Tag: thalassemia

Bioethics News

The First US Team to Gene-Edit Human Embryos Revealed

July 28, 2017

Be the first to like.
Share

Since Chinese researchers announced the first gene editing of a human embryo 2 years ago, many expected that similar work in the United States was inevitable. Last night, the MIT Technology Review broke the news that such experiments have happened. The research, led by embryologist Shoukhrat Mitalipov of Oregon Health and Science University in Portland, also reportedly sidestepped problems of incomplete and off-target editing that plagued previous attempts, though details could not be confirmed since the work is not yet published and Mitalipov has so far declined to comment.

If a peer-reviewed paper bears out the news story, “It’s one more step on the path to potential clinical application,” says bioethicist Jeffrey Kahn of Johns Hopkins University in Baltimore, Maryland, who served on a committee convened by the U.S. National Academy of Sciences (NAS) and the National Academy of Medicine in Washington, D.C., to address gene editing. The panel’s report earlier this year concluded that a clinical trial involving embryo editing would be ethically allowable under narrow circumstances.

The first published human embryo–editing work, in 2015, used nonviable embryos and targeted a gene mutated in the heritable blood disorder beta thalassemia. But it revealed major shortcomings in applying the increasingly popular CRISPR gene-editing technology. The few embryos that took up the change made by CRISPR were a patchwork of edited and unchanged cells, and they bore unintended edits outside the targeted gene.

… Read More

Be the first to like.
Share

Science Magazine

Tags: , , , , , , , , ,

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

Ten years since the discovery of iPS cells. The current state of their clinical application

Photo Neurons derived from human iPS cells Stem Cells Australia

Background

Few biomedical discoveries in recent decades have raised so many expectations as the achievement of adult reprogrammed cells or induced pluripotent stem (iPS) cells.1

Pluripotent cells are obtained from adult cells from various tissues that, after genetic reprogramming, can dedifferentiate to a pluripotency state similar to that of embryonic cells, which allows for subsequent differentiation into different cell strains.2,3

In our opinion, this discovery is relevant not only to biomedical issues but also to ethical ones, given that iPS cells could replace human embryonic stem cells (see HERE) – whose use raises numerous ethical problems – in biomedical experimentation and in clinical practice. However, after the last 10 years, the use of iPS cells has still not been clarified. A number of expectations have been met, but other mainly clinical expectations are still far from being achieved.

Current research limitations with iPS cells

There is a notable low efficacy in the techniques employed for obtaining a sufficient proportion of iPS cells, which represents a difficulty in its clinical application.4  Another limitation is the incomplete reprogramming, which depends on the type of cell employed,5 and the problems of mutagenesis resulting from inserting exogenous transcription-factor coding genes, which can cause tumors in the employed cells used.6 Recent studies aim to mitigate this effect.7 A clinical trial for treating macular degeneration with retinal pigment epithelium cells derived from autologously obtained iPS cells has recently been halted.8 After an initially successful experience with the first treated patient, the genetic sequencing of the iPS cells obtained from the second patient revealed mutations in 3 different genes, one of which was classified as oncogene in the Catalogue of Somatic Mutations in Cancer.

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

Chronic Pain and the Opioid Epidemic: Wicked Issues Have No Simple Solutions

Written By Myra Christopher
My mom was a steel magnolia (i.e., southern and perfectly charming), but she had a steel rod up her back. After her first surgery for stomach cancer at age 53, she refused pain medication because she said that she “could take it.” She was young and strong and committed to “beating cancer.” After nearly two years of chemotherapy, radiation and two more surgeries, the cancer won. Eventually, I watched her beg nurses to give her “a shot” minutes before another was scheduled and be told they were sorry but she would have to wait. I could tell by the expressions on their faces they truly were sorry.

Calls of Desperation

When the Center for Practical Bioethics began more than 30 years ago, I frequently had calls and letters from other family members telling me that an elderly loved one was dying in terrible pain and that the care team refused to give pain medication more often than scheduled or to increase the dose because they were told their loved one might become addicted and/or because a higher dose of morphine might affect the patient’s respiration and hasten death.
·      ICU nurses regularly reported calling physicians and pleading for orders to increase pain medication only to be told, “Absolutely no and do not call again!”
·      Physicians told me about patients who refused medication and suffered unnecessarily because they believed their pain was punishment from God and that their pain was “redemptive.”
·      A case I will never forget involved a father who coaxed his son dying of bone cancer to “be a man” and refuse the pain meds his doctor had prescribed.

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

Blood Diseases Could Show Crispr’s Potential as Therapy

November 29, 2016

(Wired) – But the jury’s still out on whether Crispr will be as transformative as a medical therapy as it has been as lab tool. Plenty of gene-editing techniques have been attempted as therapies, but few have made significant impacts—especially when it comes to diseases as complex as cancer. A better place to start testing gene therapies is with inherited blood disorders, like sickle cell anemia and beta thalassemia.

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 Gene-Editing Technology Successfully Cures a Genetic Blood Disorder in Mice

October 27, 2016

(Physorg) – A next-generation gene-editing system developed by Carnegie Mellon University and Yale University scientists has successfully cured a genetic blood disorder in living mice using a simple IV treatment. Unlike the popular CRISPR gene-editing technique, the new technology can be administered to living animals and it significantly decreases unwanted, off-target gene mutations. The findings, reported in Nature Communications, offer a new therapeutic approach to treat genetic diseases of the blood like beta thalassemia and sickle cell disease by targeting faulty genes in hematopoietic stem cells.

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

Interview: Carrie D. Wolinetz of the NIH on gene editing

Interview: Carrie D. Wolinetz of the NIH on gene editing

New gene editing technologies like the CRISPR-Cas9 technique hold great promise for medicine and the biological sciences. Some researchers say we may soon be able to eradicate infectious diseases like malaria, and edit HIV out of the genome of AIDS sufferers. Others believe we can use gene editing techniques to make animal organs suitable for human transplants. 

Yet there are many ethical questions attentant to research in the area, and ethicists are struggling to catch up with scientists eagerly refining the new gene editing techiques. Recently I spoke with Dr. Carrie D. Wolinetz, assistant director for Science Policy at the National Institutes of Health, about various concerns raised by bioethicists about gene editing.

Dr. Wolinetz worked on biomedical research policy issues as the Deputy Director for Federal Affairs at the Association of American Universities (AAU) and the Director of Scientific Affairs and Public Relations at the Federation of American Societies for Experimental Biology (FASEB). She also served as the President of United for Medical Research, a leading NIH advocacy coalition. Outside of NIH, Dr. Wolinetz teaches as an Adjunct Assistant Professor at Georgetown University in the School of Foreign Service’s program on Science, Technology & International Affairs.

******

Xavier Symons: The NIH is funding research into gene editing, but has stopped short of assisting projects involving human embryos. Why?

Carrie D. Wolinetz: On April 29, 2015, the NIH Director, Dr. Collins, issued a statement that “NIH will not fund any use of gene-editing technologies in human embryos.”

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

Human Gene Editing: A Global Discussion

Françoise Baylis explains “On Human Gene Editing: International Summit Statement” to the participants at the American Association for the Advancement of Science 2016 Annual Meeting.

__________________________________________

Last December, at the end of the three day International Summit on Human Gene Editing in Washington D.C., the Organizing Committee issued a closing Statement. This statement included four discrete conclusions. As the science and politics continue to evolve, a quick refresher is in order.

First, the Committee formally endorsed basic and preclinical research on any and all human cells, provided this was done in accordance with “appropriate legal and ethical rules and oversight.” This would include lab research on somatic cells (i.e., body cells whose genomes are not transmitted to subsequent generations) as well as research on eggs, sperm and human embryos (i.e., germ cells whose genomes are transmitted to subsequent generations if they are used in reproduction).

This conclusion demonstrated approval for past and forthcoming gene editing research involving human embryos. Accordingly, the experiment involving the editing of human embryos published in April 2015 by a group of Chinese scientists would be considered “legitimate.” This is not a comment on the ethics or the science of the research. This is merely to say that the research in non-viable human embryos using CRISPR-Cas9 technology to “repair” the HBB gene that can cause beta-thalassemia was done in accordance with applicable rules in China (and, for that matter, applicable rules in a number of other countries). Similarly, the research approved in February 2016 by the Human Fertilisation & Embryology Authority in the United Kingdom, to better understand the basic biology of human development, would also be considered “legitimate.”

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 Editing: A CBC Interview of Margaret Somerville and Julian Savulescu

The following is a transcript of an interview conducted by Jim Brown from Canadian Broad Casting Corporation’s program, The 180, on 3 December between Margaret Somerville and Julian Savulescu

Margaret Somerville is the Founding Director of the Centre for Medicine, Ethics and Law, the Samuel Gale Chair in Law and Professor in the Faculty of Medicine at McGill University, Montreal. She’s also the author of the new book ‘Bird on an Ethics Wire: Battles about Values in the Culture Wars’.

Julian Savulescu is Uehiro Chair in Practical Ethics and Director of the Oxford Uehiro Centre for Practical Ethics at the University of Oxford.

JB: Julian Savulescu, if I could begin with you. You argue that there is a moral imperative for us to pursue gene editing research. Briefly, why do you think it’s so important for us to embrace this technology?

JS: Genetic engineering has been around for about 30 years, widely used in medical research, and also in agriculture, but gene editing is a new version of genetic engineering that is highly accurate, specific, and is able to modify genomes without causing side effects or damage. It’s already been used to create malaria-fighting mosquitoes, drought-resistant wheat, and in other areas of agriculture. But what’s currently being proposed is the genetic modification of human embryos, and this has caused widespread resistance. I think there’s a moral obligation to do this kind of research in the following way. This could be used to create human embryos with very precise genetic modifications, to understand how we develop, why development goes wrong, why genetic disorders occur.

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

Exploring the Future of Gene Editing

by Christopher Thomas Scott

In April 2015 a team of Chinese scientists reported in a little known journal, Protein & Cell, the use of CRISPR/Cas9 to cleave and then repair the HBB gene in nonviable human embryos. The mutated form of HBB causes B-thalassemia, a potentially fatal blood disease. To say the experiment prompted controversy is an understatement. It was published on the heels of two high-profile commentaries in Nature and Science, both of which urged caution about using CRISPR/Cas9 and other technologies to edit the human germline; the Nature authors went so far as to recommend a stop of experiments precisely like the one reported in Protein & Cell. The Liang et al. paper seemed to fly in the face of the recommendations. Though the researchers used triponuclear human embryos (an essential fact missed by some of the breathless reporting in the days after), they designed the experiment as a test of a possible therapeutic strategy. If eventually proven safe, a diseased embryo would be corrected using CRISPR/Cas9 with the intent of eventually making a healthy baby. Importantly, the authors reported notable off-target effects of CRISPR-based gene editing, low efficiency of homologous recombination directed repair (HDR), mosaicism, and unwanted mutations. They concluded:

Taken together, our data underscore the need to more comprehensively understand the mechanisms of CRISPR/Cas9-mediated genome editing in human cells, and support the notion that clinical applications of the CRISPR/Cas9 system may be premature at this stage. (364)

In the avalanche of commentary that followed was a blink-and-you-missed-it defense of the decision to publish the paper by Xiaoxue Zhang (2014), the editor of Protein & Cell.

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 last psychopath: using the brain to root out disorder

Eleanor Worthington Cox plays Jessie in Tomcat / Richard Davenport  

It is compulsory for expectant mothers to have their unborn child genetically screened for disabilities or traits considered to be a burden to society. If a genetic “defect” is found, termination is mandatory. Those who refuse to comply face court orders.

This scenario is still science fiction, but for how long?

The subject is tackled in James Rushbrooke’s excellent play, Tomcat, which is currently running at Southwark Playhouse in London.

Twelve-year-old Jessie (Eleanor Worthington Cox) is the protagonist of the play. She is the last human carrying the genetic marker for psychopathy and has been the subject of a research project for ten years. She lives in captivity and is observed by a team of doctors and scientists who want to understand the biological basis of psychopathy. The researchers believe that it is not possible for the environment to save her from her genetic destiny.

Rushbrooke powerfully portrays a near future in which society has traded freedom and respect for humanity for a “healthy” populace, free of disability and disorders. The play raises the question: if we had the technology to get rid of the traits that cause a burden to society, should we use it?

But what counts as an illness or a disability? And is there a value in conserving disability?

We already have pre-implantation genetic diagnosis that, in the UK, can be used to screen for thalassemia, cystic fibrosis, and other genetic disorders. It can also be used to screen for traits traditionally considered a disability, such as deafness.

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.