TAG | genetics
A few months ago, after a fertility procedure at a Mexican clinic, a healthy baby boy was born in New York to a couple from Jordan. It was the first live birth of a child who has been called — to the dismay of scientists who say the term is grossly misleading — a three-parent baby.
“This is huge,” said Dr. Richard J. Paulson, president-elect of the American Society for Reproductive Medicine, after the birth was reported on Tuesday.
The method used to help the couple is one that reproductive scientists have been itching to try, but it is enormously controversial because it uses genetic material from a donor in addition to that of the couple trying to conceive. The purpose is to overcome flaws in a parent’s mitochondria that can cause grave illnesses in babies.
And why exactly should this helpful procedure be ‘enormously controversial’?
Part of the answer lies in that term ‘three-parent baby’, rightly described as grossly misleading.
The New York Times:
Mitochondria, the cell’s energy factories, are separate from the DNA that determines a child’s inherited traits. But mutations in these little organelles can be devastating, resulting in fatal diseases involving the nerves, muscles, brain, heart, liver, skeletal muscles, kidney and the endocrine and respiratory systems that often kill babies in the first few years of life.
The technique that led to the healthy birth was to move the DNA from an egg of the mother, who had mutated mitochondria, and place it in the egg of a healthy egg donor — after first removing the healthy donor’s nuclear DNA from her egg cell. Then that egg, with its healthy mitochondria and the mother’s DNA, could be fertilized….
A small number of children each year are born with faults in their mitochondrial DNA which can cause diseases. Mitochondria are small structures that sit inside our cells and provide them with energy. They have their own set of 37 genes which are separate from the 20,000 or so genes that shape who we are.
… On a genetic level, all of the 20,000 genes on the child’s 23 pairs of chromosomes come from the child’s mother and father. The donor only contributes DNA that sit in the mitochondria, less than 0.2% of the total.
The New York Times:
“Mitochondria,” Dr. Paulson said, “do not define who you are.” The genes for traits that make up a person’s appearance and other characteristics are carried in the nuclear DNA. If a white woman got mitochondria from an Asian woman, for example, her babies would be white, with no traces of the Asian mitochondrial donor. The ban, said Dr. Paulson, “is not scientific, not rational, not evidence-based.”
The Catholic church opposes one form of mitochondrial transfer, called pronuclear transfer, because a fertilised egg from the mother is destroyed in the process. Catholic ethicists have also complained that mitochondrial transfer introduces a “rupture” between mother and father and “dilutes parenthood”.
Roman Catholic objections to that first form of mitochondrial transfer are consistent with that church’s opposition to abortion, and in that sense are understandable.
But there is a second method, called mitochondrial spindle transfer (MST).
The Guardian explains:
In this, doctors use standard IVF procedures to collect eggs from the mother. They take the nucleus from one of the eggs and drop it into a healthy donor egg that has had its own nucleus removed. The reconstituted egg contains all the normal genes from the mother, but her faulty mitochondria are replaced by those from the healthy donor. The egg is then fertilised with the father’s sperm. The resulting embryo has the usual 23 pairs of chromosomes that hold the mother and father’s DNA, but the 37 mitochondrial genes, about 0.2% of the total, come from a third person, the donor.
So no fertilized egg is destroyed.
Problem! Enter those ‘Catholic ethicists’ talking about a “rupture” between mother and child as grounds for objecting to all types of mitochondrial transfer. Their evidence for this ‘rupture’ is what exactly?
Let’s not forget that this is a church that, when it’s not opining on the scientific basis for exorcism, is also a church that claims to be a scientific authority on climate change.
It is also a church that likes to proclaim its compassion.
Mitochondrial diseases tend to strike in childhood and get steadily worse. They often prove fatal before adulthood. The parts of the body that need most energy are worst affected: the brain, muscles, heart and liver. Conditions include Leigh’s disease, progressive infantile poliodystrophy and Barth syndrome. Faulty mitochondria have also been linked to more common medical problems, including Parkinson’s, deafness, failing eyesight, epilepsy and diabetes…There are no cures for mitochondrial disorders.
The New York Times:
When Dr. Zhang [the doctor who led the team that carried out the procedure] told the Jordanian couple about the technique, they hesitated. They already had a child who was terribly ill with Leigh syndrome, a mitochondrial disease, but there was a chance they could have a normal baby on their own — a quarter of the woman’s mitochondria were mutated, but mitochondria are distributed at random in eggs. If an egg with mostly good mitochondria happened to be fertilized, the baby would be fine. They decided to take their chances.
The couple returned to Jordan and had a baby. But the baby had the same mitochondrial disease, Leigh syndrome. It is a terrible disease, Dr. Zhang said. Babies progressively lose their ability to move and breathe. The baby had a tracheotomy and a feeding tube, he said, and the parents had to suction the baby’s lungs every hour.
The first baby died at age 6; the second baby at 8 months.
And so far as the church is concerned, that’s sad, doubtless, but not something that can be helped.
The New York Times:
The couple returned to Dr. Zhang, ready to try the mitochondrial transfer technique. New Hope Fertility Center has a clinic in Mexico, so he suggested doing the procedure there because it is effectively banned in the United States. More than a decade ago, the Food and Drug Administration ordered clinics to file an application to do such work. Later, Congress attached a rider to a bill making it impossible to fund such research.
By six months of pregnancy, the woman said she knew this baby was different. It kicked constantly — the others, affected even in the womb, had hardly moved. Now the boy is 5 months old and healthy, and has normal mitochondria. The birth was first reported on Tuesday by New Scientist magazine.
Reproductive scientists who have been frustrated by the ban were both gratified by Dr. Zhang’s success and angry that it took so long. Britain recently allowed research on mitochondrial transfers to proceed, but nothing has changed in the United States.
In this case, however, highlighted by the Washington Post, they have got things right:
An elite panel of scientists and bioethicists offered guarded approval Wednesday of a novel form of genetic engineering that could prevent congenital diseases but would result in babies with genetic material from three parents.
The committee, which was convened last year at the request of the Food and Drug Administration, concluded that it is ethically permissible to “go forward, but with caution” with mitochondrial replacement techniques (MRT), said chairman Jeffrey Kahn, a bioethicist at Johns Hopkins University.
No, I’m not sure why it is up to them to decide what is or is not “ethically permissible”, but still…
But the advisory panel’s conclusions have slammed into a congressional ban: The omnibus fiscal year 2016 budget bill passed by Congress late last year contained language prohibiting the government from using any funds to handle applications for experiments that genetically alter human embryos.
Thus the green light from the scientists and ethicists won’t translate anytime soon into clinical applications that could potentially help families that want healthy babies, said Shoukhrat Mitalipov, a pioneer of the new technique at Oregon Health & Science University in Portland, Ore.
“It seems like the FDA is disabled in this case by Congress,” Mitalipov said. “At this point we’re still not clear how to proceed.”
Congress should get out of the way.
The FDA released a statement Wednesday saying it will carefully review the report from the advisory committee, but added that the congressional ban prohibits the agency from reviewing applications “in which a human embryo is intentionally created or modified to include a heritable genetic modification. As such, human subject research utilizing genetic modification of embryos for the prevention of transmission of mitochondrial disease cannot be performed in the United States in FY 2016.”
The new clinical procedures should be used rarely, with extreme care and with abundant government oversight, and they initially should be applied only to male embryos, the advisory panel said. The group delivered its report at a morning news conference at the National Academy of Sciences headquarters in Washington.
The report comes at a time of dazzling advances in genetic engineering and a commensurate struggle to understand the ethics of “playing God,” a phrase uttered twice Wednesday by committee member R. Alta Charo, a professor of law and bioethics at the University of Wisconsin.
Then again, as it’s most unlikely that God played God…
The FDA last year asked the Institute of Medicine, now part of the National Academies of Sciences, Engineering and Medicine, to review the ethical implications of MRT since this other method of genetic engineering would result in what has been loosely referred to as “three-parent babies.” British officials have already approved investigatory experiments involving the technique.
Certain serious congenital diseases can be passed from a mother to child via the tiny amount of genetic material contained in the mitochondria, which are small organs within a cell that are often described as the cell’s energy factories or power plants. New experimental techniques involving in vitro fertilization make it possible to replace mutated and potentially disease-associated mitochondrial DNA (mtDNA) with non-pathogenic mtDNA donated from another woman.
Mitochondrial DNA contains 37 genes and is distinct from nuclear DNA (nDNA), which in humans has upwards of 20,000 genes. The mitochondrial DNA is not found in sperm, only in eggs, and thus is passed only from mother to child. That’s why the panel recommended limiting the experimental procedures at first to male embryos.
The males-only guideline is intended to prevent the introduction of unwanted, irreversible genetic changes to the human species. Any genetic changes associated with this kind of engineering will meet a dead end in males.
“If there are adverse events, they would not be reverberating down the generations,” Charo said.
The procedure should be extended to female embryos only after the long-term effects of such novel genetic engineering are better understood, the committee concluded.
Nuclear DNA is by far the more significant form of genetic material for determining most human characteristics. As the committee put it, “[W]hile mtDNA plays a central role in genetic ancestry, traits that are carried in nDNA are those that in the public understanding constitute the core of genetic relatedness in terms of physical and behavioral characteristics as well as most forms of disease.”
As a result, the modification of mitochondrial DNA “is meaningfully different.”
But panel members said that they took the philosophical issues seriously, noting that someone with genetic material from two different maternal bloodlines would potentially have to wrestle with questions about identity, kinship and ancestry.
Not really. The babies who benefit from this technology will have about 0.1 percent of their DNA attributable to a third party. It’s a (very) crude way of looking this, but think how many great, great-grandparents away it would take to account for 0.1% of someone’s ancestry….
To describe the donor as a third “parent” is, to put it mildly, a stretch.
And, as a reminder of what this is about:
The donor provides only their mitochondria. Often called the “power plants” of the cell, the mitochondria converts energy from food into energy that can power a cell. When someone’s mitochondria don’t function properly, it’s bad news indeed…
As one ‘ethicist’ notes:
It is not part of what makes us genetically who we are.It doesn’t affect height, eye color, intelligence, musicality. It simply allows the batteries to work properly…
And as to what’s at stake;
Mitochondrial diseases can cause a whole host of life threatening problems, and it’s estimated that as many as 4,000 children are born with such conditions in the United States each year.
Again, politicians should get out of the way.
The Daily Telegraph reports:
A group of 34 European politicians, including eight British MPs and peers, has signed a declaration attacking plans which will make the UK the first country in the world to permit the new IVF technique. Under legislation being drawn up by ministers the treatment will be offered to a handful of parents at high risk of having children with conditions such as muscular dystrophy, as early as next year.
The therapy can dramatically reduce the risk of children inheriting disorders of the heart, brain and muscle which are caused by faults in the mother’s mitochondria, structures which supply power to cells. But it has proved controversial because it involves substituting a small fraction of the mother’s damaged DNA with that of a healthy female donor.
Because the swap takes place at the “germ line”, the third party’s DNA would not only be passed on to the child, but also to any future generations down the female line. The therapy was recommended to government by the Human Fertilisation and Embryology Authority earlier this year after a public consultation revealed general support. Doctors developing the treatment have emphasised that the DNA in question lies outside the nucleus of the cell and will have no bearing on the child’s personality or appearance.
But a declaration made by members of the Council of Europe, a human rights and ethics organisation made up of politicians from across Europe [it’s rather more than that], strongly condemned the decision to permit the technique.The declaration proposed by Jim Dobbin, a British Labour MP, which compared the technique to a “eugenic practice”, was signed by 34 members of the human rights organisation’s 318-strong parliamentary assembly.
It said: “The undersigned members of the Parliamentary Assembly affirm that the creation of children with genetic material from more than two progenitor persons, as is being proposed by the United Kingdom Human Fertilisation and Embryology Authority, is incompatible with human dignity and international law”.
Superstition, nothing more. Well, on reflection, monumental arrogance too.
It was signed by five other Labour MPs and peers as well as Edward Leigh, a Conservative MP, and the Earl of Dundee, a hereditary peer along with politicians from twelve other nations. The declaration, in effect a statement of opinion by the signatories, does not reflect the view of the whole Council but could now become the subject of a full debate or report.
That Leigh, supposedly a conservative, believes that this is a matter for some international and unaccountable body rather than something to be decided by Britons for themselves only makes matters worse.
Should people be allowed to see details of their own genetic information?
The public discussion about DNA testing tends to focus on ethical dilemmas: What if doctors find that a person’s father isn’t really? Should they tell a patient about a DNA glitch if it’s only occasionally linked to disease? What if, while looking for mutations that could explain a known sickness, they stumble on others that might predict late-life dementia or indicate the presence of HIV? Would adding this data to someone’s medical record affect health insurance rates? What if—gasp—we end up with a real-life Gattaca?
These questions are worth talking about. But the genetics community and popular press spend too much time debating when and how the medical establishment should “protect” people from their children’s or their own DNA.
For example, many bioethicists argue that DNA glitches shouldn’t be disclosed if they’re ambiguous or linked to untreatable conditions. Doing so “may create unwanted psychosocial burdens on parents,” according to a commentary on newborn sequencing in the Journal of the American Medical Association.
Ah yes, bioethicists.
They really are a useless, worthless bunch, philosopher-princelings and wannabe clergymen who hawk their insulting and condescending babble to a political class always looking for new reasons to tell people what not to do.
It is way past time for 25 or so states that have restricted the right of citizens to obtain their genetic information from direct-to-consumer companies to lift their bans.
Indeed it is.
From a WSJ review of a new book chronicling the Minnesota Study of Twins Reared Apart:
The Minnesota study’s IQ results hit a nerve years before their publication in 1990, overshadowing other controversies that might have been. Many of its findings are bipartisan shockers. Take religion, which almost everyone attributes to “socialization.” Separated-twin data show that religiosity has a strong genetic component, especially in the long run: “Parents had less influence than they thought over their children’s religious activities and interests as they approached adolescence and adulthood.” The key caveat: While genes have a big effect on how religious you are, upbringing has a big effect on the brand of religion you accept. Identical separated sisters Debbie and Sharon “both liked the rituals and formality of religious services and holidays,” even though Debbie was a Jew and Sharon was a Christian.
Just another example of the ‘God Gene’ at work, I suppose, and, as such, just another reminder that there is little or no prospect of ever weaning mankind off religion (Professor Dawkins, please note).
I have been travelling, and so blogging has been light from my end for a while now. But I thought I would point readers to a long post I put up over at Discover Blogs on Jewish genetics. The post wasn’t long enough really to say everything that needs to be said, so I’ll follow up, but I didn’t have more time than an afternoon to devote to it. Of more relevance to Secular Right readers, I’ll be posting a moderately negative review of Larry Witham’s Marketplace of the Gods: How Economics Explains Religion over there too. Shorter: more a bibliography than a précis, and a bit ill-timed in regards to capitalizing on the boom of economics-explains-everything books (writing began before the 2008 Financial Crisis).
A year ago there was a paper on the effect of diet on enzyme production, Diet and the evolution of human amylase gene copy number variation. That human evolution skeptic, P. Z. Myers, has just noticed the paper, and says:
This work by Perry and others went on to look for patterns in different human populations with different dietary historys, and discovered that there is a correlation: cultures with diets heavy in starch, agricultural populations such as Americans, Europeans, and Japanese, or hunter-gathers who live on many roots and tubers, have a higher average copy number than cultures that depend more on hunting and fishing.
Look at the distributions! Populations with little starch in their diets also have a relatively low copy number of 5.44 amylase genes per individual; we french fry eaters have a higher number of 6.72 amylase genes per individual. The difference is small, and the distributions also overlap significantly (note that some with high starch diets only have 2 copies, and some living on low starch diets have 13 copies), but the difference is measurable and significant. It implies that there may have been some selection for greater copy numbers in cultures with diets high in starchy plants.