Tuesday, May 7, 2019

gene drives

This is huge and surely is mimicked in the wild as well.  Of course our early focus lies with the low hanging fruit.  Yet this also open the door for shifting a population with useful traits as well.

How about making a population domesticatable?  Today few species are, but a number are hugely prospective.  That it has not happened merely confirms that they are not amenable as human attempts will not be scarce.

All good as this serves to rapidly alter known populations and to block all forms of d8sease vectors..
Gene drives

May 02, 2019

Driving out a disease on the rise


Fever. Chills. Joint problems. Neurological issues. Sometimes even an irregular heartbeat.

These are some symptoms of Lyme disease, a common bacterial infection that affects tens of thousands of Americans per year. And it’s becoming even more common—the number of diagnosed cases nearly doubled from 2004 to 2016 as the disease’s geographic range has expanded. People get Lyme disease through a tick bite, but the ticks aren’t born carrying the bacteria. They get it after biting a particular species of mouse.

A scientist at MIT has a bold plan to stop the disease in its tracks. It’s called a gene drive, which combines genetic modification and evolution to change a species (though he’s also developed ways of geographically limiting that change). To do so, he’ll have to manipulate whole populations of wild mice for generations.

It’s controversial, but this is probably not the last time we’ll see it—as climate change makes tropical diseases more common in higher latitudes, scientists are getting creative in how they plan to keep people safe.

Got the bug? Read on.

We can change the DNA of an entire species—in the wild

As the inventor of the gene drive, Kevin Esvelt knows the stakes are high. It has the potential to save millions of lives by eliminating diseases like malaria. But in the wrong hands—or even in well-intentioned hands—the results could be catastrophic. How do we weigh the potential for enormous good against the terrifying unknowns?

What’s a gene drive?

How do you ensure all individual animals in a population have a desired gene? You use a gene drive

 Imagine that a scientist has altered an organism’s DNA so that it has a trait the scientist has deemed desirable (in Esvelt’s experiment, that trait is immunity to the bacteria that causes Lyme disease). The scientist ensures that the gene is highly heritable, so that it has more than a 50% chance of being passed on to the next generation. As that organism and its offspring reproduce, the desired gene affects a higher proportion of a population. Finally, a few dozen generations after the first gene-carrying individual was introduced, all organisms in a population have the desired gene. Esvelt says the effects could last for several hundred years.

It’s easy to see this effect on organisms that reproduce quickly, such as insects and rodents. If scientists did a gene drive in humans, it might take centuries for the gene to permeate a substantial amount of the population. And a gene drive happens in nature, as researchers learned when they discovered a specific gene called the P-element in wild fruit fly populations that didn’t exist before 1950.

There’s also a clear downside: A gene drive, once it’s underway, is nearly impossible to stop or undo.

That’s how Esvelt’s plan for the immune mice differs. In what Esvelt calls a daisy drive, the genetic modifications are spread out among the genome so that, as the desired trait is passed on through generations, the genes diffuse, effectively putting an expiration date on the inherited trait. He also describes a “daisy quorum drive” to prevent modifications from passing into species present in communities that haven’t consented to such experimentation, and even “daisy restoration drives” that essentially reset the changes.

By the digits

30,000: Average cases of Lyme disease diagnosed every year in the US, according to the CDC

300,000: What scientists suspect is the actual number of cases of Lyme disease in the US every year

14: US states in which 95% of Lyme disease cases are diagnosed

438,000-720,000: People worldwide killed by malaria in 2015

1: Months female mosquitoes, which transmit malaria, live in the wild

Dozens: Generations it can take for an altered gene to affect the majority of a given population

There once was a mouse from Nantucket

Evolutionary biologist Kevin Esvelt decided to start tackling Lyme on Nantucket and Martha’s Vineyard, where the disease is a big problem (as much as 40% of the population on Nantucket has had Lyme at some point). His plan: Use gene editing enzyme CRISPR to engineer mice that are resistant to the bacteria that cause Lyme, or to ticks themselves. It would function sort of like a vaccine.

According to an email he sent to stakeholders and published by Boston’s WBUR in 2016, Esvelt would begin by releasing genetically engineered white-footed mice on a “small uninhabited island”: mice resistant to Lyme, ticks, or both. Communities, regulators, and ecologists would all have input. Esvelt knows the prospect of genetically manipulating populations of animals in the wild can be a hard sell, so he’s spent a ton of time meeting with community members on Nantucket and Martha’s Vineyard to get their buy-in. The plan, which doesn’t yet have a launch date, will also face scrutiny for federal regulators as it progresses.

If Phase 1 was successful and the communities involved voted to move forward, Phase 2 would involve releasing “equivalent mice on Nantucket and/or MV [Martha’s Vineyard] in sufficiently large numbers (over two years) to achieve a similar effect.” That could involve over 100,000 mice, with a similar number removed to keep population numbers steady.

Finally, Phase 3 would tackle the mainland, but due to “dilution on the edges,” would likely require new releases of mice every decade.

“We are on the cusp of a new bio-revolution. It is like we were using saws but now we are using scalpels.”

A tool to reshape the world?

Esvelt isn’t the only one who has suggested using gene drives in a way that will benefit humans. Research teams have launched small experiments on mosquito populations in the US, Burkina Faso, Brazil, and Panama to reduce the transmission of diseases like Zika and malaria.

Some ethicists and conservationists are concerned about the potential impacts of a tool like a gene drive—that it could irrevocably alter ecosystems in ways we can’t predict, that without proper stakeholder input it can give the impression of mad scientists running amok.

But it may not be time to rule out gene drives completely. As climate change alters ecosystems, 1 billion people may be newly at risk for diseases that were previously limited to tropical climes. Gene drives could reduce that risk. Gene editing could also help save species at risk of extinction, or even bring some back from the dead (pdf). Last year the UN Convention on Biological Diversity “rejected the idea of an international moratorium on gene drive research, including experimental releases into the environment,” but recommended “free, prior and informed consent” from affected communities. That’s exactly what Esvelt plans on Nantucket and Martha’s Vineyard.

Brief history

1880s: Scientists first learn about “selfish genes,” the kind that get transmitted selectively in a gene drive

1987: Scientists discover CRISPR, in the form of repeating patterns in DNA

2003: Evolutionary biologist Austin Burt suggests using “selfish genes” as a gene drive for human benefit

2012: Biochemists Jennifer Doudna and Emmanuelle Charpentier prove CRISPR can be used reliably as a gene editing tool

2015: Scientists in California show that gene drives work in mosquitoes in the lab

2017: Zika-fighting mosquitoes are released in Florida

2019: Gene drives successfully work in mice, indicating that it could work in other mammals, too

Watch this!

Since a daisy-chain gene drive involves some tricky logic, this MIT Media Lab video might help you grok it. For the 200-level version, check out Esvelt’s 25-minute video on gene drives and his 30-minute video on localized gene drives.drives?

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