Summary

New Organisms Have Been Formed Using The First Ever 6-Letter Genetic Code

Jan 29, 2021 | 🚀 Fathership

Scientists have engineered the first ever 'semi-synthetic' organisms, by breeding E. coli bacteria with an expanded, six-letter genetic code.

While every living thing on Earth is formed according to a DNA code made up of four bases (represented by the letters G, T, C and A), these modified E. coli carry an entirely new type of DNA, with two additional DNA bases, X and Y, nestled in their genetic code.

The team, led by Floyd Romesberg from the Scripps Research Institute in California, engineered synthetic nucleotides - molecules that serve as the building blocks of DNA and RNA - to create an additional base pair, and they’ve successfully inserted this into the E. coli’s genetic code.

Now we have the world’s first semi-synthetic organism, with a genetic code made up of two natural base pairs and an additional 'alien' base pair, and Romesberg and his team suspect that this is just the beginning for this new form of life.

"With the virtually unrestricted ability to maintain increased information, the optimised semi-synthetic organism now provides a suitable platform [to] ... create organisms with wholly unnatural attributes and traits not found elsewhere in nature," the researchers report.

"This semi-synthetic organism constitutes a stable form of semi-synthetic life, and lays the foundation for efforts to impart life with new forms and functions."

Back in 2014, the team announced that they had successfully engineered a synthetic DNA base pair - made from molecules referred to as X and Y - and it could be inserted into a living organism.

Since then, they’ve been working on getting their modified E. coli bacteria to not only take the synthetic base pair into their DNA code, but hold onto it for their entire lifespan.

Initially, the engineered bacteria were weak and sickly, and would die soon after they received their new base pair, because they couldn’t hold onto it as they divided.

"Your genome isn't just stable for a day," says Romesberg. "Your genome has to be stable for the scale of your lifetime. If the semisynthetic organism is going to really be an organism, it has to be able to stably maintain that information."

Over the next couple of years, the team devised three methods to engineer a new version of the E. coli bacteria that would hold onto their new base pair indefinitely, allowing them to live normal, healthy lives.

The first step was to build a better version of a tool called a nucleotide transporter, which transports pieces of the synthetic base pair into the bacteria’s DNA, and inserts it into the right place in the genetic code.

"The transporter was used in the 2014 study, but it made the semisynthetic organism very sick," explains one of the team, Yorke Zhang.

Once they’d altered the transporter to be less toxic, the bacteria no longer had an adverse reaction to it.

Next, they changed the molecule they’d originally used to make the Y base, and found that it could be more easily recognised by enzymes in the bacteria that synthesise DNA molecules during DNA replication.

Finally, the team used the revolutionary gene-editing tool, CRISPR-Cas9 to engineer E. coli that don’t register the X and Y molecules as a foreign invader.

The researchers now report that the engineered E. coli are healthy, more autonomous, and able to store the increased information of the new synthetic base pair indefinitely.

"We've made this semisynthetic organism more life-like," said Romesberg.

If all of this is sounding slightly terrifying to you, there's been plenty of concern around the potential impact that this kind of technology could have.

Back in 2014, Jim Thomas of the ETC Group, a Canadian organisation that aims to address the socioeconomic and ecological issues surrounding new technologies, told the New York Times:

"The arrival of this unprecedented 'alien' life form could in time have far-reaching ethical, legal, and regulatory implications. While synthetic biologists invent new ways to monkey with the fundamentals of life, governments haven’t even been able to cobble together the basics of oversight, assessment or regulation for this surging field."

And that was when the bacteria were barely even functioning.

But Romesberg says there's no need for concern just yet, because for one, the synthetic base pair is useless. It can't be read and processed into something of value by the bacteria - it's just a proof-of-concept that we can get a life form to take on 'alien' bases and keep them.

The next step would be to insert a base pair that is actually readable, and then the bacteria could really do something with it.

The other reason we don't need to be freaking out, says Romesberg, is that these molecules have not been designed to work at all in complex organisms, and seeing as they're like nothing found in nature, there's little chance that this could get wildly out of hand.

"[E]volution works by starting with something close, and then changing what it can do in small steps," Romesberg told Ian Sample at The Guardian.

"Our X and Y are unlike natural DNA, so nature has nothing close to start with. We have shown many times that when you do not provide X and Y, the cells die, every time."

Time will tell if he's right, but there's no question that the team is going to continue improving on the technique in the hopes of engineering bacteria that can produce new kinds of proteins that can be used in the medicines and materials of the future.

As Romesberg asserts, "This will blow open what we can do with proteins."

The research has been published in Proceedings of the National Academy of Sciences.

Unrepentant teen with a long list of offences is why some parents shouldn't breed

Nov 25, 2021 | 🚀 Fathership

Ralph Wee Yi Kai, a 19-year-old Singaporean man, has pleaded guilty to eight charges on Nov. 25 during his plead guilty mention before District Judge May Mesenas.

The charges include consuming weed, causing unnecessary suffering to a frog, possessing imitation tobacco products, trespassing into the rhinoceros enclosure at the Singapore Zoo, and committing mischief by damaging property, reported CNA.

Another six charges will be considered during his sentencing.

Probation is "not realistic"

Wee pleaded guilty via video link from his place in remand, where he has been since Nov. 6.

The prosecution strongly objected to a probation suitability report, noting that Wee is "beyond the control of his parents, which renders probation unsuitable", according to CNA.

The prosecution asserted that probation "is not realistic" for Wee, based on his repeated offences and conduct in court.

They cited his "blatant disregard for rules", and urged for a reformative training suitability report instead.

Deputy Public Prosecutor Melissa Lee said Wee "has a tendency to abuse drugs and alcohol", which caused him to behave aggressively towards his parents.

He also "posed a risk" to them, which led him to be admitted to the Institute of Mental Health.

"Never expected it to come to this"

Wee's defence lawyer Shashi Nathan requested for the addition of a probation suitability report, according to CNA.

Shashi maintains that his family is able to supervise Wee, and added that his client "comes from a good family" who are "able to look after him".

He said that Wee was undergoing "a severe emotional crisis" when he committed his offences, and shared that the case has also affected Wee's family, especially after their home address was released to the press.

"While Ralph understands that what he did was wrong, he never expected it to come to this," said Shashi.

Difference between probation and reformative training

Wee was ordered to go though both assessments for a probation suitability report and a reformative training report, reported Yahoo News.

Offenders who undergo probation will not have a criminal record, while reformative training, which provides a more structured environment, results in a criminal record.

What Wee's lawyer said

Wee's lawyer said his client acted out after breaking up with his girlfriend, 18, who was the one who filmed the video of Wee backflipping in the zoo.

The defence lawyer, Shashi, said Wee spiralled into an emotional crisis as a result of his break-up.

Wee is homeschooled.

The court was told Wee saw a video of a man riding a giraffe and decided to make a video in the rhino enclosure, Yahoo News reported.

The ex-girlfriend had filmed the act and posted it on her private Snapchat account.

Wee posted it on his public TikTok account and a police report was made by a zoo personnel within the same day.

Wee removed the video when he was told to do so by the police, but reposted it on Dec. 18, before being told to remove it again, claiming he thought the video had been made private when he reposted it.

Wee had also included a link in his Instagram account biography to directed to a page selling t-shirts with the words "rhino ralph".

But he denied creating the merchandise profile.

He later removed the link.

Wee will return to court on Dec. 20 for his sentencing.

Timeline of events with updated details

Oct. 9, 2020, 2:40am: Allegedly committed an act of vandalism by hitting an information panel at a bus stop in Sixth Avenue, off Bukit Timah Road, causing S$900 in damage.

Allegedly caused damage to two cars -- S$2,800 to a Mercedes-Benz and more than S$1,600 to a BMW -- in nearby Sixth Crescent.

A taxi driver passing by reported him to the police, as Wee was standing in the middle of the road with a beer bottle in hand.

Dec. 16, 2020: Wee was placed on compulsory supervision for 60 months from Dec. 16. He was required to present himself for urine tests on each Tuesday and Thursday, but failed to turn up on four occasions.

He was placed on e-tagging during this period of time, after having been charged for his earlier offences.

He had to stay at home from 10pm to 6am as part of his bail conditions.

Dec. 17, 2020, 2.40pm: Accused of trespassing into the rhinoceros enclosure and taking a video.

Dec. 18, 2020: Reposted zoo video, despite taking it down earlier after being told to do so by the police. Told to remove video again.

Dec. 24, 2020: Accused of abusing a frog, which subsequently died, by hitting a ball against it on a foosball table, causing "unnecessary pain and suffering".

The incident allegedly took place at a Sentosa Cove property.

July 2021: First hauled to court and charged with two counts of mischief, as well as one count each of vandalism and criminal trespass.

Bail was then set at S$15,000.

Aug. 6, 2021: Allegedly consumed cannabis while out on bail. Arrested at his residence and two urine samples obtained tested positive for weed. S$15,000 bail revoked.

Sep. 14, 2021: Allegedly possessed an e-vaporiser and six e-cigarette pods at a ward in the Institute of Mental Health.

Three police officers showed up at IMH, where Wee was warded, to arrest him for failing to attend court.

He was admitted to IMH due to his drug and alcohol abuse, as had acted aggressively towards his parents when they demanded the drugs from him.

He was warded in IMH due to the risk he posed to his parents.

Oct. 13, 2021: Charged with one count of drug consumption while still in remand.

Bail raised to S$20,000 and Wee was released.

While out on second bail, Wee committed a string of offences, including cutting his electronic tag, according to ST, as well as not reporting for his urine tests on a few occasions, CNA reported.

The prosecution has called for an urgent bail review hearing to have Wee's second bail revoked for the alleged fresh offences.

Oct. 26, 2021: Allegedly cut a S$100 GPS ankle tag at an address on Leedon Road at about 12:10am.

Prior to this act, Wee was upset at his father, who had asked Wee to sleep early since he had to report for his urine test in the morning.

After arguing with his father, Wee decided to leave the house, and used pliers to cut off his e-tag before cycling to his friend’s house.

Upon discovering that Wee was missing, his father called the police.

The e-tag, worth S$100, was damaged and could no longer be used.

It was found in Wee’s house.

Oct. 28, 2021: Allegedly possessed an e-cigarette pod at the Leedon Road address.

Nov. 5, 2021: Warrant of arrest issued, as Wee could not wake up to attend court.

Nov. 6, 2021: Wee arrested.

Nov. 12, 2021: Slapped with four additional charges.

Nov. 25, 2021: Pleaded guilty to consuming weed, causing unnecessary suffering to a frog, possessing imitation tobacco products, trespassing into a rhino enclosure, and committing mischief by damaging property belonging to others.

Ordered to go though assessments for a probation suitability report and a reformative training report.