Welcome to Bioethics for Believers!

Welcome to Bioethics for Believers! This is the author’s companion website for Biomedicine and Beatitude: An Introduction to Catholic Bioethics by Fr. Nicanor Austriaco, OP, published by the Catholic University of America Press.

This website will allow me to provide bioethical commentary on current developments in medicine and technology from the perspective of the Catholic moral tradition, to complement the narrative in the book.

If you have any questions that you would like me to consider for this website, please do not hesitate to send me an email: bioethics4believers@gmail.com.

A Catholic Case for Germline Gene Therapy

With the revelation that Chinese scientists have successfully edited the genomes of two young baby girls, there has been much soul-searching among ethicists, scientists, and policy makers regarding the morality of using CRISPR and other gene-editing techniques to introduce heritable genetic modifications into the human genome.

Should scientists be able to modify the genome in the human germline, i.e., the sperm cells and egg cells that contribute to the next generation of individuals? If so, then the therapeutic effects of gene therapy would be transmitted to the offspring of the individual.

On one side of the secular debate, there are those who are opposed to editing the human genome in a heritable way. They are concerned that we could never be able to predict the long-term effects of editing the genome of a baby. Instead, they propose that in vitro fertilization (IVF) coupled with prenatal genetic diagnosis (PGD) to select only healthy embryos for implantation in their mother’s uterus, would be better options for parents who carry the same mutation for a disease. The authors oppose any germline modifications because “permitting even unambiguously therapeutic interventions could start us down a path towards non-therapeutic genetic enhancement.”

On the other side of the debate, there are others who propose that editing the human genome to prevent future generations from suffering and inheriting disease is a laudable goal. These ethicists and scientists want to initiate a conversation among stakeholders to identify responsible uses of CRISPR that realizes “the promise of curing genetic disease.”

Which side of this debate should the Catholic bioethicist favor?

To respond, let us consider the following clinical scenario: Assuming that scientists are able to create a safe, efficient, and reliable protocol to edit the human genome, should we use this technology for gene therapy of single-gene disorders?

Single-gene disorders are genetic diseases where a definitive link between a specific genetic mutation in a single gene and a genetic disease has been confirmed. Examples of single-gene disorders include Huntington’s disease and cystic fibrosis and polycystic kidney disease.

In principle, CRISPR gene editing could be used to correct the specific genetic mutation, restoring it to the non-diseased version found in the normal human genome. This would forever eradicate the disease from the family’s bloodline. No children would be at risk for getting this disease again

Note that this clinical scenario, where it is assumed that human gene therapy is already safe, efficient, and reliable, would put aside the Vatican’s concern that human gene editing would be dangerous to the human baby.

In Dignitas personae, its most recent statement on gene therapy, the Congregation for the Doctrine of the Faith cautioned: “Given that gene therapy can involve significant risks for the patient, the ethical principle must be observed according to which, in order to proceed to a therapeutic intervention, it is necessary to establish beforehand that the person being treated will not be exposed to risks to his health or physical integrity which are excessive or disproportionate to the gravity of the pathology for which a cure is sought” (no. 26).

Returning now to our clinical scenario, I begin by noting that we already acknowledge that it is a great good to prevent disease in our children. Spina bifida which means “split spine” in Latin, is a birth defect where the backbone does not develop completely leaving the spinal cord exposed. Children with severe forms of spina bifida suffer in different ways. Spina bifida is easily prevented by taking 400 micrograms of the B-vitamin, folic acid every day. Not surprisingly, pregnant women are advised to take their daily vitamin pill, precisely because it is a great good to ensure the health and well-being of our children.

For the same reason, I believe that it would be a great good for us to use a safe, effective, and reliable gene editing technology to correct a single-gene mutation if we knew that this would prevent a child from inheriting a disease. And it would be a great social good for us to help parents who are carrying a disease mutation to achieve this great good. Again, this assumes that the gene therapy is safe, effective, and reliable.

But what about those who are concerned that allowing gene therapy would inevitably lead to the illicit use of gene editing to create designer children? This slippery slope argument would only apply if there were other options for achieving the great good of ensuring that healthy children are brought into the world. If no other viable options existed, then we would have reasons to strive for the good while avoiding any evils that could also result.

There is an opioid crisis in the United States that has led to the overdose deaths of hundreds of thousands of people. Despite this great evil, there are still good uses of opioids, especially for pain control. It is not surprising therefore that we are not arguing that we should ban all opioid use because of the evil that could result.

In the same way, it is not reasonable to argue that we should ban the use of safe, effective, and reliable gene therapy, only because it could or even would lead to abuse. If germline gene therapy can be used for good, then it should be used to achieve that good, especially if there are no other good alternatives.

Opponents of germline gene therapy have argued that IVF and PGD together could be used to select for healthy embryos whose genes have been edited. Diseased embryos could be discarded. Tragically, however, this approach inevitably instrumentalizes and commodifies the human being, treating him as a product that is manufactured, subjected to quality control, and, if found defective, discarded and destroyed. It is a therapeutic strategy that fails to acknowledge the intrinsic dignity of the human person from the moment he comes into being as an organism.

As the Vatican has noted, again in Dignitas personae: This sad reality, which often goes unmentioned, is truly deplorable: The ‘various techniques of artificial reproduction, which would seem to be at the service of life and which are frequently used with this intention, actually open the door to new threats against life’” (no. 15).

Returning once again to our clinical scenario, I therefore have to make one additional caveat: For germline gene therapy to be morally acceptable to the Catholic, it must eschew IVF and all the other forms of artificial reproductive technology (ART) that replace the conjugal act.

Thus, the only form of germline gene therapy that would be licit in the eyes of the Catholic moral tradition would involve altering the genomes of gonadal stem cells. These are the stem cells that give rise either to sperm (spermatogonial stem cells) or to eggs (oogonial stem cells) in the human body.

In principle, CRISPR could be used to correct a genetic mutation in these gonadal stem cells so that they could produce normal sperm or eggs, once they are put back into the patient’s body. Human spermatogonial stem cells have already been identified and isolated from men. And there is data that suggests that female mammals have oogonial stem cells that develop into healthy eggs in the adult ovary, that could, when fertilized, develop into healthy baby progeny under natural conditions.

One additional advantage for this gene therapy approach using gonadal stem cells is that it would allow scientists to make sure that the genetic modification made in the stem cells is accurate and safe before it is introduced back into a human patient.

In sum, I believe a robust Catholic case can be made for germline gene therapy, as long as the technology is proven safe, effective, and reliable. It is a great good for parents to bring healthy children into the world, and gene therapy is good because it can be used to achieve this great good.  

Using CRISPR Gene Drives for Pest Control

For millennia, farmers have had a pest control problem with rats and mice. These rodents are carriers for numerous diseases, some of which are harmful to human beings, and are capable of contaminating food and water supplies. Several years ago, a scientific paper reported that German and Spanish mice are rapidly evolving resistance to some of the strongest chemical poisons used for pest control prompting scientists to look for the next generation approach to pest control.

Two weeks ago, a team of scientists at the University of California, San Diego, described their efforts to use CRISPR for pest-control measures against rodents. As I described in an earlier blog post, CRISPR is a gene editing tool that allows scientists to make precise changes to the DNA of any organism, including humans. It can be used to remove genes, to add novel genes, and to change genes in specific ways that alter their function.

In their paper published in Nature a couple of weeks ago, the San Diego group used CRISPR to make mice whose DNA includes a genetic cut-and-paste machine, called a gene drive, that makes them able to pass on a gene to more than 80% of their offspring. Usually, mice and humans can only hand on their genes to 50% of their pups because each individual inherits one gene from its father and another from its mother. Gene drives had already been built for flies and mosquitoes.

In principle, a gene drive can be used as a mechanism for pest control in the following way: Mice would be genetically engineered so that their DNA would contain a gene drive mechanism that carries and propagates a gene that would make the mouse infertile. Over several generations, the proportion of fertile mice in the population would decrease, leading to a drop in the absolute numbers of rodents. A CRISPR gene drive has already been developed that could wipe out an entire population of disease-carrying mosquitoes in about eight to twelve generations.

How are we to think about the ethical ramifications of this emerging technology? First, I think that most would agree that controlling the size of a population of pests, whether they are rodents or mosquitoes, can be justified because of its positive impact on the common good.  There are clear benefits for the health and well-being of human populations when we decrease the numbers of pests that spread human disease or destroy food stocks. We already do this routinely with chemical pesticides that kill mosquitoes, rats, and mice. Indeed, a CRISPR gene drive would not kill the pests, which would be morally significant for some. Rather, the gene drive would simply sterilize them. Is this not a more ethical approach to pest control?

In my view, in principle, I can see the social goods that could be brought about by this technology. However, my primary moral concern with CRISPR-based pest control systems is that we cannot really anticipate the ecological impact of this technology at this time. I am concerned that eradicating a population of pests, which in itself could be beneficial to some, could destabilize our fine-tuned ecologically system in unexpected ways that would poison the common good by triggering widespread ecological damage.

I am especially concerned because I do not know if we could undo this damage once CRISPR-engineered gene drives are released into the wild. We can always stop using chemical pesticides, but it is not clear if we can stop using a gene drive. Therefore, if this technology is to be advanced for the purpose of pest control, I think that it needs to be constructed in a reversible manner that would allow us to bring back a pest population from the verge of extinction. We may be surprised to discover that some pests may be essential parts of an ecological whole, of which we too are only a part.

The Ethics of Cloning Pets and other Domestic Animals

A couple of days ago, a newspaper article reported that a celebrity dog was cloned in China. Named “Justice”, the canine earns substantial amounts of money for its owner as a popular canine actor.

For historical context, it is important to know that farmers in the USA have been cloning livestock for the past twenty years to produce breeding stock. Animals with desirable traits like disease resistance, fertility, and market preference, are often cloned to retain these traits.

Pet dogs were first cloned in South Korea nearly fourteen years ago. Barbra Streisand recently cloned her beloved 14-year old Coton du Tulear. Companies like Sooam Biotech in South Korea and ViaGen in Texas offer a pet cloning service to those very few who can spend tens of thousands of dollars on the technology.

The cloning of human beings has been universally condemned – rightfully so, in my opinion – but little has been said about the ethics of cloning of animals, especially of domestic animals. Should we clone them?

I think we need to begin by reflecting upon the role that animals play in creation. As the Catechism of the Catholic Church teaches animals are, first and foremost, God’s creatures (CCC, nos. 2415-2418). By merely existing, they bless Him and give Him glory. Thus, we have to treat them with kindness and with respect.

However, it is also clear from the sacred Scriptures that God entrusted them to the stewardship of those whom He created in His own image and likeness. Hence, as the Catechism makes clear, it is legitimate to use animals for food and clothing. They can be domesticated to help us in our work and our leisure. And they can be used for medical and scientific experimentation as long as that experimentation is reasonable and contributes to the well-being of human beings.

We obviously can do a lot with pets that we cannot do with human beings. We can buy and sell them. We can breed them at will. We can pamper and dress them. We can kill them. We can even eat them.

But there are still ethical limits to what we can do with them and other domestic animals precisely because we are their stewards. We have a moral obligation to care for them in a reasonable manner. We are also morally obligated not to cause them unreasonable harm and suffering. The best pet to have is a happy and healthy pet.

We can do a lot with our pets, but should we clone them?

Cloning involves the process of first taking the immature eggs of a female animal – in the case of the cloning of “Justice”, from a female dog – and removing its genetic material. The DNA of the animal to be cloned is then transferred into this empty egg. This donor DNA can easily be obtained. In Justice’s case, his DNA was taken from skin cells scraped from his lower abdomen.

Once the egg is reconstituted with the donor DNA taken from the animal to be cloned, it is activated to become an embryo, which is then transferred into a surrogate female who carries it to term. Since the embryo is formed and moved by the donor DNA, it resembles the donor like an identical twin does. Notably, however, the failure rate of animal cloning is high. Typically, only 10% or so of cloned animals survive the process.

Does cloning harm the cloned animal? As the Food and Drug Administration’s Center for Veterinary Medicine explains, there are no complications that are unique to cloning. The biological problems that are sometimes seen with cloned animals are also seen in animals that are born after a natural mating or with artificial reproductive technologies. For the most part, cloned animals are healthy and behave just like conventionally bred animals.

Opponents of pet cloning have raised several objections. Bioethicist Jessica Pierce believes that the practice of animal cloning leads to the “exploitation of the canine underclass.” The Humane Society of the United States and People for the Ethical Treatment of Animals oppose cloning because these organizations believe that it involves the wasteful use of economic resources that should be used instead to care for the millions of abandoned dogs waiting for an adoptive home. In their view, cloning is an abusive use of power.

In my view, there is nothing intrinsically immoral about the cloning of animals. If we can buy and sell animals, and kill and eat them, then we should be able to clone them, again as long as we care for them during the process, we do not cause them unreasonable suffering, and we clone them for legitimate reasons that contribute to the well-being of human beings.  

For instance, I can imagine scenarios where the cloning of an animal of a particular genetic makeup would benefit scientific research or agricultural production. I do not think that this would be morally illicit. Animals can be used in reasonable ways that genuinely benefit human beings.

However, I do have ethical concerns about the cloning of pets. To justify the cloning of pets, we have to be able to show that it contributes in some reasonable way to the well-being of some human individual or individuals.

I do not think that this can be done. Owners who want to have their pets cloned expect to get their beloved pet back. In their view, this would help with the grief that comes with the loss of the pet.  

But this simply can never be the case. A cloned puppy may look like the original foo foo dog, but it is not the original animal. Though the original and cloned canines have the same genes, genes are not enough to determine the entire makeup of an individual animal.

As Barbra Streisand herself noted, her cloned dogs may look like her beloved Samantha, but they certainly do not behave like her. Individual pets are singular creatures with their unique traits and characteristics.

Thus, cloning cannot truly restore a beloved pet to an owner. It can only provide him or her with a very good facsimile of the original canine. But if this is the case, then there truly is no need for a pet to be cloned. One could simply obtain another similar animal to replace the loss of original. This would be a cheaper and more reasonable response to the death of a beloved pooch that acknowledges the individuality of animals, the grief of loss, and the hope of new beginnings.

It would also forego the loss of animal life – the 90% of cloned animals that die during any attempt to clone one pet – that truly cannot be morally justified without a proportionate benefit for human beings.

Responding to the Vatican’s Recent Responsum on Hysterectomies

An ob-gyn who has just delivered a new born baby after a caesarian section realizes that his patient’s uterus has been so weakened by the previous five caesarians she has had over the past ten years that he does not think that he can repair the woman’s womb. Instead of attempting to repair the structurally unsound womb that he knows will not be able to sustain a future pregnancy, may the ob-gyn perform a hysterectomy and remove the uterus instead?

The Congregation for the Doctrine of the Faith (CDF) at the Vatican has just published a doctrinal note, called a responsum, addressed to individuals who have wondered if it is morally permissible to remove a woman’s uterus if it is deemed unable to sustain a future pregnancy. The medical concern here is that a future pregnancy would put the mother’s life and the life of her unborn child in great risk because of the structural weakness of the womb. The CDF has replied that such a medical procedure would be morally acceptable because it does not constitute an act of direct sterilization.

To put it another way, according to the CDF, the ob-gyn described above could remove the uterus instead of repairing it. He would not be performing an act of direct sterilization, which would be immoral in itself. Why is direct sterilization immoral? Because it would deprive a person of her ability to procreate, in the same way that an act to blind someone would deprive the individual of his ability to see. Both would be acts of mutilation.

The precise medical diagnoses that prompted this note from the CDF were not specified. Historically, as we described above, the medical concern has been raised by women who have had multiple caesarean sections that have detrimentally weakened the structural integrity of the uterus and are therefore at risk for uterine rupture. Uterine rupture during pregnancy is considered a catastrophic complication that puts the lives of both the mother and her unborn child into immediate jeopardy.

Though I agree with the moral conclusion proffered by the CDF, I find the rationale they provide to support their proposal to be ambiguous and potentially confusing for two reasons.

First, in the classical account of human acts, an act is defined by its object. In its Responsum, the CDF proposes that object of the act of procreation “is to bring a baby into the world.” This is inaccurate. The object of the act of procreation is the generation of an individual of the same specific kind. This occurs when the sexual gametes fuse during conception. Thus, we say – correctly – that a couple who has conceived a child but who have suffered a miscarriage have already procreated even if they have not brought a baby into the world. We all agree that they are already parents.

The uterus is an organ ordered not towards procreation but to gestation, which is the act of nourishing and protecting an immature human being until he is able to survive outside the uterine environment. However, a hysterectomy can still be anti-procreative, not because it prevents an immature human being from being brought to term, but because it can prevent conception from happening in the first place.

Second, the CDF proposes in the Responsum that in the medical scenario that we are discussing here, “we are not dealing with a defective, or risky, functioning of the reproductive organs.” This is true, but it is also potentially misleading. We are not dealing with a defective functioning of the uterus, but we are dealing with a defective uterus. The organ itself is defective.

Consider: Any organ that is not able to realize its end is defective. An eye that is unable to see is defective, and a heart that is unable to pump blood in the circulatory system as it should is also defective. Thus, a uterus that is not able to gestate an immature human being until he is viable is not able to attain its end, and is therefore defective. It is a defective organ even if the woman is not pregnant.

Furthermore, we are dealing with a defective organ whose continued existence in the woman’s body, because it is defective and unable to attain its proper end, could place the life of the woman in grave jeopardy in the future. As such, I believe that its surgical removal can be justified by the principle of totality.

Recall that the principle of totality, as it was articulated by St. Thomas Aquinas, justifies the removal of a part of the body if it is decayed and therefore a source of corruption to the whole organism (cf. Summa theologiae II-II.65.1). Over the centuries, Catholic moral theologians have appealed to the principle of totality to justify different scenarios that involved the sacrifice of a bodily organ for the sake of the whole human organism

In light of this moral tradition, I propose that removing a structurally unsound uterus, when “medical experts have reached the certainty that an eventual pregnancy will bring about a spontaneous abortion before the fetus is able to arrive at a viable state” is an act that can be morally justifiable by the principle of totality because the continued presence of the now defective organ in the woman’s body places her long-term health and well-being at risk. As such it can be surgically removed.

An analogous scenario obtains with patients with chronic kidney disease. A failing kidney is at grave risk for turning malignant in the future. It would not be unreasonable, therefore, and I think that it is also morally justifiable by the principle of totality, for surgeons to remove a failed kidney even if it is not yet cancerous. Notice that in this case the removal of the failed kidney is not an act to prevent cancer. The patient may never have gotten cancer. It is an act to remove a non-functioning, defective organ whose ongoing presence in the patient is a risk to his long term well-being and health.

Next, though the act of removing the structurally unsound uterus is in itself an act that sterilizes the woman because it would prevent any future conceptions occurring after the conjugal act, this surgical procedure can still be justified by the principle of double effect. Here, the sterilization is a foreseen but unintended consequence of a surgical act whose object is to remove a defective organ whose continued presence in the woman’s body places her health and long-term well-being at risk.

Finally, in light of my moral analysis, I do not think that one can justify tubal ligations in this medical context. Here, the surgical procedure is done to ensure that conception does not take place. It is a direct act of sterilization. It is not an act to remove a defective organ whose continued presence endangers the long-term health of the woman.

The Case Against CRISPR Babies

[First Published on First Things on December 12, 2018]

A few days after Thanksgiving, a Chinese scientist named He Jiankui shocked the global community by announcing that he had created the world’s first gene-edited, designer babies—twin girls named Lulu and Nana. The two “CRISPR babies” had been born a few weeks earlier to their HIV-positive father Mark and his wife, Grace. Many scientists expressed anger and frustration at the announcement.  U.S. National Institutes of Health Director, Francis Collins, described Jiankui’s work as a “profoundly unfortunate,” “ill-considered,” “unethical,” “scientific misadventure” that “flout[ed] international ethical norms.”

CRISPR is a cutting-edge, molecular editing tool that can be used to alter every gene in any organism, whether it is an elephant, an orchid, or a human infant. If you imagine the human genome—the genetic information found in most of our cells—as an encyclopedia of forty-six volumes with approximately six billion letters, CRISPR gives us the power to change the letter “A” on column two of page 1311 of the third volume of that encyclopedia to a “C.” In theory, we can now edit the genes of any child at will to create designer babies with specific characteristics and desirable traits.

Theory became reality when Jiankui used CRISPR to edit Lulu’s and Nana’s genomes. Using standard IVF procedures, he and his team fertilized their mother’s eggs with their father’s sperm and then injected CRISPR into the embryos as soon as they had formed. The research team attempted to edit the twins’ CCR5 gene so that it would resemble a variant of the same gene, found among 10 percent of Europeans, that makes a person relatively immune to HIV-AIDS. After testing the embryos to determine if their CCR5 genes had been edited, Jiankui and his colleagues implanted them into Grace’s womb, and she gave birth to the girls in November. Jiankui has argued that he undertook this experiment so that Lulu and Nana would be genetically vaccinated against the HIV virus that had infected their father.

The scientists and ethicists who are critical of Jiankui’s work have three major concerns. First, and most worrisome to me: It is not clear if the Chinese team’s CRISPR technology was even safe enough to use with human subjects. At this time, CRISPR is prone to off-target mistakes that alter the genome at random sites other than the intended target gene. Returning to the encyclopedia image, off-target mutations would involve changing a random “C” to a “G” on the wrong page of the wrong volume of the text—a mistake that could increase a patient’s risk for cancer and other life-threatening diseases. Though Jiankui claimed that he and his team found no mistakes in either Lulu’s or Nana’s genomes, they were not able to check every single gene in each of their cells. They failed to adhere to the foundational ethical principle of medicine: Primum non nocere. First, do no harm.

Second, it is not clear that there was a medical need for this particular genetic intervention. Jiankui claimed he wanted to immunize the girls from their father’s HIV. However, there are simpler, cheaper, and less controversial ways of reducing the risk of HIV transmission from father to daughter. Moreover, editing CCR5 reduces, but does not eliminate, the risk of HIV infection. The virus can use another molecular doorway called CXCR4 to enter human cells. In fact, changing the CCR5 gene actually makes a child more susceptible to infection from the West Nile and Japanese encephalitis viruses. Therefore, critics contend that Jiankui took advantage of a vulnerable couple struggling with the stigma of HIV-AIDS to undertake an experiment that had no clear benefit that would outweigh the inherent risks of every genetic intervention.

Finally, critics are concerned that the work of rogue scientists like Jiankui could undermine and delegitimize CRISPR. There are numerous laboratories and biotech companies around the world exploring how CRISPR might ameliorate and even cure many genetic diseases. Just a few days ago, the U.S. Food and Drug Administration approved an application from Editas Medicine in Cambridge, Massachusetts, to begin human clinical trials that use CRISPR to treat Leber Congenital Amaurosis type 10 (LCA10), an inherited disease that leads to vision loss and blindness. The worry is that this high-profile Chinese scandal and others like it could hold back genuine scientific progress like this exciting clinical trial. As Francis Collins put it, “should such epic scientific misadventures proceed, a technology with enormous promise for prevention and treatment of disease will be overshadowed by justifiable public outrage, fear, and disgust.”

These are legitimate ethical concerns. But in my view, they do not address the central moral question raised by CRISPR and other gene editing technologies: Putting aside the moral concerns raised by IVF, which are many, what are the ethical parameters for tinkering with the lifeblood of our children and grandchildren? Should we even be allowed to change the genes of future generations of persons? As I have explained in more detail elsewhere, I think a reasonable case can be made to justify therapeutic interventions that alter the genomes of individuals, both young and old, born and unborn, as long as the genetic surgery is safe and therapeutically beneficial. If it is a great good to heal a child from a genetic disease, then it should also be a great good to prevent him from getting sick in the first place.

However, once the CRISPR technology is deemed safe and effective, it will be difficult for our postmodern and pluralistic society to establish limits for the genetic engineering of our children. I do not believe our commonweal will have the moral courage to tell Manhattan parents, who are willing to pay hundreds of thousands of dollars so that their four-year-old toddlers can attend luxury preschools, that they will not be allowed to spend a meager few thousand dollars to endow those same children with desirable genetic traits thought to be personally and socially advantageous. The advent of designer babies is upon us.