On Reverse Engineering the Human Embryo


(system) #1
Exciting advances in biotechnology present us with difficult ethical questions about the earliest stages of human life.
This is a companion discussion topic for the original entry at https://biologos.org/blogs/guest/on-reverse-engineering-the-human-embryo

#2

Being pedantic here… What was described is not ‘reverse engineering’. Researchers aren’t trying to reproduce or redesign embryos. They’re doing basic research in developmental biology and regulation of biochemical pathways.


(Roberto L Hernandez) #3

I do not think you are being pedantic.

I also think that the essay is poorly written:

“CRISPR/Cas now makes it possible to determine what specific genes (and their products) are doing in the building of an embryo.”

Scientists have been knocking out genes for decades to determine this. CRISPR/Cas only makes it easier, faster and cheaper.


#4

Since it’s “Nobel season” again, I wonder whether the Nobel for the CRISPR work will be awarded before or after the patent dispute is resolved. :grin:


(Darrel R Falk) #5

Reply to Argon’s first comment: Although I realize that you’re right that “reverse engineering” is often expressed in the terms you describe, Argon, I would also like to point out that it is not unusual for the term to be used in way that I have used as well. For example several years ago Nature published a paper entitled “Reverse Engineering the Mouse Brain” (Nature 461:923) and BMC Bioinformatics (16:269) published an article on using reverse engineering to determine modulators of transcription factors. In both cases the papers were about “taking apart” components so that they could deduce function. I could give other examples where the term is used in the way I have used it.

Regardless, however, the purpose of the experiments as I outlined ever so briefly in this blog was to disrupt one key element of the process of early human embryonic development and they did this with the express long range goal in mind of being able to more effectively repair (i.e. rebuild) developmental processes that go awry.


(Darrel R Falk) #6

Reply to Roberto Hernandez: I apologize if because of space limitations I was not able to fully address all of the points that I would like to have made. You are correct that geneticists have been using gene knockouts to analyze gene function for decades—well over a century actually. In fact the mutation-tool is the geneticist’s equivalent of the carpenter’s hammer and the painter’s brush. Genetics is not genetics without the study of the effects of mutations.

However—quite possibly because I was not clear enough—you may not have fully appreciated the point of this work which really is of revolutionary importance. This has never been done in a human embryo. It’s not just easier, faster, and cheaper—it has never been done before. We’ve never been able to knock out both copies of a specific gene in a human embryo at a specific time in a specific way to discern its function. Until now, the closest organism to humans in which this has been done (using classical techniques) was the mouse. What the workers in the experiment I describe have shown clearly is that you can’t extrapolate from the mouse embryo to the human embryo even though they were studying the same homologous gene that worked in a similar but by-no-means-identical way.

This investigation opens up the possibility of studying the processes at work in the building of a human embryo in a manner that parallels the exquisitely beautiful work done to show how a fly embryo is built. For the first time, it will be possible to do work like that with human embryos. Personally, I would never have imagined that it would be possible to do work like that with humans!!

My space was limited and what I really wanted to address was just how amazing it is that the research has moved to this stage, but even more importantly I wanted for us Christians to begin to think carefully about the ramifications of the fact that this is now possible. As Christians, how ought we think about such experiments? And just as important: how ought we discuss what we think about them—especially when the thoughts in our communities are at two opposite extremes, each firmly grounded in the same exact Christian calling: concern for human dignity.


#7

I understand where your coming from. However, being pedantic again, the “long range goal” is essentially a throwaway line at the end of the discussion section. You know that we write that stuff like that all the time in papers and grants, much like writing “researching Hox genes might contribute to curing cancer”. The work in this paper is really about understanding developmental pathways and evaluating tools (CRISPR) that allow high efficiency and high specificity genetic manipulation.

There are other, specific proposals for the therapeutic use of genome editing in fertilized eggs and embryos. Those may rely on similar techniques but that work involves a whole other category covering a deep plunges into ethics, clinical trials and safety evaluations. The field of genetic manipulation has made significant progress and I think there may be some medical conditions that might be feasibly corrected. There will be some the “low hanging fruit” of readily understood, highly specific defects but I don’t think we’ll have the understanding to address the majority of problems this way for a couple decades.

The possibilities definitely have profound implications but with regard to Christian thought, I wonder if the problems could disentangled into questions related to in vitro fertilization and questions about when medical intervention is justified. Both areas are already being tackled by theologians and ethicists.

To be honest, I’m much more concerned about the intentional cloning of specific humans. There’s something very distinct about why one might desire for that.


(Darrel R Falk) #8

The work I describe was done in the U.K. It would have been illegal to do this work in Michigan, Illinois, Louisiana or North Dakota and would have been illegal to use federal funding for it anywhere in the United States. The Nature editorial and the National Academies of Sciences and Medicine (see footnote 2) both come out strongly in favor of this type of research. Have you seen much reasoned public discourse of both views on this matter in the Christian community? I haven’t.

According to the Pew Study (see footnote 3) only 38 percent of white evangelicals (23% of black protestants and 18 percent of protestants in general) find stem cell research morally wrong, Interestingly, only 14 percent of white evangelicals (and a similar number of other protestants) find in vitro fertilization morally wrong. Both usually involve some embryos being stored away in freezers only to eventually die. Why the discrepancy? The end result is similar—frequent death of the embryos.

Are we Christians sufficiently engaged (and informed!) about issues like this? Do we sincerely seek to understand each other’s views in loving ways, or are we afraid to talk about them because of potential flare up?

I wrote this blog (and my previous one) because of my conviction that too many Christians have little real understanding of the biological issues. We have diverse views, but given the importance of these issues for the future of humankind, we have a responsibility to be sure these diverse views are grounded in the real biological world.

We need well-informed ethicists, theologians, scientists, and most importantly, pastors guiding us into these discussions. Our well-reasoned voice ought not be so muted.


#9

To be honest, I haven’t seen much reasoned public discourse on any internally divisive or strongly emotion-laden subject in the Christian community as a whole. This isn’t to criticize the Christian community specifically but a comment on how we humans ‘reason’ as a collective when confronted with difficult subjects. You mention that this work is illegal in many US states and not permitted federal funding for research. I’d cite the response in the US as confirmation of the profound difficulty with reasonably addressing emotionally-laden subjects. Individual sects/sub-sections of Christian communities may have what it takes to hold informed discussions (I’d point to the Catholic church as one likely example), but the pan-Christian community simply doesn’t have the shared, requisite traditions necessary. Require a degree of scientific understanding to an issue and all bets are off.

That said, I think one can dissect the issue into two pre-existing areas for improved clarity. The first is in vitro fertilization (IVF) and its associated technologies. If one’s religious understanding concludes that the loss of potentially viable embryos inherent in the process is a non-starter, then genetic-modification of embryos is out as well. It relies on the same preparation of excess fertilized eggs. Under Catholic doctrine, this is a problem, though like contraception, not one that necessarily stops many Catholics from utilizing IVF.

For those who think IVF is not a moral hindrance, we then confront the varying beliefs related to medical treatments. There are related precedents here as well, including such areas as: consent for irreversible treatments, genetic screening & decisions on whether to ‘throw the genetic dice’ or not, and benefit vs. risk assessment. The one new twist to the discussion concerns germ-line genetic modification. And even this subject has been actively discussed at least since the first use of restriction enzymes to clone specific DNA fragments, circa the early 1970s.

I am certainly in favor of discussion but not so optimistic about success. As with many technological advancements, I think that after the efficacy of a treatment is demonstrated it will eventually become available and accepted by society as a whole. Religious moral frameworks will play a game of catch-up as many church members adopt the technology. There will be dissenters and some schisms, but that is thoroughly in keeping with long Protestant tradition.


(Darrel R Falk) #10

I really appreciate your realistic assessment, Argon, but being an idealist, my hope is that Christians ought to be beginning to lead society into carefully reasoned discussion of the issues. We are moving into an era in which the genetic makeup of humanity may be significantly altered—if not through gene editing in the short term—then certainly through PGD (pre-implantation genetic diagnosis) beginning right now. Ought not our Christian thought-leaders and influential pastors be getting together to explore the ramifications in a scientifically informed manner? Is this not especially germane given the unique Christ-centered teleology that is our touchstone as opposed to the more vacuous teleology that arises when humanity is simply the end result of a 4 billion year old algorithm? Can’t we set aside our differences and sit down and reason together? I think we can. Indeed, perhaps BioLogos–through its many private and public discussions with those who think differently on evolution–might serve as a tentative example for how to discuss the broader issues now before us. To illustrate the gravity of the situation and the issues involved, I think these two Nature News items illustrate the serious concerns now upon us (here and here).


#11

What are your thoughts of the subject? Lay out some foundational propositions to highlight how you interpret the morality of particular treatments.

Back to precedents…
For the first news article cited, I suspect that genetic screening of embryos again combines two areas with precedents: IVF and genetic counseling.I don’t think considerations in those individual subjects become something different when combined. There are also previous ethical works related to things like sex selection by parents.

The second article is great, IMHO, particularly in providing a reminder that we cannot achieve perfection. On the issue of consent and how the subjects of treatment can’t provide it… This has some precedent as well. First, nobody can give consent for their birth. The genetic makeup of the child is chosen by the parents in the sense that parents decide with whom to have children and whether, given knowledge of their genetics, opt to have children with certain characteristics or not. On the lighter side, I’ve known people to sarcastically thank their parents for passing on their big noses.

We also have precedent on prenatal care and how health conditions and the decisions the mother takes while pregnant can have permanent impact on their child. We have many cases where children are given irreversible medical treatments without their consent. There are even cases of prenatal surgery.

Overall, ample precedents with perhaps a few new twists.


#12

You certainly can’t get anywhere without hope and idealistic belief of how things might be different. There are individual Christians that are taking some leads in this area. However, I think the distance between established Christian positions (e.g. even on IVF and genetic counseling), is significantly greater than in many societies as a whole. Or to put it perhaps more clearly, the standard deviation for Christian positions on the subject is greater than the standard deviation for the entire population. This is because I think various Christian camps hold stronger positions on either end of the spectrum.

Ought not our Christian thought-leaders and influential pastors be getting together to explore the ramifications in a scientifically informed manner?

They certainly ought to. But for the US in particular, how well have influential pastors done on simple things like global warming, the age of the Earth or even the death penalty? Many are spot-on. But many more leaders fail spectacularly. Possessing “leadership” and “influence” often does not correlate with being “scientifically informed”. Idealism cuts both ways.


(Roberto L Hernandez) #13

[quote=“DarrelFalk, post:6, topic:36797”]
You are correct that geneticists have been using gene knockouts to analyze gene function for decades—well over a century actually. In fact the mutation-tool is the geneticist’s equivalent of the carpenter’s hammer and the painter’s brush. Genetics is not genetics without the study of the effects of mutations.[/quote]
In scientific terms, knockouts are made by us, so only for decades.

How do you know it has never been done just not reported? The ESC technology for the mice is available for humans too.

That is only true for some cases and we already know that. Do you not know that there are many, many genetic disease that affect humans just the same as mice?

[quote=“DarrelFalk, post:6, topic:36797”]As Christians, how ought we think about such experiments?
[/quote]If your target is evangelicals against abortion, they don’t think clearly about them. If life starts at concepcion, abortion is murder, but IVF is mass murder. Yet when I worked in the US, I never saw protestors at IVF clinics.

So if you can’t get christians to think clearly about IVF you can’t get them to think clearly about this, since it has a similar embryonic death count.


#14

There are actually many who are very much against that technology because excess embryos are produced. Others may oppose it because they are opposed to medical interventions (e.g. along with blood transfusing or perhaps antibiotics). The Catholic church is very much against IVF. However, they are also politically aware and in the US, they are tightly aligned with other Conservative causes. I suspect there is little appetite to protest what is essentially a lost cause. IVF is too medically successful and too broadly supported to be blocked by what most others believe is a much less significant concern.


(kendra) #15

Dr. @DarrelFalk
Thank you for your two blogs discussing this topic. I fully agree that this is a conversation that must be had, and as Christians, we need to lead in that conversation and be open to discussing, with gentleness and charity, the ramifications of research on human embryos.

I am not a scientist and I will not pretend to fully understand the details of this very complex issue. I can only respond as a Christian, mother of three and a strong believer in defending the unborn.

I just want to share by “initial” response and feelings about this topic and acknowledge that with understanding comes changed perspectives. I also recognize that there is a fragile balance of seeing IVF embryos as sources of scientific research that could lead to the relief of suffering for many (in the future) and seeing IVF embryos as humans, not yet born, who have the same rights to their protection of life as you and me.

So my initial response is to feel distraught with what is happening. I watch the video of those cells dividing and I see the beginning of my kids lives! I read that these embryos would have developed into “full-fledged human beings”, but all died in the research and it breaks my heart. I am a big believer of “what could have been” with these unborn humans and what they could have contributed to our world if they were given the opportunity to live! However, I realize that I have to apply that same belief towards people that would live as a result of the advances made from this research. I am left with the question…who is more important, the current unborn embryos or the future embryos who benefit from the research? This might be a simplistic question, but I believe it warrants consideration by those involved.

This topic troubles my heart, but I know it is an issue that can’t be ignored. There are no easy answers, but I am thankful for you and BioLogos for tackling these tough issues and opening up the conversations!


(Darrel R Falk) #16

Thank you, Kendra, your note is beautifully written and brings tears to my eyes as I sense your Christ-centered love for others, and your concern that we prayerfully move into the new era with hearts that are open to each other’s thoughts and concerns In my case, I think of my granddaughter and grandsons as I watch the embryos divide and the tears come again as I think of the miraculous beauty of the process that brought them into being.
At the other end of life’s journey, I have spent time with very special people who suffer terribly because things are awry with their bodies or their minds. Their hurting becomes our hurting and we’re called to bring healing.

The issue is complex and the temptation is not to think about it…just to coast. When we do that, it will be the politicians–those who function by listening to the loudest voices–who will make the decisions for us. It doesn’t have to be that way. It can begin with our Christian communities sitting down together, prayerfully seeking wisdom, placing Christ’s love in the center of our discussions and his leadership in the center of our lives. This can in turn lead to our leaders engaging the issues with their output spreading outwards bit by bit into society as a whole.

As Jesus said, “You are the salt of the world, but if the salt has lost its taste, how can its saltiness be restored?” Matthew 5:13. Christ’s presence is sorely needed and we are called to be that presence in life’s complexities. And as we do so, we’ll find there’s much joy!


#17

IVF procedures produce an excess of fertilized eggs. This reflects the need to ensure that enough fertilized eggs are made for successful implantation. Implantation normally involves 2-4 fertilized eggs per attempt and multiple attempts are often required until a successful pregnancy occurs.

At least until a pregnancy is successful, the remaining fertilized eggs are stored in deep freeze. They may be stored much longer in case the mother wants subsequent implantations for additional children.
However, even in deep freeze, fertilized eggs become non-viable over time. Thus the fate of most fertilized eggs made in the clinics matches the fate of most fertilized eggs created in natural, human reproduction. They do not implant and thus die.

In this discussion, I think it’s critical to identify the core concerns. What are the decision points and what root, ethical/moral/religious principles come into play that should guide one’s decisions?


#18

Darrel, what are your thoughts about it? Do you plan to expound on the thought making process you’ve come to in this thread or are you confining this to a call for discussion? I can appreciate not wanting to have, by your association, Biologos somehow tied to any particular position.


(kendra) #19

@DarrelFalk
Thank you for your response!

I fully agree that many want to ignore these hard issues. I wonder if this is motivated by fear; fear of what we don’t understand and the work it would take to understand? But because “perfect love casts out all fear”, placing Christ in the center of these complex issues and our discussions around them( as you so wonderfully stated) should take precedence and be encouraged!

The use of human IVF embryos for scientific research worries me, but I desire to understand it more. Ultimately, it is something that I will pray about and be open to where the truth leads.

Thanks again-


(kendra) #21

@RHernandez

Thank you for your questions.

Of course that worries me as well! We play God in so many ways; to our benefit and to our detriment. However, I have friends who have had to use IVF to conceive and I know it is a very painful subject for many and if is essential to be sensitive to that. You could even start talking about the pill and other forms of birth control, but this article is not about whether IVF and birth control is morally acceptable. It is about the research that is being done and will be done in the future on IVF embryos and how we as Christians do and should respond. That is what I chose to respond to.