What If Dr. He Was Trying to Engineer CRISPR Super-babies?

In November 2018, a scientist from China revealed that he had modified the genes of embryos using CRISPR technology and implanted the embryos into a woman.  She later gave birth to twins, Lulu and Nana — the first babies born with CRISPR-modified genes.

A near-universal outcry followed.  The scientist, Dr. Jiankui He, was criticized for his unscientific methods, and the potential danger to the children.  

At the time, Dr. He stated that his purpose was to make the children immune to the Human Immunodeficiency Virus (HIV) and therefore, immune to AIDS, the disease caused by HIV.  Dr. He did this by disabling the CCR5 gene, which codes for a receptor that sits on the surface of a type of immune cell (T-cells). HIV utilizes this receptor to enter T-cells, where it takes over the cell’s nucleus and produces a multitude of copies of itself, leading to AIDS.

Without the CCR5 gene/receptor, most1 strains of HIV can’t enter T-cells, and the person usually can’t become infected.             

Dr. He’s intentions seemed noble — using genetic engineering to make children immune to a horrible disease.  Still, he was harshly criticized for avoiding oversight by other scientists, failing to appropriately inform the parents of the children, and experimenting on embryos which have now become live children.

It’s possible, however, that his intentions were not as noble as they seemed.  Since he revealed his work, it has come to light that his intentions may have been somewhat self-centered — that his real motive may have been fame and accolades.  

On top of this, his work might not have been related to HIV/AIDS at all.  MIT Technology Review and other publications have noted that knocking out the CCR5 gene can also improve learning and memory, a fact that Dr. He was aware of.

Further, Dr. He has been somewhat ambiguous, and possibly even untruthful, about where he received his funding, and also whether he notified his university and the Chinese government about his research.

And as others have noted, there are other, safer — rigorously tested and proven — ways to prevent HIV transmission to an unborn child.  His research, as he portrayed it, did not address any unmet medical need. Finally (and worse still) as this article shows, Dr. He’s approach cannot prevent infection by every known variety of HIV — it wasn’t really the foolproof guarantee that he described.

So it seems entirely reasonable to ask if creating genetically engineered super-smart babies might have been his purpose all along.  

And even if it wasn’t, if Lulu and Nana turn out to be relatively healthy, someone else will likely try this soon.  The genie is out of the bottle, and it can’t be put back in.

A much smarter person than me has explored the idea of what we, as Christians, should think about genetically modifying embryos.  But these new revelations suggest that we might want to take another look.

Wait — About this CCR5 Gene…

For the inquisitive, a question arises from all of this: if the absence of this gene correlates with improved learning and memory as well as potential immunity to AIDS, why do people have this gene at all?  Put differently, what exactly is the purpose or function of this gene in the first place?

At the end of this article, I’ve included a non-scientific, speculative explanation of how all these things might work (TLDR: CCR5 likely plays an important role in fighting off diseases like West Nile virus and Tick-borne encephalitis).

A Genetically Engineered Dilemma

At first, Dr. He’s intentions seemed good, though his methods — unsupervised and untested genetic modifications of people — were alarming.

If his intention was to prevent AIDS, the possibility of susceptibility to another type of disease — even encephalitis — would seem like a reasonable trade-off.  AIDS is widely feared, and becoming more prevalent in China; West Nile and tick-borne encephalitis might not be.

But what if Dr. He’s intentions all along were to create genetically modified learning-enhanced super-babies?  Then, the trade-off is more troubling. Would you want your kids to be potentially smarter, yet vulnerable to a horrible, yet relatively rare disease?

How Should Christians Think About all This?

Even if this wasn’t Dr. He’s primary motive, someone else may soon try it.  Therefore, regardless of his motive, this question will likely come up in secular discussion in the near future.  

So how should we, as Christians, think about this?

I think our motivation is the key.  However, discerning our motivation itself can be a challenge.  In 1 Sa. 16:7 God says , “Man looks at the outward appearance, but the Lord looks at the heart.”  Jeremiah the prophet doesn’t even want to guess, saying, “The heart is deceitful above all things, and desperately wicked, who can know it?” (Jer. 17:9)

Discerning motives, even our own, is difficult at best and impossible at worst.  But the Bible gives instruction on some motives — and I’ll come back to this below.

The Bible also talks about fighting and preventing disease.  Jesus said, “They that are well have no need of a physician, but those who are sick.” (Luke 5:31) Christ’s intent may have been metaphorical (about going to preach to the lost) and not to affirm the medical profession.  But by setting up his metaphor using an agreed upon fact, Christ is tacitly affirming just that — that it is good to utilize doctors’ services to fight disease. By extension, this could also include using CRISPR technology to heal.

On the other hand, there might be some theological concerns about tampering with unborn children.  Psalm 139:13 says, “You knit me together in my mother’s womb.”2  We could interpret this to mean that the womb, and what happens in it, is a miracle that belongs to God only.  The following verse is worth noting as well: “… I am fearfully and wonderfully made.” (Ps. 139:14). Here, it seems that the womb is established as God’s domain, and that we are “fearfully and wonderfully” created.  This suggests that this type of work shouldn’t be taken lightly, without serious thought and prayer, and maybe it should not be done at all.

But what would Jesus do, if faced with parents carrying a child with a terrible disease?  I think that Jesus would heal. Why? That’s what he always did. Or to look at it from another way, when did he refuse to heal?  And what did he do when confronted with a sick child? He healed them. Always — at least I can’t think of a situation when Jesus didn’t.  Certainly there were “a great multitude” of sick and disabled people at the pool of Bethesda (see: John, ch. 5), and Jesus only healed one, but he healed the one he spoke with.  

Should it be any different with us?  If I were a doctor faced with parents carrying a child with a terrible disease, and I had the technology and the ability to cure the child, I don’t think I could say say no.  

I’ve thought about Psalm 139, and I also remember that Jesus invites us to participate in his work.  In chapter 6 of Mark’s gospel and chapter 11 of John’s gospel, Jesus invites — in fact, he commands his disciples — to participate in the miracles.  Mark writes that when Jesus miraculously fed 5000 people, he gave instructions to the disciples about organizing the people and passing out the food. And when John tells the story of raising Lazarus from the dead, he instructs the disciples to roll away the stone.  (If he could raise the dead, it would seem that miraculously moving a big stone would be a much easier task — in fact, that’s exactly what happened at the end of the gospel story — see Mark, ch. 16.)

CRISPR could very well be a miracle of modern medicine.3  But there is yet another aspect to the CRISPR dilemma: genetic and biological complexity.  The CCR5 gene shows how a single gene can affect inflammation, immunity, HIV/AIDS susceptibility, memory and learning, and fighting off insect borne diseases.  CRISPR is still far from perfected: unintended consequences, and imperfect and off-target editing are still very real issues.  Some of these might be present in Lulu or Nana’s genome.  Possibly, there are other effects as well — maybe a lot — and they may be even more profound than the ones I’ve mentioned.  

Our genetics are immensely (“fearfully and wonderfully”) complex.  

Also, from an ethical perspective, we can’t experiment on genes and observe the effects throughout a person’s life.  The science might not catch up to the scientist’s desire here. This sort of speculation — genetically modifying an unborn child to save his/her life — might never be possible or realistic.

Still, speculating only, if I were a doctor, and parents approached me with a disease I could cure, how could I not do it?    

I recognize that other Christians may not have these same views.  (In my own discussions, the responses I’ve heard have ranged from an emphatic “No!” To a polite, “That’s interesting…”)  And the more I think about it, the less certain I am.

But if I’m going to err, I’d rather err on the side of love and compassion.

With compassion as our motive and Jesus as our guide, the path — though it is filled with the thorns of ethical and moral hazards —  is clear to me in this situation.

Super-babies

What about genetically engineering super-babies?  Here, the motivations seem much murkier. Who wouldn’t want their children to be smarter?  But messing with their genes, when it could make them vulnerable to an awful disease, seems like what the Greeks called hubris — defying the norms of the time, out of pride, in a way that could bring about one’s own downfall.4 

Parents may want many things.  They may want their children to have a better life than they did.  They may want their children to be the best that they can be. Or they may want their children to be better than other children.

Better and Best

To me, there’s an important distinction here.  I think every parent wants their children to be smart.  That’s one reason why they read to them and talk to them at length, long before the child can speak.  Parents want children to be the best that they can be. But altering their genes is an entirely other matter.  

Striving to that extreme, it seems to me, comes from a desire that the child would be better than others.  Not merely the best that she or he can be, but better than other children.

Jesus has something to say about this.  “The last will be first, and the first last” (Mat. 20:16).  Jesus’ description of himself is helpful as well. “I am gentle and lowly in heart.” (Mat 11:29 — the King James Version says: “… meek and lowly in heart.”)

In the kingdom of heaven, Jesus seems to say, better (than others) is worse.  As the passage from chapter 11 of Matthew’s gospel says, striving for ourselves and our children can make us “heavy laden” with labor.  In contrast, Jesus offers “rest for our souls.”

I pray for this type of rest–for Lulu and Nana, their parents, and Dr. He.

—————

Notes:

1But not all strains.  See: https://www.statnews.com/2019/04/15/jiankui-embryo-editing-ccr5/

2This, and the following verse from Psalm 139, are from the New International Version of the Bible; all others are from the New King James Version

3STAT mentions “Huntington’s, Tay-Sachs, cystic fibrosis, and perhaps familial Alzheimer’s” as diseases that present unmet medical needs which CRISPR might address.

4Or the downfall of one’s child, as in the case of Achilles’ mother, who famously tried to make him invulnerable to injury. Encouraged by what seemed to be his own invulnerability, Achilles lived his life as a warrior in frequent battle, until an arrow to his heel — his one vulnerable area — led to his death at a young age.

Additional thoughts: Thinking about CCR5, the HIV Virus, Inflammation, and Susceptibility to Encephalitic Disease

Below, I’ve included a brief, unscientific, and very speculative explanation of the CCR5 gene/receptor, its role in HIV infection and inflammation and how it might help protect from insect-borne encephalitic disease.

The CCR5 gene codes for a cell receptor.  It sits on the membrane of the cell, waiting to be “activated” by a signaling molecule.  It is like a lock on the cell surface with a keyhole: when a cell signaling molecule with the precise ‘key’ comes along and fits, it ‘signals’ an effect — or a group of effects — by the cell.  

CCR5 is on the surface of special immune cells (T-cells).  When activated by the appropriate signaling molecule, CCR5 seems to play a part in the activation of the immune system, especially, perhaps, in the inflammatory response that sends chemicals and immune cells to an area of attack or injury, to conquer or mitigate the threat.

It just so happens, evidently, that the Human Immunodeficiency Virus (HIV) also has a ‘key’ on its surface that precisely fits CCR5.  Viruses work by deception: they have a ligand — a key — on their surface that so closely matches one of our own natural signaling molecules, that the cell is fooled into unlocking and letting it in.

Once in the cell, the virus infiltrates and takes over the cell’s reproductive machinery (its DNA) and effectively turns it into a factory for reproducing itself.  Vast numbers of the virus are then released from the cell, sent out to infect other cells and make more virus copies.

This is what HIV does: it takes over the T-cell and turns it into a virus factory.  The T-Cells are destroyed in the process, until there are lots of viruses floating around the body, and very few T-Cells left to infect.  Since they are an important part of the immune system, the person then becomes “immuno-deficient” — their immune system can’t function properly.  They become vulnerable to infection and disease — even some forms of cancer which are usually fought off by a healthy person’s immune system.

If inhibiting this gene can make one immune to some strains of AIDS and also enhance learning and memory, then what’s the downside to doing this?  CCR5 actually has an important purpose, mentioned above, in the immune response.  

These articles suggest that its effects could be prominent in diseases that target the brain or central nervous system — its inflammatory response seems to target threats to nerve cells or systems.  The absence of the CCR5 gene (and the associated receptor) has been linked to increased mortality from the West Nile virus and Tick-borne encephalitis.  These diseases affect the central nervous system, and for most people with healthy, intact immune systems, they lead to symptoms similar to a bad case of the flu.  Without CCR5, the diseases can be much worse, with symptoms as horrific as the word ‘encephalitis’ (swelling of the brain) implies. Severe headaches, confusion, and in the worst cases, untreatable seizures, paralysis and death.

How Does this Work?

Inflammatory systems and responses are challenging to think about. On the one hand, they are a necessary part of the immune and healing system.  But their work is kind of clumsy and “brute force” they flood an area with chemicals and signaling molecules that can both attack infection and promote healing, while also inhibiting or affecting the functioning of that body part or system.  Think of a broken bone or a sprain: a bone, joint, or ligament is injured, and the area is soon flooded with the body’s own tools for healing and rebuilding. That flood is inflammation, and while that part is inflamed, the joint or bone can’t be moved — at least not without great pain.  This is a good thing — it keeps us from further injuring a vulnerable part of our body, until the healing is sufficient. So, inflammation is good for healing and fighting infection, but it also keeps that part of the body from working. This is why an overactive immune system (think: allergies or asthma) is bad.

And this could be why the CCR5 receptor’s activity can inhibit learning and memory.  (Note: this is completely speculative — I can’t cite any literature or evidence to support this.  I’ll have to perform and publish my own research, after the grant money comes…) If CCR5’s effects are directed toward attacks on nerve cells, then just as in the case of a badly sprained joint, which is unusable while it is flooded with swelling and inflammatory fluids, those nerve cells in the brain may not function normally (learning and building memories) when an inflammatory response is active.  

Inhibiting learning and intelligence seems like a high price to pay, and it would be if it were permanent, but it isn’t.   Just as the inflammatory response keeps a joint from being used (causing further injury — possibly to the point of making the join completely unusable) and allowing it to heal so that it can be used again.  The inflammatory response in the brain may be necessary to save it from destruction by disease.

In summary, the CCR5 gene and receptor seem to help protect us from viruses that threaten the central nervous system, like West Nile virus, and tick-borne encephalitis.  West Nile virus attacks the nervous system, and causes fever, pain, convulsions, even paralysis and death. And as the articles above show, people without the CCR5 receptor are more vulnerable to these diseases.

On the one hand, inhibiting or “knocking out” the activity of the CCR5 receptor may be beneficial for promoting learning and memory retention, and for resistance to HIV/AIDS.  But on the other hand, the CCR5 gene and receptor appear to play a vital role in keeping us alive, by enabling us to defend ourselves against insect-borne pathogens.

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