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Gene Editing May Have Cured HIV. Here’s Why We’re Not Celebrating.

There is a treatment out there that could prevent HIV infections. At the very least, it could prevent those infections from becoming AIDS. This same treatment could prevent certain cancers and help stop many other viruses from gaining a foothold in the body. It could save millions of lives. So why don’t we use it?

Before we get there, let’s talk about what this treatment is.

It’s an itsy-bitsy genetic modification. That’s all. We just need to pop out a few bits of your DNA and HIV can no longer affect you. It’s the same genetic modification that Chinese scientist, He JianKui, used on those twins last week. Nerds call it “knocking out the CCR5 gene.” You just need to chop out a few chunks of DNA and, suddenly, you’re all but immune to HIV. If you don’t have this gene, HIV proteins cannot enter your cells and cannot infect you. The children that this Doctor genetically modified have exactly that genetic change. They’re likely immune from HIV. That sounds pretty appealing, but, as you may imagine, knocking it out is not so simple and the loss of this gene could lead to dire consequences.

An artist’s rendering of the HIV Virus from BruceBlaus [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], from Wikimedia Commons

So why don’t we knock it out? Why don’t scientists just kick it off so we can prevent most HIV infections?

Well, like most things, it’s complicated.

CCR5 may not do much day to day, but those without it can face serious consequences.

There are quite a few individuals without this gene. This group has a special name. Get ready. They’re called: Homozygous for CCR5-Δ32. I get goosebumps just writing that. In seriousness though, there are quite a few people with this genetic modification built in. You may even be one of them and have no idea! The vast majority of these individuals lead completely normal lives. For some though, there are dire consequences.

These consequences are summed up nicely in the title of an article from the Journal of General Virology: “CCR5 deficiency predisposes to fatal outcome in influenza virus infection.” Ouch. Influenza, in case you didn’t already know it, is what we normally call “the flu”. It’s a remarkably common, rapidly mutating virus with multiple strains spread around the globe. Each year you (should) get a flu shot that protects you against some of them, but still, you’re exposed to many more. We don’t exactly know how CCR5 helps protect us from deadly complications from the flu, but we know that it does, and that’s pretty valuable to most of us.

That’s not the only way that CCR5 can help protect us. The CCR5-Δ32 individuals (again, those without a functioning CCR5 gene) have also been shown to be more susceptible to West Nile Virus, Tick-borne encephalitis, and potentially other harmful viruses as well. With West Nile in particular, CCR5 appears to be hugely important as a protector of the brain, at least in mouse models.

Still though, these aren’t really bad diseases. Not nearly as bad as HIV at least. Yet we still don’t just knock out this gene. Why not?

An artist’s rendering of the CCR5 protein receptor from Thomas Splettstoesser (www.scistyle.com) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)], from Wikimedia Commons

There’s one more complication. Germ lines.

This isn’t the regular type of germ that you learned about in school. A germ line is a series of cells all descended from cells that came earlier in the series. That’s a nerdy way of saying that these are the cells from which all other cells in your body develop. To make changes on a large scale, a scale so large as to affect every single one of a certain cell type, you need to make changes in the germ line. In humans, those changes have to be at the egg and sperm level. And we don’t do that.

He Jiankui does, but most of use don’t.

This is the genetic mutation that this doctor performed on the Chinese children. He knocked out the CCR5 gene in these children by modifying their germ line cells when they were embryos. As far as we can tell, two of these children have already been born and one more is on the way. Theoretically, they’ll be all but immune to HIV/AIDs, but we saw earlier that there could be significant consequences to that immunity. There’s one more thing to add to this puzzle of HIV resistance. Prevalence.

A map of mosquito-associated virus incidence in China from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866263/

In China, where these children were born and/or will grow up, HIV exists. According to Avert.org, there were about 115,000 new HIV cases in China in 2015. That’s about four cases for every 100,000 people in the country. Influenza exists too, at a much higher prevalence. 33 cases per 100,000 people. Mosquito-borne viruses are a growing problem as are tick-related diseases. These are exactly the conditions that these children are especially prone to. If one of these HIV-immune children is exposed to the flu or the wrong mosquito-borne virus, they’re much more likely to suffer life-threatening complications than the average person.

I wish that this HIV cure was as simple and effective as it seems. That’s certainly how Dr. He Jiankui is selling his treatment. But it’s not. The body is complicated. No part stands alone and can be removed without consequence not even the appendix. It’s very dangerous to start poking around the genome, picking which diseases you want immunity from and which are worth the risk. Aside from any ethical considerations about informed consent, human gene editing, and the future of our species, chopping out genes is dangerous and requires much more care than this doctor apparently took. These children, while immune from HIV, will be at risk for life-threatening diseases for which we do not have effective treatments.

Where do we do from here? That’s up to the scientific community. They’re currently knee-deep in squabbles over this topic and have been for quite a while. Who knows where the future may lead. It’s quite possible that medical science will decide that this is a worthwhile trade-off. In the future, HIV may be traded in for life-threatening flu. We’ll just have to wait and see. Today, we just don’t have enough information.

Whether you think the world is ready for genetic modifications of humans or not, there is a lot more to investigate about the implications of every little change. Bold ideas and experiments do push the scientific community forward, this one may have been a bridge too far.


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