CRISPR-Cas9: understanding gene editing, for the rest of us

Everybody’s talking about this new gene-editing technology borrowed from bacteria—but is there any way to make it understandable to normal folks?

Let’s try.

This is new stuff. It matured to usefulness only in the past three or four years—the original paper was just published in 2012 It lays out the technology folks casually call CRISPR-Cas9.

 

The system lets laboratories essentially cut-and-paste genetic material, with accuracy previously unattainable. Sometimes it just lets you go in and flick a switch, turning something off. It is based on the immune system used by some bacteria, as well as most of the life forms called archaea.

The technique lets researchers select a very specific spot in DNA, and snip it open to remove or insert something. The cell then naturally repairs itself.

The difference from the old genetic engineering techniques, is essentially like the difference between doing archaeology with a backhoe or with tweezers. It's like using a word processor to cut-and-paste instead of paper, glue and scissors.

FOR STARTERS

It’s useful to know a tiny bit about DNA and RNA—the genetic components of anything that is alive. 

DNA is the basic blueprint. In life, it is what dictates whether something will be a temperate fruit tree, or an edible mushroom, or an ocelot or a human.

RNA carries out the instructions of the DNA. 

If it were a football game, DNA would be the rulebook and RNA would be the players.

Is that too strange an analogy? How about this: DNA is the plan; RNA carries out the plan.

BACTERIA DEFEND THEMSELVES

So, researchers in the 1980s noticed that in some bacterial DNA, they were occasionally seeing a repeating pattern. There were sections where a certain bit of DNA would repeat between random other sections, like the apples in this example: Apple, orange, apple, pear, apple, grapefruit, apple, banana …

They called it CRISPR, for Clustered Regularly-Interspaced Short Palindromic Repeats. It was an interesting pattern, but what did it mean?

A couple of researchers figured out that the repeating apples were actually pieces of DNA of a virus that was attacking the bacteria. Those apple pieces would make RNA that would launch and attach itself onto the attacking virus.

Meanwhile, the intervening DNA bits—the orange, pear, grapefruit, banana—would follow up and work with a protein (called Cas9) to go and split apart the virus DNA. 

Thus, the virus was inactivated. And the bacterium was cured from viral disease. Cool stuff.

The immune system of a bacterium acted like a genetic pair of scissors with its own GPS. The GPS gets it to a specific location, and then the scissors snip the DNA open.

Another way to think about it: the bacterium has the ability to recognize a new enemy, and can send out its genetic ninja teams to attack the enemy.

THE LIGHT COMES ON

As they studied it, scientists realized this was a potential tool kit for adjusting genetics--that they could adapt this system to pluck a piece out of DNA changing how the organism works. And they also figured out how to insert a new piece of DNA if necessary, before the cell healed the cut ends.

A genetic Swiss army knife.

A pretty clear explanation of all this is here . 

Here’s a video with some interesting graphics that discusses the system. 

And here is a video of one of the discoverers, Jennifer Doudna, which is a little tougher to understand, but she’s a key player. There are plenty of YouTube videos of her describing the process.

And how important is it? Well, Doudna and Charpentier are getting really famous. They have been named among Time Magazine’s 100 most influential people in the world. They’ve picked up the $500,000 Gruber Genetics Prize and the $3-million Breakthrough Prize in Life Sciences. They just missed this year's Nobel Prize, but they might get it next year.

APPLICATIONS

The world moves forward on the CRISPR front with amazing speed. 

The technology is being used to amend tobacco DNA to produce anti-cancer drugs. There’s work to use CRISPR to turn off genes in cancer cells, effectively killing the cancer. In crops, changes can be so precise that they essentially add nothing to the genome, but still have a favorable effect.

In this paper, from last month, co-author Wendy Harwood of England’s John Innes Centre, said you can make just the tiniest change to turn off a particular feature. 

“Stopping particular genes from working is one way to develop disease resistant crops, for example with resistance to mildew or to produce crops without unwanted compounds including toxins.

“The final plants produced in this way have no additional DNA inserted so they are essentially the same as plants with naturally occurring changes to genes or plants that have been bred using conventional mutation breeding methods,” Harwood said.

WHOA. A NOTE OF CAUTION

Doudna, of the University of California, who worked with Emmanuelle Charpentier of the Max Planck Institute for Infection Biology, in making the discovery, talks here about some of the ethical implications of their finding.

Well, yes. You might be able to cure cancer and cystic fibrosis and sickle-cell anemia and maybe HIV. And you might be able to make new medicines to cure other diseases. And you might be able to engineer crops to fight disease without pesticides. And maybe make mosquitoes that can’t transmit dengue and malaria. 

But you might also bioengineer humans. You want a baby boy who will grow to 6-foot-2, with an IQ of 145, curly black hair and green eyes, and can run a 40-yard dash faster than Usain Bolt? We might be able to engineer that.

Maybe that’s good, but, um, maybe not. Remember the Nazis and eugenics?

Doudna and her team are thrilled about the possibilities of their technology, but wary about some of the implications.

She has called for a “global pause” in redesigning human embryos while we think about those implications.

John Travis, of the journal Science, wrote earlier this month about the National Academy of Science’s International Summit on Human Gene Editing. 

He quotes a mother who lost a child to genetic disease: “"If you have the skills and the knowledge to eliminate these diseases, then freakin' do it.”

But genetic changes are permanent, and “before we make permanent changes to the human gene pool, we should exercise considerable caution,” said another participant at the summit.

Most of the concern expressed to date about CRISPR involves its use in engineering human genetics, not so much other life forms. The Center for Genetics and Society and Friends of the Earth have issued a position statement opposing the use of the technology in humans.

© Jan TenBruggencate 2015

The Top Ten Energy Stories in Hawai`i, 2015

Whew, it’s been a big year for energy in the Islands—big enough that it’s risky to pick just 10 of the biggest Hawai`i energy

stories of 2015.

But we’re not shrinking violets at RaisingIslands, so with the caveat that folks can disagree, here we go.

Number One: The top energy story of the year is certainly the controversial proposal by the Florida electric behemoth NextEra Energy to merge with Hawaiian Electric Industries, the corporation that includes Hawaiian Electric, Maui Electric and Hawaii Electric Light. The merger was announced in December 2014 and the PUC docket seeking approval on January 14, 2015. 

It seems like every community group in the state asks to intervene in the HECO/NextEra. The PUC approves 28 intervenors, among them the Renewable Energy Action Coalition of Hawaii, Hawaii Island Energy Cooperative, Kauai Island Utility Cooperative, Hawaii Water Service Co., Ka Lei Maile Alii Hawaiian Civic Club, Maui County, Sun Edison, Hawaii Solar Energy Association, Friends of Lanai, Puna Pono Alliance, Hawaii County, Ulupono Initiative, AES Hawaii, Blue Planet Foundation, SunPower Corp., Tawhiri Power, Hawaii PV Coalition, Paniolo Power, The Gas Co., Hawaii Renewable Energy Alliance, the state Office of Planning, Sierra Club, Hina Power Corp. and the Honolulu Board of Water Supply. Those, and a few others. Some have since dropped out, but still… 

2. The state announces that its goal is for Hawai`i to be100 percent powered by renewable energy by 2045, although it is something of a theoretical standard. Under the language of the commitment, the state could meet the 100 percent standard and still burn some oil. 

3. Gov. David Ige announces in August that he’s against Hawaiian utilities using liquefied natural gas (LNG) to replace oil and coal for energy production, arguing that it would detract from the state’s movement toward renewable energy solutions. 

4. The Kaua`i Island Utility Cooperative dedicates the state’s largest to date solar array, at Anahola, Kaua`i, which replaces the previous largest array at Koloa, also on Kaua`i, which in turn replaced the next previous largest array, also on Kaua`i. KIUC has more solar power per customer on its grid than any other utility in the country. On sunny days, most of the island’s electricity is generated by solar. 

5. It’s not purely a Hawai`i story, but the federal government’s extension of renewable energy tax credits means Hawai`i’s solar and wind industries get a big boost—federal tax credits stay at 30 percent through 2019. 

6. NextEra/HECO merger announcement prompts neighbor island utility self-determination proposals:  Hawai`i Island Energy Cooperative is formed in hopes of capturing Hawaii Electric Light if it becomes available ; and Maui Mayor Alan Arakawa studies a municipal power utility for Maui County. 

7. The Department of Hawaiian Home Lands announced a contract with NextEra affiliate Boulevard Associates LLC for a 60-megawatt wind farm at Kahikinui on Maui, which is a little smaller than the state;s biggest,  the 69 megawatt Kawailoa wind farm on O`ahu. But if built, the Kahikinui windfarm would make Maui the wind capitol of the Islands, adding to the 51 megs of wind power at Kaheawa and 21 megs at Auwahi.

8. KIUC announced plans with Solar City to build the biggest dispatchable solar/battery plant in the nation: a 13-megawatt solar array with a 52-megawatt-hour battery. 

9. Continuing on the battery front, Tetris owner Henk Rogers, through his company Blue Planet Energy, starts selling Sony’s lithium ion phosphate battery technology along with Blue Planet’s own software suite, under the name Blue Ion. And several other vendors are also marketing battery systems for solar arrays.

10. Finally, solar development rolls on. The PUC approved nearly140 megawatts of new solar for O`ahu. Three projects are by Sun Edison and one by Eurus Energy. These, if built, will finally knock Kaua`i out of first place in the biggest-solar-farm category, since each of these plants is bigger than the biggest one on Kaua`i. 

(Full disclosure: This blog’s author, Jan TenBruggencate, serves on the elected board of directors of the Kaua`i Island Utility Cooperative.)

© Jan TenBruggencate 2015

Murky water might actually help bleached corals--how weird is that?

Okay, this is just weird--something we think is bad turns out to be good.

(Image: Bleached Seriatopora coral colonies in the Philippines. The shaded one at lower right has retained some pigmented algae and will survive, the central one in full sun has severely bleached and will die. Credit: Robert van Woesik/Florida Institute of Technology.)

We know that overwarm water can cause coral bleaching, and if it lasts a long time it can kill corals.

And we know that turbidity in the water can smother corals and block sunlight their symbiotic algae need to survive.

But here’s some research that turbidity can protect corals from warming—including some of the coral populations of the Northwestern Hawaiian Islands.

Researchers Chris Cacciapaglia and Robert van Woesik, of the Florida Institute of Technology, thought that sediment in the water might shade corals, and help protect them—the way a hat or an umbrella protects you from sunburn—by physically blocking solar radiation.

“We hypothesized that some turbid nearshore environments may act as climate-change refuges, shading corals from the harmful interaction between high sea-surface temperatures and high irradiance,” they write in an article in the journal Global Change Biolog.

The article is entitled : “Climate-change refugia: shading reef corals by turbidity.” 

While many have focused on the water temperature, the Florida scientists say it’s the combination of high temperature and the brightness of the sunlight—irradiance--that cause damage to corals.

They looked at similar reefs, where some were in clear water and nearby ones in cloudy water. And they found that the corals in mildly cloudy water survived better than those blasted by the full power of both heat and light.

“Protecting the turbid nearshore refuges identified in this study, particularly in the northwestern Hawaiian Islands, the northern Philippines, the Ryukyu Islands (Japan), eastern Vietnam, western and eastern Australia, New Caledonia, the northern Red Sea, and the Arabian Gulf, should become part of a judicious global strategy for reef-coral persistence under climate change,” they wrote.

It may seem counterintuitive to protect areas with cloudy water, but at least to some degree, that might protect some oft he corals, the authors write.

“We’ve identified refuges from climate change, where naturally turbid environments will reduce the temperature stress predicted for 2100,” Cacciapaglia said in a press release.

© Jan TenBruggencate 2015

Genetically engineering: Bananas and bad situations

Sometimes you can breed yourself out of a bad agricultural situation.

Sometimes you can genetically engineer yourself out of it.

And sometimes you just give up.

(Image: Banana suffering from Fusarium wilt. Credit: American Phytopathological Society.)

Traditional plant breeders look for traits in closely related varieties that they can cross-breed into commercial varieties of crops.

Grape breeders, as an example, are working hard to breed fungus resistant varieties with commercially appealing varieties to develop commercial crops that don’t need so much fungicide. 

But breeding doesn’t always work and it can be very slow. The story of pineapple in Hawai`i is an example. 

The Pineapple Research Institute developed tens of thousands of crosses with various qualities, but found little that could beat the industry standard, the Smooth Cayenne. Some of their varieties have made it into the fresh pineapple industry, but they’re not perfect.

Genetic engineering provides a leg up on standard breeding. The most famous Hawaiian example is the insertion of a part of the ringspot papaya virus into papayas, to cause the papaya to be resistant to that virus—a kind of genetic inoculation against disease.

There has been a lot of criticism of combining distant species genetically, but in some cases traditional breeding even between close species doesn’t work well—like potatoes. There, a technique called cisgenesis has been used to cross potato relatives to get disease resistance from one potato into another potato, when traditional breeding doesn’t work. 

They’re still potato genes added to potato genes, but genetic engineering techniques are used because it’s hard to get them to cross naturally.

With bananas, when a fungal disease attacked the world’s most popular banana variety, Gros Michel, the world took Door Number Three: it gave up on the Gros Michel. There was no cure, and the banana was very susceptible, and the technology wasn't very advanced.

The Fusarium wilt essentially killed off the banana that had dominated the industry for a century—the tasty banana that made bananas popular.

If you’re old enough to remember the Gros Michel, you know how good a banana can be. Growers switched to the blander Cavendish. Not as tasty, but it was resistant to the fungus that killed the Gros Michel.

Now, a new crisis has arisen. There’s a new disease attacking the Cavendish. It is a soil fungus related to the one that killed Gros Michel. It is called Fusarium oxysporum f. sp.cubense (Foc), and is commonly called Fusarium wilt or Panama disease.

A good review of the issue is at the ProMusa site. (Musa is the name of the banana genus.) 

There is some suggestion that there might be Fusarium-resistant strains of Cavendish. Growers from the Philippines are shipping partially resistant Cavendish bananas, but most folks don't consider that a final solution.

Most industry folks suggest that the only savior is likely to be genetic engineering. Even the leftist literary leader Mother Jones says so. “The only way to save your beloved bananas might be genetic engineering,” says the headline in today’s issue (December 21, 2015)

If you simply switched to a different banana variety, the Fusarium fungus might just target that one next, Mother Jones author Maddie Oatman worries.

Why does any of this matter? Because banana is the most popular fruit in the world. As a report in the PLOS Pathogens journal says, they are grown in tropical and subtropical areas globally. For many cultures globally, banana eating and banana growing are essential to survival.

As happened with the Gros Michel, most of the Cavendish bananas are clones of each other—meaning a disease that gets traction can get lot of traction.

“Any disease management eventually fails in a highly susceptible monoculture,” that article says.

There’s a lot going on with bananas. Research labs around the world are working on genetic solutions. Classic breeding is problematic in bananas, and most domesticated bananas have been selected from among wild varieties, not bred.

One question is that if we’re going to make a banana resistant to Fusarium wilt anyway, then instead of the Cavendish, seems like it would make sense to go after the Gros Michel—a much tastier banana? 

And if we can get any good Fusarium resistant banana, how soon will it be available. I’ll be trying to get an answer to those questions.

© Jan TenBruggencate 2015