Tag: disease

Bioethics Blogs

Dueling BRCA Databases: What About the Patient?

The news release Monday morning grabbed my attention:

“Study finds wide gap in quality of BRCA1/2 variant
classification between Myriad Genetics and a common public database.”

Myriad Genetics had been exclusively providing tests, for
$3000+ a pop for full BRCA gene sequencing, for 17 years before the Supreme
Court invalidated key gene patents back in 2013. Since the ruling a dozen or so
competitors have been offering tests for much lower prices. Meanwhile, Myriad
has amassed a far deeper database than anyone else, having been in the business
so much longer. And it’s proprietary.

CLASSIFYING GENE VARIANTS

(NHGRI)

Public databases of variants of health-related genes have
been around for years too. The best known, ClinVar, collects and curates data
from the biomedical literature, expert panels, reports at meetings, testing
laboratories, and individual researchers, without access to Myriad’s database.
ClinVar uses several standard technical criteria to classify variants as
“pathogenic,” “benign,” or “of uncertain significance.” (“Likely pathogenic”
and “likely benign” were used more in the past.)

ClinVar lists 5400 variants just for BRCA1. The criteria
come from population statistics, how a particular mutation alters the encoded
protein, effects on the phenotype (symptoms), and other information.
Bioinformatics meets biochemistry to predict susceptibility. The BRCA1 protein
acts as a hub of sorts where many other proteins that control DNA repair
gather. DNA Science discussed the genes behind breast and ovarian cancers here.

As gene sequences accumulate in the databases and troops of
geneticists and genetic counselors annotate them, the proportion of pathogenic
and benign entries will increase as that of the unsettling “variants of
uncertain significance” — VUS — will decrease.

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

Dueling BRCA Databases: What About the Patient?

The news release Monday morning grabbed my attention:

“Study finds wide gap in quality of BRCA1/2 variant
classification between Myriad Genetics and a common public database.”

Myriad Genetics had been exclusively providing tests, for
$3000+ a pop for full BRCA gene sequencing, for 17 years before the Supreme
Court invalidated key gene patents back in 2013. Since the ruling a dozen or so
competitors have been offering tests for much lower prices. Meanwhile, Myriad
has amassed a far deeper database than anyone else, having been in the business
so much longer. And it’s proprietary.

CLASSIFYING GENE VARIANTS

(NHGRI)

Public databases of variants of health-related genes have
been around for years too. The best known, ClinVar, collects and curates data
from the biomedical literature, expert panels, reports at meetings, testing
laboratories, and individual researchers, without access to Myriad’s database.
ClinVar uses several standard technical criteria to classify variants as
“pathogenic,” “benign,” or “of uncertain significance.” (“Likely pathogenic”
and “likely benign” were used more in the past.)

ClinVar lists 5400 variants just for BRCA1. The criteria
come from population statistics, how a particular mutation alters the encoded
protein, effects on the phenotype (symptoms), and other information.
Bioinformatics meets biochemistry to predict susceptibility. The BRCA1 protein
acts as a hub of sorts where many other proteins that control DNA repair
gather. DNA Science discussed the genes behind breast and ovarian cancers here.

As gene sequences accumulate in the databases and troops of
geneticists and genetic counselors annotate them, the proportion of pathogenic
and benign entries will increase as that of the unsettling “variants of
uncertain significance” — VUS — will decrease.

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

An Assessment of Mitochondrial Replacement Therapy

By: Alexa Woodward

Last year, a baby boy was born from an embryo that underwent mitochondrial replacement therapy (MRT). MRT was used to prevent this child from inheriting a mitochondrial disease from his mother, specifically infantile subacute necrotizing encephalomyelopathy – a disease that affects the central nervous system and usually results in death within the first few years of life. While controversial, assisted reproductive technologies (ARTs) such as MRT provide prospective parents with additional options and have the potential to improve the quality of human life by preventing disease.

This story is of bioethical interest because this technique results in germline modification, which is the alteration of DNA in the reproductive cells of humans that will be passed on to their offspring. Implementing MRT in humans has consequentially garnered much criticism, from simple health-related implications (such as unknown harms to potential offspring and eugenics concerns) to the futuristic next logical step of scientific intervention; directly editing the nuclear genome.

With MRT, modifications affect the mitochondrial genome (mtDNA), not the nuclear genome. Researchers emphasize the lack of bearing that mtDNA has on personal characteristics and the overall maintenance of “genetic integrity,” especially when compared to using the whole donor egg with an “unrelated” nuclear genome.1 Even so, additional concerns arise regarding the long-term anthropological effects, blurring the distinction between therapy and enhancement, and issues of resource allocation.

Mutations and deletions  in the mitochondrial genome can result in mitochondrial diseases affecting the neurological, musculoskeletal, cardiac, gastrointestinal, renal, and other systems, all of which are incurable.  MRT uses the intended parents’ nuclear DNA in conjunction with a donor’s mitochondria.

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

Open ethical debate: Are gene editing techniques ethical in reproductive medicine?

Author’s opinion: The use of these techniques is currently medically and ethically unjustifiable.

The United Kingdom has recently approved mitochondrial transfer (3 parents children) to prevent the development of mitochondrial diseases in the children of mothers affected by these types of conditions (See HERE). This has opened an ethical debate on the use of such techniques, especially if they can modify the germline.

Now, a recent article has addressed their use in the field of reproductive medicine and discussed their use in infertility treatment and disease prevention (see HERE).

It is well known that the efficacy of assisted reproduction techniques is limited, with pregnancy rates when in vitro fertilisation is used of 29.1% per aspiration cycle and 33.2% per embryo transferred; when intracytoplasmic sperm injection is used, these rates are 27.9% and 31.8%, respectively.

It is therefore thought that identifying possible genetic abnormalities and then applying personalised medicine could improve these figures. It is also believed that they could help to resolve human infertility, since half of the cases are thought to be due to a genetic cause, and could be remedied by correcting the corresponding mutation responsible for infertility using genome editing. This has already been applied in different cases of genetic mutations in sperm in the case of azoospermia.

Gene editing in reproductive medicine

However, in the author’s opinion, the use of these techniques is currently medically and ethically unjustifiable for three reasons. First of all, there is still very little experience in genetic modification in humans, as fewer than ten products have been approved for use in these diseases.

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

Kathy Greenlee’s Reflections on Paths to Person-Centered Planning

Challenging Us to See the Whole Person at All Stages of Life

Kathy Greenlee, VP for Aging and Health Policy

The Center for Practical Bioethics hosted the Joan Berkeley symposium on Thursday, April 6. The title for the day was “Paths to Person-Centered Planning.” In planning the event, my objective was to focus on tools and techniques grounded in a disability policy perspective that could benefit healthcare professionals and bioethicists. The day brought articulate and engaged speakers, raised new questions, introduced different language, and ultimately affirmed the strength of a multi-disciplinary approach to supporting people and their families as they face serious illness and end of life. 

Four distinct concepts emerged:
1) the perspective of the person as patient,
2) similarities and differences between shared decision-making and supported decision-making, 
3) the balance between what is “important to” a person and “important for” a person, and
4) the need to see a patient within the context of their family, however defined.

Person-Centered Communication

The panelists who opened the day demonstrated the importance of listening to people and the first speaker stole the show. 
Cathy Enfield, member of Self-Advocates Becoming Empowered (SABE), is an articulate adult woman with a developmental disability. She uses an iPad for communication assistance. She gave a first-person account of having healthcare providers look past her and talk directly to her caregiver. 
To communicate, Cathy needs support. Yet, public policies ranging from transportation to healthcare create barriers and financial disincentives that require her to be accompanied by someone to assist. Cathy’s comments were so compelling one of the medical educators in the audience intends to make them required reading for his first-year medical students.

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

Missing Genes Point to Possible Drug Targets

Every person’s genetic blueprint, or genome, is unique because of variations that occasionally occur in our DNA sequences. Most of those are passed on to us from our parents. But not all variations are inherited—each of us carries 60 to 100 “new mutations” that happened for the first time in us. Some of those variations can knock out the function of a gene in ways that lead to disease or other serious health problems, particularly in people unlucky enough to have two malfunctioning copies of the same gene. Recently, scientists have begun to identify rare individuals who have loss-of-function variations that actually seem to improve their health—extraordinary discoveries that may help us understand how genes work as well as yield promising new drug targets that may benefit everyone.

In a study published in the journal Nature, a team partially funded by NIH sequenced all 18,000 protein-coding genes in more than 10,500 adults living in Pakistan [1]. After finding that more than 17 percent of the participants had at least one gene completely “knocked out,” researchers could set about analyzing what consequences—good, bad, or neutral—those loss-of-function variations had on their health and well-being.

Gene knockouts are expected to occur more frequently in certain countries, such as Pakistan, where people sometimes marry and have children with their first cousins. That makes it much more likely that a person carrying a loss-of-function gene variation will have inherited that same variation from both of their parents.

In the latest study, a team led by Sekar Kathiresan at the Broad Institute of Harvard and MIT, Boston, turned to the Pakistan Rise of Myocardial Infarction Study (PROMIS) in hopes of finding more gene knockouts.

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

Breakthrough Immunotherapies Seem Like a Dream Come True for Children with Leukemia

Guest Post: Nancy Jecker, Aaron Wightman, Abby Rosenberg, Doug Diekema

Paper: From protection to entitlement: selecting research subjects for early phase clinical trials involving breakthrough therapies

A breakthrough therapy to cure cancer in children suffering from acute lymphoblastic leukemia (ALL) is a dream for many families.  New immunotherapies appear to make this dream a reality. Such therapies use a person’s own immune cells to recognize and combat their disease. In the largest study to date of ALL patients treated with a form of immunotherapy known as Chimeric Antigen Receptor (CAR) T-Cell therapy, a 93% remission rate was reported. Such results are a glimmer of hope for those whose prognoses were previously considered very poor.

However, the good news is tempered by the fact this potentially lifesaving experimental therapy may not be available to everyone who might benefit. And demand is growing as word spreads. Since CAR T-cell therapy for ALL is available only through clinical trials, do patients have a right to participate? How should we choose among medically suitable candidates?

We have faced these questions before. Most recently, with ZMapp to treat Ebola Virus Disease, azidothymidine (AZT) to treat HIV and AIDS, and Immunitab (Gleevac) to treat Chronic Myleogenous Leukemia. Are patients suffering from devastating, life-threatening diseases entitled to breakthrough therapies?

In a recent paper, we argue that benefit is a continuum, from the complete uncertainty associated with standard research, to an intermediate stage where evidence of benefit mounts and reaches a peak, to a final stage of clearly demonstrated benefit that is sufficient to gain approval for clinical applications.

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

Donald Trump’s Mental Health (again)

The speculation about Donald Trump’s mental health that was doing the rounds earlier in the year seems to have died down a bit.  That’s to be expected; like it or not, his Presidency is now part of normal life.  But I’ve been lagging in my blogging here, and so it’s only now that I’ve got a moment to mention in passing an op-ed article about Trump in the New Scientist that appeared just after I posted last on the topic.  (February.  I know, I know.)

It’s by Allen Frances, and it takes issue with what he calls “armchair diagnosis” of the president.  He’s right to say that there’s something disquieting about armchair diagnosis: “psychiatric diagnosis is already done far too casually and inaccurately in medical and mental health practice.  Armchair diagnosis further cheapens its currency.”  However, I do wonder whether we ought to pay some attention to whose armchair it is.  Often, it’s an armchair occupied by the genuinely ignorant, or the spiteful.  That’s the internet for you.  Accusing someone of being mentally ill or having a personality disorder on this account may be simply mistaken; or it may be intended as a jibe, the subtext of which is that there’s something shameful about having a mental health problem.  But not every armchair is the same: as Frances’ article admits, a letter with 35 signatories who work within the mental health field appeared in the New York Times.  That letter may be misguided, or ill-motivated.  But it is by people who, presumably, know a thing or two about the topic.  Their armchair is not my armchair.

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

How Apple, Google, and Other Tech Titans Aim to Shake Up the Way We Treat Disease

…[E]ven if Silicon Valley does deliver a useful project, the rest of the health care system will need time to catch up and work through issues such as patient privacy and data security.

Source: Bioethics Bulletin by the Berman Institute of Bioethics.

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 situation of the clinical use of stem cells

In January 2017, an article was published in JAMA (The Promise of Palliative Care – Translating Clinical Trials to Clinical Care) which, in our opinion, summarises the situation of the clinical use of stem cells extremely well.

It begins by referring to the possible sources of stem cells: embryonic, adult and induced, the latter known as iPS cells.

Stem cells clinical use

It continues by saying that stem cells have many clinical applications, especially stem cells from bone marrow; these are used particularly in haematological diseases, but also in bone fractures, retinal diseases, spinal cord injuries, Parkinson’s and Huntington’s disease, and in myocardial infarction, although many of these treatments are still in the experimental phase.

While stem cells might sooner or later help to treat many patients, they can also have negative side effects if not used correctly, as these cells can emigrate to other parts of the body and create problems, as well as causing tumors.

Finally, the authors refer to the proliferation of clinics offering stem cell treatments, warning that many of these do not meet the necessary quality requirements, since they are not supervised by the health control agencies of the different countries and, as such, they offer the possibility of remarkable cures that are not yet medically proven. Cosmetic treatments and treatments for arthritis and autism are particularly sought after.

See our Special Report about this matter.

La entrada The situation of the clinical use of stem cells aparece primero en Bioethics Observatory.

Source: Bioethics Observatory.

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.