Repairing a lethal human mutation

Investment Analysis Clubs Macro Economic Trends and Risks
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https://www.nytimes.com/2025/05/15/health/gene-editing-personalized-rare-disorders.html

Baby Is Healed With World’s First Personalized Gene-Editing Treatment

The technique used on a 9½-month-old boy with a rare condition has the potential to help people with thousands of other uncommon genetic diseases.

By Gina Kolata, The New York Times, May 15, 2025

…
KJ has made medical history. The baby, now 9 ½ months old, became the first patient of any age to have a custom gene-editing treatment, according to his doctors. He received an infusion made just for him and designed to fix his precise mutation…

More than 30 million people in the United States have one of more than 7,000 rare genetic diseases. …

Illnesses like KJ’s are the result of a single mutation — an incorrect DNA letter among the three billion in the human genome. Correcting it requires pinpoint targeting in an approach called base editing.

To accomplish that feat, the treatment is wrapped in fatty lipid molecules to protect it from degradation in the blood on its way to the liver, where the edit will be made. Inside the lipids are instructions that command the cells to produce an enzyme that edits the gene. They also carry a molecular GPS — CRISPR — which was altered to crawl along a person’s DNA until it finds the exact DNA letter that needs to be changed…

While KJ’s treatment was customized so CRISPR found just his mutation, the same sort of method could be adapted and used over and over again to fix mutations in other places on a person’s DNA. Only the CRISPR instructions leading the editor to the spot on the DNA with the mutation would need to be changed. …

It eventually could also be used for more common genetic disorders like sickle cell disease, cystic fibrosis, Huntington’s disease and muscular dystrophy… [end quote]

This is truly amazing! This particular baby has a rare mutation but these other mutations are far more common.

The development required an immense amount of work from multiple research teams.

The payoff can be in many saved lives. Macro impact? Maybe.

Wendy

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I just read about this, super cool story. Macro impact? Certainly! Genetic disorders are devastating. Not only do they cause suffering, they’re expensive to treat and may often require family members to act as care givers.

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Stop the bus, cut the funding!

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Didn’t read the whole article. Interesting science. Biggest question, are they able to alter the germ line? That is, can this mutation still be passed on to the next generation or has it been edited out?

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I’m unclear on how this works in practice. I get the “edit the gene” in a particular cell, but there are millions of cells in the body. How do we get the “super new and improved cell” to tell all the others “Hey, I’ve great this great new mutation…”

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No, they didn’t alter the germ line. They injected the treatment into the liver where the defective mutant gene has its function. The mutation will have a 50% chance of being passed to the next generation if it’s a dominant gene (heterozygous) and a 100% chance if it’s a recessive gene (homozygous).

Wendy

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How much does this cost to save one baby? Nature is geared to just letting the weak die off and the strong survive.

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That is over 50 generations, not one generation. You do not get survival of the fittest just by letting a child die.

We can cheat nature here.

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The cost of this treatment was immense. The article said that multiple scientists in several groups stopped their regular work to focus on developing this treatment.

Human society, dating all the way back to the Neanderthals, was developed to protect individuals when Nature would have killed them. Neanderthals provided care for their sick and injured, demonstrating a level of compassion and social organization. This care included things like provisioning food and water, protection, and potentially active treatment of injuries. The fossil record has preserved skeletal remains proving this.

The question of how much to spend to protect one individual life is very much a current Macroeconomic issue.

During the early 1990s, the Oregon legislature appointed a panel of doctors to list treatments in order of cost effectiveness. The first on the list was childhood vaccination because a few pennies worth of vaccine could prevent illness or death. Lower on the list were expensive treatments that benefited only a few.

Oregon drew a line at the point the legislature felt the state could afford (for Medicaid). Any treatment below the line would not be treated. Expensive ongoing treatments (e.g. cancer chemotherapy) were limited to a specific dollar amount.

I didn’t live in Oregon but I felt that this was a sensible plan.

However, President George H.W. Bush sued Oregon on the basis that this law violated the Americans with Disabilities Act. Oregon lost the suit. The law was dropped.

Nature intended me to die at age 16 when I developed ITP, an autoimmune blood disorder. Fortunately this was cured by a splenectomy. Expensive surgery.

As an adult I had a hysterectomy, bilateral mastectomy (for double breast cancer) and open-heart surgery to replace my aortic valve and ascending aorta.

Was all this expensive surgery worth it to society to keep me alive and functioning?

As for the new science to repair a lethal mutation…
Our METAR member, my older brother @OrmontUS , tragically lost his only son to Duchenne’s muscular dystrophy despite writing doctors all over the world seeking a cure. The most common type of MD, Duchenne muscular dystrophy (DMD), affects about 1 in 3,500 male births. That is not rare! A cure to save these lives would have Macro impact.

Wendy

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This was a “proof of concept” exercise.
The first run is always more expensive than later, scaled, runs.

Now that society knows it “works” we’ll figure out how to make it more economical.
And broader applications of the treatment.

:disguised_face:
ralph

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Human society is not good at saving human lives. Hundreds of millions of humans have been killed in wars and mass killings over centuries by human societies past and present. The Holocaust was a genocide in which German SS killed six million Jews and Roma during World War II. Currently the Jews are killing Arab civilians in Gaza which is also a genocide. The US dropping atomic bombs on Japan and killing hundreds of thousands civilians is genocide.

Humans societies have been mining, processing, creating and dumping toxic materials into our atmosphere and waters for centuries. These human society activities have killed hundreds of millions of people past and present.

Also, human societies have been destroying the environment for centuries resulting in the killing people, flora and fauna.

These are the real macroeconomic issues of the past and present. The individual life protection is an insignificant macroeconomic issue.

Jaak

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