FDA examines genetic tinkering

(Excerpted from "FDA raises concerns about three-parent embryo procedure," USA Today, February 26, 2014) - In two days of hearings ending Wednesday, a federal committee proved quite skeptical about research that might help some patients birth healthy children — but might also open the door to human gene manipulation. The procedure being considered, called mitochondrial transfer, would mix the genes of two women in hopes of creating a healthy baby.

Although the panel, which advises the federal Food and Drug Administration, did not take a vote, many members questioned the ethics of the procedure, and whether the research into it is as far advanced as some supporters claim.

All people carry two sets of genes in every cell: the 20,000 genes in the cell's nucleus, which determine traits like height, eye color and intelligence; and the 37 genes in the mitochondria, which provide energy for each cell. The mitochondrial transfer procedure would combine the nuclear genes from the mother with the mitochondrial genes of a donor woman. When fertilized, it would lead to babies with genetic material from three "parents."

The procedure promises to help women who carry defective genes that can lead to devastating mitochondrial problems in children, including blindness, organ failure and stroke. It might eventually also help resolve some types of infertility.

The committee considered what scientists would need to do before they could try the technique in people, and whether it would be possible to design a clinical trial to answer the many outstanding questions about the procedure. David Prentice, a cell biologist and senior fellow for life sciences at the Family Research Council, a conservative advocacy group, told the panel he strongly objects to any mixing of genetic material.

"The individuals created are experiments," he said by phone after the meeting ended. "You're actually creating and destroying young human life which we object to. It just seems a very wrongheaded way to proceed."

Commentary

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CMDA CEO Dr. David Stevens debated this issue with Ethicist Arthur Caplan on the Fox and Friends national news program, cohosted with Elisabeth Hasselbeck this morning. Dr. Stevens noted the destruction of human embryos in the proposed procedure and non-destructive alternatives to pursuing the cure. He also highlighted the ethical issue of foisting genetic changes, with unknown consequences, on successive generations.

"Germ line manipulation is something that has been prohibited in science all over the world up until the present time," Dr. Stevens noted.

Dr. Caplan replied, "I understand the concern about where we might go. I'm going to worry about that when I get there."

Watch the video here

CMDA CEO David Stevens, MD, MA (Ethics): “Dr. Caplan is not a scientist so maybe he doesn’t understand the grave dangers that germ line manipulation can cause. In some mice studies using ‘mitochondrial replacement therapy,’ there were decreased survival rates, developmental delays, fertility problems and behavioral changes in progeny. No one knows what will happen if it is tried in humans, but we do know that if problems occur, they will continue through every generation. We should be worrying about that now, not when ‘we get there.’ By then, it will be too late.

“As an Ethicist, Dr. Caplan should be concerned that the scientists experimenting on the unborn can’t get informed consent from that child’s granddaughter before doing experiments that will affect her life. He should be concerned that two of the methods of replacing ooplasm require cannibalizing another human embryo causing their death.

“Forty-one years ago, the Supreme Court decided a child could be destroyed if a woman didn’t want it. The FDA is now deciding whether a woman has the right to construct the child she wants. That decision is based on a genetic mutation problem that only causes serious disease in 400 to 600 of the four million babies born each year. If women get this new right, how can society deny them exercising it to correct more serious problems like obesity, diabetes or heart disease, if this ability becomes available through germ line manipulation? Look at all the money society would save on healthcare! Wouldn’t people be happier?

“While the scientist is tinkering, why stop at just making members of that family tree skinny? Why not add making them all six-foot tall, blue eyed and athletic? Welcome to the brave new world of designer babies and two classes of humans, the enhanced and unenhanced.

“As a society, we should not cross the clear line in the sand prohibiting germ line manipulation. It’s science too dangerous to use.”

Executive Director of The Tennessee Center for Bioethics & Culture D. Joy Riley, MD, MA: (from her testimony before the FDA, Feb. 25, 2014) – “It is remarkable to note that while more than 40 nations have prohibited germ line modification, we are contemplating stepping over that bright line. It is imperative that we reflect upon the words of philosopher George Santayana, who presciently wrote, ‘Those who cannot remember the past are condemned to repeat it.’ This applies in several ways.

“First of all, consider that this change is being evaluated by the ‘Cellular, Tissue and Gene Therapies’ Advisory Committee of the FDA. While this is your purview, it is not merely cells, tissues or genes which are being affected by this decision. No, it is human beings – human beings at their earliest stages – who are the subjects of this research. These are your and my children, grandchildren, nieces, nephews and cousins being considered here today. Their Petri dish appearance should not confuse us. They are very much human.

“Secondly, consider codes of international standing:

“The Declaration of Geneva proclaimed for physicians worldwide, ‘The health of my patient will be my first consideration.’

“The Declaration of Helsinki stated, ‘In medical research involving human subjects, the well-being of the individual research subject must take precedence over all other interests.’

“In the Council of Europe’s Convention on Biomedicine and Human Rights, intervention on the human genome is countenanced ‘only if its aim is not to introduce any modification in the genome of any descendants.’

Finally, a major requirement of research on human subjects is that of fully informed consent by the human being whose life, health and posterity will be impacted by the proposed human experiment. This is not therapy for the ones undergoing experimentation. Their very formation is the experiment under consideration here. They are not able to give consent; neither are all their descendants who come after them able to give consent, yet the proposal is to experiment on all of them by virtue of altering their germ line for all time.

Resources:
CMA Letter to FDA on Oocyte Modification in Assisted Reproduction
CMDA Genetics Resources

Pushing back against genetically designing babies

Excerpted from "You Can't Predict Destiny by Designing Your Baby's Genome." commentary by Megan Allyse and Marsha Michie, published in The Wall Street Journal, Nov. 8, 2013 - In the 1997 film "Gattaca," wealthy parents regularly use what's called preimplantation genetic diagnosis to pick children with the most desirable characteristics. Using in vitro fertilization, PGD creates several embryos and then uses the most genetically promising one to attempt a pregnancy.

As distant as a Gattaca-style dystopia may seem, recent developments suggest it's not as far-fetched as it once was. California genetic testing company 23andMe announced in October that it has patented a method for determining the traits, including eye color and height, a hypothetical child would inherit from its parents.

Sperm donors deemed genetically inferior--or invalid, in Gattaca terms--will presumably be rejected and have to pass on their genetic material the old-fashioned way. These innovations expand on an existing service for prospective parents called carrier screening. The screening detects gene variants that, when present in both parents, significantly increase the risk of certain diseases in offspring.

The question is no longer whether we can design our offspring, but if we should-and what happens when we try. It may seem like creating the perfect child will eventually be a matter of who can pay for it. But predicting whether a couple's offspring will be the next Mozart or Einstein is about as easy as predicting the precise location and airspeed of a hurricane nine months in advance. That's because our genes are too complex to predict.

Parents have always tried to control their children's destiny, and complex gene algorithms are merely the latest manifestation of those efforts. But these techniques will only reveal that human life is too multifaceted to be reduced to a mathematical formula.

Commentary

CMDA Member and Senior Fellow for Family Research Council David Prentice, PhD: “Our genes are not our destiny. Even with the ultimate genetic selection technology—cloning—the cloned animal offspring are not exact duplicates of the progenitor from which they were cloned. Yes, despite the fact that the cloning process uses the exact DNA of another individual (technically ‘somatic cell nuclear transfer’ is the most common form of cloning attempted) in an attempt to replicate that individual, the few clones that survive show that we are all more than just a readout of a genetic menu. One of the clearest examples of this lack of ‘genetic determinism’ is CC, the ‘carbon copy’ cat, which was cloned in 2001. She has a different coat pattern than the cat from which she was cloned, and different behavioral patterns.

“We are not our genes! Epigenetics (which genes are expressed, when and where) and environment have a huge effect. Even our experiences in the womb help shape who we are.

“This newest eugenic attempt to control our children and their outcomes, whether by ‘screening out’ less desirable traits or individuals, or ‘designing in’ what we might consider more desirable or fashionable traits, is a self-centered exercise that lacks respect for the uniqueness of each individual’s genetic endowment. The new human becomes the created property of another, designed and crafted to meet the maker’s desires; it is man making man in his own image, yet without any higher standard to which the craftsman is held. A key ingredient is lacking—love. Each new human individual is a gift to be loved. We are each of us fearfully and wonderfully made!”

Resources

CMDA Genetics Resources

Proposed treatment to fix genetic diseases raises ethical issues

Excerpted from “Proposed treatment to fix genetic diseases raises ethical issues,” Shots: Health News from NPR. August 14, 2013 -- The federal government is considering whether to allow scientists to take a controversial step: make changes in some of the genetic material in a woman's egg that would be passed down through generations. Mark Sauer of the Columbia University Medical Center, a member of one of two teams of U.S. scientists pursuing the research, calls the effort to prevent infants from getting devastating genetic diseases "noble." Sauer says the groups are hoping "to cure disease and to help women deliver healthy, normal children."

But the research raises a variety of concerns, including worries it could open the door to creating "designer babies." Specifically, the research would create an egg with healthy mitochondrial DNA (mtDNA). Unlike the DNA that most people are familiar with—the 23 pairs of human chromosomes that program most of our body processes—mtDNA is the bit of genetic material inside mitochondria, living structures inside a cell that provide its energy.

Scientists estimate that 1 in every 200 women carries defects in her mtDNA. Between 1 in 2,000 and 1 in 4,000 babies may be born each year with syndromes caused by these genetic glitches; the syndromes range from mild to severe. In many cases, there is no treatment, and the affected child dies early in life. "We have developed a technique that would allow a woman to have a child that is not affected by this disease, and yet the child would be related to her genetically," says Dieter Egli of the New York Stem Cell Foundation.

But this is all still very controversial. First of all, the baby would be born with genes from three different people: from the father, from the woman trying to have a healthy baby, and from the woman who donated the healthy egg. There are even bigger concerns, which start with whether the technique is safe for the resulting infant, and whether by trying to fix one problem, scientists may inadvertently introduce mistakes into the human genetic code. That's why this sort of thing has always been off-limits — even banned in many countries, according to Marcy Darnovsky of the Center for Genetics and Society.

Commentary

CMDA CEO David Stevens, MD, MA (Ethics): “Germline genetic engineering, where a portion of the egg or sperm’s genome replaced, changed or supplemented, is unethical, unnecessary and unsafe. It crosses a bright line in the bioethical sand labeled, ‘That shalt not!’


“It is unethical because it permanently changes the child’s genes and any unforeseen consequences that occur are passed on to every generation that follows. Thus, it violates the ethical principle of autonomy. How does the doctor get informed consent from their grandchild yet to be conceived? Some of the techniques proposed involve destroying human embryos, not just manipulating women’s eggs. For example, some propose discarding female embryos created and only implanting male embryos to avoid the risk of passing on an inheritable defect.

“It is unnecessary. Women who have an identified high risk with a high mutation load, (under 18 percent mutations of mtDNA, there is 95 percent certainty of no risk) already have the option of not having children, adopting, utilizing a donated egg, preimplantation genetic diagnosis and prenatal diagnosis with abortion. Some of these options are unethical because they destroy life, but they are legal. Scientists are trying to justify germline manipulation so that women with this genetic liability might have the option of having a child with their genes. While this ambition is understandable, because there are alternatives, and because there are significant risks to generations of offspring, we should prohibit this option.

“It is unsafe. This type of genetic manipulation is not human cloning but uses similar techniques that have been associated with serious problems when used in animals—large organ syndrome, malformations and miscarriages.

“The ‘hard cases’ have been historically used to justify crossing the ‘bright lines’ in bioethics. We saw this in abortion, but once society agreed that abortion was justified because the mother didn’t want a child because of rape, incest or a genetic defect, it soon became justified for a woman not wanting a child for any reason. In other countries, physician-assisted suicide was justified for patients who had lives ‘not worthy to be lived’ because they were terminally ill and suffering. Now it is allowed for any reason the patient conceives that their life is unworthy to live. It is not unreasonable to predict if society says germ line manipulation is okay to avoid having a child with an imperfect genome that society will soon open the door for germline genetic engineering in the quest for perfect children.”

Resources
Novel techniques for the prevention of mitochondrial DNA disorders
Position Paper on Human Germline Manipulation
CMDA Resources on Reproductive Technology and Health