Germline Science & Embryo Use - The Law & Scope for Applied Research


NIH statement on editing human embryo DNA
The recent reiteration by the Director of the NIH, Dr. Francis Collins, that the long held legal position of the US Federal Government is to not fund destructive embryo research, brings the US debate on germ line editing front & center in practical terms.


"Use" of human embryos, for their own benefit, is written into the established Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 Recital(42) on the legal protection of biotechnological inventions in European states et al and is a foundational document addressing this area. The interpretation of this document has led to the European Patent Office guidelines and appeal rulings. 

However, apart from the embryo "use" issue, the Directive (Chapter 6.2.b) specifically states that "processes for modifying the germ line genetic identity of human beings" are prohibited from Patentability.
Also, the "Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine Oviedo,4.IV.1997" states "An intervention seeking to modify the human genome may only be undertaken for preventive, diagnostic or therapeutic purposes and only if its aim is not to introduce any modification in the genome of any descendants." This forms part of the overall European Convention on Human Rights, in all its parts "The Convention."

So in Europe the issue of Human Rights & Innovation Patentability are determined by guideline standards applied mainly throughout the membership via The Convention & the BioTech Directive, while Individual National Laws are deferred to, fundamentally by design, in determining the applicable interpretations & standards governing the specific ethical/moral & "ordre public" of that society in biomedical research.

In the US, it's also the actual "use" of embryos for research, including the derivation itself of ESCs, that is the Federal funding restriction. This is a result of, exclusively at the time of drafting, the destructive method employed to derive hESC lines. In addition research funding into destructive embryo studies in areas such as nuclear transfer & genetic modifications of the germ line were also restricted, as a result. The reiteration of this established position recently by the NIH reminds all of the reality of the current funding law governing destructive practices on "human embryos."
However, historically there has been somewhat of a mixed approach in practice applied to federally funded embryonic research in the US. The NIH has authorized funding for decades using donated IVF supernumerary embryonic stem cell lines for research. On the one hand the law states that no funding is allowed that destroys embryos (e.g. blastocyst ICM extraction of stem cells, or in this most recent case genetic editing on embryos that would result in their destruction). However, on the other hand, this law doesn't apply when work is done on Federal registry approved embryonic stem cell lines (see NIH guidelines). This reality is a middle way compromise to support the nascent field of advanced research into developmental biology and has resulted in significant progress in the understanding and therapeutic potential of pluripotent cell technologies.
Of note, more recent non-destructive methods, nor research using non-viable embryos, have yet to be written in. For example, non-embryo-destructive sourced Blastomere ESCs, nor non-viable SCNT-ESCs or Parthenogenetics-hpESCs, are notably excluded from federal support. So the actual working model isn't that current nor flexible to the evolving technology, which is reason to review the legislature as a result of the sector’s broadening scope.
The use of natural eggs in SCNT-ESCs/hpESCs was perhaps the concern and avowed aspect of these methods to the Federal Government - but has there been a recent review on this position given IVF has become a standard option in fertility treatment? Also the sector is moving fast and emerging reprogramming techniques look to create synthetic eggs, what then? Is this not a reasonable question to be asking now, given the discussion?     
This line can and may very well be taken further with technology to create synthetic sperm. Will the combination of synthetic eggs and sperm be the next ethical issue? I believe there needs to be a concerted effort to get ahead of the science & write updated Laws that apply new guidelines with scientifically prudent standards, while remaining open and flexible to potential benefit & future possibilities.

Further, the European Court of Justice has ruled recently that non-viability is a determining characteristic of the definition of a "human embryo," therefore non-viable zygotes & arrested/mutated pre-embryos that cannot develop do not fall within the restrictions of the Biotechnology Directive, as they have been ruled not to be considered by definition an "human embryo." However controversial this position may seem to some it is an accurate reflection and interpretation of the foundational biotechnology law in Europe, while deferring to national member states the issue of ethical/moral & "ordre public."

Fundamentally the underlying principles of the protection of life in the Chapter 1 Article 2 of The Convention doesn't state explicitly that germ line cells, nor for that matter an embryo or fetus, are to be given specific reserved consideration. This has been tested at the European Court of Human Rights. Should national laws allow in-vitro research on embryos The Convention states in Chapter 5 Article 18 that they should "ensure adequate protection of the embryo" and that "the creation of human embryos for research purposes is prohibited." This is the general positioning at the European Human Rights level, as a result of the union of culturally diverse member states. As previously indicated, individual countries apply local Laws to their societal ethical positions, which they all do in regard to embryos/ESCs, genetics, IVF & fetal development, considering The Convention. Generally the principle of human rights & dignity extends to all human beings and for that the definition of a "human being" is central to The Convention's interpretation. The UN's Universal Declaration of Human Rights is similarly worded and looks to respect individual human rights, while leaving the question of developing life to individual societies.

With regard to cloning there was a specific Protocol added to The Convention in 1998, and enacted by other governing bodies internationally, as a result of the discussions surrounding animal cloning at the time. Specifically, The Convention states that "any intervention seeking to create a human being genetically identical to another human being, whether living or dead, is prohibited."

The objections to assisted reproduction by the Vatican or Christian Right may very well be subjectively valid, from their reasoned perspective, but that view, however correct or positioned to be morally sound, doesn't acknowledge nor properly address the very real practical issues inherent in today's advanced fertility, cell & genetic sciences. Many of the issues previously debated are being clinically applied with results. New ethical challenges and redefinitions are required by all as the science evolves, with appropriate regulatory & societal frameworks adapted, as necessary.
The fact that new technological advancements are being designed to address medical needs of those that suffer from, or may fall victim to, potentially treatable biological conditions warrants considered thought as to how best to unify behind the effort to achieve a host of goals in the process. Through public education and the application of successful next generation technology the substance and impact science can have on solving the very issues that divides opinion is possible.

The ethics of today will give way to the ethics of tomorrow, and so on - it's nature's way. Man plays his part in this cycle and uses what is available with intellect and inventiveness. Change is a process of adjustment and one could say that is the will of nature's law. The only unnatural aspect would be if man himself becomes defined as synthetic, which is, from this writer's perspective not the goal.

Germ line editing in clinical practice is indeed unnecessary at present until proven otherwise. However, basic research using gene editing technology of germ line cells is necessary, based on clearly defined updated ethical frameworks - with governmental support, if possible. The recent ISSCR Connect discussion on the issue was well presented and reasoned. More open dialogue is required and opinion sought from all stakeholders. There are too many questions yet unanswered to not search for the clues by all means so one day we may apply that knowledge to human frailty & suffering in developing or developed humans. That goal would be best served by furthering basic research efforts using genetics back to our original cells. iPS technology wouldn't have been invented had it not been for human embryonic research, which wouldn't have been possible without animal cloning studies…. the shoulders' metaphor applies.

From my perspective if gene editing research using germ line cells and pre-embryos is to be limited entirely to private companies then that would curtail potential scientific progress in research using non-viable donations or technology methods which cannot develop into a human by design.

Congress has the opportunity to get ahead of these issues and address squarely this area of leading biotechnology innovation in new legislation. This was shown to be important during the protracted court case against the Federal Govt.’s funding of scientific research using approved hESC lines. The high court ruled in favor of the Govt. but there was considerable discussion in legal circles of the need to update the law. The underlying legal basis being the Dickey Wicker amendment, which was written in 1995, and is considered by many to be too ambiguous and not a suitable legislative document for the sector moving forward. The need for a comprehensive bill is generally acknowledged. The use of Federal funds in developmental biology research should allow for opportunities to explore all non-destructive areas of the science to advance medical knowledge so that it does not impede the progress of scientific discovery for the benefit of all. Patients' interests must be considered paramount and consensus sought on majority based positioning. Public education can be an effective tool in defining such efforts.  
For example, currently there is an area of ambiguity with the written NIH hESC text on embryo donations, as a cell can be harvested from a pre-embryo and used for that embryo's own benefit, if not for all.

Ethical considerations are required to be taken into account, but not at the expense of an agreed roadmap to progress. If after broad inclusive deliberations legislative regulations & sector guidelines are updated, then that achieves the goal. However, I would add a caveat, it’s important to include into any new laws the non-viable/non-destructive aspects succinctly, as well as a considered inclusion of a benefit review for technologies applied to viable potential human embryos in-vitro & in-vivo.

However, "use" of embryos isn't the full picture. There remain issues of scope with respect to reprogramming technology, assisted reproduction techniques et al which should be clearly stated as part of new regulations & guidelines in the area.

Clarification is needed as to the somatic reprogramming limits that are acceptable and where there should be restrictions, if any, applied. Synthetic forms of human germ line cells and the creation of pure or part-synthetic embryos for cellular harvest cannot be overlooked and needs similarly considered language. Issues such as same sex couples wishing to use technology to assist having "natural" babies using reprogrammed cells back to the germline, artificial wombs and attempts at eugenics et al should be broadly covered in the legislative language.  

If there were clear legislature on the issues, after dialogue with all stakeholders, this would assist in eliminating the negative spin on today's advancing scientific discoveries that looks squarely to cure disease. Science would benefit from that clarity. The future possibilities would remain, however, guidelines would be established.

Consider if you will that if the science advances and we are able to achieve that long string of .999s on safety, what will be the benefit/risk scenario if implementation occurs some time in the future? Such science can be debated at that point and submitted for consideration, as long as there's a benefit window.
Generally in the future there may be a manner in which genetic technology proves its human potential for the application of germ line intervention. Leaving that door closed while holding a preexisting key isn't such an unethical position IMO - flexibility in today's fast paced scientific world is important.

The challenge in establishing regulations in this area will not be easy, but it isn't insurmountable. A flexible legal & regulatory basis for steps forward in the research is what is required IMO. Checkpoints along the way so that the whole map is not null if one road is opened up upon the presentation of correct documentation. A straightforward mechanism should be agreed for the review process that encompasses the appropriate nominated bodies. Congressional oversight may be appropriate but the nature of such a flexible system would be best served to have it's own adaptation authority once the law is written.

I have stated previously that the reduction in IVF supernumerary embryo creation should be a stated goal with new specific governance stipulations & authority guidelines over the fertility sector. This I believe is central to a consensus building working model.

The point is we as a society cannot any longer avoid the reality of the present and promise of the future by applying yesterday's fixed reasoning to bear. Without informed, concise & regularly updated language of the day the necessary support and freedom to research innovative solutions to pressing medical and biological issues will be unnecessarily limited.

Today the US is the leader in ethical biomedical technology but without Bold Action, Decisive New Legislature and Increased Government Support, across the board, the promise of tomorrow's technology with not meet the expectations of the people nor address the full potential for American solutions for the Common Good.

Cheers


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