HHGE and the ethics surrounding it Flashcards
who are the ‘stakeholders’ in rank order, where HHGE technology is concerned?
1 sufferers/patients
2 friends and family
3 healthcare providers
4 pharmaceutical companies/shareholders
5 scientists/researchers
6 government
7 public
8 future generations (v. important for HHGE)
genome editing - an ethical review (Nuffield)
key concerns on genome editing in human health? (X5)
*Concerns about the risks of unintended effects due to off-target DNA alterations
- Implications of genome editing in reproductive treatment, e.g. making
changes that will be passed on to future generations. Issues including outcomes, risks, costs and
societal impact have implications for governance and regulation - Concerns that widespread of genome editing may amount to ‘liberal’ eugenics driven primarily by
the choices of parents - Concerns that potential benefits and harms of genome editing might not be distributed equitably (social inequality)
- Concerns about how to delineate (distinguish) morally acceptable and unacceptable uses of genome editing for
governance purposes
genome editing - an ethical review (Nuffield Council, 2016)
key concerns regarding food production, wildlife and ecosystems?
about the welfare of intensively farmed animals
* whether or not food produced using genome editing should be classed as ‘GM’ due to consequences for regulation, labelling and public perception
possible uses in creation and release of genetically altered insect species to control infections disease or crop
pests, e.g. altered mosquitos to halt the spread of malaria and dengue fever
Key ethical concerns:
uncontrolled proliferation of gene drives in the wild which may upset
fragile ecosystems or have unintended ecological consequences
genome editing - an ethical review (Nuffield Council, 2016)
applications and ethical concerns in the military + amateur use?
Applications may include:
in bacteria - production of fossil fuel alternatives, antibiotics and
vaccines
Defence interests that may exploit genome editing to counteract biological or chemical aggression
Amateur applications include the use of the low cost technology by DIY ‘garage’ scientists
Key ethical concerns:
*Genome-edited organisms (as with all genetically modified organisms) pose a possible risk to those
handling them, to others, or to natural ecosystems if they are released or escape from controlled
environments
*The possibility of the technology being put to harmful uses, for example in the production of bacteria
intended to cause a disease outbreak
what issues does Nuffield’s report see as urgently in need of addressing?
potential application of genome editing in
human reproduction – i.e. intergenerational
alterations (e.g. for the purpose of avoiding genetic disease).
The use of genome editing in livestock (e.g. to improve animal husbandry and food production)
Nuffield - issues to be kept under review (lowest priority)
the governance of genome editing to develop new cell-based therapies for existing diseases
Genome editing and human reproduction: social and ethical issues (Nuffield Council, 2018)
what are the two overarching principles the report suggests should guide the use of ‘heritable genome editing interventions’ for them to be ethically acceptable?
they must be intended to secure, and
be consistent with, the welfare of the future person; and they should not increase disadvantage, discrimination or division in society
Genome editing and Human reproduction (Nuffield Council, 2018)
when do they recommend heritable genome interventions should be permitted?
and if it is permitted it should be?
there has been a sufficient opportunity for broad and inclusive public debate about its use and possible implications;
further research has been carried out to establish standards of clinical safety; and
the risks of adverse effects for individuals, groups and society as a whole have been appropriately assessed and measures are in place to monitor and review these
It adds that, if it were to be permitted, it should be:
strictly regulated (by the HFEA in the UK);
introduced only in the context of a clinical study, with monitoring of the long-term effects on individuals and groups; and
licensed on a case-by-case basis, ensuring that that each application is evaluated within its specific ethical context, allowing for a more nuanced and thorough ethical assessment
NAS - human genome editing, science, ethics and governance (2020)
major recommendations for basic lab research, and somatic genome editing?
Basic Laboratory Research
Use existing regulatory processes to oversee
human genome editing laboratory research
Somatic Genome Editing
Use existing regulatory processes for human
gene therapy to oversee somatic human
genome editing research and uses
Limit clinical trials or therapies to treatment
and prevention of disease or disability at this time
Evaluate safety and efficacy - risks vs benefits of intended use
Require broad public input prior to extending
uses
NAS major recommendations on germline genome editing?
Permit clinical research trials only for compelling purposes of treating or preventing serious disease or
disabilities, and only if there is a stringent oversight system able to limit uses to the specified criteria
Ongoing reassessment and public participation should precede any heritable germline editing
NAS views on using genome editing for enhancement?
don’t do any of it yet - not for anything other than treating/preventing disease and/or disability
encourage public debate on somatic human genome editing for uses other than treatment/prevention of disease and/or disability
how is genome editing used to treat B-thalassemia?
Treatment first involves chemo to kill patient blood cells
Then comes the genome editing -
In this condition, the gene for the B chain present in haemoglobin is incorrect/produces faulty protein, but patients will definitely have a functional gamma-subunit gene for foetal haemoglobin, it’s just been silenced
In a haematopoietic stem cell, you silence a transcription factor that normally silences foetal haemoglobin gene by altering the enhancer region of the transcription factor
This allows foetal haemoglobin to be transcribed and avoids the dysfunctional gene for B chain of haemoglobin
Treatment has seen to be very effective with foetal Hb rising massively and adult Hb production decreasing
cons of genome editing?
Not affecting the gene you want - unintended target and consequence
Mosaicism - the presence of two or more populations of cells with distinct genotypes within an individual. It can occur when the genetic modification introduced by genome editing tools such as CRISPR-Cas9 is not successfully incorporated into every cell during early embryonic development
Germline editing - passing on to future generations, ethics on consent, concerns for long term safety
Social concerns - expensive, inaccessible in certain countries etc…
Immune response if a virus/viral vector is used
benefits of genome editing?
Cure disease/improve quality of life
Improved techniques in the area that could be applied to other diseases
Reducing future healthcare costs of the patient
