Category Archives: Transhuman News

SARS-CoV-2, the virus that causes Covid-19, wasnt intentionally created in a lab. We dont have much evidence one way or the other whether its emergence into the world was the result of a lab accident or a natural jump from animal to human, but we know for sure that the virus is not the product of deliberate gene editing in a lab.

How do we know that? Bioengineering leaves traces characteristic patterns in the RNA, the genetic code of a virus, that come from splicing in genes from elsewhere. And investigations by researchers have definitively shown that the novel coronavirus behind Covid-19 doesnt bear the hallmarks of such manipulation.

That fact about bioengineered viruses raises an interesting question: What if those traces that gene editing leave behind were more like fingerprints? That is, what if its possible not just to tell if a virus was engineered but precisely where it was engineered?

Thats the idea behind genetic engineering attribution: the effort to develop tools that let us look at a genetically engineered sequence and determine which lab developed it. A big international contest among researchers earlier this year demonstrates that the technology is within our reach though itll take lots of refining to move from impressive contest results to tools we can reliably use for bio detective work.

The contest, the Genetic Engineering Attribution Challenge, was sponsored by some of the leading bioresearch labs in the world. The idea was to challenge teams to develop techniques in genetic engineering attribution. The most successful entrants in the competition could predict, using machine-learning algorithms, which lab produced a certain genetic sequence with more than 80 percent accuracy, according to a new preprint summing up the results of the contest.

This may seem technical, but it could actually be fairly consequential in the effort to make the world safe from a type of threat we should all be more attuned to post-pandemic: bioengineered weapons and leaks of bioengineered viruses.

One of the challenges of preventing bioweapon research and deployment is that perpetrators can remain hidden its difficult to find the source of a killer virus and hold them accountable.

But if its widely known that bioweapons can immediately and verifiably be traced right back to a bad actor, that could be a valuable deterrent.

Its also extremely important for biosafety more broadly. If an engineered virus is accidentally leaked, tools like these would allow us to identify where they leaked from and know what labs are doing genetic engineering work with inadequate safety procedures.

Hundreds of design choices go into genetic engineering: what genes you use, what enzymes you use to connect them together, what software you use to make those decisions for you, computational immunologist Will Bradshaw, a co-author on the paper, told me.

The enzymes that people use to cut up the DNA cut in different patterns and have different error profiles, Bradshaw says. You can do that in the same way that you can recognize handwriting.

Because different researchers with different training and different equipment have their own distinctive tells, its possible to look at a genetically engineered organism and guess who made it at least if youre using machine-learning algorithms.

The algorithms that are trained to do this work are fed data on more than 60,000 genetic sequences different labs produced. The idea is that, when fed an unfamiliar sequence, the algorithms are able to predict which of the labs theyve encountered (if any) likely produced it.

A year ago, researchers at altLabs, the Johns Hopkins Center for Health Security, and other top bioresearch programs collaborated on the challenge, organizing a competition to find the best approaches to this biological forensics problem. The contest attracted intense interest from academics, industry professionals, and citizen scientists one member of a winning team was a kindergarten teacher. Nearly 300 teams from all over the world submitted at least one machine-learning system for identifying the lab of origin of different sequences.

In that preprint paper (which is still undergoing peer review), the challenges organizers summarize the results: The competitors collectively took a big step forward on this problem. Winning teams achieved dramatically better results than any previous attempt at genetic engineering attribution, with the top-scoring team and all-winners ensemble both beating the previous state-of-the-art by over 10 percentage points, the paper notes.

The big picture is that researchers, aided by machine-learning systems, are getting really good at finding the lab that built a given plasmid, or a specific DNA strand used in gene manipulation.

The top-performing teams had 95 percent accuracy at naming a plasmids creator by one metric called top 10 accuracy meaning if the algorithm identifies 10 candidate labs, the true lab is one of them. They had 82 percent top 1 accuracy that is, 82 percent of the time, the lab they identified as the likely designer of that bioengineered plasmid was, in fact, the lab that designed it.

Top 1 accuracy is showy, but for biological detective work, top 10 accuracy is nearly as good: If you can narrow down the search for culprits to a small number of labs, you can then use other approaches to identify the exact lab.

Theres still a lot of work to do. The competition looked at only simple engineered plasmids; ideally, wed have approaches that work for fully engineered viruses and bacteria. And the competition didnt look at adversarial examples, where researchers deliberately try to conceal the fingerprints of their lab on their work.

Knowing which lab produced a bioweapon can protect us in three ways, biosecurity researchers argued in Nature Communications last year.

First, knowledge of who was responsible can inform response efforts by shedding light on motives and capabilities, and so mitigate the events consequences. That is, figuring out who built something will also give us clues about the goals they might have had and the risk we might be facing.

Second, obviously, it allows the world to sanction and stop any lab or government that is producing bioweapons in violation of international law.

And third, the article argues, hopefully, if these capabilities are widely known, they make the use of bioweapons much less appealing in the first place.

But the techniques have more mundane uses as well.

Bradshaw told me he envisions applications of the technology could be used to find accidental lab leaks, identify plagiarism in academic papers, and protect biological intellectual property and those applications will validate and extend the tools for the really critical uses.

Its worth repeating that SARS-CoV-2 was not an engineered virus. But the past year and a half should have us all thinking about how devastating pandemic disease can be and about whether the precautions being taken by research labs and governments are really adequate to prevent the next pandemic.

The answer, to my mind, is that were not doing enough, but more sophisticated biological forensics could certainly help. Genetic engineering attribution is still a new field. With more effort, itll likely be possible to one day make attribution possible on a much larger scale and to do it for viruses and bacteria. That could make for a much safer future.

A version of this story was initially published in the Future Perfect newsletter. Sign up here to subscribe!

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How biological detective work can reveal who engineered a virus - Vox.com

Since June, the export of about 500 tonnes of rice from India has triggered an uproar in several European countries on the grounds that it was genetically modified (GM) rice. This emerged during a check by the European Commissions Rapid Alert System for Food and Feed that was testing rice flour by the French company Westhove. In June, France had issued a notification for unauthorised GM rice flour, identifying India as the point of origin, and alerting Austria, Belgium, the Czech Republic, Germany, Italy, the Netherlands, Poland, Spain, the U.K. and the U.S. as the possible destination of products made with the flour. So in August, the American food products company Mars, fearing GM contamination, announced that it was recalling four of its product lines of Crispy M&M. GM-free rice that is tagged as organic rice is among Indias high-value exports worth 63,000 crore annually. India does not permit the commercial cultivation of GM rice, but research groups are testing varieties of such rice in trial plots. So the suspicion is that rice from some of these test-plots may have leaked into the exported product. The Indian government has denied this possibility with a Commerce Ministry spokesperson alleging that the contamination may have happened in Europe to cut costs. However, India has indicated that it will commission an investigation involving its scientific bodies.

Indias history of crop modification using GM is one of test-plants finding their way to commercial cultivars before they were formally cleared. Thus, Bt-cotton was widely prevalent in farmer fields before being cleared. Though they have not been cleared, Bt-brinjal and herbicide-tolerant cotton varieties too have been detected in farmer fields. Though the Genetic Engineering Appraisal Committee is the apex regulator of GM crops, it is mandated that trials of GM crops obtain permission from States. Because of the close connections between farmers and State agriculture universities, which are continuously testing new varieties of crops employing all kinds of scientific experiments ranging from introducing transgenes to other non-transgenic modification methods, and the challenges of ensuring that trial plots are strictly segregated from farms, there is a possibility that seeds may transfer within plots. Because many Indian farmers are dependent on European imports, the Centre must rush to assuage importers that Indias produce is compliant with trade demands. The fractious history of GM crops in India means that passions often rule over reason on questions of the safety of GM crops, and so India must also move to ensure that research into all approaches GM or non GM should not become a casualty in this matter of export-quality compliance.

Read the rest here:
Plugging the leak: On the GM rice controversy - The Hindu

The United States produces 18% of the worlds beef with 6% of the worlds cattle. Thats why genetics are important, said Dr. Alison Van Eenennaam, Professor of Cooperative Extension in Animal Genomics and Biotechnology at the University of California, Davis. Van Eenennaam gave her presentation titled Gene Editing Today and in the Future during the Beef Improvement Federation (BIF) Symposium June 24 in Des Moines, Iowa.

Van Eenennaam explained the concepts of introducing editing components into the genome.

Genetic engineering vs gene editing

The 2009 sequencing of the bovine genome allowed for the development of a 50,000 SNP chip, also known as the 50K. Very rapidly adopted by the global cattle breeding community, the genomic test result is incorporated in the genomic-enhanced expected progeny difference (GE-EPD) as an additional data source. GE-EPDs are made up of the animals pedigree, performance, progeny and genomic test result. This technology has evolved greatly since 2010 when DNA information competed with EPDs.

According to Van Eenennaam genome editing allows the introduction of double strand breaks at a specific sequence in the genome.

Genetic engineering, or GMOs, to use the more controversial term, is basically introducing a trait to a breeding program that brings a useful characteristic along, she explained. The difference with genome editing is you can very precisely target any location in the genome for the introduction of a new gene or also just tweaking the DNA within an animal. It is that precision that is kind of new with genome editing, which opens up opportunities to very precisely inactivate genes in the genome without necessarily introducing transgenic or exogenous DNA from another species. This is one of the distinguishing factors between genetic engineering and genome editing.

Gene editing technologies

Van Eenennaam explained that gene editing will be able to introduce useful alleles without linkage drag and potentially bring in useful novel genetic variation from other breeds. There are various advantages and disadvantages of somatic cell nuclear transfer (SCNT) cloning to produce an animal carrying a targeted genome edit. Advantages include germline transmission, confirmed genotype with higher knock-in efficiency in somatic cells. Disadvantages are very low cloning efficiencies, use of a single cell line and not all cell lines clone well.

Van Eenennaam also explained that cytoplasmic injection (CPI) of editing reagents into embryos has multiple advantages and disadvantages. Advantages include no cloning artifacts, diversity of germplasm, and a high efficiency for gene knock-outs. Disadvantages of this technology are mosaicism (more than one genotype in an individual), variable rates of obtaining an edited genome in calves born, and gene knock-in is less efficient in early embryos.

I envision gene editing impacting breed associations and future genetic evaluation by offering an opportunity to repair deleterious genetic conditions, and an opportunity to introduce useful alleles into breed germplasm. It is currently primarily used for single gene or Mendelian traits, and it could potentially be used to alter a defining characteristic of a breed, Van Eenennaam said.

To watch Van Eenennaams full presentation, visit https://youtu.be/ioMx-c2N2PM . For more information about this years Symposium and the Beef Improvement Federation, including additional presentations and award winners, visit BIFSymposium.com.

Read the rest here:
Gene Editing in Today's Beef Industry and the Future - Bovine Veterinarian

Earlier this week, surgeons at New York Universitys Langone Transplant Institute successfully performed a pig kidney transplant. This in itself would be unremarkable. What does mark the achievement as unprecedented is the identity of the donor a genetically modified pig.

Some days post-surgery, the recipient, a brain-dead patient whose family consented to the experimental procedure, has not rejected the kidney and tests show that it is functioning normally. This incredible feat is significant both as a demonstration of scientific control over biological systems and as a beacon of hope to others in line for a transplant.

The idea of using other species for organ transplants is not new; we have used pig heart-valves for over 50 years. Yet whole organs have presented several challenges, most notably the risk of rejection. This occurs because the body believes the transplant is an invader that must be destroyed, leading to an immune response that attacks the organ. While the triggers for rejection are not completely understood, one of the biggest barriers to cross-species transplantation is a molecule known as alpha-gal, a carbohydrate that immediately elicits a massive immune response.

To counteract this, scientists used a powerful tool of genetic engineering, CRISPR, to modify the pigs genome so that it does not produce alpha-gal. CRISPR has existed for less than a decade, yet its ability to accurately cut and paste specific pieces of genomes is already leading to breakthroughs in many areas of biology including in the development of COVID-19 vaccines.

At present, over 100,000 people in the United States are awaiting an organ donation, among whom 83%, ~91,000, are in need of a kidney. Though 54% of US citizens are registered organ donors, less than 1% of deaths result in useable organs, so supply will always outstrip demand.

Consequently, wait times for a kidney can range from four months to six years depending on blood type, geographic location, disease severity, immune system activity, and other factors. Most of those on the waiting list must have their blood cleaned via hemodialysis, a process that entails commuting to a dialysis centre and spending four hours a day, three times a week, attached to a machine simply to stay alive. The longer they are on dialysis, the smaller their chance of a successful kidney transplant becomes as the procedure can only partially compensate for the damaged organ.

Every year, 5,000 people die waiting for a transplant and another 5,000 are removed from the list because they are no longer healthy enough to receive it, meaning that only 65% of those placed on transplant lists will receive a kidney in time. This latest development could prove to be a gamechanger.

But there will be difficult questions about the ethics of modifying other species to fit our needs, and the event may spark further dialogue on the conditions pigs and other animals are currently raised in. There are also still many unanswered questions surrounding the efficacy of cross-species transplantation. Can pig kidney transplants to humans save lives? Well, before we get to an answer, more robust, longer-term trials will have to take place.

Yet the significance of this pig kidney transplant demonstration should not be underestimated this is a momentous step towards saving the lives of tens of thousands of people awaiting a transplant, not to mention the half a million with kidney failure who do not even qualify because of scarcity. It also speaks to the potential of biotechnology more broadly to transform the health outcomes of millions of people.

Written by

Cameron Fox, Project Specialist, Shaping the Future of Health and Healthcare, World Economic Forum

The views expressed in this article are those of the author alone and not the World Economic Forum.

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A cross-species kidney transplant from a pig has worked. What you need to know - World Economic Forum

In the Netherlands, around 90 thousand people have a chronic intestinal disease, such as Crohns disease. These inflammations are easy to detect. The only thing you need for that is an endoscopy: a camera that goes into the intestinal tract. Invasive and unpleasant, says Luke Rossen, team manager of the iGEM student team in Eindhoven. The team developed a method where gas bubbles from E.coli bacterium and an ultrasound machine reveal whether there is an infection and where it is located.

If you have an inflammation in your intestines, your body produces a substance, Rossen explains. That substance can bind with certain proteins which can trigger the production of gas bubbles. If you introduce these proteins into E.coli bacteria, then it acts as a kind of sensor. Those gas bubbles that then form can subsequently be visualised using ultrasound. That way, you can detect the inflammation with an ultrasound machine. All the patient has to do is take a pill containing the bacteria the day before.

The team is participating in the global iGEM competition, part of the International Genetically Engineered Machine (iGEM) Foundation with their discovery. An independent, non-profit organisation dedicated to the advancement of synthetic biology, the (re)design and construction of organisms or parts thereof. This year, 356 student teams from countries in Europe, Asia, North and South America and Australia are competing in the competition. Each year there is a Giant Jamboree, although this year a smaller version is being held digitally in Paris due to corona.

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It is also the case nowadays that people suffering from intestinal complaints first take a self-test, Rossen goes on to say. That test is not very specific. Even if there is nothing wrong, a person is sometimes still sent to hospital for an expensive invasive endoscopy examination. That person has to make sure their bowels are empty beforehand, so the day before, they have to take strong laxatives and fast. They are also given an anaesthetic during the treatment. A trained doctor and two nurses are present during an endoscopy. Whereas in almost 30 per cent of cases, this is not necessary.

The iGEM teams so-called IBDetection method falls somewhere between the self-test and the extensive follow-up examination. The students have modified the intestinal bacterium E. Coli so that it acts as a sensor. That implies cutting and pasting with DNA, says Rossen. Its like doing a puzzle with very small building blocks. We put some DNA and the bacterium together and examine what does and doesnt work. You take out a certain piece, see what the reaction is and keep going until you have the right reaction with those gas bubbles.

Actually, the biology textbooks of primary and secondary schools should be rewritten, Rossen states. Because working with so-called genetically modified organisms (GMOs) is still new, the team manager notes. You hardly ever learn anything about it in primary and secondary schools. In order to educate young people about genetic engineering, the team gives guest lectures. For example, we show them what soap does. You wash your hands every day, but what happens? Actually, it is just a molecule that binds water and fat. We want to explain the basic principles, which can also be applied to what we do. For instance, how a protein binds to a substance.

The team also came up with an escape room, escape the cell. You walk through parts of a cell in each room and have to solve a puzzle. That is how you learn what a cell looks like. A number of secondary schools are now making use of the escape room to try it out, Rossen adds.

On 21 October, the team uploaded everything from their cases, documentation, research and tests into a wiki. Like their research that they did in collaboration with a student team from Vienna that is developing something similar. The teams interviewed people with chronic inflammatory bowel disease about whether they would prefer an examination using an endoscopy or an ultrasound machine and swallow a pill. This revealed that people were sympathetic to our idea, says Rossen. Very different from what we had assumed beforehand. We thought people would be more negative about it because we are working with genetic manipulation.

In addition, the students participated in the RIVM Safe by Design competition to demonstrate that their method is safe. During the Sustainable Healthcare Challenge, the team finished in third place. The last test results were also a success: the team succeeded in inserting the definitive DNA into the bacteria.

After 21 October everything will be open to the public. Rossen: If you want to know exactly what we do, then it is in there. After that time, there will be a period of relative calm. It was a lot of hard work and then it was finished. To bridge the time until the Giant Jamboree, the iGEM team is organising a mini jamboree for the Benelux. Everything in miniature but with judges and a prize.

Rossen signed up for participation in the team at the end of last year. His professor sent all his students a call out to participate I had only just had a taste of some practical lessons when the lockdown started. I missed doing practical work. Being able to participate in this was a godsend. The masters student in Biomedical Engineering worked full time on the project from May. Once the competition is over, the team will hand over the baton to a new team.

If it all works out, the biggest challenge is to change legislation so that it can be put into practice, Rossen says. Thats lagging behind in Europe. He spoke to Lucie McMurtry of EuropaBio, about the European Legislation on Genetically Modified Organisms (GMOs). What is the future outlook? My reply was that there is not much chance of our concept being approved within the next ten years. Purely because we use living GMOs as sensors, regardless of whether it is safe or not. Rossen is convinced that research within synthetic biology makes sense. We want to use fundamental research to show that it is safe. It is a first step towards the future: there is potential in it, its not scary, as long as you think about it properly and thoroughly and test everything meticulously. Then its just like any other drug only a bit more complex.

Also interesting: If a section lights up a color, a biomarker has been found

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Detecting chronic intestinal inflammation with a pill - Innovation Origins