Edited Twins, Genetic Engineering and Bioethics

SPL (Science Photo Library)'s image: In vitrio fertilization light microscope. (2015) via BBC News, used w/o permission.

Gene-editing rules showed up in my news feed last Monday. So, indirectly, did genetically-edited twins who, as far as I know, are still alive.

If I’d known how little I’d be able to verify about Dr. He Jiankui’s famous (or infamous) twins, maybe I’d have picked another topic.

But I did find a fair amount of information about genetic editing technology, and a hint at why Dr. He’s science project produced twins:

Gene-Edited Twins

SPL (Science Photo Library)'s image: 'Gene editing has the potential to treat numerous inherited disorders.' (2023) via BBC News, used w/o permission.
Gene editing could treat many inherited disorders.

China’s new human gene-editing rules worry experts
Pallab Ghosh, BBC News (March 6, 2023)

New rules in China to regulate gene editing in humans don’t go far enough, a leading expert has warned scientists.

Dr Joy Zhang of Kent University, a global expert on the governance of gene editing in China, said authorities are susceptible to ‘regulatory negligence’….

“…China says the new laws are in line with international rules.

“They set requirements for ethical approval, supervision and inspection, but experts worry that they may not apply to the private sector.

“Dr Zhang, one of the main speakers at an international human genome-editing summit in London, told BBC News: ‘My biggest concern is that the new measures fail to cover a chronic and increasing problem in trying to deal with private ventures that are taking place outside of conventional scientific institutes.

“‘The new rules may struggle to keep up with the burgeoning innovation that is happening in China.’…”

On the ‘up’ side, China’s government says their new laws are up to international standards.

They may be right about that. There was a major stink back in 2018, when Professor He Jiankui told the world, in a series of YouTube videos, that he’d made two twin girls. And that, thanks to his genetic engineering, HIV couldn’t infect them.

Since HIV viruses are the ones that cause HIV/AID, Professor He’s engineered immunity sounded like a good idea.

A remarkable number of scientists didn’t agree.

I can see why, but suspect that the professor’s ‘YouTube first, published paper later’ strategy encouraged their “significant doubts”.

On the other hand, Professor He’s videos may have been a matter of making the best of a bad situation. Seems that the MIT Technology Review worked out what he’d been doing, based on a Chinese clinical trials registry.1

At Least Two “World’s First”

SPL (Science Photo Library)'s image: IVF embryo. (2015) via BBC News, used w/o permission.I gather that Professor He’s problems stem mainly from his tweaking the genes of healthy babies.

But his claim that he’d made “the world’s first genetically edited babies” arguably needs clarification.

For example, differences between his edited babies and the ones back in 2017. Aside from terminology, that is.

China baby gene editing claim ‘dubious’
Michelle Roberts, BBC News (November 26, 2018)

Significant doubts have emerged about claims from a Chinese scientist that he has helped make the world’s first genetically edited babies.

“Prof He Jiankui says the twin girls, born a few weeks ago, had their DNA altered as embryos to prevent them from contracting HIV.

“His claims, filmed by Associated Press, are unverified and have sparked outrage from other scientists, who have called the idea monstrous.

“Such work is banned in most countries….”

Human embryos edited to stop disease
James Gallagher, BBC News (August 2, 2017)

Scientists have, for the first time, successfully freed embryos of a piece of faulty DNA that causes deadly heart disease to run in families.

“It potentially opens the door to preventing 10,000 disorders that are passed down the generations.

“The US and South Korean team allowed the embryos to develop for five days before stopping the experiment.

“The study hints at the future of medicine, but also provokes deep questions about what is morally right….”

I think curing and preventing disease is a good idea, for reasons I’ll get into later.

Defining “First”

OHSU's image: genetically modified embryos. (2017) via BBC News, used w/o permission.At first glance, the BBC News articles of 2018 (first genetically edited babies) and 2017 (first human embryos freed of a disease) seem contradictory.

But, given my culture’s assumptions, they’re both right. The 2017 announcement involved genetically editing human “embryos”. He’s 2018 experiment was about the first human “babies”.

An ‘up’ side of the 2017 announcement was that the “embryos” were identified as human. But that didn’t keep the scientists from treating them as disposable lab materials:

“…The US and South Korean team allowed the embryos to develop for five days before stopping the experiment….”
(James Gallagher, BBC News (August 2, 2017) [emphasis mine]

My hat’s off to Professor He. For whatever reason, he didn’t kill his edited kids after demonstrating that he’d done something nifty.

Instead, he apparently worked with a couple: and allowed his experimental subjects to stay alive, at least for nine months or so. Given current values, and the trouble he got into later, that’s praiseworthy.2

That’s good news.

Not-So-Good News

He JiankuiLab / Image's photo: 'Dr He Jiankui served a three-year prison sentence following claims that he created the world's first gene-edited children five years ago'. (March 6, 2023) BBC News)
Dr. He Jiankui: genetics pioneer, sentenced to three years in prison for improper pioneering.

I don’t know why so many “experts” have aimed so much ill will at Dr. He’s experiment. Although there’s enough dubiously-proper procedure in the professor’s activities to warrant a raised eyebrow or two:

New technologies may have already introduced genetic errors to the human gene pool. How long will they last? And how could they affect us?“, Zaria Gorvett, BBC Future (April 12, 2021)

“…He had broken laws, forged documents, misled the babies’ parents about any risks and failed to do adequate safety testing. The whole endeavour left many experts aghast — it was described as ‘monstrous’, ‘amateurish’ and ‘profoundly disturbing’ ….

“…However, arguably the biggest twist were the mistakes. It turns out that the babies involved, Lulu and Nana, have not been gifted with neatly edited genes after all. Not only are they not necessarily immune to HIV, they have been accidentally endowed with versions of CCR5 that are entirely made up – they likely do not exist in any other human genome on the planet. And yet, such changes are heritable – they could be passed on to their children, and children’s children, and so on….”
[emphasis mine]

An ‘up’ side in the current mess is that apparently misleading the parents of an experimental child is now regarded as not entirely proper.

That’s a big step forward from the good old days of 1977, when Louisa Joy Brown’s parents had been told that in vitro fertilization (IVF) was experimental.

But not that, if it worked, they’d have the first surviving IVF baby. And even then, there was talk of informed consent being important.

And a really big step or two from 1951, when a doctor noticed that I was defective. But didn’t tell my parents, since letting my glitch go untreated would give him grist he could grind into a learned paper. And that’s almost another topic. Which, again, I’ll go into later.

Under the circumstances, and granting that it’s still early days for Lulu and Nana, the edited babies seem to have been rather lucky. Not only are they apparently still alive, but they don’t seem to have been gifted with any spectacularly obvious surprises.3

CRISPR Technology and Surprisingly Long-Tongued Rabbits

Alamy's photo: a rabbit after gene editing, with an unexpectedly long tongue. via BBC Future, used w/o permission.There’s much more in that BBC Future article, but if I don’t move along I won’t get this thing ready by Saturday.

So I’ll settle for sharing this bit:

“…there have been no shortage of surprises in the field. From the rabbits altered to be leaner that inexplicably ended up with much longer tongues to the cattle tweaked to lack horns that were inadvertently endowed with a long stretch of bacterial DNA in their genomes (including some genes that confer antibiotic resistance, no less) — its past is riddled with errors and misunderstandings….”
New technologies may have already introduced genetic errors to the human gene pool. How long will they last? And how could they affect us?“, Zaria Gorvett, BBC Future (April 12, 2021) [emphasis mine]

Next, here’s an excerpt from another discussion of genetic editing:

“…It is rapidly becoming apparent that a wide variety of cardiovascular diseases may one day be curable using CRISPR-Cas9 or similar technology, including many that heretofore have been entirely untreatable. Germline genome editing promises to permanently resolve monogenic cardiovascular disorders for the offspring and subsequent generations of affected individuals. … this approach remains ethically controversial. … In addition, further technical matters will need to be more fully resolved, including those of long-term risks, off-target effects, mosaicism, and applicability to a wider variety of mutations and cardiovascular conditions….”
(“Therapeutic Genome Editing in Cardiovascular Diseases“, David M. German, MD, MPH; et al.; Journal of the American College of Cardiology/Basic to Translational Science (published online February 25, 2019) [emphasis mine]

I gather that “off-target effects” are surprises like long-tongued rabbits and possibly-antibiotic-resistant cattle.

Mosaicism, in this context, is what happens when some of an embryo’s cells get edited, while others don’t. As an adult, the “embryo” has one set of genetic instructions in some cells, another set in others.

We’ve known about mosaicism at least since 1929. Apart from recent experiments, it’s the result of natural phenomena, along with mutation and horizontal gene transfer.4

Procedures, Perspectives and People

MeloneGuru's diagram of the primary sequence of CCR5, a seven membrane spanning G protein, on the cell membrane. (July 5, 2016) via Wikipedia, used w/o permission.
MeloneGuru’s diagram of CCR5 on a cell membrane.

As I said before, there’s enough dubiously-proper behavior on Dr. He Jiankui’s part to warrant sanctions of some sort.

Seems that he forged ethical review papers, which helped him talk eight couples into going along with his experiment; raised his own funds instead of going through official channels; and even had foreigners working with him.

Small wonder Shenzhen’s Southern University of Science and Technology fired him.

I don’t know whether I’m impressed that his sentence included fines amounting to nearly a half-million U. S. dollars, plus three years in prison; or that his sentence was so comparatively light.

Getting back to the eight couples, two pregnancies, and twin girls: as I see it, that means there is at least one dead baby in the mix. Unless the twins spent their gestation in two separate individuals.

But I’m not an expert, so the powers that be in China and others have different perspectives on Dr. He Jiankui’s actions:

“…He had ‘deliberately evaded oversight’ with the intent of creating a gene-edited baby ‘for the purpose of reproduction’, according to the initial findings of an investigating team set up by the Health Commission of China in southern Guangdong province, Xinhua news agency reported….”

“…Many scholars pointed to a 2003 guideline that bans altered human embryos from being implanted for the purpose of reproduction, and says altered embryos cannot be developed for more than 14 days.…”
(“Chinese scientist who gene-edited babies fired by university” … Reuters (January 21, 2019)) [emphasis mine]

I figure that helps explain why 2017’s genetically edited kids were killed.

Keeping them alive for another nine days would likely have gotten the U. S./South Korea research team into trouble. Might even have raised suspicions that the researchers thought their “embryos” were people.5

CCR5Δ32, Recent History and Speculation
. Strickland Constable's illustration of 'low types'. (1899)
“Low types”, left and right; a person of the “superior races”, center (1899)

An angle to the ‘edited twins’ issue I haven’t seen discussed is the particular gene Dr He had been trying to add to their chromosomes: CCR5Δ32/CCR5 Delta32.

CCR5 is a protein that’s on the walls of white blood cells. It acts as a receptor for a particular sort of molecule, and is part of our immune system.

CCR5 genes come in several varieties, alleles in geek-speak. CCR5Δ32 is an allele of CCR5 that’s in maybe 1% of the genetic code of folks who are northwestern Europeans. Or, in my case, whose ancestors are from northwestern Europe. And those are pretty much the only folks who have it.

Now, I wouldn’t have a problem with someone who looks a bit like me having genes that are more common among folks whose ancestors are, say, Chinese.

But then, I wouldn’t.

By some standards, I’m a second-generation result of miscegenation.6 Or, as one of my ancestors said of an Irishman who’d taken an interest in the daughter of a decent American family, “He doesn’t have family: he’s Irish.”

Again, Dr. He Jiankui’s failure to fill out paperwork and generally play ball with a government bureaucracy would be sufficient to account for his fines and imprisonment.

But I could imagine that both working with foreigners, and knowingly polluting Chinese chromosomes with foreign genes, pretty much guaranteed that he’d land in the hoosegow.

Under the circumstances, I could be mildly surprised that he didn’t simply disappear.

Chromosomes, Science and Twins

National Institutes of Health's diagram: 'Epigenetic mechanisms are affected by several factors and processes....' (2015) via Wikipedia, used w/o permission.
Epigenetic Mechanisms: regulating gene expression, switching genes on or off.

Another aspect of the Chinese twins brouhaha was that the kids are twins. This is speculation, but I think maybe Dr. He’s team wanted twins — and kept the kids alive — so that they could see how their epigentic mechanisms developed.

Here’s where I’d like to geek out, but I’m running out of time. So you’re in luck, I’m keeping this short.

Chromosomes aren’t just DNA. Among other things, the DNA is wound around histones: which pack the DNA more compactly.

Histones also have molecular mechanisms that turn individual genes on or off. Identical twins have identical epigenetic mechanisms when they start out. But if they keep on being alive, their epigenetic mechanisms generally stop being identical.

So I figure Dr. He and company wanted to see how their edited twins changed as they grew.

About epigenetics and all that, I put links to ‘for more information’ stuff near the end of this post.7

TALEN and CRISPR: Repurposing Prokaryotic Molecules

Kazi1111's illustration: showing how TALE proteins are used for epigenome editing. (2014) via Wikipedia, used w/o permission
Epigenome editing, using TALE proteins.

A fair number of articles about Dr. He and the edited twins mention that the researchers used CRISPR gene editing tech.

Again, I’m running short on time: so I’ll keep this short(ish).

CRISPR stands for clustered regularly interspaced short palindromic repeats. It’s part of the prokaryotic molecular tool kit. Prokaryotes are single-celled critters that don’t have nuclei.

CRISPR gene editing tech is a simplified version of the prokaryotic CRISPR-Cas9 antiviral defense system.

TALEN, which stands for transcription activator-like effector nuclease. A TALEN is what we get when we fuse a TAL effector DNA-binding domain to a DNA cleavage domain. What can I say? It’s complicated.

TALEN isn’t in the news much these days. It’s not the hot item that CRISPR is, at any rate.

But TALEN is in today’s gene-editing toolbox. And we got these molecules from prokaryotes, too.8

A Genomic Revolution: New(ish) Territory

Francesco Veronesi from Italy's photo: a red junglefowl, Kaeng Krachan National Park, Thailand. (2013) via Wikipedia, used w/o permission.
A red junglefowl: one of the birds we used to make chickens.

If I look at where CRISPR and TALEN gene editing molecules come from, I could see them as natural. Or as natural as any part of this world that we’ve modified.

Or I could go all apocalyptic prophet of doom, denounce all technology developed after some arbitrary date, and hope that nobody remembers where chickens come from.9

Lobby card for Cahn and Siodmak's 'Creature with the Atom Brain.' (1955)But that strikes me as being right up there with warning against atomic Nazi zombies.

So I’ll note that we’re dealing with new technology, quote what someone said, and move on.

“…The births of Lulu and Nana have pushed the boundary of genomic revolution to include generation of genetically engineered babies. This act has been widely condemned as premature, dangerous, alarming and unethical. Given this development, we likely will be hearing of an increasing number of reports on genetically engineered babies in the future. Yet, another woman in China is expecting the birth of a child with genetic modifications. This is new territory.

“Like it or not, this development forces us to ask, where do we go from here?…”
(“Lulu and Nana open Pandora’s box far beyond Louise Brown“; Shiva M. Singh, PhD; Canadian Medical Association Journal (June 10, 2019) via PubMed Central, National Library of Medicine, National Institutes of Health)

Louise Joy Brown, HEK 293 and Me

An HEK 293 variant: 293FT cells.On the one hand, I’m glad that we’ve got rules about using people as lab animals. And that there’s even some discussion regarding reviewing the rules.

Like the one that says using very young humans is okay, as long as they don’t live more than 14 days.

“…The adoption of the 14-day rule in public policy is generally attributed to two major points of origin: in the USA, the 1979 report of the Ethics Advisory Board to the Department of Health, Education and Welfare (HEW) on embryo research and, in the UK, the report of the Warnock Committee of Inquiry into Human Fertilisation and Embryology. From these foundations, the rule has acquired widespread influence elsewhere: almost every country in which embryo research is specifically permitted by regulation, soft or hard, employs a version of the 14-day rule….”
How and Why to Replace the 14-Day Rule“, Sarah Chan, Current Stem Cell Reports (published online July 16, 2018) via PubMed Central, National Library of Medicine, National Institutes of Health

The 14-day rule makes sense, from some viewpoints, since very young humans lack the abilities many of us develop if we’re not killed.

But I can’t say that I’m okay with killing someone who’s too young to matter. That may take a bit of explaining.

Because I’m Catholic, I must see every human being as a real person.

The divine image is in each of us. We’re all people: no matter who we are, who our ancestors are, or what we’ve done. (Genesis 1:2627, 2:7; Catechism of the Catholic Church, 355-357, 361, 369-370, 1700, 1730, 2268-2269, 1929, 2273-2274, 2276-2279)

That means I think the girl whose designation was cell line HEK 293, the first person to survive in vitro fertilization, a convicted murderer, and someone who’s mentally ill are all people: each with a share in humanity’s transcendent dignity. (Catechism, 1928, 1934-1938)

Thinking that human beings — all human beings — are real people, and that we all matter, puts me at odds with assorted political positions. But it’s something I’m stuck with, if I’m going to take my faith seriously.

Responses to the first person to survive in vitro vertilization, Louise Joy Brown, ranged from all-too-familiar malignant virtue to Cardinal Albino Luciani’s “unexpected” application of Catholic beliefs to everyday life. And that’s another topic.10 Topics.

“…in August 1978, Cardinal Albino Luciani — shortly to become Pope John Paul I — unexpectedly refused to criticise Louise’s parents for using IVF, saying they had simply wanted to have a baby.

“‘It helped to counteract some of the negative things people were saying,’ Louise says.

“‘My mum got loads of letters from people. They were mostly positive, but there was some hate mail.

“‘They got an awful box from America which had a broken test-tube, fake blood and a pretend foetus inside. It came with a threat that the people who sent it were coming to see them.’…”
(“How has IVF developed since the first ‘test-tube baby’?“, Adam Eley, BBC News (July 23, 2015))

Making Sense: It’s an Option

'At the Sign of the UNHOLY THREE' cartoon, warning against fluoridated water, polio serum and mental hygiene. And 'communistic world government.' (1955)Maybe life would be easier for Catholics if we were told that any technology developed after 1928 was Satanic. That’s when polyester was patented, and that’s yet another topic.

Like I said, maybe life would be easier if being Catholic meant blindly believing nonsense like ‘polyester is Satanic’ or ‘QR codes are the mark of the beast’.

But that’s not how we work.

Okay. I’ve gone through this before, and will again, but here goes.

Starting with that time someone asked Jesus what the top commandment was —

“He said to him, ‘You shall love the Lord, your God, with all your heart, with all your soul, and with all your mind.
“This is the greatest and the first commandment.
“The second is like it: You shall love your neighbor as yourself.
“The whole law and the prophets depend on these two commandments.'”
(Matthew 22:3740)

That’s simple enough. I should love God and my neighbor. And see everybody as my neighbor. Everybody. No exceptions. (Matthew 5:4344, 22:3640; Mark 12:2831; Luke 10:2537; Catechism, 1706, 1776, 1789, 1825, 1849-1851, 1955)

But “simple” isn’t “easy”, and we’ve needed reminders about what terms like “love” and “neighbor” mean. And why we should treat folks like people: all folks.

Human life is sacred, because it involves God from the get-go. That’s all human life: no matter how young or old, healthy or sick we are. (Catechism, 2258, 2261, 2268-2283)

We are rational creatures, able to think and decide how we act. And we can think about whether what we do is a good idea: or not. God gives us brains. Using them is a good idea. (Genesis 1:2627, 2:7; Catechism, 1730, 1778, 1950-1960, 2292-2295)

Science and technology, studying this universe and using what we learn, is part of being human. It’s what we’re supposed to do. (Catechism, 2292-2296)

Getting and staying healthy is a good idea. Within reason. (Catechism, 2288-2291)

But putting science, technology, health — anything or anyone that’s not God — at the top of my priorities is a bad idea and I shouldn’t do it. (Catechism, 2112-2114)

Bioethics, From a Former Lab Rat’s Perspective

Willowbrook State School.It’s late Friday afternoon now, and I still haven’t said why I think curing and preventing disease is a good idea.

Sure, ‘because the Church says so’ is a reason. But I’ve got personal reasons for how I see medical practices and bioethics. I’ve talked about this before.

A doctor my parents initially trusted correctly diagnosed my congenital hip dysplasia almost immediately after I was born.

This was 1951. Options were limited back then, so maybe he figured I was a hopeless case, doomed to a defective life. Either way, he didn’t tell my parents.

USAF Staff Sgt Eric T. Sheler's photo: A two week-old's Phenylketonuria, or PKU, screening. (2007) via Wikipedia, use w/o permission.“…Instead, he had them bring me in at intervals to see what my hips were doing.

“He made notes about what happens when hip dysplasia isn’t treated. Then he wrote a learned paper on the subject. His paper was published in a medical journal. A copy of the journal wound up in a college library’s collection.

“That’s where my father read the doctor’s learned paper.

“My mother intercepted him before he reached the doctor. She said, ‘no, I will speak with him.’ Which she did. And never shared what they discussed.

“The doctor disappeared a few days later. Maybe it would have been more humane to have let an enraged Irishman conduct the interview….”
(“COVID-19, Cells, Viruses and mRNA Vaccines”, Trust and Prudence, (December 5, 2020))

Attempted non-surgical interventions including a body cast didn’t fix my defective hips, but an operation put me on my feet. And a second operation fixed an issue that’d cropped up after the first one.

Several decades later, swapping out both joints for metal-and-plastic replacements made walking without pain an option: so I’m a happy camper.

But knowing that I’d been used as a lab rat arguably accounts for me not being overly shocked and surprised at incidents like the Willowbrook State School, Tuskeegee, Auschwitz, Dachau and Unit 731 experiments.11

On the other hand, knowing that being healthy and using our brains is okay lets me think that research can be a good idea. And that ethics matter, whether we’re using old or new tech.

One more overly-long excerpt, and then the usual links:

“…As with all medical interventions on patients, one must uphold as licit procedures carried out on the human embryo which respect the life and integrity of the embryo and do not involve disproportionate risks for it but are directed towards its healing, the improvement of its condition of health, or its individual survival. Whatever the type of medical, surgical or other therapy, the free and informed consent of the parents is required, according to the deontological rules followed in the case of children. The application of this moral principle may call for delicate and particular precautions in the case of embryonic or foetal life. The legitimacy and criteria of such procedures have been clearly stated by Pope John Paul II: ‘A strictly therapeutic intervention whose explicit objective is the healing of various maladies such as those stemming from chromosomal defects will, in principle, be considered desirable, provided it is directed to the true promotion of the personal well-being of the individual without doing harm to his integrity or worsening his conditions of life. Such an intervention would indeed fall within the logic of the Christian moral tradition’….”
Instruction on Respect for Human Life in its Origin and on the Dignity of Procreation“, Congregation for the Doctrine of the Faith; quote from “Discourse to the Participants in the 35th General Assembly of the World Medical Association”, Pope St. John Paul II (October 29, 1983)) [emphasis mine]

I’ve talked about bioethics before, and probably will again:

1 Outing a research project:

2 Genetic and legal issues:

3 One of these times I’ll talk about the Hippocratic Oath, but not this week:

4 And one of these days I’ll probably talk about this:

5 Life, death and rules:

6 Science and reasons I don’t miss the ‘good old days’:

7 Genetics, it’s complicated:

8 You’re lucky; I didn’t have time to go over most of this stuff:

9 Artificial organisms, AKA domesticated plants and animals:

'I'd force peace right down their bloodthirsty throats.' Deacon Mushrat in Walk Kelly's Pogo. (1952)10 Modern medicine, making sense, malignant virtue and more:

11 Bad ideas, (some) lessons learned:

How interesting or useful was this post?

Click on a star to rate it!

Average rating 0 / 5. Vote count: 0

No votes so far! Be the first to rate this post.

I am sorry that this post was not useful for you!

Let me learn why!

How could I have made this more nearly worth your time?

About Brian H. Gill

I was born in 1951. I'm a husband, father and grandfather. One of the kids graduated from college in December, 2008, and is helping her husband run businesses and raise my granddaughter; another is a cartoonist and artist; #3 daughter is a writer; my son is developing a digital game with #3 and #1 daughters. I'm also a writer and artist.
This entry was posted in Discursive Detours, Journal, Science News and tagged , , , , , , , . Bookmark the permalink.

Thanks for taking time to comment!