty years, influenza has been considered by global health experts as a model for the emergence of new pathogens from animal reservoirs. In the logic of zoonoses, human disease is the tip of the iceberg constituted by a wide circulation of viruses – often asymptomatic – in animals; it is often described as an “evolutionary dead-end”. As the influenza virus is composed of a single-stranded segmented RNA, it mutates and reassorts between birds and pigs before spreading to humans and causing pandemics. The regularity of flu pandemics – 1918, 1957, 1968, 2009 – is explained by that the fact that the seasonal flu is replaced regularly by new flu viruses to which humans have no immunity. Consequently, to prepare for the emergence of new flu viruses, events whose probability cannot be calculated but whose consequences are catastrophic, samples have been stored and vaccines have been stockpiled, as if the iceberg of the animal reservoir could be visualized and controlled in the fridges where humans conserve live and attenuated viruses. Storage allows public health authorities to identify a new virus as it emerges by comparison with circulating viruses, and then to raise alarm from this early warning signal. Stockpiling provides a quick immunization of the population considered as having priority in the exposure to the new virus.

I am interested in storage and stockpiling as techniques to plan and visualize the mutations of flu viruses in the ordinary work of global health, in contrast with the extraordinary management of health crises. While stamping out the animal reservoir and vaccinating the human population are techniques used during the emergence of new flu viruses, storing samples and stockpiling vaccines is practiced before and after the emergence, as part of ordinary surveillance work.

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

UK Researchers Now Say Three-Person Embryo Technique Doesn’t Work; Propose New Method

In February 2015, the UK decided to create a controversial exception to its law against any form of human germline modification to allow the creation of “three-person embryos” to prevent the transmission of some mitochondrial disease. Then and now, unresolved scientific concerns remained, and many people have been waiting to see whether the science will indeed come through.

Adding to anxiety to see these data is the enormous global attention on a different technology proposed for human genetic modification: the gene editing technique CRISPR, and current controversy over varied attempts to try it on human embryos.

However, there is only one central place where the mitochondrial research is being carried out in the UK – the Wellcome Trust Centre for Mitochondrial Research at Newcastle University. But despite opening its doors in 2012 and encouraging excitement about the importance of  this research, none of the specific research requested by the Human Fertilisation and Embryology Authority (HFEA) had been published until now.

Today, that changed. Well-known Newcastle researchers including Mary Herbert and Douglass Turnbull have just published an update to their six-years-old Nature paper, which originally described how their preferred form of mitochondrial replacement – pronuclear transfer (PNT) – “has the potential to prevent the transmission of mtDNA disease in humans.”

Shockingly, their new paper reports that the proof-of-concept studies upon which everyone had been basing their enthusiasm “were not well tolerated by normally fertilized zygotes.” In other words, the scientific basis for the controversial UK law and HFEA policy change turns out to have been unfounded. It did not work.

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

Gene Duplication: New Analysis Shows How Extra Copies Split the Work

The human genome contains more than 20,000 protein-coding genes, which carry the instructions for proteins essential to the structure and function of our cells, tissues and organs. Some of these genes are very similar to each other because, as the genomes of humans and other mammals evolve, glitches in DNA replication sometimes result in extra copies of a gene being made. Those duplicates can be passed along to subsequent generations and, on very rare occasions, usually at a much later point in time, acquire additional modifications that may enable them to serve new biological functions. By starting with a protein shape that has already been fine-tuned for one function, evolution can produce a new function more rapidly than starting from scratch.

Pretty cool! But it leads to a question that’s long perplexed evolutionary biologists: Why don’t duplicate genes vanish from the gene pool almost as soon as they appear? After all, instantly doubling the amount of protein produced in an organism is usually a recipe for disaster—just think what might happen to a human baby born with twice as much insulin or clotting factor as normal. At the very least, duplicate genes should be unnecessary and therefore vulnerable to being degraded into functionless pseudogenes as new mutations arise over time

An NIH-supported team offers a possible answer to this question in a study published in the journal Science. Based on their analysis of duplicate gene pairs in the human and mouse genomes, the researchers suggest that extra genes persist in the genome because of rapid changes in gene activity.

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

Michael Tomasello, A Natural History of Human Morality, Harvard University Press, 2016

The dust jacket to A Natural History of Human Morality advertises “the most detailed account to date of the evolution of human moral psychology.” Reading this description, you might expect a hefty, multi-volume work filled with mitochondrial maps, genotype to fitness landscapes, and appendix after appendix of experimental results. Thankfully, you will find none of these things within this slim, breezy, 163-page monograph. What you will find could be better described as an “introduction” or an “outline” to an ongoing research program, which may very well become the “the most detailed account…of the evolution of human moral psychology” that we can hope for. But the greatest virtue of A Natural History of Human Morality, to my mind, is its merciful lack of detail. Tucked between its narrow covers is a simple yet engaging story about the emergence of a new kind of cooperation among upright apes, which we call “morality.”

With its welcomed brevity and immanent readability, this book can be enjoyed by just about anyone. However, it will probably appeal most to readers who have neither the time nor the background to keep up with the many articles that Michael Tomasello publishes every year, but who want to find out what all the hubbub is about. If you’ve never read a book on the evolution of morality before, there’s no better place to begin. For those of you who have kept up with Tomasello’s work over the years, you’ll find little that you don’t already know, but you will walk away with a clearer understanding of what he’s up to and where his project is headed.

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

DNA Barcodes Could Streamline Search for New Drugs to Combat Cancer

A little more than a decade ago, researchers began adapting a familiar commercial concept to genomics: the barcode. Instead of the black, printed stripes of the Universal Product Codes (UPCs) that we see on everything from package deliveries to clothing tags, they used short, unique snippets of DNA to label cells. These biological “barcodes” enable scientists to distinguish one cell type from another, in much the same way that a supermarket scanner recognizes different brands of cereal.

DNA barcoding has already empowered single-cell analysis, including for nerve cells in the brain. Now, in a new NIH-supported study, DNA barcoding helps in the development of a new method that could greatly streamline an increasingly complex and labor-intensive process: screening for drugs to combat cancer.

The new method, reported recently in the journal Nature Biotechnology, is called PRISM, short for Profiling Relative Inhibition Simultaneously in Mixtures [1]. In their trial run of PRISM, the researchers uniquely barcoded more than 100 cancer cell lines. This allowed them to pool the cell lines and screen them all at the same time (instead of individually) against each of thousands of potential drug compounds, to see which, if any, of the barcoded cells they had the power to kill. This proof of concept suggests that PRISM, with further refinements, could help to accelerate cancer drug discovery and bring greater precision to the screening process.

This innovative research was led by the lab of Todd Golub of the Broad Institute of MIT and Harvard, Cambridge, MA. PRISM consists of two key components.

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

I had to laugh…

I had to laugh. A recent article in Annals of Internal Medicine describes an experiment to determine the “safety and behavioral effect” of disclosing to subjects the pleiotropic effect of the APOE genotype. Pleiotropy describes genes that have more than one effect.  In this case, having the APOE4 version of the gene heightens one’s risk of Alzheimer’s Disease, and also of coronary disease. The researchers concluded that participants could, indeed, handle the information that their genotype also conferred an increased risk of cardiac disease.  I was laughing because, not too long ago, the shoe was on the other foot. In the late 1990s, the pleiotropic nature of APOE4 was a favorite dilemma for bioethicists, for the opposite reason. Most people assumed that it was beneficial to tell people of their increased cardiac risk, given available medication and lifestyle changes, but as Robert Wachbroit wrote, it was ‘medically useless and socially harmful’ to reveal an increased risk for AD. It’s interesting that the perception has flipped, given that we still have no effective interventions for Alzheimer’s Disease.

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 December 2015 – Part II by Melanie Boeckmann

Find the first half of December’s post here.

New Genetics and Society

Beyond and within public engagement: a broadened approach to engagement in biobanking

Jose A. Cañada, Aaro Tupasela, Karoliina Snell

Social studies on biobanking have traditionally focused on public engagement, that is, engagement with donors, patients and the general public as an important factor of sustainability. In this article, we claim that, in order to fully understand the way biobanks work, it is necessary to pay attention to a number of other actors, which have an equal, if not greater, impact on their practices and strategies. This means taking a broadened approach to biobank engagement. By using data collected from interviews with different biobank experts based in five different countries (UK, Canada, Finland, Spain and Iceland), we identify seven communities, including the public, that emerge as relevant. Such relationships condition the way biobanks develop, act and plan. The discussion illustrates how the relationships with those seven communities are articulated. We conclude that there is a need for a broadened approach to biobank engagement in order to understand biobank sustainability.

Adoptable packages and the cost of their adoption: the craftwork of making the right cells for regenerative medicine in Japan

Koichi Mikami

The goal of regenerative medicine is to utilize biological properties of cells for therapeutic purposes. Although substantial international investment has been made in this biomedical technology, the issue of which type of cells best serves for these purposes still remains unsettled. Adopting a conceptual framework from Clarke and Fujimura that the rightness of “tools” needs to be socially constructed, this paper examines the interactions of various actors in Japan and demonstrates two kinds of craftwork as examples of attempts to construct the rightness of the cells for the technology.

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.