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Thursday, April 02, 2015

On the "ethics" of germ line DNA editing

Edward Lanphier, Fyodor Urnov, Sarah Ehlen Haecker, Michael Werner and Joanna Smolenski have published a comment in Nature with a provocative headline "Don’t edit the human germ line. They are asking scientists to agree " not to modify the DNA of human reproductive cells." The idea is that editing the genome of sperm or egg cells produces changes that will be passed on to future generations and this poses certain dangers.
In our view, genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable. Such research could be exploited for non-therapeutic modifications. We are concerned that a public outcry about such an ethical breach could hinder a promising area of therapeutic development, namely making genetic changes that cannot be inherited.
I think there's general agreement that the current procedures aren't safe enough to make it worthwhile. I can agree with the safety issue.

However, I'm not so sure about the "ethical" issue because that's complicated. We all agree that is it unacceptable to do something that endangers a patient and future offspring. We can agree that it would be "unethical" to modify a patient's germ line if we don't have a good idea of the possible ramifications. But that's really just another way of saying that we shouldn't do something stupid.

Ethical issues are hard to pin down but they usually concern conflicts between different views of what is right and what is wrong. If the vast majority of people agree on what is right then the presence of a few renegades does not make an ethical issue. What about "non-therapeutic modifications" of the human germ line? If some people think this is permissible and others think that it is not, does that make it an "ethical" issue? Of course not, not all disagreements are ethical issues.
Patient safety is paramount among the arguments against modifying the human germ line (egg and sperm cells). If a mosaic embryo is created, the embryo’s germ line may or may not carry the genetic alteration. But the use of CRISPR/Cas9 in human embryos certainly makes onward human germline modification a possibility. Philosophically or ethically justifiable applications for this technology — should any ever exist — are moot until it becomes possible to demonstrate safe outcomes and obtain reproducible data over multiple generations.
I don't think any reasonable person disagrees with this statement. This is a safety issue.

I'm interested in the part that says, "Philosophically or ethically justifiable applications for this technology—should any ever exist ...." The implication here is that there are serious ethical questions about whether one should engage in germ line editing/modification. The authors give the impression that there might be strong ethical objections even if the procedure were safe.

They go on to say ...
Because of such concerns—as well as for serious ethical reasons—some countries discouraged or prohibited this type of research a decade before the technical feasibility of germline modification was confirmed in rats in 2009 (ref. 9). (Today, around 40 countries discourage or ban it.)
What are those "serious ethical reasons"? Imagine that modifying the human germ line was proven to be perfectly safe and we knew exactly what the consequences would be for future generations. Having disposed of the safety issue, what "ethical" reasons are there for banning the procedure?

Keep in mind that this is a form of thought experiment so don't quibble about safety. If you think there's still an "ethical" problem then try and explain what you mean by an "ethical" problem. I don't see any reason to ban this procedure if it's safe. There's no "ethical problem that I can see. You may not think it's a good idea to modify the germ line but is that a reason to prevent others from doing it? Is it an "ethical problem" for you?

Why is this important? It's important because there's increasing pressure to incorporate "ethics" into science classes and often the "ethical" questions aren't really ethical question at all.

Teaching Ethics in Science: Science v Technology
Teaching Ethics in Science: Science v Technology (Part 2)


50 comments :

John Harshman said...

I fail to understand how any safe procedure that would eliminate a genetic disease would be unethical. Or why it wouldn't be a good idea in such cases. Or perhaps they're worried about accidentally causing Magneto?

Petrushka said...

Suppose for the thought experiment that a simple tweak could add a standard deviation or two to intelligence or to athletic ability or to longevity. This seems like a good thing, but suppose it is expensive and only the wealthy can afford it for their children. Is this a problem?

Jonathan Badger said...

One thing to consider is one person's "genetic disease" can be another person's culture. We know that some (if not all) forms of deafness are genetic. And to hearing people, it may seem obvious that we should eliminate deafness. But there is a Deaf culture surrounding their signed languages (which are real languages of their own, not just signed versions of English or what not). To them, elimination of deafness would be a case of ethnic cleansing.

John Harshman said...

Is a cochlear implant ethnic cleansing? I know that some are against them, but I don't know of anyone who wants to deprive others of making that choice for themselves.

Jonathan Badger said...

No, but that's very different from modifying the germ line which is what we are talking about. A Deaf person choosing to get an implant for themselves, fine. That's not getting rid of deafness for all future descendants of the person. Germ-line modification would be particularly problematical in this case because you could imagine the hearing parents of a deaf child making the decision for the child long before the child could make the decision for themselves as to whether they want to be part of Deaf culture or not.

Petrushka said...

Deaf children need the implant before they are old enough to decide. Language must be learned early.

Doughnut said...

Petrushka's comment about likely inequities of access is interesting. We already see this in the inequitable access to PGD, prenatal testing and even donor eggs. However that is doesn't directly pertain to whether the technology is ethical...

Jonathan Badger said...

But which language (and culture)? Deaf children have no problems learning their signed languages given a community of fellow signers, and those are in no way inferior to spoken languages.

Piotr Gąsiorowski said...

It isn't an "either...or" choice. Hearing children brought up in a community of signers but not locked in a cultural ghetto (before they reach the critical age) can acquire a sign language alongside a spoken one and grow up perfectly fluent in both. Multilinguality is the normal state of the majority of human beings, and confers a number cognitive benefits.

Piotr Gąsiorowski said...

... a number OF...

Marcoli said...

Similar arguments were being posed in the '70s against genetic engineering as it was taking its first baby steps. The worry then was that scientists would some day make a superbug. Others worried about the ethics of 'playing God'. I am sure there were those even within biology who wondered if we would one day start to engineer people. So once again, we see concerns being raised over safety and ethics.
The answer then was to regulate the procedures and contain the product until reasonable safety could be demonstrated. There are strict regulations regarding genetically engineering human cells, and we have what I think are very ethical practices in handling human ES cells and early human embryos. Perhaps the ethical standards for this next step are already in place.
It is good to hear calls that bring up ethics on this new application, but I also think we should move forward, in a limited way, on testing the safety and efficacy of this application to one day cure some of the human genetic diseases.

Steve Ruble said...

I think there are any number of ethical questions which could be raised by specific hypothetical modifications. (For example, would it be ethical to allow germ line modifications which resulted in a strong vulnerability to cult indoctrination?) But I don't think that's what you're asking about.

One ethical question I can think of about the technology in the abstract is the question of whether parents have the right to make decisions about genetic modification of their grandchildren on behalf of their children. (That question would be moot if reversal of the germ line modification were trivial.)

Larry Moran said...

Yes it's a problem. The procedure should ne available to everyone but in a capitalist society they've already established that the rich get special privileges. This is not an ethical problem. The capitalist society has decided that the benefits outweigh the costs.

Larry Moran said...

You used the word "ethics" several times in different contexts. What does that word mean to you?

Larry Moran said...

The first example is a good one. Hardly anyone would want to do that and the vast majority of citizens would prevent anyone else from doing it as well. It's hard to imagine a society where this would be a serious ethical problem.

However, the real problem is whether there should be rules and laws that regulate the procedure in the first place. If not, then there's no easy to prevent parents from creating compliant children.

The second question can be thought of in the context of John Harshman's question above. If society agrees that we can use germline modification to produce children who don't carry alleles for a genetic disease, then you have the answer to your question. It's "yes," we do give parents that right.

I don't see this as an ethical question, The answer seems obvious to me.

Jonathan Badger said...

Yes, bilingualism of spoken and signed languages is quite possible, and there's quite a demand for sign language interpreters for which this is required. But there is little question that if deafness was universally "cured" signed languages would fall out of use meaning the end of Deaf culture. And the Deaf community values their languages just as any minority culture does.

Diogenes said...

And now I throw some bombs around. Larry, suppose they discover an atheist gene which makes people less vulnerable to religious indoctrination. And Muslim parents want to delete that gene from their children and grandchildren etc. forever, no possibility of resurrection, so they can spawn generation after generation of jihadist Uruk-hai. Would you have a problem with that?

Diogenes said...

A modified version of Steve's question.

Larry Moran said...

Yes, I would have a problem with that. I'd also have a problem with atheist parents who want to modify the theist gene of their children.

Is this an ethical problem? Why?

Marcoli said...

I can come up with two, well lets call them three context of ethics that seem to come up in discussions about biology and medicine. They are 1) we should not engineer life at the level of their DNA b/c who are we to mold life in such a fundamental way. This brand of ethics is not one that I hold. But it of course was (and is) an argument that is sometimes used in response to genetic engineering. It was very prominent when genetic engineering was getting started. 2) We should do no harm. That is we should not engineer the DNA of human embryonic cells that would one day grow up to be a person if there exists the possibility of also harming that person. This should not be done to even attempt to cure a genetic disease if there is a risk of causing harm. Embryonic cells cannot 'volunteer' to be human. I think that we should still proceed to explore this possibility with great caution, however, if only to assess as best as we can know what are the real risks. Maybe the risks are at the same level of what we have today with test tube babies. 3) We should not engineer human DNA to augment the features of an otherwise normal human. I have not yet decided how I should feel about that one.

Jonathan Badger said...

Why would you "have a problem with it"? Presumably because you believe (and I'd agree) that such a mental mutilation of children would be unethical. How is that *not* an ethical problem?

Larry Moran said...

#2 is pretty much common sense and pretty much universal. There will be a few exceptions but for the most part there is no ethical problem there unless you can find a substantial number of people who think we should cause harm.

#3 is something that society has to debate but I've yet to see any really good arguments for banning the procedure as long as it's safe. If you could ensure that your child would grow to a normal height instead of being a giant then why shouldn't you be allowed to do that? Once we have established that it is allowed in some cases, we have established that the principle is acceptable. What's the ethical problem?

#1 counts as an ethical problem because allowing genetic engineering of humans conflicts with other deeply held worldviews. If a substantial percentage of society feels that "playing god" is wrong then there's a conflict. They want to prevent others who feel differently from acting on their view that the procedure is okay. This is the argument that was used to ban cloning in Canada but subsequent polls have revealed that it isn't really the
main objection to cloning. The main objection is the "yuck factor."

Larry Moran said...

We agree that we want to live in a society where children are not physically or mentally abused and we want to discourage the practice of abusing children by modifying their genes for behavior under some (but not all) circumstances. How do I decide which of these are ethical problems and which ones aren't?

Do you have a good definition of ethics that will help me?

Jonathan Badger said...

They are all ethical problems, although some may seem easier than others. There is no universal ethical standard that all people will agree to, but history has shown that people can and do change their opinions as to what is ethical when they better understand a situation. For example, frontal lobotomies were once considered an ethical solution to prevent mentally ill people from being danger to themselves or others but now most people agree that grossly violates the civil rights of the mentally ill as the procedure destroys much of the mental capacity of the patients. But until mental health advocates brought up the ethical problem, society didn't even think about it.

There are a lot of ethical problems with "curing" genetic disease, largely due to the fact that there isn't really a objective definition as to what is a "genetic disease". Sure, very few people would argue in favor of cystic fibrosis, but deafness isn't entirely a disease, as I brought up. Until quite recently, homosexuality was also seen as a disease, and there would be certainly be an ethical problem with straight parents modifying their gay child to be straight (if this is entirely a genetic issue, which is unclear at the moment).

judmarc said...

My guess is that by far the most frequent potential use of this would be to ensure male children in cultures that devalue women.

Petrushka said...

I've been round and round with people regarding deafness. (My academic background is special education.) Deafness is most definitely a handicapped, and to the extent there is a cure, anyone who deliberately withholds the curee from a child is an abuser, in my estimation.

We might give the benefit of the doubt so long as the cure is incomplete, but this thread assumes we have a cure.

You cannot wait until a child is old enough to make a decision. hearing is learned. You can't simply switch it on at age 12. If a child doesn't hear by age two, his brain is permanently affected. the longer you wait, the more unsatisfactory the results of an implant.

Piotr Gąsiorowski said...

I agree. If a case of deafness is curable, it would be inhuman to sacrifice a child's well-being for the sake of protecting Deaf culture.

Larry Moran said...

Jonathan Badger says,

There is no universal ethical standard that all people will agree to, but history has shown that people can and do change their opinions as to what is ethical when they better understand a situation.

You've refused to give a definition of ethics so we really can't have any further discussion. As far as I can tell from what you've written, the proper ethical behavior is decided by majority rule at any given time. So if a majority of Americans vote to ban abortion then that becomes the correct ethics. And if a majority favor the death penalty then presumably it is ethical to hang criminals.

I assume it is currently unethical, according to your view, to advocate for abolishing the death penalty or to ban abortion because the majority has spoken.

Jonathan Badger said...

Anybody with a dictionary can look up ethics to learn that it is the rules of conduct recognized by a particular culture. Obviously this means that ethics changes as culture does. It isn't at all unethical to argue that some feature of current society is unethical. People may or may nor buy the argument, but often times people never considered that there could be any problem with a given feature of society until it was pointed out to them. That's the value of ethicists - to be those critics.

Unknown said...

I think where things go awry is this:
Imagine that modifying the human germ line was proven to be perfectly safe and we knew exactly what the consequences would be for future generations.
One of the key components of any ethical system is the spectrum from intentionalism to consequentialism. Pure intentionalism judges any action by the intention of the actor, i.e. by the consequences the actor forsees, whereas pure consequentialism judges them by the actual consequences, forseeable or not. Most ethics do fall somewhere between them (most legal systems for instance persecute both people who attempt homicide - which is intentionalist - but also negligence where it leads to harm - consequentialist).
Your thought experiment is removing this distinction - if all consequences are known then the intentionalist-consequentialist spectrum collapses. But most ethical questions regarding technology are questions on how to deal with risk. We can't predict consequences perfectly - one of the key reason for this is that we live in a stochastic universe. And the question then becomes one of whether a particualr risk is worth taking. The question: "Should you play the lottery?" is one where you make arguments based on the probability of winning, the thought experiment question "Should you play the lottery if you knew which numbers will be drawn?" is not very helpful here.
Even given this level of understanding of the science involved, there are other associated risk factors. Let's look at the textbook example of heterozygote advantage: Sickle cell anemia. Homozygotes for the SCA allele have SCA, but heterozygotes are immune from malaria. If we remove the SCA allele we erradicate sickle cell anemia. But this leads to susceptability to malaria. We can take that risk away with vaccines, but now we are in a situation where we have to get the vaccines delivered and administered in regions that are often politically unstable. Alternatively we make everybody a heterozygote. And as long as we maintain the germ line editing every generation this works. But again there may be issues with keeping the technology available and if we fail to use it, we would see a generation with about 25% of the population suffering from SCA.

colnago80 said...

This was a problem during the 1 child limit imposed in China. What happened was that female fetuses were aborted in favor of male fetuses, which has resulted in a large surplus of males in the population (I understand that there are some 50 million more males then females in China). This has led to unrest because millions of males are unable to marry. This was an unanticipated consequence of the policy and certainly seems like an ethical problem to me.

colnago80 said...

It should be noted that some of the same ethically based objections were raised when IVF was introduced. These were mostly religiously based objections and often were directed at lesbian women like Mary Cheney, and unmarried women. To this day, the Catholic Church condemns the procedure and has pushed for laws outlawing it, or at least restricted to married women whose husbands are sterile.

Larry Moran said...

Your thought experiment is removing this distinction - if all consequences are known then the intentionalist-consequentialist spectrum collapses.

That's the cool thing about thought experiments.

Jonathan Badger said...

It's cool that reality is ignored? By thought experiment Thalidomide was a great idea for eliminating morning sickness. Too bad about the birth defects that arose...

Unknown said...

The reason to do thought experiments is to strip a problem of confounding factors. Since dealing with uncertainty is one of the main, if not the most central issue in ethics associated with new technologies, uncertainty is not a confounding factor.
As an analogy let's consider the neutralist-selectionist debate through the following thought experiment: All populations are at HWE and stay there. What is the difference in the positions regarding this thought experiment?

Larry Moran said...

The reason to do thought experiments is to strip a problem of confounding factors.

Exactly. So, if safety and predictability aren't an issue, is there any ethical objection to germline modifications?

Unknown said...

Sure. Who controls the process? Will we see a form of racism arising between naturals and G-mods (I grew up on Cyberpunk fiction and FASA games, I still play Netrunner regularly, particularly since its rerelease)? How much does society depend on the technology? To what degree will the ability to modify germ-line DNA lead to a resurgence of genetic determinism?
Guns are a safe technology. They don't go off accidentally if the person operating them knows what they are doing and they are very reliable (front-loading muskets would regularly explode on the firing person and even more regularly not fire at all). Do you think there are no ethical issues involving guns, just because we understand how they work?

Larry Moran said...

None of those "ethical" problems would cause me to vote for a ban on germline editing. How about you? Are they issues that really worry you or are you just reaching for examples?

Mong H Tan, PhD said...

RE: Is it Ethical: Human Germline Genetic Modification or Embryonic Gonadal Genetic Modification!?

Contrary to Larry Moran’s misrepresentation of the “ethics” debate in the Nature article: Don’t edit the human germ line, my answer to the above referenced query is that all human germline or gonadal genetic modifications are unethical -- unless all the biotechnological procedures and consequences of any germline modifications have had been well defined and characterized in, and by, any appropriate animal models!?

Furthermore, experimental safety issues aside, the subsequently genetic developmental issues from any germline modifications are currently unpredictable: as embryonically speaking, the germline modification is much much more complicated biologically and physiologically than the straightforward somatic cell genetic modification -- of which I thought Moran has had not identified nor differentiated from his representation of the germline modification!?

However, the potentially editing of the genes of human embryos could still be further tested with the following observation and precautions: as embryologically and genetically speaking, the human germline transmission is naturally (following gamete formations) and being well conserved or preserved into the subsequently development of gonads, in our human embryos!?

As such, as long as the embryonic gonadal tissues would not be affected, I thought that applying the specific genetic editing, or CRISPR targeted therapy, onto other somatic (or non gonadal) organ tissues is both biomedically and ethically relevant and justifiable -- just as in the case of the 3-person IVF therapy, wherein the parental germline genome would not be affected by the donor mitochondrial genome at all!

Best wishes, Mong 4/9/15usct5:23p; practical science-philosophy critic; author "Decoding Scientism" and "Consciousness & the Subconscious" (works in progress since July 2007), Gods, Genes, Conscience (iUniverse; 2006) and Gods, Genes, Conscience: Global Dialogues Now (blogging avidly since 2006).

Larry Moran said...

Everyone agrees that we should not modify germlines if the procedure is unsafe and/or has unpredictable consequences. Anyone who proceeds under those circumstances is being irresponsible and stupid.

Would it be "unethical"? That's the question. What definition of "ethics" would inform the debate?

TheOtherJim said...

...and witness the same play by the same players regarding the mitochondrial replacement therapy discussion in the UK. I get the feeling that their objections are actually more fundamental and of the "playing god" variety, but they use arguments that resonate with the people they are trying to persuade. For the MRT discussion, it was again about safety and harmed embryos. Amazing the level of concern they have for an embryo, but no concern what-so-ever for a child born with Leigh's syndrome .

Mong H Tan, PhD said...

RE: What definition of "ethics" would inform the debate?

Dear Larry Moran, I thought that is a good question! Now, let me see if I could explain and define the “ethics” issues, as related to the current human germline modification debate, to your satisfaction!?

First a professional disclosure: Although I’m not a “bioethics” specialist, nor do I wish to educate your readers on “ethics” issues, generally and briefly, the bioethics issues are increasingly nowadays being raised, considered, sought after or consulted, and implemented in the clinical settings, especially at least or minimally in alignment with the Hippocratic Oath: First, do no harm; and then, dispense no medicine or treatments or therapies without patient consent, and so on and so forth.

Whereas in regard to the current human germline modification debate: Specifically, unlike in animal models, and unlike in the approved 3-person IVF therapy, the human germline modification procedures have had not yet been perfected, tested, nor approved by any biomedical authorities in any clinical settings, trials or use, at any time soon!?

Furthermore, unlike somatic cell genetic modifications, the still yet unproven germline genetic modifications may complicatedly affect all the subsequently somatic tissues growth and development that would be genetically derived or inherited from the initially-modified germline, or the modified gamete genome!?

Finally and more importantly, time and again, once the germline or gamete genome has had been modified, the subsequently embryonic development of the progenitor cells of all somatic tissues and stem cells may not be currently ascertained nor proclaimed as that same normalcy of their normal or natural counterparts: as the subsequently modified growth and development, or the subsequently modified genetic expressions of any kind of tissues would be probable and possible, including the certain unintended mutation or transformation consequences, such as malignancy or any other tissue-disorders, disease-formations and/or transformations, etc within the germline-modified organism, including the human organism, itself!?

As such, is it ethical so as to modify the human germline genome, even with the currently perfected CRISPR technology, we -- including practical cell biologists, embryologists, geneticists, physiologists, biochemists, et al -- still cannot predict nor artificially control or ascertain the normalcy or malignancy of the embryonic growth and development consequences of the germline-modified gamete; as well as its subsequently somatic cell genetic mutations and expressions in our human organisms or embryos!?

Thus, as long as the human germline modification technology has had not been proven nor approved by biomedical authorities -- including clinical IRBs, FDA, etc -- the experimental application of this technology on human germline modification is unethical: as more often than not, this technology would do harms to the unconsented developing human gametes and/or embryos at any time, as I explained and defined above!? -- QED!?

Best wishes, Mong 4/11/15usct5:13p; practical science-philosophy critic; author "Decoding Scientism" and "Consciousness & the Subconscious" (works in progress since July 2007), Gods, Genes, Conscience (iUniverse; 2006) and Gods, Genes, Conscience: Global Dialogues Now (blogging avidly since 2006).

Larry Moran said...

You have not provided a satisfactory definition of "ethics" Doing sometihing that is unsafe is just plain stupid, not unethical.

I will delete any further comments that link to your articles (see your last paragraph). You have told us about them twice and that's enough.

Mong H Tan, PhD said...

Dear LAM:

I think we have different meanings on "ethics"!? So, briefly 1) Yes, "doing something that is unsafe [to oneself] is just plain stupid, not unethical!"

Whereas 2) in the current human "germline" editing debate and IMHO: Doing something that is unsafe nor predictable biologically -- to others like patients or any developing human gametes or embryos -- is clearly unethical!? Lest one has had already forgotten or forgiven both the Eugenics and the Holocaust of the 20th century!?

Best wishes, MHT.

Larry Moran said...

In my course, we teach that an ethical problem requires a conflict between competing worldviews. True ethical problems are those where most of the members of a given society experience the conflict. Capital punishment might be a good example in the USA (but not in Europe). The various trolley car scenarios are also good examples.

Doing something that wiil harm other people is not usually an ethical issue because nobody really argues that it is a good idea. If germline modification might cause harm to the next generation then this doesn't really pose any ethical problem for most people. It's clearly unacceptable.

Unknown said...

In my course, we teach that an ethical problem requires a conflict between competing worldviews.

Then you should probably modify your course. Ethical problems also arise if for some situation a particular Ethics gives no prescribed course of action. Mostly that's dilemmata, but you could also have polylemmata (where instead of merely 2 possible actions there are many).
Conflicts between ethical systems are fairly trivial, but conflicts within one ethical system are interesting, because they may point to cases where the ethical system is incoherent or where it is incomplete. The trolley car scenarios were mainly proposed as cases where particular versions of utilitarism run into problems. These have a utility function for any outcome and state that you should take the course of action that maximizes it. The trolley car scenarios are build so that for particular utility functions all choices have equal and negative utility. The key point here is the equality - maximizing utility does not help you when all options are equal in this regard.

Unknown said...

It would depend completely on what is proposed and how it is regulated. I'm worried about these issues enough to withhold an opinion until a proposal for what the legal framework for human germline editing would look like is made. I do have issues with how GNO crops are handled and they are to 90% about how patent applications are handled (for instance I would be a lot happier if a patent application had to include an alignment of wild type and modified sequence as a digital file. There have been patents granted for wild type sequences in the past, because patent offices can only deny a patent within a particular timeframe, the sequences came as printouts, but not in digital form, so they had to be typed before you could - say - BLAST them and in batches of 100s of applications. There are easy fixes for all of these).

Larry Moran said...

@Simon Gunkel

I don't understand your point. Could you define what you mean by an ethical problem and give an example? Even better, could you describe an example of a real ethical problem over germline modification? I don't see one that applies to most people in my society.

Jmac said...

I have no idea what you are both debating.

I don't think ethics can be defined in ONE WAY in the Canadian society as Larry claims. There are religious, but there are other issues as well, that need to be taken into consideration in the Canadian society. Possibly more than Larry can think of. Science can't dictate the conscience, which many people claim to have.

Unknown said...

I'm not sure what was unclear about my post. An ethical problem is a case where there are several possible courses of action and there are divergent answers on which on is to be prefered. Ethical systems are basically frameworks that provide an answer to the question "what should be done" for a wide range of situations. It is not surpising that different ethical systems arrive at different answers (though it might be useful as a means to compare them). But scenarios where one ethical system does not give a definitive answer are interesting for that particular system, because it shows either an inconsistency or an underdetermination.