Genetic Engineering: Creating Babies with Three Parents

LJP Cover Page

Naomi Z.

What will the world look like in 50 years? Maybe we will travel in hovercrafts or bullet trains that can take us from New York City to Beijing in a mere couple of hours. Cell phones will be an archaic form of communication; instead we’ll have wristbands or Google glasses that can search for movie tickets, organize schedules, and even project holographic videos. Wealthy families will vacation on the moon. Schools will be conducted via tablets or laptops, where students can download video lectures specially tailored to their interests and specific ways of learning. We’ll have made enormous strides in the medical field. Long gone will be the days where people die from organ failure. Instead, artificial organs can be grown overnight, genetically engineered to be a perfect match. Couples will go through genetic counseling before having babies. For enough money, everything can be chosen, from eye color to athletic ability.

This futuristic vision of the world may be terrifying to some, or thrilling to others. But in the field of science, certain aspects of genetic engineering are transgressing from science fiction into reality, and it’s happening right now.

Dr. Shoukhrat Mitalipov and his team at Oregon Health and Science University have found a way to prevent mitochondrial DNA mutations from being passed from mother to child. The controversial aspects of this technology have rapidly attracted public attention and even concern. If done successfully, a child born using this mitochondrial replacement technique would essentially carry genetic information from three parents – the mother, the father, and a mitochondrial donor (Tavernise).

Of course with media attention, there is always the risk of exaggeration, or misinterpretation of information. Articles in popular media sources have attempted to draw in readers with titles like “Oregon Stem-Cell Groundbreaker Stirs International Frenzy with Cloning Advance” (Budnick). While I’m not sure if the publicity surrounding Dr. Mitalipov’s research amounts to an “international frenzy,” it is undeniable that there have been many objections concerning the research; most of which can be broken down into three categories. First, the elements of the research that make it so controversial. Next, the negative scientific effects that the research could have. And finally, the bigger societal ethical consequences that people fear this research will lead to.

The two main controversial components of this research are stem cell usage and the fact that the babies will have three genetic parents (Tavernise; Budnick). The infamous stem cell debate has been going on for a very long time. Ethicists who are against stem cell research say that embryo research amounts to murder (Sandel 102). The fact that a baby born using this technology will have three genetic parents is also highly controversial. The three parents aspect is unsettling because it seems to be the most unnatural part of the research. Throughout human history, natural reproduction has always occurred with a mother and a father as the biological parents. Now, science has suddenly breached a natural boundary, and scientists possess the skills to engineer children who have three genetic parents.

Several scientists and ethicists alike have stated concerns about the potential negative scientific effects of Dr. Mitalipov’s research. The first concern, and perhaps the most valid, is that we don’t know whether the procedure is safe (Baylis). The procedure has been successfully performed in rhesus monkeys, but has yet to be performed in human subjects (Amato, Personal interview). And though the rhesus monkeys that were born using this technique appear to be healthy, it is impossible to tell whether they will experience health consequences in the future. In addition, some scientists are worried that the technique will introduce new genetic material into our gene pool, and that it could even lead to harmful genetic mutations (Tavernise).

While the concerns regarding direct scientific and societal effects were more specific towards Dr. Mitalipov’s research, the bigger picture ethical consequences often apply to genetic engineering in general. A big concern is that the technology Dr. Mitalipov is using may lead to applications such as genetically engineering children for specific traits, such as height or eye color (Tavernise). The question of whether it is morally acceptable to genetically engineer humans has always lingered in the background of genetic research, but with this recent breakthrough, the possibility of genetically engineering humans is actually becoming a reality. Another concern, is that genetic engineering will eventually lead to the creation of a super human species with enhanced traits, such as hyper intelligence or soldiers that can go for days without sleeping. Scientists also question the necessity of this procedure. Even though there isn’t a cure for mitochondrial diseases, families can avoid passing mitochondrial defects to their children by using options such as adoption or a donor egg (Cerveny). Finally, critics are drawing comparisons between Dr. Mitalipov’s research and cloning technology, which has drawn overwhelming negative response from both the scientific community and the general public (Budnick).

Regardless of the ethics of this technology, it’s important to acknowledge that the research is a huge scientific achievement. Anywhere from 1,000 to 4,000 babies in the US are born every year with mitochondrial diseases (“About”). For comparison, the CDC reports that about 6,000 babies in the US are born every year with Down Syndrome (“Facts”). There are many different types of mitochondrial diseases, from Leber Hereditary Optic Neuropathy (LHON), which only affects the eye, to Myoclonic Epilepsy with Ragged-Red Fibers (MERRF), that affects many parts of the body, including muscles and the nervous system (Chinnery). According to the United Mitochondrial Disease Foundation, symptoms of mitochondrial diseases can include stroke, seizures, blindness, deafness, muscle failure, or liver disease (United).  At this time, there are no cures for mitochondrial diseases, however symptoms can be managed through treatments including conserving energy, avoiding exposure to illnesses, pacing activities, ensuring adequate nutrition and hydration, or vitamin therapy (“About”).

I spoke with Dr. Kara Cerveny, a cell and developmental biologist at Reed College, over Skype to discuss the mitochondrial replacement research in the Mitalipov lab. I didn’t get to meet Dr. Cerveny in person, but her kind personality was evident even through the computer screen. She would often smile after I asked a question and she enthusiastically shared her knowledge with me. “In some respects, I think from an ethical or more societal perspective, I don’t really understand the strong need for this therapy,” says Dr. Cerveny. “That said, I think scientifically, it’s really exciting. I think that the idea that you can manipulate genes and cells in this way could open up lots of doors, maybe even doors that we aren’t even thinking about in terms of therapies for humans” (Cerveny).

Dr. Cerveny also brought up another interesting point. “I mean, the other thing that people don’t really think about, because they’re not biologists, when they have these kinds of difficulties conceiving, is that your child may contain 50% of your genetic material, but depending on how that genetic material is expressed and epigenetically modified, your genetic material may not be expressed to any great level in your child” (Cerveny). This means that even if a child is genetically yours, this physical resemblance may not even come through, depending on how prominently your genes are expressed.

Though the technical aspects of mitochondrial replacement can be complicated, Dr. Cerveny did an incredible job describing the research and its implications in understandable terms. She explained that a person with a mitochondrial disease will probably have both mutated mitochondria and normal, wild type mitochondria (Cerveny). Because of this range of phenotypes, or observable characteristics, some people who have a mitochondrial disease may be severely affected by the disease, while others may not even display symptoms. “So some people will have the disease and be almost, you know, 90% normal and lead almost completely normal lives,” says Dr. Cerveny.  “Other people will have the disease, and because they have almost all mutant copies of their mitochondrial DNA, they’ll have very very severe forms of the disease. And that’s a real hallmark of cytoplasmic inheritance versus nuclear inheritance. Nuclear disease you have the disease, or you are a carrier, or you don’t have it. Whereas mitochondrial inheritance, or cytoplasmic inheritance, you can have this spectrum of phenotypes” (Cerveny).

Dr. Cerveny explained that there are two main applications of genetic engineering. One is using genetic engineering as a tool in scientific research. “In the big scheme, we do this for understanding human health and disease, of course,” Dr. Cerveny says, “but, practically, the very short-term goal is simply to figure out how something works” (Cerveny). The second is using larger scale genetic engineering to provide treatments for patients. The research that Dr. Mitalipov is conducting, would fit into this category of genetic engineering. “So there’s this sort of therapeutic angle of genetic engineering and then there’s the more basic science, tool-based genetic engineering” (Cerveny).

The therapeutic sort of genetic engineering is a lot more controversial, since most of it involves firstly, actually manipulating DNA, and secondly, performing these procedures in humans. “Well, there are several lines where you start to run into more ethical questions,” says Dr. Cerveny. “The first line you cross is, are you doing this in an organism that could somehow harm humans? Could you mutate this bacterium so that it becomes highly contagious? The closer up the evolutionary chain you get to humans, the more and more ethical questions people start to ask about the type of research that they’re doing. As soon as you get to anything that will impact humans, there are huge ethical questions” (Cerveny).

I was able to discuss some of the implications of the mitochondrial replacement technology with Dr. Paula Amato. Dr. Amato, who works with Dr. Mitalipov, specializes in OB/GYN and infertility. We met at her office in the OHSU Center for Health and Healing near the South Waterfront. The modern building has high ceilings and abnormally tall doors. Its sleek and bold lines fit elegantly into the Portland skyline. Todd Murphy, a senior communications specialist, met me in the lobby and led me to Dr. Amato’s office on the tenth floor, which has a breathtaking view of downtown Portland. We made our way through the labyrinth of halls, offices, and labs. I felt like a child wandering through my parent’s work office, getting lost among the identical offices. In the office right before Dr. Amato’s, two researchers were looking at and discussing images on a computer screen. In the office past Dr. Amato’s, a man with his back to the door was making a phone call while surveying the view through his corner office window. The entire floor could have easily been mistaken for a law firm or banking office, had it not been for the occasional box labeled “Hazardous Biological Waste” or posters depicting proper safety protocols.

Dr. Amato has chestnut brown hair that reaches just past her shoulders and intelligent brown eyes. I met her in her office, and she shook my hand with a warm smile before we sat down to talk. I was very interested to find out how scientists, such as Dr. Amato, who are actually conducting the research respond to public controversy. “Any time there’s a new reproductive technology, people freak out,” says Dr. Amato. “And then over time, when we do it and it appears to be safe, people kind of relax about it” (Amato). This pattern of outrage followed by acceptance has appeared before. When in vitro fertilization (IVF) technology was first being used in humans, there was a huge uproar (Banerjee). Objections varied from protest against scientists playing God, to concern over what would be done with leftover embryos, to the fear of turning children into commodities (Banerjee). Today, IVF is a widely accepted technique to help women who have trouble naturally conceiving children.

With all the controversy surrounding the research, it’s easy to forget that there are many regulations to meet and approvals to collect before researchers can even start conducting trials for this type of research. “It took almost, I think two years, to get it through the IRB – which is our Institutional Review Board,” says Dr. Amato. “So there was a lot of oversight, there was a stem-cell committee, and a human subjects IRB that had to approve it. And it was a little bit controversial because it was embryo research. And we were paying the donors, and that was controversial in some circles” (Amato). Unlike Oregon, some states, such as California, do not allow researchers to pay egg donors (Schubert). “So we pay all our egg donors, even our fertility donors – and not just us, I mean that’s pretty widely accepted throughout the United States,” says Dr. Amato. “But for some reason in some states you’re not allowed to pay research egg donors, but that never made sense to me because they undergo the same sort of treatment and process and same risks, etc.” (Amato).  On the OHSU web page seeking egg donations for the study of mitochondrial disease, it is stated that egg donors will receive a full physical exam, a compensation of $5,000 for the egg, and $50 for skin donation, and a negotiable travel reimbursement (OHSU).

Some states don’t allow egg donors to be compensated because they think the monetary reward will lure women into donating eggs regardless of the risks involved in the procedure. Women who decide to become egg donors must undergo several rounds of hormonal treatments that cause their ovaries to produce many eggs in one cycle (Lahl and Tarne). There are short term risks from this procedure, such as Ovarian Hyper-Stimulation Syndrome, as well as unknown long-term effects, such as possible increased risks of developing cancer or possible harm to the donor’s fertility (Lahl and Tarne).

This mitochondrial replacement is in fact so innovative that the UK is considering changing one of its laws to allow research for the procedure to be done. Current laws in the UK forbid a genetically modified embryo to be implanted in a woman’s uterus (Lahl and Tarne). The procedure has been approved so far by the Nuffield Council of Bioethics (Sample). If the procedure gets a green light from parliament, the UK will become the first country to start offering this treatment in humans (Sample). The Human Fertilization and Embryology Authority in Great Britain has suggested that the mitochondrial donor be considered as a tissue donor (Sample). Therefore the child will not have the right to find out who their mitochondrial donor is (Sample).

In the United States, Dr. Mitalipov is still waiting for approval from the FDA (Amato). Dr. Mitalipov presented to the FDA last February, but depending on how long the FDA takes, it could be years before actual human trials take place (Murphy). Based on the current situation, it is entirely possible that the technique may first be performed in humans in a country other than the United States (Amato, Personal interview).

I also asked Dr. Amato about the concerns that this technology could lead to less benevolent applications, such as the notorious fear of selecting for certain traits, such as hair color or intelligence. Dr. Amato explained that this wasn’t a concern since mitochondrial DNA and nuclear DNA are two separate things (Amato). The technique that Dr. Mitalipov has invented involves transferring the nucleus from the mother’s egg into a donor egg that has had its nucleus removed. Since mitochondria is only present outside of the cell’s nucleus, this technique ensures that the baby will carry its mother’s DNA in a donor egg devoid of the mitochondrial defects.

In case you haven’t recently taken a high school biology class, mitochondria are about the size of bacteria, and they are scattered throughout the cell’s cytoplasm (de Duve). Their basic role is to provide energy for the cell (Lahl and Tarne). Mitochondria have their own separate genetic system, which means that they are not controlled by nuclear DNA (deDuve). Nuclear DNA is found in the nucleus of all cells: 50% of this DNA will be from the mother, and 50% from the father. However, mitochondrial DNA is inherited solely from the mother, and is found in the fluid surrounding the nucleus, known as the cytoplasm.

“Many of the characteristics that people get really worried about us selecting for are multigenic traits,” says Cerveny. “So like intelligence, or even height, weight, all those types of things” (Cerveny). However, the environment that we grow up in and live in has a huge impact on our genes. “There’s almost always some sort of interaction between the genes and the environment,” says Amato (Amato).

Dr. Amato took us down a couple of floors to the lab where much of the research and procedures are done. From the outside, the lab door is rather inconspicuous, albeit huge. Dr. Amato waved her badge in front of the security pad, and as the light bleeped green we entered into a short hallway leading to a spacious lab filled with rows of matte black lab benches. Above and below the desks were drawers and shelves packed tight with beakers, cardboard boxes, and carefully labelled containers. Even the lab desks were covered with labware and other various supplies. The walls were decorated with various machines, hooks for aprons, and drying racks for labware. This wasn’t some sort of impeccably white and clean lab that you often see in science fiction movies; this was the type of lab where research, along with all its mess and materials, took place.

The three rows of lab benches to the far left were marked “Mitalipov Lab”. Dr. Amato led me down one of the aisles where someone working in the lab was depositing tiny amounts of liquid into equally tiny test tubes. The researcher excitedly relayed information to Dr. Amato concerning the growth of some of the embryos. We circled around the lab benches towards a separate room, where the mitochondrial replacement actually took place. Due to lab protocols concerning sanitation and contamination, I wasn’t allowed into this room. But through the window in the door, I was able to catch a glimpse of many complicated and expensive-looking microscopes with countless knobs covering the desk that ran along the wall.

It was surreal to contemplate the enormity of the research happening in this lab. It struck me how incredible it is that the Mitalipov lab is able to perform a mitochondrial replacement on something as tiny as a human egg. Even more incredible, is the realization that research on something as tiny as a human egg, is forcing us to consider the tremendous questions of genetic engineering and what it means to be human.

“When people hear about any kind of genetic engineering they worry about things such as eugenics and trying to make a perfect baby,” says Amato. “And that’s not really our intention. We’re not using this to enhance traits or to make babies smarter, or taller, or better looking. It’s more about treating – or preventing – a serious disease” (Amato).

Something that Dr. Amato and Dr. Cerveny both agreed on, was that despite ethical considerations, it is still a good idea to continue researching genetic engineering. “I don’t think it’s ever a good idea to ban research,” says Dr. Cerveny. “Because as soon as you ban something somebody’s going to do it and then you have no… sort of way to keep track of it. It just becomes more sinister” (Cerveny).

“You know, the technology, like any technology, could always be misused,” says Dr. Amato. “But that’s true of military technology and computer technology. It doesn’t mean we shouldn’t do it just because, you know, potentially some people might misuse it” (Amato). The more we know about genetic engineering, the more potential applications we will be able to find for it.

“As we learn more about how diseases are related to our genes, I think there will be more and more applications,” says Dr. Amato. “But I always think it’s important to remember that we’re more than just our genes”.

Works Cited

“About Mitochondrial Diseases”. Mito Action. Mito Action, n.d. Web. 1 Dec. 2014.

Amato, Paula. Personal interview. 17 Nov. 2014.

Amato, Paula, Masahito Tachibana, Michelle Sparman, Shoukhrat Mitalipov. “Three-Parent in Vitro Fertilization: Gene Replacement for the Prevention of Inherited Mitochondrial Diseases.” Fertility and Sterility. 101.1 (2014): 31-35. Web. 16 Nov. 2014

Banerjee, Amit. “An insight into the ethical issues related to in vitro fertilization.” The Internet Journal of Health. 6.1 (2006). n.p. Web. 18 Nov. 2014.

Baylis, Françoise. “The Ethics of Creating Children with Three Genetic Parents.” Reproductive BioMedicine. 26 (2013): 531-534. Web. 22 Oct. 2014.

Budnick, Nick. “Oregon Stem-Cell Groundbreaker Stirs International Frenzy with Cloning Advance.” Oregon Live. Oregon Live LLC. 4 June. 2013. Web. 2 Dec. 2014.

Cerveny, Kara. Personal interview. 14 Nov. 2014.

Chinnery, Patrick. “Mitochondrial Disorders Overview.” Gene Reviews. (2014): n. pag. Web. 1 Dec. 2014.

de Duve, Christian. Guided Tour of the Living Cell. 1st ed. Vol. 1. New York, NY: W. H. Freeman and Company, 1984. Print. 2 Vols.

“Facts about Down Syndrome.” Centers for Disease Control and Prevention. Division of Birth Defects and Developmental Disabilities, NCBDDD, Centers for Disease Control and Prevention, 7 Aug. 2014. Web. 22 Oct. 2014.

Lahl, Jennifer, and Gene Tarne. “UK Government Approves Genetically Engineered ‘Three-Parent’ Embryos”. 2 April 2013. Web. 19 Nov 2014.

Murphy, Todd. Personal interview. 17 Nov 2014.

OHSU. “Egg Donation Study for Mitochondrial Disease.” OHSU Center for Women’s Health. Oregon Health and Science University. n.d. Web. 19 Nov. 2014.

Sample, Ian. “Britain combats ‘three-person embryos’ to combat genetic diseases.” The Guardian. The Guardian. 20 March 2013. Web. 19 Nov 2014.

Schubert, Charlotte. “California Bill Poised to Lift Restrictions on Egg Donation.” Nature. 18 June 2013. Web. 19 Nov. 2014

“Shoukhrat Mitalipov.” Oregon National Primate Research Center. Oregon Health and Science University. n.d. Web. 17 Nov. 2014

Tavernise, Sabrina.  “His Fertility Advance Draws Ire.” The New York Times. The New York Times Company. 17 March 2014. Web. 23 Oct. 2014.

United Mitochondrial Disease Foundation. “Understanding Mitochondrial Disease.” United Mitochondrial Disease Foundation. United Mitochondrial Disease Foundation. n.d. Web. 19 Nov. 2014.

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