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First life with ‘alien’ DNA

First life with ‘alien’ DNA 86

(nature) For billions of years, the history of life has been written with just four letters — A, T, C and G, the labels given to the DNA subunits contained in all organisms. That alphabet has just grown longer, researchers announce, with the creation of a living cell that has two ‘foreign’ DNA building blocks in its genome.

Hailed as a breakthrough by other scientists, the work is a step towards the synthesis of cells able to churn out drugs and other useful molecules. It also raises the possibility that cells could one day be engineered without any of the four DNA bases used by all organisms on Earth.

“What we have now is a living cell that literally stores increased genetic information,” says Floyd Romesberg, a chemical biologist at the Scripps Research Institute in La Jolla, California, who led the 15-year effort. Their research appears online today in Nature.

Each strand of the DNA’s double helix has a backbone of sugar molecules and, attached to it, chemical subunits known as bases. There are four different bases: adenine (A), thymine (T), cytosine (C) and guanine (G). These letters represent the code for the amino-acid building blocks that make up proteins. The bases bind the two DNA strands together, with an A always bonding to a T on the opposite strand (and vice versa), and C and G doing likewise.

Test-tube letters

Scientists first questioned whether life could store information using other chemical groups in the 1960s. But it wasn’t until 1989 that Steven Benner, then at the Swiss Federal Institute of Technology in Zurich, and his team coaxed modified forms of cytosine and guanine into DNA molecules. In test-tube reactions, strands made of these “funny letters”, as Benner calls them, copied themselves and encoded RNA and proteins.

The bases engineered by Romesberg’s team are more alien, bearing little chemical resemblance to the four natural ones, Benner says. In a 2008 paper, and in follow-up experiments, the group reported efforts to pair chemicals together from a list of 60 candidates and screen the 3,600 resulting combinations. They identified a pair of bases, known as d5SICS and dNaM, that looked promising. In particular, the molecules had to be compatible with the enzymatic machinery that copies and translates DNA.

“We didn’t even think back then that we could move into an organism with this base pair,” says Denis Malyshev, a former graduate student in Romesberg’s lab who is first author of the new paper. Working with test-tube reactions, the scientists succeeded in getting their unnatural base pair to copy itself and be transcribed into RNA, which required the bases to be recognized by enzymes that had evolved to use A, T, C and G.

The first challenge to creating this alien life was to get cells to accept the foreign bases needed to maintain the molecule in DNA through repeated rounds of cell division, during which DNA is copied. The team engineered the bacterium Escherichia coli to express a gene from a diatom — a single-celled alga — encoding a protein that allowed the molecules to pass through the bacterium’s membrane.

The scientists then created a short loop of DNA, called a plasmid, containing a single pair of the foreign bases, and inserted the whole thing into E. coli cells. With the diatom protein supplying a diet of foreign nucleotides, the plasmid was copied and passed on to dividing E. coli cells for nearly a week. When the supply of foreign nucleotides ran out, the bacteria replaced the foreign bases with natural ones.

Alien control

Malyshev sees the ability to control the uptake of foreign DNA bases as a safety measure that would prevent the survival of alien cells outside the lab, should they escape. But other researchers, including Benner, are trying to engineer cells that can make foreign bases from scratch, obviating the need for a feedstock.

Romesberg’s group is working on getting foreign DNA to encode proteins that contain amino acids other than the 20 that together make up nearly all natural proteins. Amino acids are encoded by ‘codons’ of three DNA letters apiece, so the addition of just two foreign DNA ‘letters’ would vastly expand a cell’s ability to encode new amino acids. “If you read a book that was written with four letters, you’re not going to be able to tell many interesting stories,” Romesberg says. “If you’re given more letters, you can invent new words, you can find new ways to use those words and you can probably tell more interesting stories.”

Potential uses of the technology include the incorporation of a toxic amino acid into a protein to ensure that it kills only cancer cells, and the development of glowing amino acids that could help scientists to track biological reactions under the microscope. Romesberg’s team has founded a company called Synthorx in San Diego, California, to commercialize the work.

Ross Thyer, a synthetic biologist at the University of Texas at Austin who co-authored a related News and Views article, says that the work is “a big leap forward in what we can do”. It should be possible to get the foreign DNA to encode new amino acids, he says.

“Many in the broader community thought that Floyd’s result would be impossible,” says Benner, because chemical reactions involving DNA, such as replication, need to be exquisitely sensitive to avoid mutation.

The alien E. coli contains just a single pair of foreign DNA bases out of millions. But Benner sees no reason why a fully alien cell isn’t possible. “I don’t think there’s any limit,” he says. “If you go back and rerun evolution for four billion years, you could come up with a different genetic system.”

But creating a wholly synthetic organism would be a huge challenge. “A lot of times people will say you’ll make an organism completely out of your unnatural DNA,” says Romesberg. “That’s just not going to happen, because there are too many things that recognize DNA. It’s too integrated into every facet of a cell’s life.”

Science & Technology

The European Space Agency has released a game about the settlement of Mars

The European Space Agency has released a game about the settlement of Mars 99

The European Space Agency, together with the British company Auroch Digital, released the game Mars Horizon. This is a simulator of the colonization of Mars.

In Mars Horizon, players will have to manage scientific activities, processes in the colony and, of course, finances. You will need to complete missions to make money before sending your astronauts to Mars. The agency directors, who will play the role of the players, will have to fight other large space agencies that pursue the same goals – sending colonists to Mars.

During missions, players are faced with intense turn-based gameplay and each step determines their success or failure. Each individual decision is critical – will you waste time repairing a faulty antenna? How about saving energy in the event of a fuel leak? Maybe if you decide to delay the dispatch of the mission by three months, it will prevent a disaster?

Auroch Digital has created Mars Horizon in collaboration with ESA. The developers consulted with the agency’s staff, including members of the ExoMars mission. ESA provided technical assistance to game developers, provided gameplay advice and tested the game. The developers were given the opportunity to try to manage space projects at the agency’s facilities themselves.

Today you can install the game on PC, Xbox One, PlayStation4 and Nintendo Switch. In the future, the developers want to create special educational versions of the game and put them in schools to show how such large international projects as the colonization of Mars are actually carried out.

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Science & Technology

What’s in store for us in the next decade?

What's in store for us in the next decade? 100

About 70 thousand years ago, Homo Sapiens was an insignificant animal living somewhere on the African continent. But in the millennia that followed, the Sapiens became the rulers of the planet: we subdued the environment, increased food production, built cities and connected them with trade networks. 

But our achievements, no matter how beautiful they look from the outside, have a downside, because our civilization has endangered more than one million species of animals and plants, and the rapid climate change (also the work of man) brings catastrophic consequences every year. But if other, now non-existing civilizations dominated the planet before us, does this mean that we are rapidly approaching sunset? Nobody knows the exact answers to these questions, but let’s try to figure it out.

Great civilizations of the past

Humans have been around for several hundred thousand years, but until the last 7,000 years, we roamed the earth in small groups, hunting, gathering edible plants and fearing threats from other people, animals and weather. Everything changed after the development of tools, weapons and fire, and the first major step towards civilization was the domestication of animals for food, clothing, transportation and communication.

As William R. Nester writes in his work entitled “The Rise and Fall of Civilizations” , plant domestication followed, with small groups settling in river valleys, planting and harvesting. Over the centuries, some of these settlements have developed into complex civilizations that include most or all of the following components:

  • cattle breeding and agriculture; complex, hierarchical political, social, economic, military, and religious institutions, each with a division of labor;
  • the use of metals, wheels and writing; clearly defined territories;
  • trade with other people.

The first “civilization” is believed to have originated in Mesopotamia around 5000 BC. BC, and over the next 6,500 years or so, great civilizations grew and appeared elsewhere, expanded their rule, and then perished for a variety of interconnected political, technological, economic, military, and environmental causes.

What's in store for us in the next decade? 101
Roman civilization originated around the sixth century BC. 
At the height of its power, the Roman Empire ruled over a vast tract of land, and all modern Mediterranean countries were part of ancient Rome.

Roman civilization originated around the sixth century BC. At the height of its power, the Roman Empire ruled over a vast tract of land, and all modern Mediterranean countries were part of ancient Rome.

Recently, scientists have finally solved the mystery of the death of the Mayan civilization – one of the brightest civilizations in the history of mankind, the dawn of which came approximately in the III-IX centuries. As the results of several scientific studies have shown, among the reasons for the death of the Maya, researchers single out several factors at once – droughts, wars, food shortages, etc.

Where is our civilization heading?

According to the data obtained using the ESCIMO computer model, we have just passed the “point of no return” – the moment when humanity could prevent the most severe consequences of rapid climate change. In a paper published in the journal Nature Scientific Reports, the researchers write the following:

“Even if all emissions of harmful substances into the atmosphere are reduced to zero right now, this will not stop the rise in global temperatures.”

And yet, despite this disturbing news, let’s hope that we will meet 2030 and all the decades to come, caring for the environment and looking to the future with optimism. We do not want it, the passage of time is inexorable, and with it the changes in all areas of everyday life. Thus, many researchers regard the near future as a time even more technological than ours.

What will our world be like in 10 years?

Fighting fake news

As stated in an article published on the Science Focus portal, technology can lead us to a world where we will not be sure what is real and what is not. At the same time, thanks to technology, we can distinguish fact from fiction, which is especially relevant in the era of fake news and Deepfake.

For example, some AI startups use machine learning algorithms to identify fakes and errors on the Internet. 

“Fake news and social media have eroded trust in traditional media that have failed to adapt to the new reality. Solving the problem of fake news requires rebuilding the news ecosystem and educating people to think critically and to be more responsible on social media,” Michael Bronstein said, co-founder of AI startup Fabula, a professor of computing at Imperial College London. Well, let’s hope this fight against fake news will be successful.

What's in store for us in the next decade? 102
Most likely, by 2030, technology will help us lead a better life, morally and physically healthy. Jobs are also expected to undergo a number of major changes.

Genetic revolution

Today, many researchers have high hopes for the genome-editing CRISPR method, which can treat hereditary diseases or significantly reduce the risk of developing Alzheimer’s disease. There is even talk of the possibility of reversing the biological aging process. 

But how far can we go in this war on disease? After all, most ailments are caused not by one gene, but by a combination of several genes and environmental factors. Some genes that predispose us to one disease simultaneously protect us from another.

The researchers point out that one of the main challenges today is the costly availability of CRISPR. Moreover, editing the human genome also raises ethical dilemmas – for example, a widely publicized act of a Chinese scientist who used CRISPR-Cas9 technology on unborn babies, for which he is now serving time in prison.

What's in store for us in the next decade? 103
Perhaps over the next 10 years, we will be able to address a number of difficult ethical issues.

However, many scientists hope that in the future, doctors will be allowed to use this technique for the benefit of people, but the “finer details” have yet to be determined. It appears that different cultures will approach ethical issues differently. So in this regard, the future is complex and difficult to predict.

Space revolution

The last time a human foot set foot on the lunar surface was in 1972. Then few could predict that people would not return to Earth’s satellite for another 50 years. As for the latest plans of the world space agencies (both private and public), the plans for the next decade include not only the launch of robotic vehicles, such as the Europa Clipper (scheduled to start in 2021), the James Webb Space Telescope, but also a return to the Moon and human flight to Mars.

In general, speaking about space exploration, we would like to believe that studies of the solar system and the observed Universe in the next 10 years will bring long-awaited news and answers to questions that excite the imagination. 

Technologies of the future from 2020 to 2030

More than 800 experts, economists, businessmen and executives surveyed by the World Economic Forum (WEF) predict the following technologies will be trending. They will make a technological revolution in our world (watch the video below about technologies of the future).

1. AI 2 IoT
3. Blockchain
4. 3D printing
5. Mobile technologies
6. Autonomous cars (transport)
7. Mobile Internet
8 Robotics
9. VR / AR
10. Wireless Power
11. Quantum computing
12. 5G/6G
13. Voice Assistant
14. Cybersecurity
15. Cloud (cloud computing)

Who knows, maybe in 2030 humanity will know for sure that it is not alone in the vastness of the infinite universe. What do you think the world will be like in the near future? 

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Science & Technology

Cancer vaccine shown to be safe and effective has entered human trials

Cancer vaccine shown to be safe and effective has entered human trials 104
University of Montreal

A person, like any living creature, can be vaccinated against cancer, although this disease is fundamentally different from viral infections against which vaccines are traditionally used. 

This has been proven by scientists at Ohio University, who developed a methodology for the use of immune checkpoint inhibitors. Animal studies have shown 90% effectiveness of this therapy and complete safety for the body.

Cancer tumors are extremely insidious and have a defense mechanism against the body’s immune system in the form of the signaling protein PD-1. It is present on both healthy and cancerous cells, and is responsible for the friend-or-foe recognition procedure when immune B and T cells approach them. As long as PD-1 proteins in cancer cells and PD-L1 proteins in lymphocytes are working normally, the immune system simply ignores the infection, not seeing it as a target to attack.

The idea of ​​Dr. Pravin Kaumay, the developer of the inhibitors, is to interfere with the identification procedure. For this purpose, special monoclonal antibodies have been developed, which are injected into the body, seek out PD-1 proteins and settle on them, preventing proper contact with PD-L1 proteins. Lymphocytes cannot recognize these cells and automatically start the procedure for destroying them – the immune system itself begins to eradicate cancerous tumors in the body.

More importantly, blocking the signaling system destroys the usual comfortable environment for cancer cells, they are constantly threatened, cannot grow and spread throughout the body. 

This is the beneficial effect of vaccination with inhibitors – this therapy is called PD1-Vaxx. The technology has been thoroughly tested, it uses second-generation inhibitors, which are much more effective. The first human patients have already been recruited in the US and Australia to test PD1-Vaxx.

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