CIA Just Invested In Woolly Mammoth Resurrection Tech – The Intercept

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As a rapidly advancing climate emergency turns the planet ever hotter, the Dallas-based biotechnology company Colossal Biosciences has a vision: To see the Woolly Mammoth thunder upon the tundra once again. Founders George Church and Ben Lamm have already racked up an impressive list of high-profile funders and investors, including Peter Thiel, Tony Robbins, Paris Hilton, Winklevoss Capital and, according to the public portfolio its venture capital arm released this month, the CIA.

Colossal says it hopes to use advanced genetic sequencing to resurrect two extinct mammals not just the giant, ice age mammoth, but also a mid-sized marsupial known as the thylacine, or Tasmanian tiger, that died out less than a century ago. On its website, the company vows: Combining the science of genetics with the business of discovery, we endeavor to jumpstart natures ancestral heartbeat.

In-Q-Tel, its new investor, is registered as a nonprofit venture capital firm funded by the CIA. On its surface, the group funds technology startups with the potential to safeguard national security. In addition to its long-standing pursuit of intelligence and weapons technologies, the CIA outfit has lately displayed an increased interest in biotechnology and particularly DNA sequencing.

Why the interest in a company like Colossal, which was founded with a mission to de-extinct the wooly mammoth and other species? reads an In-Q-Tel blog post published on September 22. Strategically, its less about the mammoths and more about the capability.

Biotechnology and the broader bioeconomy are critical for humanity to further develop. It is important for all facets of our government to develop them and have an understanding of what is possible, Colossal co-founder Ben Lammwrote in an email to The Intercept. (A spokesperson for Lamm stressed that while Thiel provided Church with$100,000 in funding to launchthe woolly mammoth project that became Colossal, he is not a stakeholderlike Robbins, Hilton, Winklevoss Capital, and In-Q-Tel.)

Colossal uses CRISPR gene editing, a method of genetic engineering based on a naturally occurring type of DNA sequence. CRISPR sequences present on their own in some bacterial cells and act as an immune defense system, allowing the cellto detect and excise viral material thattries to invade. The eponymous gene editing technique was developed to function the same way, allowing users to snip unwanted genes and program a more ideal version of the genetic code.

CRISPR is the use of genetic scissors, Robert Klitzman, a bioethicist at Columbia University and a prominent voice of caution on genetic engineering, told The Intercept. Youre going into DNA, which is a 3-billion-molecule-long chain, and clipping some of it out and replacing it. You can clip out bad mutations and put in good genes, but these editing scissors can also take out too much.

The embrace of this technology, according to In-Q-Tels blog post, will help allow U.S. government agencies to read, write, and edit genetic material, and, importantly, tosteerglobal biological phenomena that impact nation-to-nation competition whileenabling the United States to help set the ethical, as well as the technological, standards for its use.

In-Q-Tel did not respond to The Intercepts requests for comment.

In recent years, the venture firms portfolio has expanded to include Ginkgo Bioworks, a bioengineering startup focused on manufacturing bacteria for biofuel and other industrial uses; Claremont BioSolutions, a firm that produces DNA sequencing hardware; Biomatrica and T2 Biosystems, two manufacturers for DNA testing components; and Metabiota, an infectious disease mapping and risk analysis database powered by artificial intelligence. As The Intercept reported in 2016, In-Q-Tel also invested in Clearista, a skincare brand that removes a thin outer epidermal layer to reveal a fresher face beneath it and allow DNA collection from the skin cells scraped off.

President Joe Bidens administration signaled its prioritization of related advances earlier this month, when Biden signed an executive order on biotechnology and biomanufacturing. The order includes directives to spur public-private collaboration, bolster biological risk management, expand bioenergy-based products, and engage the international community to enhance biotechnology R&D cooperation in a way that is consistent with United States principles and values.

The governments penchant for controversial biotechnology long predates the Biden administration. In 2001, a New York Times investigation found that American defense agencies under Presidents George W. Bush and Bill Clinton had continued to experiment with biological weapons, despite a 1972 international treaty prohibiting them. In 2011, The Guardian revealed that the CIA under President Barack Obama organized a fake Hepatitis B vaccine drive in Pakistan that sought to locate family members of Osama bin Laden through nonconsensual DNA collection, leading the agency to eventually promise a cessation of falseimmunization campaigns.

CIA Labs, a 2020 initiative overseen by Donald Trumps CIA director, Gina Haspel infamous for running a torture laboratory in Thailand follows a model similar to In-Q-Tels. The program created a research network to incubate top talent and technology for use across U.S. defense agencies, while simultaneously allowing participating CIA officers to personally profit off their research and patents.

In-Q-Tel board members are allowed to sit on the boards of companies in which the firm invests, raising ethics concerns over howthe non-profit selects companies to back with government dollars. A 2016 Wall Street Journal investigation found that almost half of In-Q-Tel board members were connected to the companies where it had invested.

The size of In-Q-Tels stake in Colossal wont be known until the nonprofit releases its financial statements next year, but the investment may provide a boon on reputation alone: In-Q-Tel has claimed that every dollar it invests in a business attracts 15 more from other investors.

Colossals co-founders, Lamm and Church, represent the ventures business and science minds, respectively. Lamm, a self-proclaimed serial technology entrepreneur, founded his first company as a senior in college, then pivoted to mobile apps and artificial intelligence before helping to start Colossal.

Church a Harvard geneticist, genome-based dating app visionary, and former Jeffrey Epstein funding recipient has proposed the revival of extinct species before. Speaking to Der Spiegel in 2013, Church suggested the resurrection of the Neanderthal an idea met with controversy because it would require technology capable of human cloning.

We can clone all kinds of mammals, so its very likely that we could clone a human, Church said. Why shouldnt we be able to do so? When the interviewer reminded him of a ban on human cloning, Church said, And laws can change, by the way.

Even when the methods used for de-extinction are legal, many scientists are skeptical of its promise. In a 2017 paper for Nature Ecology & Evolution, a group of biologists from Canada, Australia, and New Zealand found that [s]pending limited resources on de-extinction could lead to net biodiversity loss.

De-extinction is a fairytale science, Jeremy Austin, a University of Adelaide professor and director of the Australian Center for Ancient DNA,toldthe Sydney Morning Herald over the summer, when Colossal pledged to sink $10 million into the University of Melbourne for its Tasmanian tiger project. Its pretty clear to people like me that thylacine or mammoth de-extinction is more about media attention for the scientists and less about doing serious science.

Critics who say de-extinction of genes to create proxy species is impossible are critics who are simply not fully informed and do not know the science. We have been clear from day one that on the path to de-extinction we will be developing technologies which we hope to be beneficial to both human healthcare as
well as conservation, Lamm wrote to The Intercept. We will conitnue [sic] to share these technologies we develop with the world.

It remains to be seen if Colossal, with In-Q-Tels backing, can make good on its promises. And its unclear what, exactly, the intelligence world might gain from the use of CRISPR. But perhaps the CIA shares the companys altruistic, if vague, motives: To advance the economies of biology and healing through genetics. To make humanity more human. And to reawaken the lost wilds of Earth. So we, and our planet, can breathe easier.

Update: September 28, 2022, 1:00 p.m. ETThis story has been updated with a statement from Colossal co-founder Ben Lamm.

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CIA Just Invested In Woolly Mammoth Resurrection Tech - The Intercept

Engineering the Perfect Baby | MIT Technology Review

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Indeed, some people are adamant that germ-line engineering is being pushed ahead with false arguments. That is the view of Edward Lanphier, CEO of Sangamo Biosciences, a California biotechnology company that is using another gene-editing technique, called zinc fingers nucleases, to try to treat HIV in adults by altering their blood cells. Weve looked at [germ-line engineering] for a disease rationale, and there is none, he says. You can do it. But there really isnt a medical reason. People say, well, we dont want children born with this, or born with thatbut its a completely false argument and a slippery slope toward much more unacceptable uses.

Critics cite a host of fears. Children would be the subject of experiments. Parents would be influenced by genetic advertising from IVF clinics. Germ-line engineering would encourage the spread of allegedly superior traits. And it would affect people not yet born, without their being able to agree to it. The American Medical Association, for instance, holds that germ-line engineering shouldnt be done at this time because it affects the welfare of future generations and could cause unpredictable and irreversible results. But like a lot of official statements that forbid changing the genome, the AMAs, which was last updated in 1996, predates todays technology. A lot of people just agreed to these statements, says Greely. It wasnt hard to renounce something that you couldnt do.

The fear? A dystopia of superpeople and designer babies for those who can afford it.

Others predict that hard-to-oppose medical uses will be identified. A couple with several genetic diseases at once might not be able to find a suitable embryo. Treating infertility is another possibility. Some men dont produce any sperm, a condition called azoospermia. One cause is a genetic defect in which a region of about one million to six million DNA letters is missing from the Y chromosome. It might be possible to take a skin cell from such a man, turn it into a stem cell, repair the DNA, and then make sperm, says Werner Neuhausser, a young Austrian doctor who splits his time between the Boston IVF fertility-clinic network and Harvards Stem Cell Institute. That will change medicine forever, right? You could cure infertility, that is for sure, he says.

I spoke with Church several times by telephone over the last few months, and he told me whats driving everything is the incredible specificity of CRISPR. Although not all the details have been worked out, he thinks the technology could replace DNA letters essentially without side effects. He says this is what makes it tempting to use. Church says his laboratory is focused mostly on experiments in engineering animals. He added that his lab would not make or edit human embryos, calling such a step not our style.

What is Churchs style is human enhancement. And hes been making a broad case that CRISPR can do more than eliminate disease genes. It can lead to augmentation. At meetings, some involving groups of transhumanists interested in next steps for human evolution, Church likes to show a slide on which he lists naturally occurring variants of around 10 genes that, when people are born with them, confer extraordinary qualities or resistance to disease. One makes your bones so hard theyll break a surgical drill. Another drastically cuts the risk of heart attacks. And a variant of the gene for the amyloid precursor protein, or APP, was found by Icelandic researchers to protect against Alzheimers. People with it never get dementia and remain sharp into old age.

Church thinks CRISPR could be used to provide people with favorable versions of genes, making DNA edits that would act as vaccines against some of the most common diseases we face today. Although he told me anything edgy should be done only to adults who can consent, its obvious to him that the earlier such interventions occur, the better.

Church tends to dodge questions about genetically modified babies. The idea of improving the human species has always had enormously bad press, he wrote in the introduction to Regenesis, his 2012 book on synthetic biology, whose cover was a painting by Eustache Le Sueur of a bearded God creating the world. But thats ultimately what hes suggesting: enhancements in the form of protective genes. An argument will be made that the ultimate prevention is that the earlier you go, the better the prevention, he told an audience at MITs Media Lab last spring. I do think its the ultimate preventive, if we get to the point where its very inexpensive, extremely safe, and very predictable. Church, who has a less cautious side, proceeded to tell the audience that he thought changing genes is going to get to the point where its like you are doing the equivalent of cosmetic surgery.

Some thinkers have concluded that we should not pass up the chance to make improvements to our species. The human genome is not perfect, says John Harris, a bioethicist at Manchester University, in the U.K. Its ethically imperative to positively support this technology. By some measures, U.S. public opinion is not particularly negative toward the idea. A Pew Research survey carried out last August found that 46 percent of adults approved of genetic modification of babies to reduce the risk of serious diseases.

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Engineering the Perfect Baby | MIT Technology Review

Genetic Engineering Science Projects – Science Buddies

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Genetic engineering, also called gene editing or genetic modification, is the process of altering an organism's DNA in order to change a trait. This can mean changing a single base pair, adding or deleting a single gene, or changing an even larger strand of DNA. Using genetic engineering, genes from one organism can be added to the genome of a completely different species. It is even possible to experiment with synthesizing and inserting novel genes in the hopes of creating new traits.

Many products and therapies have already been developed using genetic engineering. For example, crops with higher nutritional value, improved taste, or resistance to pests have been engineered by adding genes from one plant species into another. Similarly, expression of a human gene in yeast and bacteria allows pharmaceutical companies to produce insulin to treat diabetic patients. In 2020, scientists had their first successful human trial with CRISPR (a genetic engineering technique), to correct a mutant gene that causes sickle cell anemia, a painful and sometimes deadly blood disease.

There are many different genetic engineering techniques, including molecular cloning and CRISPR, and new techniques are being developed rapidly. Despite this variety, all genetic engineering projects involve carrying out four main steps:

Learn more about genetic engineering, and even try your hand at it, with these resources.

Measure Static Electricity With An Electroscope!

How to Make Paper Circuits

Build a light following robot

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Genetically engineering humans: a step too far?

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Gene therapy involves inserting a gene into a patients cells to treat or prevent disease instead of using drugs or surgery. Although still experimental, gene therapy aims to target the root cause of a disease, such as gene transfer into the individual cell types of the complex lung structure in cystic fibrosis patients, and has the potential to save a patient from a lifetime of complicated treatments all the while suffering the condition.

Research into using gene therapy to prevent diseases such as cancer and diabetes is showing some potential. However, it is the power of gene therapy to enhance humans that is causing the greatest concern. In September 2015, scientists at Londons Francis Crick Institute applied for a licence to use technology based on the CRISPR/Cas9 system a recently developed technique for precisely editing genomes to study early human development to edit genes in human embryos.

By Robert Sparrow, professor of philosophy, Monash University, Australia

Scientists, philosophers and science fiction authors have been discussing designer babies since the 1930s. However, the issues they have been discussing have remained theoretical because of the difficulty in getting genes to do what they want. The new technology of genome editing, known as CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats), which makes possible precise modifications of the genetics of organisms, changes things dramatically. Genetic modification of humans now looks all too possible.

Researchers and corporations are rushing to investigate and hopefully exploit the potential of this new technology to modify human beings genetically.

Many of the proposed applications would involve modifying patients somatic cells (any cell of the body except sperm and egg cells) in the hope of curing, or at least ameliorating, particular diseases and genetic disorders, thus eliminating the need for a lifetime of medical and drug treatment. Such uses of CRISPR/Cas9 would hold tremendous promise. However, they are not my concern here.

Some scientists have been quick to tout the potential of this new technology as a possible cure for some forms of infertility and to prevent various genetic diseases affecting future individuals[1]. These hypothetical techniques would entail editing the genome of human embryos or of stem cells a practice currently outlawed in the UK that might then be coaxed into developing into sperm and eggs. What makes such hypothetical uses of genome editing especially controversial is that the genetic modification would or at least could affect the germline of the individuals who were brought into existence. Should something go wrong, multiple generations would be at risk.

Yet, discussion of the therapeutic potential of germline modification is in many ways a distraction. The real potential of CRISPR/Cas9 lies elsewhere.

There are already means to allow affected individuals to have healthy children[1],[2]. In particular, preimplantation genetic diagnosis (PGD) allows doctors to choose which of a number of embryos created outside the human body to implant into a womans womb in order to ensure that a child is born without particular undesirable genes. Only when a couple is unable to produce viable embryos that do not carry genes for a disorder using their own gametes would there be any grounds for attempting to cure affected embryos by editing their genomes. Even in such cases, couples could always have children using donor sperm and/or donor ova. Similarly, individuals who are unable to produce viable gametes are able to use donor gametes to create embryos and secure a pregnancy.

Rather than a cure for a disease, then, genome editing would function solely as a means to satisfy the preferences of couples to raise children who were their genetic offspring. One cannot help but marvel at the success of the marketing of reproductive medicine, which has brought us to the point where it could seem reasonable to prefer a child who had been genetically modified rather than a child who was related to someone other than his or her social parents.

What germline modification could do that existing technologies cannot is produce embryos with particular genes associated with desirable traits[1]. If scientists can find genes that are associated with above-species-typical traits for example, higher intelligence, longevity, concentration or memory CRISPR/Cas9 will allow them to insert these genes into embryos. In theory, at least, the CRISPR/Cas9 system would allow parents to insert genes for as many desirable traits as they liked into the genome of their child.

No matter how many animal trials we perform, there will be no way to be sure how the modification will affect a human child as they mature. It is also worth admitting the limits of our ability to bend living things to our designs even with this incredible new tool.

The more we learn about genetics, the more complicated the interactions between genes and the environment which produces the phenotype of the organism appear. It is one thing to be able to cut and paste DNA but it is another to know what the result will be, especially because modifications to one part of the genome can have unexpected effects elsewhere. Of course, concerns about risks to health are arguably as much of a barrier to therapeutic use of CRISPR/Cas9 as they are to its use for human enhancement.

Cynically, it seems that references to risk often serve as a smokescreen to defuse public anxiety about potential applications of new reproductive technologies, while research on them continues. While scientists cannot do something, it would be too risky to try. The moment they can do it, the potential benefits mean that it would be irresponsible not to.

Let us not be deluded, then, that the renewed debate about germline genetic engineering, prompted by CRISPR/Cas9, is about rescuing a small number of individuals from the burden of genetic disease. It is nothing less than a debate about what it will mean to be human in the future. Will our grandchildren or perhaps even children be born all equally subject to the vicissitudes and the joys of the genetic lottery?[3]Or will they be made? Stronger, better perhaps children of the wealthy more so than others but are created by designers and so are vulnerable to obsolescence[4].

There is a choice to be confronted here but it is a difficult one. To make a decision wisely we will need to draw on all our resources and, in particular, our deepest values about what sort of world we want to live in, with what sorts of human flourishing. It would be a dreadful mistake to allow enthusiasm for impressive science and the vague promise of therapeutic benefits to distract us from the vital importance of this debate.

By Glenn Cohen,faculty director, Petrie-Flom Center for Health Law Policy, Biotechnology & Bioethics, Harvard Law School, Cambridge, Massachusetts

CRISPR-Cas9 allows DNA sequence changes in pluripotent embryonic stem cells that can then be cultured to produce specific tissues, such as cardiomyocytes or neurons[5]. The hope is that it will lead to much more refined approaches to a range of human diseases, but there are also concerns that it can be used to change the DNA in the nuclei of reproductive cells that transmit information from one generation to the next (an organisms germline), prompting a group of prominent scientists and ethicists to recommend a temporary (at least) moratorium on any human clinical uses.[5]

Gene editing is but one of a series of forms of human enhancement. And while it perhaps poses the most safety risks in its germline form, the fear is we will make changes that pose risks that may not manifest until many generations downstream when the cat will be out of the proverbial bag.

Genetic engineering is not a single phenomenon. It represents a series of different subcategories and they have to be examined individually. By seeing the full panoply of cases, we can see that sometimes we may be engaged in a k
ind of biological exceptionalism that what strikes us as scary in the biological context is something we do in the non-biological context routinely, and we need to examine whether the biological versus non-biological, as well as other lines, are morally significant ones.

When discussing the issue of gene therapy and, ultimately, genetic engineering, it is useful to make a distinction between biological and non-biological enhancement[6]. For example, a hypothetical pill or surgery to raise ones performance on standardised testing versus tutoring to improve ones performance on standardised testing. The first seems to concern us, while the second is common place. Some might also distinguish genetic from non-genetic biological enhancement. We should also consider the concept of choosing for ourselves as opposed to choosing for others. For example, an adult using anabolic steroids versus providing human growth hormone for a child.

Some enhancements are like swiss army knives in that they can improve the prospects for a child, whatever the child chooses to do with his or her life, for example, improvements in intelligence or disease resistance. On the other hand, some enhancements will serve to close off certain life plans while they improve the chances in others. To give a trivial example, enhancing height may increase a persons chance of becoming a professional basketball player, but decrease their chance of riding a racehorse to glory. The same is true regarding non-biological enhancements. Ethicists are usually more worried about the latter category.

Some would draw distinctions between treatment to correct disease or disability as opposed to enhancement to make people better than well. For example, a colleague of mine defines the distinction in relation to species typical functioning[7]. Others, including myself, are sceptical and think this falls prey to a classic baseline problem and treats our status quo states of health or other goods as morally significant.

Some would also draw a finer sub-distinction between enhancements to the upper bounds of what people already have versus enhancements that add beyond human nature as it now stands but, again, one might wonder why give moral pride of place to our own current status quo.

Finally, some goods, such as being tall, are beneficial primarily in a positional sense they are desirable to have only because others lack them. By contrast, other goods, such as immunity to disease, are primarily absolute goods, in the sense that one would want to have the enhancement even if everyone were to have it.

Using enhancement for positional goods may particularly exacerbate inequalities of access and also impose costs (to our health, for example) that create a kind of evolutionary rat race where people must enhance merely not to fall behind.

Most traits, though, are mixes of positional and absolute goods, in that they are sought to confer positional advantage and because they have absolute benefit. Indeed, determining just how much a particular trait is valued for positional as opposed to absolute value may be difficult or costly to determine.

To evaluate whether the law should permit or prohibit or otherwise regulate any particular form of human enhancement, it is useful to first situate it within this taxonomy. When enhancements impose costs on the enhancer, or especially externalised costs, that is more problematic when the good sought is more positional than absolutely beneficial. The less reversible an enhancement, the more the concerns about safety but also its effects on social change loom large. And so on.

Some enhancements have the potential to improve the human condition as we know it and some have the potential to wreak havoc on our lives and social structure. Anyone who has a position on enhancement has not thought deeply enough on the question. The right answer to the regulatory, legal, and ethical questions can only be answered on a category-by-category basis.

Either way, pharmacogenetics, gene therapy and, ultimately, genetic engineering will continue to progress. We have already seen this earlier this year, when Chinese scientists reported editing the genomes of human embryos[8]. The results were published in the journalProtein & Cell[9]and sparked widespread debate about the ethical implications of such work.

No doubt, this debate will continue.

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Genetically engineering humans: a step too far?

‘Vesper’ Ending, Explained: What Happens To Vesper And Camellia? What Does He Do With The Seeds? | DMT – DMT

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Vesper is a delightful concoction of detail and simplicity, one that is easy to gulp down and leaves an effect for a long time. Although the drama films premise is a science-fiction post-apocalyptic world, its story is universal and relatable enough to make it seem almost like a coming-of-age tale. With the eponymous protagonist, Vesper, learning to find her way and take responsibilities in a world with no hope, the adventures she comes across and the ultimate choice that she has to make turn Vesper into a lovely tale of hope as well.

Spoilers Ahead

Set in the future world termed the New Dark Ages, the plot unfolds in a barren wasteland. Humans had made an attempt to prevent the ecological crisis by investing in genetic technology largely, but the process ultimately had failed. Instead, genetically engineered viruses and other harmful organisms escaped into the world and killed off vast numbers of life forms. While some humans survived, all food sources, be they plants or animals, were wiped out and left human society starkly divided. On the one hand are the rich and affluent, who live in protected cities called citadels, and on the other hand, everyone else, who are never permitted into these citadels. Although these citadels grow their own food from the seeds they had presumably preserved before the apocalypse, those outside rely only on these seeds that the citadels trade with them in exchange for other items. Even more harshly, these seeds traded are coded to produce a single harvest, and therefore the outsiders need to forever stay in need of the mercy of the citadels.

In such a world, Vesper is a thirteen-year-old girl with an exceptional talent for studying organisms of this new world and creating new life by mixing them with each other. However, her responsibilities weigh more than her respite for passionate experimentation, for Vesper has to look after her ailing father, especially since her mother left them about a year or so ago. The father, Darius, is bedridden and cannot move or speak on his own but communicates through the body of a metallic drone. It is with this drone, essentially her father, that Vesper goes around searching for new plants and forms of life to gather for food, medicine, and her own research. The world has other factions of danger, too, for a group of humans calling themselves the pilgrims mysteriously roam around, scavenging any and every metal they can find, and Vespers mother, too, had joined this group of pilgrims. Along with that, there are also raiders and bandits who go around looting and, on one occasion, visit Vespers house as well, taking away all the power resources. When she finds her father struggling for life without power because his heart and other organs are supported and kept running through external power, Vesper looks for help at her uncle Jonas farm. However, Jonas is a crooked leader of a group of outsiders, and he runs a business of trading the blood of young children in exchange for food and resources with the citadels. Vesper, too, has had to give her blood to get some minor help from her uncle once or twice, but she denies turning into a blood-breeding machine for Jonas.

One day, while sneaking around Jonas farm in search of food and medicine, Vesper gets hold of a great treasureshe manages to enter a room full of seeds that Jonas had received from the citadel and steals a few of them. On her way out, though, she also spots a few citadel drones flying in the sky, of which one falls out and crashes, and this poses a new possibility in Vespers young life.

Although Vesper manages to steal the seeds, they are clearly not worth much since they would only yield one harvest, and they would again have to depend on Jonas supply. But in young Vespers mind, she is confident that she will be able to engineer a way to decode the seeds and remove the single-harvest characteristic from them. With this, she plans to approach the citadels and secure a job and residency inside them, and then get her fathers ailment treated. All these plans keep buzzing in her head when she goes out the next day in search of more supplies. She spots a young woman lying unconscious in the forest and brings her back to her house. Vesper treats her back to health, and the woman is introduced as a member of the rich society living inside the nearest citadel. Camellia, as she is called, regains consciousness and looks for a man who had been inside the drone when it crashed. She tells Vesper that the missing man is her father, Elias, and offers to help the young girl and her father if she helps her find him. Camellia herself seems to possess special powers, as she can calm down and put one to sleep instantly with a kiss, as she does to Darius one night when he struggles with his pains.

On the other side, Vesper goes through the forest looking for the crashed drone and finds it too, but before she can rescue the trapped man inside, Jonas and his cult of children join her. They strip open the drone, and Jonas murders Elias and then collects whatever useful material they can find on him and the drone. Vesper returns home disheartened, but she does not tell Camellia anything about her fathers death. The young girl soon develops a bond with the woman, and she even takes her to see the countless different experiments Vesper had done and their results. Camellia also grows affectionate towards Vesper and learns more about her parents and their lives. But all things come to a sharp halt when Vesper is one day caught sneaking around Jonas farm. The cruel uncle had been suspecting that Vesper was stealing his germinating seeds, and now he confronts her. Vesper tries to run away but is intercepted by the children of the cult inside the forest, and they brand her with Jonas mark, meaning that she is considered part of the blood-selling group from now on. She runs back home and is comforted by Camellia, and now Vesper cannot help but reveal the truth that she has been keeping hidden for so long. She tells Camellia about her fathers fate and even takes her to the place where Jonas had thrown the mans body, and Camellia has an outburst of grief and anguish. She now makes revelations of her own and tells Vesper that she is not a real human being but is instead a Jug, an artificial humanoid that people inside the citadels create to keep them as workers, almost like slaves. Despite it being a major crime to create a Jug with human-like intelligence, Elias had created Camellia exactly like a human being and had kept her safe for so long. But, her true nature had been revealed, and she and her father, therefore, had to escape from the citadel. They had indeed been escaping the citadel in their drone and were being chased by the authoritarian drones when their vehicle crashed, and they landed in the outside wastelands.

Hearing all this, Vesper realizes that her plan of escaping to the citadels with Camellias help is never an option, and she throws a childish fit at the woman. This further affects Camellia, and even though Vesper gets over her grief in some time, Camellia has a tougher time dealing with hers, and she tries to kill herself. Vesper intervenes, and then she asks Camellia if she could study a sample of her, and the woman agrees to let her do it. While researching the humanoids genetic sample, Vesper finally makes an immense breakthrough. She realizes that the real reason Elias had made Camellia was to hide inside her the secret to breaking the code of seeds yielding only a single harvest. When they had escaped their citadel, Elias had already made an agreement with a different citadel where they were promised safe shelter in exchange for Elias engineering masterpiece. Vesper now learns of it and immediately starts off to gather ingredients for her new research. However, Jonas visits her house in the meantime and finds Camellia there, and he also quickly learns that the woman is a Jug. Vesper returns and stops the man from causing any serious harm, and the two women take control of the situation. Although they can kill Jonas, Vesper decides to let him go
instead and even treats the wounds he incurred. Before setting him free, the young girl tells him that she wants to make a deal with the citadels and would therefore want him to contact them. But Jonas seems to have something else in mind. As a man regularly trading with the citadels, he does have direct contacts there, and he does get in touch with them too, but only to inform them that he knows the location of Camellia, the Jug they have been looking for.

Much like most other things in the film, the character of Vesper is a fine balance between emotions and intelligence. From early on, she yearns for love and affection. She desires to have a family. The young girl still does not understand why her mother had left them, and she even has a close affection for a dead, unmoving human skeleton inside their old laboratory. It is because of this yearning that she takes Camellia into her life very quickly and opens up to her so easily. Perhaps the womans age makes her a good fit to be Vespers elder sister or young mother. In the end, when Vesper declines to kill Jonas, it is perhaps because the man is her uncle, her own blood tie, even though he had never wanted any good for them. On the other hand, Vesper is also not emotional enough to immediately use the power of her knowledge to help everyone around her. She decides to take the seeds and the new science she has learned to the citadel because, after all, she wants personal favorsto cure her fathers sickness.

The citadel police quickly arrive at the wasteland settlement, and the very first thing they do is cruelly shoot their informer, Jonas, dead. Knowing well that there was no way to avoid the citadel police force, Darius convinces Vesper and Camellia to escape the house and hide in the swamps while he distracts the police and sends them some other way. The girl reluctantly agrees and goes to the swamps, from where she painstakingly sees her house, and therefore her father, get blown to bits. Two of the personnel chase them inside the swamp too, and ultimately, Camellia decides to surrender herself to the police in order to save Vesper. The young girl continually pleads with her not to do so, not to leave her completely alone, but the more mature Camellia perhaps realizes the worth of Vesper to the world if she lives. With a kiss, she puts Vesper to sleep and then turns herself in; although her fate is not shown or mentioned, it is most likely that Camellia is immediately killed in the citadel.

The next morning, Vesper wakes up and finds herself all alone in the woods. She returns to her house, which is just debris now and plants three of the genetically modified seeds in the ground. Hearing scuffling noises, Vesper looks up to see that some of the children who had been part of Jonas cult are now following her since their leader is now dead. She walks across the vast barren land, clearly looking for something, and the kids follow her around. Gradually they become a group, and they come across the pilgrims, and Vesper now follows them to their camp. She had, in fact, always wanted to follow pilgrims to find out where they went, and now she sees that they have built a giant tower in the middle of the forest with all the scavenged wood and metal pieces. Vesper climbs up the tower and sees the citadels in the distance. Perhaps knowing too well that there was no need for any personal favors now since she had lost her father and also everyone else, Vesper decides to let the seeds go into the air, where they will naturally grow into new life wherever they land. A sad tale of loss and suffering thus ends with a bright ray of hope. Even though she could not perhaps save her own dream, Vesper compensates it with the dream of a new world with no shortage of food and supply.

Vesper is a 2022 drama science fiction film directed by Kristina Buozyte and Bruno Samper.

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'Vesper' Ending, Explained: What Happens To Vesper And Camellia? What Does He Do With The Seeds? | DMT - DMT

India’s GM Crops Regulation Should Be Based on a Gene’s Effects, Not Its Source The Wire Science – The Wire Science

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Representative photos of cotton and brinjal: Wikimedia Commons, CC BY

India has a long and dubious record of regulating genetically altered crops for agriculture. While the nation began at the same time as many other countries with the same ambitious goals to deploy new genetic engineering tools to address agricultural vulnerabilities it has fallen behind. Only one crop, modified with molecular techniques pest-resistant cotton has been approved by regulators.

In an attempt to expand farmers access to genetically engineered crops, in March of this year, the Indian government exempted crops with certain kinds of genetic modifications introduced by genome editing (also known as gene editing) from the cumbersome and time-consuming regulations previously imposed on the commercialisation of all crops genetically modified with molecular techniques.

Specifically (and as explained in more detail below), the new policy exempts crops with simple tweaks to genes that are already natural to the plant but that have not had any foreign DNA added. This approach may be expedient but it is not scientifically sound.

Bt cotton and Bt brinjal

Genetically modified cotton came first to India because of its economic importance and environmental externalities. Specifically, Bt cotton was the first product in the country modified with modern molecular genetic techniques. However, it sparked fierce political debate instigated by internationally visible but misguided activists.

Bt is shorthand for Bacillus thuringiensis, a bacterium found mainly in the soil that produces proteins toxic to some insects, especially the cotton bollworm. The genes that express these proteins were introduced by recombinant DNA technology a.k.a. gene splicing into the genome of various crop plants to protect them from pests.

Bt cotton soon became ensnared in spurious societal battles around neo-colonialism, the purported evils of Monsanto, organic agriculture and farmers suicides. It was officially regulated and socially stigmatised as a GMO, short for genetically modified organism. After 10 years, it remains Indias only approved genetically engineered crop.

The Indian versions of insect-resistant Bt-cotton proved highly successful in controlling the bollworm that had ravaged cotton crops. They contained only one transgene, or a gene introduced from an unrelated organism, for one trait and for only a single species of bollworm. Yet, because of the presence of this single newly introduced gene, this first successful application of molecular genetic engineering in Indian agriculture was subjected to a long and costly development process.

Herbicide tolerance as a weed-control trait also proved popular, although it was never approved and therefore its cultivation was, and is, illegal.

At the same time, farmers demand in underground markets moved the transgenic frontier forward in a poorly regulated and awkward way. Farmers vote with their ploughs, and many officials lack the knowledge and/or the incentives to contest illegal plantings.

Also read: Does India Need Transgenic Mustard?

The biggest flaw in Indias cumbersome and poorly understood regulatory system emerged vividly with the introduction of a second genetically engineered crop candidate: Bt brinjal1, a staple of some of the worlds poorest rural populations.

Brinjal in India is attacked by a boring insect larva (Leucinodes orbonalis) that is susceptible to the same protein as the cotton bollworm. But as with cotton, there is no naturally occurring gene in the brinjal family tree that conventional breeding could utilise. This is why researchers introduced the Bt gene into a brinjal variety, thus rendering it a transgenic organism.

Brinjal is not extensively traded internationally but is very important for small farmers income and both local and national consumption. There is also no environmentally acceptable, effective alternative for farmers to use as insecticides against brinjal pests.

Field trials of the transgenic brinjal cultivars were extremely promising, even compared to the successes of Bt cotton. The fact that the transgene and the cultivars were both indigenous also suggested that the variety would be nationally acceptable in a way that Bt cotton couldnt be.

The Genetic Engineering Approval Committee of India approved Bt brinjal but it was vetoed in 2010 by the then-environment-minister, Jairam Ramesh. It has since been stuck in regulatory limbo in India. During this time, India donated the genetic event EE12 to Bangladesh and the Philippines.

After EE1 was introduced into Bangladeshi varieties of eggplant and tested, the government approved them and they have been extremely successful. Interestingly, some of the altered brinjal has spread to India, and is found growing happily in India but on an unknown scale and unapproved by bureaucrats.

Regulatory discrimination

Both Bt cotton and Bt brinjal in India tell the same story: that advances for farmers unavailable through conventional, pre-molecular plant-breeding techniques have proved useful not panaceas but incrementally beneficial, trait by trait, with more in the pipeline. However, the regulatory system is slow, unscientific, inconsistent and obstructionist. Its concerns often reflect more urban politics and the blandishments of activists than farmers interests.

Nonetheless, there is hope that the most recent advances in the seamless continuum of genetic modification of plants represented by genome editing will fare better. These techniques allow genetic material to be added, removed or altered at specific locations in the genome.

The best known of these techniques is CRISPR-Cas9. This system is faster, cheaper, more precise and more efficient than earlier genome editing methods. It is also more democratic, by being less dependent on the political heft and huge resources of the multinational plant science corporations. Innovation is thus often centred in universities and individual research teams.

This said, if genome editing is to live up its potential, its regulation will need to be scientifically defensible and risk-based.

This is why the UK has reconsidered its highly prohibitive stance on molecular genetic engineering. Even the generally anti-genetic engineering EU is discussing a revised legal framework that incorporates genome editing. Consistent with this global trend, in March 2022, India announced that it would exempt certain categories of genome-edited crops from regulatory oversight.

As part of this, it has categorised genome-edited alterations as SDN-1, SDN-2 and SDN-3 (SDN stands for site-directed nuclease3). Variants made using SDN-1 and SDN-2 involve simply tweaking particular traits that already exist in a genome whereas SDN-3 involves the insertion of genes from external, or foreign, sources. So making brinjal resistant to insect predators by introducing genes from B. thuringiensis would put it in the SDN-3 category.

India has announced that SDN-1 and SDN-2 will be regulated as non-genetically engineered organisms, as there are no distinguishable sequence changes made between them and those resulting from conventional crop breeding. SDN-3, however, which involves the incorporation of a foreign DNA sequence, will continue to be heavily regulated.

This approach to regulation is unscientific and short-sighted. It has no demonstrated connection to enhanced risk. Instead, the SDN categories are based simply on considerations of how close to nature the new constructions are. Bt cotton, which was introduced to India over 20 years ago and has transformed Indias economy, will be classified as an SDN-3 crop as will Bt brinjal. So as such, the latter looks set to remain stuck in the regulatory quagmire it has been in since the beginning of its development.

There is no scientific rationale for a regulatory policy that distinguishes SDN-3 crops from SDN-1 and -2 crops. The difference between these categories is determined by the presence or absence of a foreign
gene, but the term foreign has many connotations, none of which is meaningful for regulation in the current context.

Through advances in genome sequencing, we now know that foreign genes i.e. genes that originated in an unrelated organism are present in many crop plants. They may be thought of as natural GMOs. From sweet potato to several species of grass, genes from unrelated organisms have found their way into the most unexpected places.

Also read: The Strange Case of Indias First Public-Sector Bt Cotton Variety

Failed tests

What matters from a risk and therefore regulatory perspective is not the source of a gene but its function and its effect on phenotype4. A construct that results from the addition of a foreign gene via molecular techniques should not be held to a different standard or subjected to a more stringent regulatory regime unless the modification could in some way increase risk.

Baseless regulatory discrimination against transgenic i.e. SDN-3 crops means that some new varieties that could drastically improve the fortunes of resource-poor people and environmentally vulnerable places will, for practical purposes, remain proscribed and unavailable except through the stealth practices of farmers.

The regulatory policies of the governments of India, the EU and many other countries fail this test of scientific logic. The regulation of molecular genetic engineering has been based more on political considerations than on sound science, and as such cripples progress.

Flawed regulation is not the only problem related to genetically engineered crops in India. Another is the chronic lack of transparency about agricultural technology generally and genetic engineering in particular. Data that supports government policies and specific regulatory decisions have been consistently and conspicuously lacking from government sources. That stokes public suspicion about incompetence or even corruption.

That is unfortunate and puzzling, because there is plenty of evidence they could cite. We have more than 20 years of data on commercialised genetically engineered crops worldwide. It is very clear that they are as safe as, or in some cases safer than, crops from other breeding methods. Put another way, there is no evidence that the use of molecular genetic engineering techniques confers unique or incremental risks.

The European Academies Science Advisory Council said in 2013, There is no valid evidence that [genetically engineered] crops have greater adverse impact on health and the environment than any other technology used in plant breeding. Even the WHO a component of the notoriously risk-averse UN agrees: it said in a 2014 report that

[genetically engineered] foods currently available on the international market have passed safety assessments and are not likely to present risks for human health. In addition, no effects on human health have been shown as a result of the consumption of such foods by the general population in the countries where they have been approved.

Literally hundreds of other analyses by governmental and professional groups have echoed these findings.

Genome editing is both a continuation of plant modifications humans have depended on for millennia and a promising new frontier. Nevertheless, striking a balance between too little and much caution is not difficult, given the great precision and predictability of newer molecular techniques. Science shows the way, and politicians and regulators everywhere should follow it.

Henry I. Miller is a physician and molecular biologist and a senior fellow at the Pacific Research Institute. He was the founding director of the FDAs Office of Biotechnology and a consulting professor at Stanford Universitys Institute for International Studies. Kathleen L. Hefferon teaches microbiology at Cornell University. Ronald Herring is emeritus professor of government and International Professor of agriculture and rural development at Cornell University.

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India's GM Crops Regulation Should Be Based on a Gene's Effects, Not Its Source The Wire Science - The Wire Science

Should University Agricultural Research Scientists Partner With Industry? – Genetic Literacy Project

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Paul Vincelli, extension professor and Provosts Distinguished Service Professor at the University of Kentucky| March 7, 2017

HIGHLIGHTS:

Biases, conflicts of interest come from many sources, including associations with industry, advocacy groups, other non-profits Industry funding of studies on GE crops does not appear to be important bias source Personal experience suggests corporations receptive to negative results, as they improve products, limit liability Limited resources for much agricultural research without industry support Dubious shill accusations against biotech scientists discourage public engagement, depress discourse

Agricultural scientists who interact with the public often feel under enormous scrutiny. One of the most common concerns is that professional ties with industryespecially obtaining funding from industrycompromise scientific credibility. This concern is particularly acute in the area of genetically engineered crops (GE crops, commonly known as GMOs).

Research into genetically engineered crops is not my specialtymy work is focused on plant pathologyand I have never solicited nor received private-sector funding on this issue. Over my career, my industry interactions have dealt with non-GMO products for plant disease control. My interest in GE crops arises from their potential to address genuine human needs and to reduce the environmental footprint of agriculture. And I am concerned that a dark shadow has been cast over many independent scientists because of their collaborative efforts with various stakeholders, including companies.

Biases From Many Sources

Across multiple disciplines, industry-funded projects may be more likely to report positive outcomes, or less likely to report negative outcomes [1-4]. However, industry funding is not always associated with biased outcomes [5, 6]. Furthermore, many sources of funding NGOs, non-profits, other civil and governmental organizationsmay engender conflicts of interest (COIs) and biases that influence reported research. Powerful biases may arise for non-monetary reasons [7] in both researchers and in non-researcherspossibly including you and me.

Regarding GE crops, I am aware of three journal articles on the topic of industry funding and bias. In the first [8], the authors found no evidence of bias due to financial COIs (studies sponsored by an industry source that may benefit from the outcome), but they did document bias associated with professional COIs (where at least one author was affiliated with a company that could benefit from the study outcome). In that study, among the 70 studies examined (see their Table 2), 61% had either a financial or a professional COI. Among the much larger sample size (698 studies) examined by Sanchez [9], the majority had no COI, and only one quarter had COIs related to author affiliation and/or declared funding source.

A recent study by Guillemaud et al [10] had similar findings: among 579 studies with definitive COI information (see their Figure 3), the majority did not report a COI. However, among those with COIs, there was a higher probability of reported outcomes favorable to the GE crop industry. In addition to these journal articles, another independent analysis [11] suggested that industry funding did not bias study outcomes for GE crops, but these data have not been analyzed statistically nor published in a peer-reviewed journal.

Thus, while evidence to date shows that the majority of studies on GE crops are not influenced by COIs, some fraction is so influenced. Therefore, there is value in remaining alert to the possibility of bias and in continuing to practice full disclosure. I believe it is important to remain alert to COIs and biases of all sortsnot only those associated with corporate influences, but also those of NGOs or other civil organizations that may have explicit or implicit agendas.

Some people simply do not trust corporations. This is understandable, given the indefensible behavior of some in business, such as the tobacco industry, the chemical industry, Exxon, and Volkswagen [12-15]. Consequently, some members of the public perfunctorily dismiss commercial-sector scientists who may have solid scientific skills and high personal integrity. I personally must admit to a measure of distrust of corporations, which may even express itself occasionally as an anti-industry bias. But I also believe it is unwise to categorically reject all industry-funded data, solely on the basis of their provenance. In fact, I would label such an attitude a bias itself. Thoughtful, evidence-based analysis must always trump bias and ideologyand does, for a good scientist.

Why do researchers accept industry funding? Public-sector and private-sector scientists may share common interests. Industry scientists and I share a common interest in knowing what works in the field and what doesnt. Consequently, industry sources provide funding for field tests of their products for plant disease control. Furthermore, public funding for science in the USA is insufficient to support even a fraction of the worthy research projects. Inadequate funding can quickly and thoroughly undercut a career in science at any stage. Since researchers are hired to do research on important topics and not to whine about the difficult state of public funding, some will welcome funding from commercial sources, if it allows them to continue to do research they believe is intellectually compelling, important to society, or both. Also, industry scientists may have knowledge, skills, and facilities that we public scientists may not.

My Funding Choices: Scientific Rigor Coupled With Personal Integrity

Discussing my own practices should provide an idea of how many scientists work. Roughly half of my funding over the years has been from industry, primarily to support product testing for plant disease control. I have commonly tested synthetic fungicides, but I have also tested natural products of various sorts. In fact, commercial pesticide manufacturers can fairly accuse me of an anti-pesticide bias. I say this because I have tended to favor testing products that might be perceived as more consistent with sustainability (biocontrol products, for example) than applications of synthetic chemicals, often requesting limited, or no, funding for such tests. Besides industry funding, I have received federal funds for research and outreach on detection and management of plant diseases.

I publish all efficacy trials in Plant Disease Management Reports. We commonly publish data showing inadequate efficacy or phytotoxicity, and I never consider funding sources when the report is drafted. In fact, the reports are drafted by the Senior Research Analyst who conducts the field work, and he doesnt know who provided funding nor for what amount. Thus, our testing program does not suffer from publication bias. This approach is not exceptional [16, 17].

I accept no personal giftsmonetary or materialfrom private-sector sources.

I have no hesitation about challenging multinational corporations. For example, I provided a degree of national leadership in challenging a major pesticide manufacturer over certain uses of a commercial crop fungicide. I was one of the lead authors of a letter to the US Environmental Protection Agency raising questions about the paucity of public data to support plant health claims. I gave a similar talk in a major scientific conference, the 2009 American Phytopathological Society meeting.

Several factors may help me and other scientists to offset natural human tendencies towards bias:

A common concern is that providing funding buys access to researchers. This may sometimes be the case, but for me, this criticism doesnt fit. I am an Extension Specialist everybody has access to me and my expertise. I dont recall a single instance in my entire career when I failed to return a phone call or email from anyone. In fact, it is a federal requirement that Extension programming be grounded in engagement with diverse stake- holdersincluding,
but certainly not limited to, industry [18].

What Happens When Data Fall Short Of Company Expectations?

We regularly see poor product performance in our experiments. In a memorable instance, we observed visible injury to a creeping bentgrass putting green from a particular formulation of the widely used fungicide, chlorothalonil. On the day of application, the turfgrass was suffering exceptionally severe drought stress, due to an irrigation equipment failure, which probably was a predisposing factor.

I notified the company of my observations, which is my standard practice if a product provides unexpectedly poor performance or unexpected phytotoxicity. This is not to provide the company the opportunity to help me see the error of my ways. Rather, this is simply good scientific practice. I want industry scientists to collect their own samples, so that they may better understand the poor results obtained; and to offer hypotheses or insights that may account for the unexpected results, as they often know things about their product and its performance that I do not.

In the case of the turfgrass injury caused by chlorothalonil, a company representative and I visited the experiment together and shared observations. I listened to the representatives hypotheses and shared my own. After the meeting and additional lab work, I reported my findings in various outlets. In my research program, unfavorable results get reported no differently than favorable results.

I must state emphatically that, in my 34 years of product testing for plant disease control, I cannot recall a single instance where a company representative attempted to pressure me to report favorable results. Company representatives do not like to receive bad news, but in my experience, almost every company representative I have interacted with has been professional enough to recognize the importance of discovering the limitations of their products sooner rather than later. The consequences of introducing an inadequate product can be catastrophic for a corporation.

Corporate Funding for Outreach

What about private-sector funding for outreach? To my knowledge, such funds are never provided with a quid pro quo that the scientist will make particular claims about a companys products. To the contrary, private-sector representatives take note of speakers whose scientific understanding is consistent with their own. They may approach those speakers to discuss possible support for outreach, but without specifying the content of such presentations. Although I refuse industry funding for all aspects of GE crops, I do not suspect undue industry influence when funds are provided for travel expenses or supplies of invited speakers. Even honoraria or stipends for speaking engagements dont particularly concern me. This is true for such funding across the full spectrum of possible funding sources, ranging from advocacy groups for organic agriculture to multinational pesticide manufacturers. I want to see the scientific methods and data, no matter who did the study.

Who Should Pay For Research?

Should publicly funded professors even do product testing? Yes: there is a public interest in independent assessments of how products perform. The more public data on performance, the better.

If you agree that third-party testing is desirable, the question arises, Who pays for it? I believe that, usually, the manufacturer is responsible, not the taxpayer. Of course, this raises concern about funding bias. If a researcher wishes to avoid funding bias, can they tap into other sources? Not in my discipline. Pools of public funding for product testing are essentially non-existent.

What about studies of possible impacts of products to the environment? Who should pay for that? Again, in my opinion, such costs fall to the manufacturer, although in some cases, there is a compelling public interest that justifies the use of public funds for product testing.

Final thoughts: Does industry-researcher cooperation undermine the credibility of scientific research?

For me, the answer is, No. We should be cognizant of possible biases and COIs due to source of fundingwhether the source is industry, NGOs, advocacy organizations, or other sources. Disclosure is critical [7, 19]. However, industry scientists are often excellent scientists who take pride in their work, no differently than any industry critic. Yes, we should exercise a degree of caution when reviewing industry-funded research, but the same holds for research funded by advocacy organizations, since each has an agenda. Personally, in all cases, I will not reject either source out of hand; I will judge the work based on its scientific merit.

Sometimes the bias against industry-funded research on GE becomes hurtful, especially in the social media. Witnessing dedicated public servants being unfairly attacked as industry shills is demoralizing to public scientists, and it has the unintended consequence of discouraging public engagement by scientists who already have very busy professional and personal lives. Such unfounded charges are not only divisive and unproductive: they are unkind and can be abusive. (Sadly, unkind behavior can be found in all sides of the GMO debate.)

My freedom from industry funding on all aspects of GE protects me from similar accusations. Yet it doesnt surprise good scientists that, after years of studying the scientific literature, I independently arrived at an understanding very similar to that presented in the re- port of the National Academy of Sciences, Engineering and Medicine (NASEM) published earlier this year [20]. This isnt because industry has somehow influenced me or the members of the NASEM review committee. It is because there is a substantial body of credible science supporting the conclusions presented in the NASEM report. In reviewing the body of peer-reviewed scientific literature on GE crops, one is likely to arrive at similar conclusions. I had an identical experience with the scientific consensus on climate change [21].

Ultimately, with enough careful study of evidence from credible sources, fidelity to good scientific practice, and a degree of humility, it is hard not to arrive at findings rather similar to those of journal-published experts of a scientific discipline. They actually do know something about their subject after all.

Paul Vincelli is an Extension Professor and Provosts Distinguished Service Professor at the University of Kentucky. Over the 26 at UK, he has developed specializations in management of diseases of corn, forages, and turfgrasses, molecular diagnostics, and international agriculture. He also has provided Extension programming on climate change and on genetic engineering of crops. He currently is UKs Coordinator for the USDAs Sustainable Agriculture Research and Education program, and he serves as Councilor-At-Large for the American Phytopathological Society.

The Genetic Literacy Project is a 501(c)(3) non profit dedicated to helping the public, journalists, policy makers and scientists better communicate the advances and ethical and technological challenges ushered in by the biotechnology and genetics revolution, addressing both human genetics and food and farming. We are one of two websites overseen by the Science Literacy Project; our sister site, the Epigenetics Literacy Project, addresses the challenges surrounding emerging data-rich technologies.

Acknowledgements

Thanks are expressed to John R. Hartman and Jon Entine, for reviewing earlier drafts of the manuscript.

Disclosure Statement

The author declares no conflicts of interest in the topic of GE crops. Detailed disclosure documents may be found here. The author donated the full amount of his monetary honorarium for writing this article to Human Rights Watch.

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Should University Agricultural Research Scientists Partner With Industry? - Genetic Literacy Project

Large-scale bovine vaccine study reveals the role of genetics in immune response – The Hub at Johns Hopkins

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BySydney Portale

Vaccines are a critical tool in the protection of humans and animals against pathogens, but a major challenge for vaccine development is understanding why vaccines work better for some individuals than others.

To answer this question, a research team led by Yana Safonova, assistant professor in the Department of Computer Science at the Johns Hopkins Whiting School of Engineering, studied black angus cows and their varying responses to the Bovine Respiratory Disease, or BRD, vaccine. The team's findings were recently published in the journal Genome Research.

BRD is the leading cause of natural death for cows and costs the cattle industry an estimated $900 million a year. Medication is expensive, so cattle producers rely on vaccinations to mitigate the problem.

Conducting research for the U.S. Department of Agriculture, Safonova and researchers from the University of California, San Diego sought to understand how the unique genetic structure of cows and other bovine animals such as bison, buffalo, and antelopes were creating antibodies from the BRD vaccine.

A large-scale study of human immunogenetics could aid in understanding vaccine response variations ahead of the next pandemic.

"We wanted to answer one particular question: Why are some individuals within the population of black angus cows responding very differently to the same vaccine?" Safonova said.

The researchers examined a distinguishing feature of bovine immunity: the long complementarity-determining region H3 loops in the antibodies they create. Bovine antibodies with such ultralong CDR H3 loops have been found to neutralize certain strains of HIV, and Safonova and her team have discovered that they are also one key to developing antibody responses against BRD.

Using a new computational tool that they designed, Safonova and her team analyzed sequencing data from antibodies produced by the black angus cow population and pinpointed genetic variations in antibodies associated with immune responses.

The researchers found that while the creation of these unique antibody structures was triggered by each vaccine dose, vaccine efficacy (how well the vaccine actually works) is determined long before the individual mounts an immune response. Segments of DNA called variable, diversity, and joining immunoglobulin genes, also referred to as IG genes, are what produce antibodies and control individual responses to a vaccine.

This means vaccine efficacy for an individual is pre-determined before the vaccine is even administered.

Because the team's method can reveal these genetic markers, cattle producers could potentially use this information to selectively breed cows that are less susceptible to BRD based off their genetic predisposition, said Safonova.

The researchers say that their study is the largest personalized immunogenetics study across any species to date, and that their results open doors to applying immunosequencing to human vaccine studies. In-depth immunogenetics research would allow scientists to discover patterns in the human genome that determine the body's programmed response to vaccines. In fact, Safonova says a large-scale study of human immunogenetics could aid in understanding vaccine response variations ahead of the next pandemic.

Safonova explained, "With new strains of COVID-19, new variants, and the need for vaccinations, we can show that this type of study will work for many different subjects. We want to highlight how we can study [the vaccination process] across different genomes."

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Large-scale bovine vaccine study reveals the role of genetics in immune response - The Hub at Johns Hopkins

CRISPR and Cas Genes Market is Anticipated to Reach US$ 7,234.5 Mn by 2026, Increase in Incidence of Genetic Disorders to Drive the Market – BioSpace

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Albany NY, United States: CRISPR cas systems are commonly used in microbial engineering that includes immunization of cultures, bacterial strain typing, and self-targeted cell killing. Further, CRISPR and cas genes market system is also applied to control metabolic pathways for an improved biochemical synthesis. This technology is also used for the improvement of crop production. These factors further drive growth in the CRISPR and cas genes market.

CRISPR and cas genes system has been a revolutionary initiative in the biomedical research field. The application of this technology in somatic cell genome editing events has targeted to its application. The technologies are commonly used for the treatment of different genetic disorders. But, the ethical issues while using the system from the CRISPR and cas genes market are somewhere curtailing the growth in the industry. Furthermore, the market is also witnessing a lack of proficient professionals, which restrains its growth opportunities.

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The market forecast on CRISPR and cas genes market was estimated US$ 1,451.6 Mn. Now it is predicted to climb US$ 7,234.5 Mn during forecast period from 2018 to 2026. The market is estimated to reach a compound annual growth rate (CAGR) of 20.1% from 2018 to 2026.

Multiple Applications and Diverse Dominating Factors in CRISPR and Cas Genes Market

The report from market research on CRISPR and cas genes industry has marked its division on the basis of region, end-user, application, and product type. DNA-free cas and vector-based cas are the two types in which the CRISPR and cas genes market is bifurcated on the basis of product type. Between these two types, the vector-based cas section has dominated the market at international levelin 2017. This expression system is helpful for the researchers who are focusing to enrich Cas9-expressing cells and concentrate on the establishment of a stable cell line. The vector-based cas is available with an analytical that is used to support the creation of durable cell lines. These lines are designed with minimal possible background expression.

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The major advantages of the DNA-free cas segment boost growth in the CRISPR and cas genes market. DNA-free cas components are used for the reduction of potential off-targets. They also find application to trace correlations with human illnesses.

Knockout/activation, functional genomics, disease models, and genome engineering are the classification types in the CRISPR and cas genes market on the basis of application in different verticals. Contract research organizations, government and academic research institutes, pharmaceutical and biotechnology companies are some of the key end-use industries in the market. Further, as per the market analysis report on CRISPR and cas genes market, the industry is spread in different regions that include Middle East & Africa, Latin America, Asia Pacific, Europe, and North America.

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The industry players from market have adopted inorganic and organic growth strategies for the expansion of product offerings, capturing market share, increasing consumer base, and strengthening geographical reach. Some of the key players in the CRISPR and Cas genes market include Dharmacon, Synthego, GenScript, OriGene Technologies, Inc., Applied StemCell, Inc., Addgene, and Cellecta, Inc.

Genome Engineering to Dominate CRISPR and Cas genes market

On the basis of application, the genome engineering section has dominated in the CRISPR and cas genes market. The genetic materials can be added, detached, and altered with the help of CRISPR technology at any specific location in the genome. Genomic engineering is related to the synthetic assembly of comprehensive chromosomal DNA, and it has been commonly taken from natural genomic sequences.

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The CRISPR and Cas genes market has been dominated by pharmaceutical and biotechnology companies in terms of end-user. The strategic partnerships and innovations may boost growth in the market.

North America and Europe are the regions that account for the maximum share in the CRISPR and Cas genes market. Rising technological advancements and research activities are driving growth in the market.

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CRISPR and Cas Genes Market is Anticipated to Reach US$ 7,234.5 Mn by 2026, Increase in Incidence of Genetic Disorders to Drive the Market - BioSpace

Tenaya Therapeutics Launches Operations of New Genetic Medicines Manufacturing Center to Support the Development of Potentially First-In-Class…

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Facility to Provide Clinical Supply of Lead Gene Therapy Programs TN-201 and TN-401 for Planned First-in-Human Studies

94,000 sq. ft. Modular Facility has Initial Production Capacity at the 1000L Scale

SOUTH SAN FRANCISCO, Calif., June 16, 2022--(BUSINESS WIRE)--Tenaya Therapeutics, Inc. (NASDAQ: TNYA), a biotechnology company with a mission to discover, develop and deliver curative therapies that address the underlying causes of heart disease, today announced that it has completed the build-out and operational launch of its Genetic Medicines Manufacturing Center in Union City, California. Tenaya is advancing a pipeline of therapeutic candidates, including several adeno-associated virus (AAV) gene therapies, for the potential treatment of both rare and prevalent forms of heart disease.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20220616005336/en/

Tenayas Genetic Medicines Manufacturing Center located in Union City, CA (Photo: Business Wire)

"Tenaya made an early, strategic commitment to internalize several core capabilities to optimize the safety, efficacy, and supply of our product candidates on behalf of patients. With todays announcement we have made a big leap forward on that commitment by establishing end-to-end in-house manufacturing capabilities for our pipeline of AAV-based gene therapies," said Faraz Ali, Chief Executive Officer of Tenaya. "The operational launch of Tenayas Genetic Medicines Manufacturing Center represents an important milestone as we prepare to advance our robust pipeline of potentially first-in-class cardiovascular therapies into initial clinical studies."

Tenayas Genetic Medicines Manufacturing Center is designed to meet regulatory requirements for production of AAV gene therapies from discovery through commercialization under Current Good Manufacturing Practice (cGMP) standards. Initial production efforts will support first-in-human studies of Tenayas lead gene therapy, TN-201. TN-201 is being developed for the treatment of genetic hypertrophic cardiomyopathy (HCM) due to MYBPC3 gene mutations. Tenaya plans to submit an Investigational New Drug (IND) application for TN-201 to the U.S. Food and Drug Administration (FDA) in the second half of this year. The facility will also support cGMP production for TN-401, Tenayas gene therapy program being developed for the treatment of genetic arrhythmogenic right ventricular cardiomyopathy (ARVC) due to PKP2 gene mutations, for which the company plans to submit an IND to the FDA in 2023.

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"The investment in our own world-class manufacturing facility provides Tenaya with greater control over product attributes, quality, production timelines and costs, which we believe will ultimately translate into better treatments for patients," said Kee-Hong Kim, Ph.D., Chief Technology Officer of Tenaya Therapeutics. "Tenayas Genetic Medicines Manufacturing Center complements our established internal genetic engineering and drug discovery capabilities and is designed to meet our near- and long-term needs such that we can readily scale and expand as our pipeline matures and evolves."

Tenaya completed customization of approximately half of the 94,000 square foot facility to incorporate manufacturing suites and labs, office space and storage. Utilizing a modular design, the state-of-the-art facility is now fully operational with initial capacity to produce AAV-based gene therapies at the 1000L scale, utilizing Tenayas proprietary baculovirus-based production platform and suspension Sf9 cell culture system. The excess space and modular design of the Genetic Medicines Manufacturing Center is intended to provide Tenaya with considerable flexibility to expand manufacturing capacity by increasing both the number and the scale of bioreactors to meet future clinical and commercial production needs.

The Union City location, approximately 30 miles from Tenayas South San Francisco headquarters, is expected to enable the seamless transition of Tenayas science from early research through commercial manufacturing. The selection of this location is intended to foster a culture of close collaboration across teams at all stages of developing and testing novel AAV capsids, de-risk the translation from research to process development and create opportunities for improvements in production processes. The Genetic Medicines Manufacturing Center is staffed by a growing in-house team with expertise in all aspects of gene therapy manufacture, including process development, analytical development, quality assurance and quality control.

About Tenaya Therapeutics

Tenaya Therapeutics is a biotechnology company committed to a bold mission: to discover, develop and deliver curative therapies that address the underlying drivers of heart disease. Founded by leading cardiovascular scientists from Gladstone Institutes and the University of Texas Southwestern Medical Center, Tenaya is developing therapies for rare genetic cardiovascular disorders, as well as for more prevalent heart conditions, through three distinct but interrelated product platforms: Gene Therapy, Cellular Regeneration and Precision Medicine. For more information, visit http://www.tenayatherapeutics.com.

Forward Looking Statements

This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Words such as "potential," "will," "plans," "believe," "expected," and similar expressions are intended to identify forward-looking statements. Such forward-looking statements include, among other things, statements regarding the therapeutic potential of Tenayas pipeline of therapeutic candidates; Tenayas plan to use the cGMP manufacturing facility for the production of TN-201 and TN-401; Tenayas belief that its cGMP manufacturing facility will enable seamless transition from early research through commercial manufacturing and translate into better treatments for patients; the expected timing for submission of IND applications for TN-201 and TN-401; and statements by Tenayas chief executive officer and chief technology officer. The forward-looking statements contained herein are based upon Tenayas current expectations and involve assumptions that may never materialize or may prove to be incorrect. These forward-looking statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, including but not limited to: risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early stage company; Tenayas ability to successfully manufacture product candidates in a timely and sufficient manner that is compliant with regulatory requirements; Tenayas ability to develop, initiate or complete preclinical studies and clinical trials, and obtain approvals, for any of its product candidates; the timing, progress and results of preclinical studies for TN-201, TN-401 and Tenayas other programs; Tenayas ability to raise any additional funding it will need to continue to pursue its business and product development plans; negative impacts of the COVID-19 pandemic on Tenayas manufacturing and operations, including preclinical studies and planned clinical trials; the timing, scope and likelihood of regulatory filings and approvals; the potential for any clinical trial results to differ from preclinical, interim, preliminary, topline or expected results; Tenayas manufacturing, commercialization and marketing capabilities and strategy; the loss of key scientific or management personnel; competition in the industry in which Tenaya operates; Tenayas reliance on third parties; Tenayas ability to obtain and maintain intellectual property protection for its product candidates; general economic and market conditions; and other risks. Information regardi
ng the foregoing and additional risks may be found in the section entitled "Risk Factors" in documents that Tenaya files from time to time with the Securities and Exchange Commission. These forward-looking statements are made as of the date of this press release, and Tenaya assumes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220616005336/en/

Contacts

Investors Michelle CorralVice President, Investor Relationship and Corporate CommunicationsTenaya TherapeuticsIR@tenayathera.com

Media Wendy RyanTen Bridge CommunicationsWendy@tenbridgecommunications.com

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Genetic Engineering Market Competitive Insights and Precise Outlook 2021 to 2028 | Thermo Fisher Scientific Inc., GenScript, Amgen Inc. -…

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The Global Report on Genetic Engineering Market Size, Status, Growth and Forecast 2021-2027.

The Genetic Engineering Market research report is a significant wellspring of astute information for business methodologies. The report starts from outline of Industry Chain structure, and depicts industry climate, then, at that point, examinations market size and figure of Genetic Engineering by item, locale and application, also, this report presents market contest circumstance among the sellers and friends profile, in addition, market value investigation and worth chain highlights are shrouded in this report.

Prominent Key Players-

The report incorporates the serious scene in light of a broad evaluation of the key vital advancements embraced by driving business sector members in the business over the past four years (2018-2021). The central members working in the worldwide Genetic Engineering market are Thermo Fisher Scientific Inc., GenScript, Amgen Inc., Genentech, Inc., Merck KGaA

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Effect of COVID-19 on the Genetic Engineering market:

The COVID-19 pandemic massively affects the Genetic Engineering market, trailed by the restricted reception of modern control and interaction arrangements across application ventures in 2020. The spread of Covid overall brought about cross country lockdowns and restricted tasks of a few modern areas, impermanent end of assembling exercises, and upset stockpile chains. These variables and the decay of new modern arrangements in the pandemic because of immense misfortunes have contrarily affected the Genetic Engineering market. In any case, with the returning of creation offices and modern activities, the market began to recuperate in 2021 with the interest to mechanize these offices. This is because of the requirement for least human contact with the recently fabricated items to forestall additionally spread of the infection and control the tasks through robotized control arrangements.

Geographic Analysis (Regional Production, Demand & Forecast by Countries etc.):

North America (U.S., Canada, Mexico)Europe (Germany, U.K., France, Italy, Russia, Spain etc.)Asia-Pacific (China, India, Japan, Southeast Asia etc.)South America (Brazil, Argentina etc.)Middle East & Africa (Saudi Arabia, South Africa etc.)

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Global Genetic Engineering Market Scope:

This report segments on the basis ofTypesare:

This report segments on the basis of Application are:

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Genetic Engineering Market Competitive Insights and Precise Outlook 2021 to 2028 | Thermo Fisher Scientific Inc., GenScript, Amgen Inc. -...

World Tour: ACSH Makes The Case For GMOs In The UK – American Council on Science and Health

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As part of the European Union, the UK was a stronghold of anti-GMO opposition. Post-Brexit, however, Britain is changing its outlook for the better. After more than a year of intense public debate, the country'sDepartment for Environment, Food & Rural Affairs (DEFRA) recently announced less restrictive rules that will help the UK's biotech sector develop gene-edited crops designed to boost sustainable farming:

The rule changes, made possible by the UKs departure from the EU, will mean that scientists across England will be able to undertake plant-based research and development, using genetic technologies such as gene editing, more easily.

The rules will apply to plants where gene editing is used to create new varieties similar to those which could have been produced more slowly through traditional breeding processes and will unlock research opportunities to grow crops which are more nutritious, and which require less pesticide use.

This is a tremendous step in the right direction for a country that has denied farmers the benefits of crop biotechnology for decades. Conspicuously missing from DEFRA's announcement, though, was any reference to transgenic crops, the wrongly maligned "GMOs" we're all familiar with. [1] While transgenic technology could benefit UK farmers and consumers, as it has in dozens of other countries, regulators remain unwilling to take on the politically charged fight that would precede the reformation of Britain's GMO regulations, at least for now.

In the spirit of hastening the UK's acceptance of all crop biotechnology, I recently partnered with the London-based Adam Smith Institute to produce a new report titled Splice of Life: The case for GMOs and gene editing. In it, I survey more than two decades' worth of research documenting the benefits of growing and consuming GMOs. The key takeaways are as follows:

How could the UK so liberate its biotech industry? I argue that the ideal regulatory framework is a case-by-case risk assessment that evaluates each novel organism based on the harms it may pose to humans and the environment, regardless of which breeding method produced it. The organisms characteristics and intended use would determine the degree of scrutiny applied by regulators.

Matt Ridley, legendary science writer and member of the UK's House of Lords, had this to say about Splice of Life:

The governments sluggishness in embracing gene engineering is disappointing. This technology, in which Britain could be world-leading, provides immense benefits to farmers, consumers and the environment. Yet, as this important new report from the Adam Smith Institute highlights, gene editing will be severely hampered and GMOs will be left behind. Scientific evidence, not activist superstition, should be at the centre of policy making.

[1] For the record, "GMO" is a nonsense term no scientist uses in a professional context. Nearly all food crops we consume were the products of traditional plant breeding, which "genetically modified" them in all sorts of ways. Transgenic plants are not unique in this respect.

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World Tour: ACSH Makes The Case For GMOs In The UK - American Council on Science and Health

Viewpoint: Canada poised to join expanding number of countries endorsing crop gene editing. That’s encouraging but global reform remains elusive -…

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Gene editing, which allows precise edits to the genome, has been widely used for a variety of applications in laboratories worldwide since its discovery a decade ago. It has tremendous potential: Researchers hope to use it to alter human genes to eliminate diseases; improve the characteristics of plants; resist pathogens; and more. The two scientists who discovered the iconic gene editing technology, the CRISPR-Cas9 system, were awarded the 2020 Nobel Prize in Chemistry.

In spite of the fact that gene editing is essentially a refinement of earlier, less precise, less predictable techniques for genetic modification, finding the right approach to regulating it has been elusive. Initially, many nations treated it as a stringently regulated GMO, or genetically modified organism, which posed conceptual problems from the outset. For one thing, theres really no such thing as a GMO, except in the fevered imagination of bureaucrats, legislators, and activists, but that didnt prevent this pseudo-category from being subjected to onerous regulation.

Genetic engineering, or genetic modification, is a seamless continuum of techniques that have been used over millennia, including (among others) hybridization, mutagenesis, somaclonal variation, wide-cross hybridization (movement of genes across natural breeding barriers), recombinant DNA, and nowgene-editing. The primary distinction between the last two and the others is they are far more precise and predictable than the earlier techniques.

Since the advent in the 1970s of recombinant DNA technology, which enables segments of DNA to be moved readily and more precisely from one organism to another, molecular genetic engineering techniques have become ever more sophisticated, precise, and predictable. This evolution has now culminated in the most recent discoveries, the CRISPR-Cas9 system and variations of it. Its a way to find a specific bit ofDNAinside a cell and then to alter that piece of DNA. CRISPR can also be used to turn genes on or off without altering their sequence.

CRISPR(short for Clustered Regularly Interspaced Short Palindromic Repeats) is a natural defense system that a range of bacteria use against invading viruses. CRISPR can recognize and guide the system to specific DNA sequences, while the enzyme Cas9 (or other Cas proteins) cuts the DNA at the recognized sequence. As often happens in science and reminiscent of mutagenesis a century ago and recombinant DNA technology in the 1970s molecular biologists and genetic engineers quickly copied and adapted the naturally occurring system. Using CRISPR-Cas9, scientists can target and edit DNA at precise locations, deleting, inserting or modifying genes in microorganisms, plants and animals, including humans. CRISPR-Cas9 is cheaper, faster, easier, more precise, and more predictable than its genetic engineering predecessors, and scientists are continuously improving the technique, its predictability and safety.

The USand Canada have deregulated gene-edited organisms in principle, moving towards risk-based regulation, while Europe, with its long-standing, intractable opposition to genetic engineering, has decided to equate gene editing with heavily regulated, and sometimes even banned, GMOs. Other nations, such as the UK, are beginning to move away from Europes hostile regulatory climate, with hopes of improving their farmers livelihoods as well as finding new partners for international food trade, besides their European friends.

The polar extremes of acceptance of genome editing in different countries appear to be a reflection of a social transformation around food which values natural products. Some have argued that genome editing should be distinguished from other new agricultural technologies such as the generation of transgenic plants by recombinant DNA (gene-splicing) techniques. This argument may be based on the fact, as mentioned above, that with genome editing, only a few nucleotides of a plant genome sequence may be altered (and, therefore is more natural), while transgenesis introduces genes from other species, such as viruses, bacteria, or eukaryotes. As such, the discussions of these issues become almost theological in nature, not unlike debates overhow many angels can dance on the head of a pin, rather than based on science.

Some observers believe that the concept of cisgenesis (as opposed to transgenesis) could be a way to assuage or minimize the concerns that some people have about genetic engineering with the newer, more precise techniques. It refers to the genetic engineering of a recipient plant with genes from a crossablesexually compatibleplant. The process adds no new genes or sequences not found in a compatible plant, and also absent are all selectable marker sequences such as antibiotic resistance or luciferase (which makes a recipient light up), whose presence in transgenic plants is often problematic for anti-GMO activists. Cisgenesis is sometimes proposed as a way to accomplish rewilding, that is, reintroducing into crop varieties desirable properties such as resistance to pathogens or drought present in wild relatives.

History is instructive. Humans have been selecting and breeding to introduce or enhance desirable traits such as yield or taste for millennia, but because of the imprecision of the techniques, this has often led to various beneficial wild genes eventually, inadvertently being bred out and lost over time. Precision and predictability are important to ensure that the results are safe and achieve their desired ends. There are notable historical examples of the use of older, pre-molecular techniques of genetic modification in agriculture that turned out to be problematic. Examples include theLenape potato, which contained elevated, harmful levels of a plant alkaloid; the creation of hyper-aggressiveAfricanized honeybeesby crossbreeding African and European species in the 1950s; and inadvertently causing some varieties of corn in the United States to becomemore susceptible to the Southern Corn Leaf Blight fungus, which resulted in significant crop losses in 1970.

We emphasize that cisgenesis is aresult, not a technique or technology. Only selected genes are introduced into the cultivar, but not unwanted genes that may be responsible for toxicity or other undesirable traits such as bad taste or lower yield. The easiest way by far to accomplish this is by the use of molecular techniques, such as recombinant DNA technology or gene editing.

If plant breeders try to rewild crops using conventional approaches, they are often faced with linkage drag, in which unwanted, sometimes deleterious genes get passed along with the desired trait. That then requires successive generations of recurrent backcrossing and simultaneous selection to create a cultivar in which the gene of interest is no longer linked to any undesirable genes. This can be a long and slow process, taking many years, depending upon how tightly linked the genes are and the generation time of the plant.

By contrast, cisgenesis isolates only the gene(s) of interest from the donor wild plant, which makes it possible to produce disease-resistant trees, such as apples resistant to fire blight fungus disease, for example, or potatoes resistant to late blight disease. It is particularly appropriate for the lengthy process of tree breeding, as well as for producing vegetative crops such as grape, potato, or banana. Cisgenesis can also facilitate the stacking of resistance genes from several sexually compatible plants, in order to introduce resistance to multiple threats. Also, because the sequences introduced into cisgenic crops are derived from plants that are sexually compatible, the resulting plants are indistinguishable from their traditionally bred counterparts. They contain no foreign sequences, thanks to the use of enzymes that remove selectable marker genes.

Research studies of European consumers acceptance of cisgenic crops have been encouraging, and some have argued that if the category of cisgenic crops, whatever the techniques used to craft t
hem, were deemed acceptable for cultivation by European regulators, that could cause a paradigm shift in regulation. In other words, cisgenics would be a kind of Trojan Horse, opening the way to future deregulation. Thus, there is amovement in some quartersto regulate cisgenic plants crafted with molecular techniques no differently than similar plants made with conventional techniques. Health Canada is expected to announce that policy any day. But even with our current state of knowledge about the seamless continuum of techniques of genetic modification with respect to risk, by regulating gene-edited crops like conventionally modified ones, their food regulators create a meaningless distinction between cisgenic gene editing and transgenic, recombinant DNA modifications.

We find that approach flawed and unpersuasive, because it is unscientific. The mere fact of transgenesis the process of introducing atransgene(i.e. an exogenous gene) from one organism into another so that it exhibits a new, heritable property isunrelated to risk. Moreover, genomic sequencing has revealed that extensive DNA changes occur during conventional breeding, and that some plants such as sweet potato have, over time, incorporated into their own genome fragments of DNA from the pathogenic microorganism Agrobacterium and are thus, in effect, natural GMOs.

Simply stated, whether it encompasses gene editing or not, GMO is an arbitrary and meaningless pseudo category, and regulating it more stringently than conventional breeding makes no sense. Once we spurn science as the basis for regulatory policy, weve relegated ourselves to a game of, How stupid and irrational do we intend to be? In other words, where is the limit on accepting false assumptions?

The science tells us that there is a seamless continuum of genetic modification processes from the natural selection that occurs as the result of Darwinian evolution, including the natural GMOs alluded to above; selection and breeding; mutagenesis; somaclonal variation; wide crosses; recombinant DNA; and gene editing. But many national regulatory agencies continue to ignore this and impose oversight regimes that discriminate against the use of the most precise and predictable techniques, exactly the opposite of what risk analysis dictates. Although a strategy of favoring cisgenics might result in some genetically engineered plants being cultivated in Europe and other countries with stringent regulation of those superior techniques, it would further stigmatize transgenic crops. It would represent expediency over principle.

How do we resolve this regulatory conundrum? There have, in fact, been workable models of scientifically defensible, risk-based approaches to regulation (such as hereandhere), but they have not been widely or comprehensively adopted. Even so, we take the long view that sound science must prevail in crafting regulatory policy. Many of us in the scientific community will settle for nothing less. Forsaking science does not end well.

Henry Miller, a physician and molecular biologist, is a senior fellow at the Pacific Research Institute. He was a Research Associate at the NIH and the founding director of the FDAs Office of Biotechnology. Find Henry on Twitter @henryimiller

Kathleen Hefferon, Ph.D., teaches microbiology at Cornell University. Find Kathleen on Twitter @KHefferon

A version of this article was originally posted at Human Events and has been reposted here with permission. Human Events can be found on Twitter @HumanEvents

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Viewpoint: Canada poised to join expanding number of countries endorsing crop gene editing. That's encouraging but global reform remains elusive -...

Genetic Engineering – Courses, Subjects, Eligibility …

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Genetic Engineering additionally called genetic modification or genetic manipulation is the immediate control of a living being's genes using biotechnology. It is an arrangement of innovations used to change the hereditary forms of cells, including the exchange of qualities inside and across species limits to create enhanced or novel living beings.

Genetic Engineering has been connected in various fields including research, medicine, industrial biotechnology and agriculture. In research, GMOs are utilized to contemplate quality capacity and articulation through loss of function, gain of function, tracking and expression experiments. By thumping out genes responsible for specific conditions it is possible to create animal model organisms of human diseases. And in addition to producing hormones, immunizations and different drug genetic engineering can possibly fix hereditary diseases through quality treatment. Similar strategies that are utilized to create medications can likewise have mechanical applications, for example, producing enzymes for detergents, cheeses and different products.

The ascent of commercialised genetically modified crops has given a financial advantage to agriculturists in a wide range of nations, however, has additionally been the wellspring of a large portion of the debate encompassing the innovation. This has been available since its initial implementation, the primary field trials were destroyed by anti-GM activists. In spite of the fact that there is a logical accord that at presently accessible sustenance got from GM crops represents no more serious hazard to human wellbeing than regular nourishment, GM sustenance security is the main concern with critics.

Genetic engineering is the study of genes and the science of heredity. Genetic engineers or geneticists study living organisms ranging from human being to crops and even bacteria.

These professionals also conduct researches which is a major part of their work profile. The experiments are conducted to determine the origin and governing laws of a particular inherited trait. These traits include medical condition, diseases etc. The study is further used to seek our determinants responsible for the inherited trait.

Genetic engineers or Geneticists keep on finding ways to enhance their work profile depending on the place and organization they are working with. In manufacturing, these professionals will develop new pharmaceutical or agricultural products while in a medical setting, they advise patients on the diagnosed medical conditions that are inherited and also treat patients on the same.

Skill sets for Genetic engineers or Geneticists

Strong understanding of scientific methods and rules

complex problem solving and critical thinking

ability to use computer-aided design (CAD)

graphics or photo imaging

PERL, Python

word processing software programs

excellent mathematical, deductive and inductive reasoning, reading, writing, and oral comprehension skills

ability to use lasers spectrometers, light scattering equipment, binocular light compound microscopes, bench top centrifuges, or similar laboratory equipment

Typical responsibilities of a Genetic Engineering or Geneticist includes:

When a genetic engineer gains a year of experience, one of the regions they can indulge into is hereditary advising, which includes offering data, support and counsel on hereditary conditions to your patients.

An individual aspiring to pursue a professional degree in Genetic Engineering can begin the BTech course after his/her 10+2 Science with Physics, Chemistry, Maths and Biology.

Admission to BTech in Genetic Engineering is made through entrance tests conducted in-house by various universities or through the scores of national engineering entrance examination like JEE for IITs/NITs & CFTIs across the country.

Genetic Engineering professionals require a bachelors or masters degree in Genetic Engineering or Genetic Sciences for entry-level careers. In any case, a doctoral qualification is required for those looking for free research professions. Important fields of study in Genetic Engineering incorporate natural chemistry, biophysics or related fields.

Genetic Engineers require a solid comprehension of logical techniques and guidelines, and in addition complex critical thinking and basic reasoning aptitudes. Phenomenal scientific, deductive and inductive thinking aptitudes, and in addition perusing, composing, and oral cognizance abilities are additionally expected to work in this field.

A semester- wise breakup of the course is tabulated below

SEMESTER I

SEMESTER II

Mathematics 1

Mathematics 2

English

Material Science

Physics

Principles of Environmental Science

Chemistry

Biochemistry

Basic Engineering 1

Basic Engineering 2

-

Cell Biology

-

Value Education

SEMESTER III

SEMESTER IV

Enzyme Technology

Basic Molecular Techniques

Genetics & Cytogenetics

Molecular Biology

Immunology

Stoichiometry and Engineering Thermodynamics

Microbiology

Bio-press Principles

Mechanical Operations & heat Transfer

Biostatistics

German Language Phase 1/French Language Phase 1/Japanese Language Phase 1

German Language Phase 2/Japanese Language Phase 2/French Language Phase 2

-

SEMESTER V

SEMESTER VI

Advanced Molecular Techniques

Recombinant DNA Technology

Functional Genomics and Microarray Technology

Bioinformatics

Momentum Transfer

Chemical Reaction Engineering

Bioprocess Engineering

Gene Therapy

Biophysics

Biosensors and Biochips

Plant Tissue Culture and Transgenic Technology

-

Personality Development

-

SEMESTER VII

SEMESTER VIII

Bio-separation Technology

Project Work

Animal Cell Culture and Transgenic Technology

Bio-Safety, Bio-ethics, IPR & Patients

Nano-biotechnology in Healthcare

-

Stem Cell Biology

-

Aspirants who wish to join the engineering industry as a genetic engineer can apply for the following jobs profiles available:

JOB PROFILE

JOB DESCRIPTION

Genetic Engineer

They apply their knowledge ofengineering, biology, and biomechanical principles into the design, development, and evaluation of biological and health systems and products, such as artificial organs, prostheses, instrumentation, medical information systems, and health care and management.

Lecturer/Professor

They teach at undergraduate and graduate level in areas allocated and reviewed from time to time by the Head of Department.

Research Scientist

They are responsible for designing, undertaking and analyzing information from controlled laboratory-based investigations, experiments and trials.

Scientific/Medical Writer

The research, prepare and coordinate scientific publications. The medical writer is responsible for researching, writing and editing clinical/statistical reports and study protocols, and summarizing data from clinical studies.

Most of the engineering educational institutes shortlist candidates for admission Into BTech in Genetic Engineering course on the basis of engineering entrance exams. These entrance exams are either conducted at the national level like JEE or held in-house by various engineering institutes in the country.

Some of the popular engineering entrance examinations aspirants should consider appearing for admissions to UG and PG level Automobile engineering courses are:

Q. Which college is best for genetic engineering?

A. SRM University Chennai Tamil Nadu, Bharath University Chennai Tamil Nadu, Aryabhatta Knowledge University Patna Bihar, Jawaharlal Nehru Centre for Advanced Scientific Research Bangalore are some of the institutes offering genetic engineering

Q. Is Jee required for genetic engineering?

A. NITs and II
Ts across India does not offer genetic engineering. But there are 23 collages which take admission on the basis of JEE main

Q. What is the qualification for genetic engineering?

A. For admission to BTech Genetic Engineering course, the candidate is needed to have passed the Higher Secondary School Certificate (10+2) examination from a recognized Board of education with Biology, Physics and Chemistry as main subjects with a minimum aggregate score of 60%.

Q. Does IIT offer genetic engineering?

A. No, IIT directly does not offer genetic engineering. Candidates have to take Life Sciences in graduation or Biotechnology from any engineering college in India.

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Genetic Engineering - Courses, Subjects, Eligibility ...

Alexis Battle and Sarah Hrst receive President’s Frontier Awards – The Hub at Johns Hopkins

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BySaralyn Cruickshank

Two Johns Hopkins faculty members have received the university's prestigious President's Frontier Award, which recognizes exceptional scholars who are on the cusp of transforming their respective fields.

In a surprise virtual presentation Monday, JHU President Ron Daniels presented the award to Alexis Battle, an associate professor in the Department of Biomedical Engineering, and Sarah Hrst, an associate professor in the Department of Earth and Planetary Sciences. Both researchers will receive $250,000 to pursue new lines of research, expand their laboratories, or support their lab members.

"Let me take this moment to say how dazzled we were, Alexis and Sarah, by the ambitions and scope of your research and how highly your colleagues, mentors, and students regard each of you," said Daniels in the virtual presentation. "Having a way to honor those qualities in our faculty was a reason why we created this amazing award eight years ago. You both join a cadre of truly remarkable people from across all our divisions whose work truly stands apart."

The President's Frontier Award was originally launched with a commitment of $2.5 million from trustee Louis J. Forster, A&S '82, SAIS '83, and is now paired with a $1 million donation from alumnus David Smilow, A&S '84. Winners have spanned the university's divisions and included molecular biologist Andrew Holland (2021), mathematician Emily Riehl (2020), astrophysicist Brice Mnard (2019), nephrologist and epidemiologist Deidra Crews (2018), composer Michael Hersch (2017), molecular biologist Scott Bailey (2016), and stem cell research Sharon Gerecht (2015).

The award typically recognizes one winner and one finalist each year, but Battle and Hrst were both selected this year based on the strength of their applications and the demonstrated impact and continued potential of their work.

"The two of you embody in some sense the incredible breadth of research that goes on at JHU," said Ed Schlesinger, dean of the Whiting School of Engineering. "From the very smallest genetic materials that define what life is all about to the planets, space, the cosmos, and the search for life beyond our own worldthere is something particularly poetic about the juxtaposition of both of [your work]."

During the presentation, both Battle and Hrst discussed the transformative impact the award would have on their research teams.

"Last night and today, I was thinking, What do I really want to do if I get this award? And I was really laying out some of the exciting things that I'm hoping will happen over the next few years," Battle said. "So that makes me even more excited now, to know those things are going to be possible. I'm so thrilled, and I'm thrilled to see my students thrive even more."

Image caption: Alexis Battle

Image credit: Will Kirk / Johns Hopkins University

Battle is an internationally recognized leader in the field of biomedical engineering whose work has vital implications in the fields of human genetics, computational genomics, and precision medicine. Her research focuses on how genetic variation between individuals leads to changes in gene expression, and how these changes then lead to disease risk and progression. Using machine learning and probabilistic modeling, Battle and her lab create computational models capable of interpreting vast sets of genomics and health data to identify variations in gene expression and follow trends in disease progression caused by these changes in DNA. She has pioneered the use of time-series data to understand the impact of genetic variation at critical time points relevant to disease development.

Her breakthrough computational system, Watershed, holds great promise in the field of personalized genomics. Watershed's advanced modeling system combines personal genetic data and diverse cellular measurements to improve predictions of which genetic sequence differences found in a specific individual will affect that person's health. Applying this system across ancestries, families, and new data types has the potential to improve the diagnosis and treatment of rare diseases.

"There is increasing need for creative computational methods in genomics," wrote Michael Miller, director of the Department of Biomedical Engineering, in a letter nominating Battle for the President's Frontier Award. "Seeing the full impact of genomic data on biological and medical research therefore relies on the type of creative and careful methods development Alexis does."

Battle was a senior leader on the GTEx Consortium Project, a massive multi-institution effort that collected and analyzed thousands of human tissue samples to better understand gene expression. With dozens of principal investigators on studies related to the project, Battle's lab played a central role and she served as a senior author on the project's flagship papers.

Educated at Stanford University, Battle received her BS in symbolics systems and her MS and PhD in computer science. She completed a postdoctoral research specialization in genetics at the Howard Hughes Medical Institute at Stanford. She joined the faculty at Johns Hopkins in 2014 after working as a staff software engineer and engineering manager at Google. She has previously won a Johns Hopkins Catalyst Award (2017), which recognizes early career researchers with a $75,000 grant for their research and creative endeavors, and a Johns Hopkins Discovery Award (2019), which provide grants to cross-divisional teams. She was named a 2016 Searle Scholar and received a 2019 Microsoft Investigator Fellowship. She currently mentors four postdoctoral fellows, one medical fellow, 11 PhD students, and serves as an adviser for three undergraduates in the Department of Biomedical Engineering.

Hrst, a planetary scientist, studies the composition and characteristics of aerosols in the atmospheres of early Earth and other planets. Using laboratory experiments, modeling, and remote sensing and in situ measurements of atmospheric chemistry, Hrst and her lab work to understand how small molecules transition to become aerosols and the resulting physical and chemical properties of those particles.

Image caption: Sarah Hrst

The work has implications for assessing the habitability of other planets and for the search for life beyond our solar system. Under the right conditions, adding energy to simple mixtures of common gases can produce much more complex molecules like amino acids, which form the building blocks of living organisms.

Essential to her work is her groundbreaking approach to laboratory science. Using a custom-built Planetary Haze Research laba one-of-its-kind experimental labHrst and her group simulate the chemical reactions that contribute to the formation of aerosols in planetary atmospheres. With this approach, she can experiment with a vast range of temperatures (90-800 degrees Kelvin, or -297-980 degrees Fahrenheit) and can use different energy sources to initiate chemical reactions across a variety of atmospheric gases and conditions. Her lab is the first in the world to be dedicated to studying photochemical haze production in exoplanet environments, and she has published research on Saturn, Saturn's moon Titan, and early Earth.

Hrst's work is directly relevant to important space missions, including two upcoming NASA missions: Dragonfly, which will investigate prebiotic organic chemistry and habitability on Saturn's largest moon, Titan; and DAVINCI+, which will probe the chemical composition of the atmosphere of Venus.

"Particularly impressive is her ingenuity and creativity in developing and leading a new scientific field essentially from scratch: extrasolar planet atmosphere laboratory studies," wrote Sabine Stanley, a Bloomberg Distinguished Professor and chair of the Department of Earth and Planetary Sciences, in a letter nominating Hrst for the award. "Her work has already had major impact on the global effort to observe and characterize exoplanet atmospheres."

She received the 2020 LA
D Early Career Award from the American Astronomical Society's Laboratory Astrophysics Division and the prestigious 2020 James B. Macelwane Medal from the American Geophysical Union, widely considered the highest honor for early career scientists in the field of geological and planetary sciences. She received a Johns Hopkins Catalyst Award in 2017 and was a co-investigator on a Discovery Award led by Maya Gomes in 2020.

Hrst received two bachelor of science degreesone in planetary science and one in literaturefrom the California Institute of Technology. She received her PhD in planetary sciences from the University of Arizona, Tucson. She joined Johns Hopkins in 2014 and currently mentors three graduate students, two postdoctoral research fellows, and an associate research scientist.

Chris Celenza, dean of the Krieger School of Arts and Sciences, gave Hrst particular praise for her emphasis on mentorship and collegiality.

"I often think that we are at our best in the arts and sciences when we're reciprocally reinforcing conversations among faculty, postdocs, graduate students, and undergraduates," Celenza said during the award presentation. "I know in your lab, you've cultivated that very type of engagement, so I want to thank you, deeply, for all you have done for this wonderful Department of Earth and Planetary Sciences and for Johns Hopkins and for the Krieger School."

Hrst's dedication to her lab members was evident from the moment they "Zoom bombed" the meeting, joining in on the coordinated surprise. "When I saw the names popping up on the screen, all I could think was how much more great science the people who are already working with me are going to get to do," Hrst said through tears. "And that means the absolute world to me."

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Alexis Battle and Sarah Hrst receive President's Frontier Awards - The Hub at Johns Hopkins

Proceeding with Caution | Harvard Medical School – Harvard Medical School

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Click on any icon to hear that co-authors perspective on what the proposed guidelines mean for the region in which they work. Map compiled by Stephanie Dutchen

HMNews: What is the main goal of having a set of international guidelines?

Kendra Sirak: While some countries have developed rigorous standards that guide the scientific analysis of human remains, many others have few or no guidelines that ensure that this work is carried out responsibly and is both scientifically robust and sensitive to community perspectives. Everyone wants practical guidance that will be positive about the research enterprise while embracing high ethical standards.

Its our hope that these guidelines will raise the integrity of ancient DNA research around the world by minimizing damage to collections of human remains; ensuring sensitivity to the perspectives of stakeholder groups, especially when these groups are marginalized; and reducing opportunities for the misuse of results. We expect these guidelines will undergo further development as the field continues to evolve.

HMNews: Why now?

Jakob Sedig: Ancient DNA as a field has been growing rapidly, evolving from a promising technology to a mature field. The discussion about how to handle human remains and how to meaningfully involve diverse stakeholders has not yet caught up. More and more people are calling for clear, strong guidance that all researchers engaged in ancient DNA work can embrace.

Ancient DNA analysis has contributed vital new insights about the human past and has helped us understand the genetic roots of human diversity. It has disrupted nationalist and xenophobic narratives. It has challenged what many of us thought we knew about who we are and where we came from. But like any field that matters, its complex.

Because of the number of ancient individuals being analyzed, the socialand political nature of the work, and the challenges that ancient DNA findings have raised about theories proposed before we had such data, people are paying attention to ancient DNA. That makes it even more vital to articulate and adopt strong guidelines that work well everywhere.

HMNews: How did the team come up with these five guidelines?

Sedig: We took cues from archaeology and modern human genetics, which have established protocols for carrying out analyses on human remains and establishing stakeholder consent. We built on aspects of existing guidelines, such as those crafted by a group of North American scholars, including Indigenous scholars, published last year in the American Journal of Human Genetics.

Our diverse co-author groupparticularly those in Central and South America, Africa, Europe, South Asia, the Pacific, and East Asiafelt that these and other suggestions, while valuable, were not applicable in all world regions. Our virtual workshop led to monthslong discussions that took many different value systems and histories into account and sought balance between local contexts and general principles. We then wrote the manuscript.

Given that there was near-unanimous support and excitement about the final document among the workshop participants, we hope the broader community will embrace and build on these proposals. It would be wonderful if the proposals form a basis for official guidelines in the future.

HMNews: Why not just follow national or local government regulations wherever a project is being conducted?

Sirak: There are some places where laws are robust enough for that to be appropriate, but in other locales, we feel that researchers need to hold themselves to a higher standard than required by the laws currently in place.

HMNews: What are some of the needs and unique circumstances in different regions that shaped the guidelines?

Sirak: We have found that guidelines that work well for one region can come across as condescending or even colonialist in another. Many co-authors on this manuscript raised the point that indigeneity has different meanings in different places and is even used in some regions as a framework for oppression and discrimination against minority groups argued to be non-Indigenous. Thus, basing research ethics on a single definition can inadvertently reinforce rather than mitigate power imbalances in conducting and interpreting genetic analyses.

The videos our co-authors have shared speak to the many nuances of ethical ancient DNA research in the places where they live and work.

HMNews: Some critics say that ancient DNA research, which to a large extent has focused on and been conducted by white people from wealthy nations, has been a colonialist endeavor that siphons agency from marginalized groups. How do the proposed guidelines address these discussions about power and ownership?

Sedig: These are important conversations. We cant reiterate enough that our goal is to learn about the past in a sensitive, thoughtful, and ethical way. We do not want to contribute to exploitation; we want to do the opposite. We need to listen to and respect the people who are stakeholders in ancient DNA studiesincluding groups from the place of origin of the human remains being studiedand make sure their perspectives are represented in discussions about study design, research questions, and whether a project should proceed at all. Theres been a huge amount of progress in recent years in seeking local perspectives from the start to the conclusion of a study and incorporating that feedback into the project and publication. We have increasingly diverse groups of people who conduct the research as well.

We want to minimize harm and reduce inequity, and I believe the ancient DNA community has an extraordinary track record of providing arguments that do so. We know that in regions with histories of settler colonialism, we have to center Indigenous perspectives. We have to confront the colonial legacies of human remains collected in unethical ways and often sent abroad, and we should seek ways to mend the harms done, such as by considering how our research findings or the methods we are using might be helpful tools for facilitating repatriation of remains. We must ensure that local scientists and communities are as engaged as can be in ancient DNA research, particularly in places with histories of scientists conducting exploitative research. Researchers working in countries outside their own must prioritize establishing equitable collaborations that benefit local scholars and avoid carrying out parachute research at all costs.

When possible, those of us in positions of privilege should contribute to reducing structural inequities. Some ideas we propose in the guidelines are to help educate and train local community members and other stakeholders, assist with raising the curatorial standards of collections or developing museum exhibits, provide funds for training or attending professional meetings, and advocate for funding agencies to build more capacity for equitable ancient DNA research. We also need to ensure that we communicate results in ways that are accessible to nonscientists and the broader scholarly community. Lastly, we have to oppose those who use genetic data to support narratives of group superiority or to justify exclusionary policies.

At the same time, as scientists we need to make sure we can proceed in a way consistent with the scientific method. We cant ethically conduct a study without the guarantee that we can follow the data where they lead. This means that once stakeholder communities agree that publishing results would not cause them harm, the relevant portion of a manuscript wont be restricted. It also means the data must be made accessible at least so others can replicate or reevaluate results.

We have a loyalty to the facts we uncover as we learn about our shared humanity. In cases where the data we generate dont align with other forms of knowledge, such as traditional expertise or cultural beliefs, it is not our job to discredit or diminish that knowledge. Rather, those discrepancies highlight how comple
x an undertaking it is to understand the past and should be flagged in papers that result from the work.

Regarding ownership, we believe that whenever researchers are granted permission to study the remains of ancient individuals, they become stewards of that material with a responsibility to care for and respect it. They do not assume ownership of the remainsor of the data that arise from sequencing it.

HMNews: Some groups assert that stakeholder communities should decide whether and how certain kinds of ancient DNA data can be used in future analyses. How does this fit with the teams push for open data?

Sirak: We advocate for stakeholders having input into how data should be distributed and we advocate for open data. We believe that both goals can coexist.

Many of our co-authors felt strongly that ancient DNA data should always be made fully and publicly available. Other co-authors argued that when it comes to data from remains that might be meaningfully connected to present-day Indigenous communities, it could be appropriate to have usage restrictions. This was one of many debates we had, and in listening to one another, some of us changed our positions.

We all agreed that open data for ancient DNA is something to strive for. The data must be made available after publicationeither through full open access, which is ideal, or distributed by a professional organization without a stake in the research resultsso scholars can reproduce or challenge analyses. This also lowers the chances study results will be misused. We are proud that the raw data for nearly all ancient genomes published so far was made publicly available at or before the time of publication.

Finally, we agreed that Indigenous-led data repositories such as those now being developed could help mediate permissions when scholars wish to use data for purposes beyond those articulated in an original study plan.

HMNews: Given that equity is a priority, how accessible will this paper be to those who, for example, dont have paid access to the journal in which its being published or who arent fluent in English?

Sirak: Weve made our paper open access and applied the most flexible Creative Commons license to it, known as CC BY 4.0. That means its available for free to anyone in the public to read, distribute, adapt, and build upon. Our team members also have translated the text into more than 20 languages that they speak.

HMNews: Do you expect pushback from scientists who feel that the guidelines are too onerous and will make it harder to carry out research?

Sedig: We did receive feedback during the review process that the guidelines were too strongthat they would create a heavy burden for researchers from smaller labs or who are in the early stages of their careers. We respect this perspective and understand that were requesting a lot in terms of engaging with stakeholders and what could be called overhead beyond the research itself. However, we firmly believe that all ancient DNA studies, from an early-career stage onwards, should meet these ethical standards.

In a way, the proposals are merely concretizing the standards that are already emerging in the field. We believe that authors and journal editors feel their way toward this ethical framework during the review process. We believe that the proposals are practical and that early-career researchersincluding many who co-authored our articlewill benefit from having the principles clearly articulated and the guesswork reduced as they aim to carry out their research in an ethically principled way.

HMNews: What enforcement would there be if someone involved in ancient DNA research didnt follow these guidelines?

Sirak: Our co-authors do not represent any official organization, so we cannot make or enforce rules for anyone except ourselves. What our paper does represent is a grassroots, community-led pledge from representatives of a nontrivial faction of worldwide researchers engaged in this type of work. We have committed to adhering to a set of strong principles, and we invite others to hold us accountable to them.

It would be a great outcome if scientific journals, professional societies, or granting agencies found these proposals useful enough to turn into official guidelines, which would mean there could be professional repercussions for not adhering to them. The fact that scholars from such a diverse array of nations and disciplines have signed on to the guidelines at this stage makes us optimistic that they will be embraced in practice by laboratories and research groups as well as other groups engaged in ancient DNA research all over the world. But either way, its important to continue the global conversation.

This work was supported by the Australian Research Council Discovery Project (DP160100811), National Research Foundation South Africa, Brazilian National Council for Scientific and Technological Development (302163/2017-4), So Paulo Research Foundation/FAPESP (2018/23282-5), Francis Crick Institute (FC001595), Cancer Research UK, UK Medical Research Council, Wellcome Trust, Dutch Research Council (VI.C.191.070), Hungarian Academy of Sciences, Science and Engineering Research Board of India, Council of Scientific and Industrial Research in India (Ministry of Science and Technology, Government of India), European Research Council (ERC-2017-StG 804844-DAIRYCULTURES), Werner Siemens-Stiftung, John Templeton Foundation (6122), Howard Hughes Medical Institute, Max Planck Society, and the Max Planck Harvard Research Center for the Archaeoscience of the Ancient Mediterranean, and the National Geographic Society.

Interviews were edited for length and clarity.

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Proceeding with Caution | Harvard Medical School - Harvard Medical School

Human-Chimp Similarity: What Does It Mean? – Discovery Institute

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Image credit: Hannes Richter viaUnsplash.

For years weve been told that human and chimp DNA is some 99 percent identical. The genetic similarity statistic is then used to make an argument for human-ape common ancestry, and human-ape common ancestry is then employed in service of the larger philosophical point that humans are just modified apes, and nothing special. It all amounts to an argument against human exceptionalism. This sort of thinking is embodied by Bill Nye (The Science Guy) in his 2014 bookUndeniable:

As our understanding of DNA has increased, we have come to understand that we share around 98.8 percent of our gene sequence with chimpanzees. This is striking evidence for chimps and chumps to have a common ancestor.

BioLogos-affiliated biologist Dennis Venemahas also arguedthat we are but a hand-breadth away from our evolutionary cousins at the DNA level. But is this really true? In response to the newly released episode ofScience Uprisingon human origins, we have recently received questions about the true degree of human-chimp similarity. With that in mind, lets review some past coverage on the issue.

In 2007, not long after the chimp genome was first sequenced, the journalSciencepublished an article, Relative Differences: The Myth of 1%, which called the idea that humans are only 1 percent genetically different from chimps a myth and a truism [that] should be retired. It observed that the genetic differences between humans and chimps amount to 35 million base-pair changes, 5 million indels [sequences of multiple nucleotide bases] in each species, and 689 extra genes in humans. The article further reported that if we consider the number of copies of genes in the human and chimp genomes, human and chimpanzee gene copy numbers differ by a whopping 6.4%.

The old statistic that we are about 99 percent or 98 percent similar to chimps pertains only to alignable protein-coding sequences. In fact the statistic first originated based upon similarity between humans and chimps in just one single gene! But many non-coding sequences are highly dissimilar, and there are sequences of the human and chimp genomes that are so different that they cant be aligned for comparison. For example, there are some parts of our genome, such as thehuman y chromosome, that are radically different from the chimp genome.

Geneticist Richard Buggs has tried to refine the methods for comparing human and chimp genomes. In a 2018 post, he observesthat The percentage of nucleotides in the human genome that had one-to-one exact matches in the chimpanzee genome was 84.38%. In 2020 he co-published anarticle in the journalFrontiers in Geneticsproviding a different method of estimating of human-chimp genetic differences, finding that human-chimp genetic similarity is about 96 percent. This papers estimate of ~4 percent genetic difference includes both coding and non-coding DNA, but it does not include centromeric DNA. If that DNA were included, the percent of genetic similarity between humans and chimps could drop to as low as ~93 percent, but probably not lower. Computational biologist Steve Schaffner has roughly estimated human-chimp genetic similarity to be ~95 percent. However, one criticism Ive heard of all current estimates is that they are based upon versions of the chimp genome that used the human genome as a scaffolding, potentially making certain sections of the chimp genome more humanlike than they ought to be. This could also artificially inflate the degree of human-chimp similarity.

What this means is that until more accurate and complete versions of the chimp genome are produced, any estimate of human-chimp genetic similarity will undoubtedly be refined in the future, and current numbers may very well be overestimates. Nonetheless, any of the above estimates of human-chimp genetic similarity 96 percent, 95 percent, 93 percent, 84 percent carries meaning in different contexts. But what exactly do they mean?

Whatever the exact percentage of human-chimp genetic similarity (however you want to measure it) turns out to be, lets grant that it will be fairly high, probably 84 percent or greater. Does this necessarily require the conclusion of common ancestry? Is the case for common ancestry, based upon the degree of similarity, an objective or rigorous argument thats capable of being falsified? For example, if a 1 percent genetic difference implies common ancestry, but then that statistic turns out to be wrong, then does a 4 percent genetic difference mean common ancestry is false? How about 7 percent or 10 percent genetic difference? 25 percent? At what point does the comparison cease to support common ancestry? Why does the percent genetic similarity even matter? Its not clear that there is an objective standard for falsification here, any identifiable reason why a particular percentage of genetic similarity should be taken to indicate common ancestry.

Indeed, Dennis Venema even seems to acknowledge this point, writing in 2018:

No one is more interested in the % genome identity thing than folks trying to cast doubt on common ancestry. Its just not a precise value that scientists are interested in, because it doesnt answer interesting scientific questions in the way other values do (emphasis added)

Thats quite a bold quote from Professor Venema when earlier he was seen emphasizing how humans are a mere genetic hand-breadth away from chimps, as part of a case for common ancestry. This is in keeping with numerous other evolution apologists over the years who have cited the 1% statistic in favor of human-chimp common ancestry. They are the ones who invented and promoted this fallacious argument, and we are simply responding to it. Yet somehow us Darwin-skeptics get blamed for spreading a fallacious argument.

Perhaps Dr. Venema has changed his mind about the import of the statisticwhich he is fully entitled to do. Whatever the case, we agree with his point here that the % genome identity provides no rigorous argument for common ancestry and does not answer very many interesting questions within this particular debate.

The case for human-chimp common ancestry is further significantly weakened once one realizes that there are other potential explanations for functional similarities: notably, design based upon a common blueprint.

Intelligent agents often re-use parts and components that perform common functions in different designs. Its a good engineering design principle to follow! Everyday examples of this include wheels used on both cars and airplanes, or touchscreen keyboards used on both phones and tablets.

It should be noted that common design, as an argument, is not intended to prove species were specially created or designed separately. Rather, its a rejoinder put forth to defeat the evolutionist assertion that genetic similarity necessarily indicates common ancestry. Genetic similarity doesnt necessarily indicate common ancestry because intelligent agents can and do independently use common parts in different designs to fulfill common functional goals. High genetic similarity could reflect design with a common blueprint rather than common ancestry.Biologist Ann Gauger, mathematician Ola Hssjer, and statistician Colin Reevesexplain this wellin Chapter 15 of the 2017 bookTheistic Evolution:

[T]here are some basic differences between the way evidence is approached by evolutionary biologists and design biologists. The chief assumption made by evolutionary biologists is that the genetic changes responsible for evolutionary change are random, and therefore, if a group of species share a trait in common that is not found in other related species, it is presumed that the common ancestor of the group developed that trait, and they all share it because of common descent. On the other hand, if genetic change is directed rather than random,the trait is most likely shared because the organisms use similar solutions to a physiological need.

Humans and chimps thus have similarities that reflect functional constraints due to design bas
ed upon a common blueprint. Gauger and her team indicate what this means for some of the basic molecular, cellular, metabolic, and physiological similarities between humans and chimps:

First, our basic building blocks, the proteins out of which our cells are made and the enzymes that carry out cellular metabolism, are very similar to those of chimpanzees, almost identical in many cases. One can think of our genes as being like the bricks and mortar, nails and wood, shingles and wires out of which houses are made. Two houses may look different but be composed of the same basic building blocks. By analogy, the building blocks out of which we are made, the genes, are very similar for chimps and humans, even if our bodily forms are different.

Second, the vast majority of our DNA does not code for protein but functions like an operating system, determining what files (genes) should be used when, and where. The routine processes of life are carried out by this operating system, and we share these basic routines with chimps. Thus in many respects our operating systems are the same as those of chimps.

Of course some will cite shared NON-functional (as opposed to functional) genetic similarities between humans and chimps as better evidence for common ancestry. I agree that non-functional shared DNA could be a potential argument for common ancestry, but Im skeptical that many of the DNA elements cited in these arguments are actually non-functional. Aswe saw recently, a new paper inGenome Biology and Evolutiondeclared, The days of junk DNA are over. Even pseudogenes, commonly cited as a form of genetic junk that supports common ancestry, have had their junk status severely questioned in recent years seehere,here,here,here, andherefor discussions.

Since many of the building blocks used by humans and chimps are similar, its no wonder that our protein-coding DNA is also so similar. Common design can explain these similarities. But its important to bear in mind that one can use identical building blocks bricks, mortar, wood, and nails to build very different houses. So its not just about having similar building blocks, but how you use them. This is where genetic similarities between humans and chimps probably arent so meaningful, when you consider how the building blocks being used can be very different.

Gauger and her colleagues thus explain that the percentage of nucleotide similarity does not tell the whole story about human-chimp genetic differences since many of the most crucial differences lie outside the protein-coding DNA:

[C]ounting raw difference is not the best way to calculate how different we are genetically speaking We now know that when, where, and how our DNA is used matters much more than an overall count of nucleotide differences. Human-specific differences in gene regulation, as we will see, are what make us unique.

They recount some of the crucial differences between humans and chimps:

And this leaves aside the vast cognitive and behavioral gulf between humans and chimpanzees. We are the only species that uses fire and technology. We are the only species that composes music, writes poetry, and practices religion. We are also the only species that seeks to investigate the natural world through science. We write papers about chimps; not the other way around. All of this is possible because we humans are the only species that uses complex language.

The human race has unique and unparalleled moral, intellectual, and creative abilities. Regardless of the level of similarity of human protein-coding DNA to chimps, clearly that similarity is only a small part of the story. If anything, it testifies that protein-coding DNA sequences are only one of multiple crucial interacting factors that determine an organisms biology and behavior.

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Human-Chimp Similarity: What Does It Mean? - Discovery Institute

UT Southwestern Team Awarded $8.8M to Participate in Genomic Variation Consortium Dallas Innovates – dallasinnovates.com

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Left to right: Gary Hon, Ph.D., UTSW Assistant Professor of Obstetrics and Gynecology; Nikhil Munshi, M.D., Ph.D., Associate Professor of Internal Medicine and Molecular Biology; W. Lee Kraus, Ph.D., Professor and Director of the Cecil H. and Ida Green Center for Reproductive Biology Sciences

The Human Genome Project identified and mapped all of the genes of the human genome, achieving the worlds largest international, collaborative biological project. That opened the door to a wide array of innovative research projectsincluding a prestigious one that UT Southwestern has just joined.

A team ofUT Southwestern faculty led by Gary Hon, Ph.D.,has been awarded a five-year, $8.8 million grant to participate in the National Human Genome Research Institutes Impact of Genomic Variation on Function (IGVF) Consortium. The consortiums goal is understanding how developmental variants contribute to developmental diseases.

Dr. Hon is an assistant professor of obstetrics and gynecology in the Cecil H. and Ida Green Center for Reproductive Biology Sciences and a member of the Lyda Hill Department of Bioinformatics.

Hon developed Mosaic-seq, a genome engineering technique that helped lead to the awarding of the $8.8 million grant. In a statement, he saidthe IGVF Consortium is the National Human Genome Research Institutes next step to unveiling the genomes role in disease.

The Human Genome Project told us that most of the genome doesnt contain genes, Hon said. One big surprise from genome-wide association studies is that gene-poor regions contain many disease signatures.

It turns out that the signatures largely overlap with DNA elements, found by the Encyclopedia of DNA Elements (ENCODE) Consortium, that control when genes turn on, Hon added. The goal of this consortium is to fill in the gaps, linking DNA sequences to genes, cell phenotypes, and disease. Ultimately, this knowledge will allow us to interpret the disease potential of any persons genome sequence.

In their work with the consortium, the UTSW teamwill combine molecular biology, genomics, high throughput screens, and computational analyses to focus on potential disease-causing genetic variations in the cardiovascular, nervous, and placental systems.

Besides Hon, the teamalso includes principal investigators Nikhil Munshi, M.D., Ph.D., associate professor of internal medicine and molecular biology, and W. Lee Kraus, Ph.D., professor and director of the Green Center.

Mosaic-seq allows high throughput analysis of the molecular events that occur during programming of embryonic stem cells into other cell types. This technique uses single-cell sequencing to study different regions of the genome at the same time.

Just one experiment can perturb thousands of regions in the genome to better understand their function, according to the UTSW team.

With Mosaic-seq, researchers no critical have to study one region at a time. Hons lab received national attention in 2017 for this significant advance, which was part of his teams grant application.

UTSW now joins Harvard, Stanford, and Yale universities as one of the 30 research sites taking part in the IGVF Consortium nationwide.The consortium will study noncoding regions of the human genome that are known to contribute to genetic diseasesincluding congenital heart disease, autoimmune disease, and blood disorders.

Dr. Kraus, a professor of obstetrics and gynecology and pharmacology who holds the Cecil H. and Ida Green Distinguished Chair in reproductive biology sciences, will use additional CRISPR-based technologies in the consortium research project. Kraus will use them to study how genetic variation in non-coding RNAs originating from the regulatory elements impacts the development of the placenta.

The placentas development is important because it supports the human fetus as it grows, as well as the fetuss heart and central nervous system.

Studying the role of genetic variation in the embryonic development of these key organs could point the way to understanding human diseases in adults, Kraus said in the statement.

Dr. Munshi believes the IGVF Consortium initiativecould potentially fill in huge pieces of the puzzle for many diseases.

If we candetermine all of the noncoding elements in the genome that impact a particular developmental pathway, then those could become candidates fordisease-associated mutations, Munshi said.

By generating catalogs of tens of thousands offunctionalvariants, we dont have to search the billons of basepairs to find where thedisease-causingmutations might lie, he added. We can really focus the search on thesetens of thousands of variants. It really gives us an encyclopediatonarrow the search.

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In partnership with the Southwestern Medical Foundation, the Cary Council awarded $50K grants to each of its three 2021 young "DocStars." On a recent "What's Up Doc?" virtual event, the young investigators spoke about how their research projects are going, what they hope to achieveand why the seed grants are a catalyst for medical innovation.

Animation and game design is boomingand UTD is on theforefront. Here's how its School of Arts, Technology, and Emerging Communication has become a national leader. ATEC is producing graduates who go on to workfor top companieslike Blizzard Entertainment, Gearbox Software, id software, Disney, and 900lbs.

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UT Southwestern Team Awarded $8.8M to Participate in Genomic Variation Consortium Dallas Innovates - dallasinnovates.com

Science, industry team up in Italy to zap virus with laser – Reuters

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A rendering of an air purifier prototype developed by Italian tech company Eltech K-laser is seen in this image obtained by Reuters on June 30, 2021. Eltech K-Laser/Handout via REUTERS

ROME, July 2 (Reuters) - A United Nations-backed scientific research centre has teamed up with an Italian tech firm to explore whether laser light can be used to kill coronavirus particles suspended in the air and help keep indoor spaces safe.

The joint effort between the International Centre for Genetic Engineering and Biotechnology (ICGEB) of Trieste, a city in the north of Italy, and the nearby Eltech K-Laser company, was launched last year as COVID-19 was battering the country.

They created a device that forces air through a sterilization chamber which contains a laser beam filter that pulverizes viruses and bacteria.

"I thought lasers were more for a shaman rather than a doctor but I have had to change my mind. The device proved able to kill the viruses in less than 50 milliseconds," said Serena Zacchigna, group leader for Cardiovascular Biology at the ICGEB.

Healthy indoor environments with a substantially reduced pathogen count are deemed essential for public health in the post COVID-19 crisis, a respiratory infection which has caused more than four million deaths worldwide in barely 18 months.

Zacchigna hooked up with Italian engineer Francesco Zanata, the founder of Eltech K-Laser, a firm specialised in medical lasers whose products are used by sports stars to treat muscle inflammation and fractures.

Some experts have warned against the possible pitfalls of using light-based technologies to attack the virus that causes COVID-19.

A study published by the Journal of Photochemistry & Photobiology in November 2020 highlighted concerns ranging from potential cancer risks to the cost of expensive light sources.

But Zacchigna and Zanata dismissed any health issues, saying the laser never comes into contact with human skin.

"Our device uses nature against nature. It is 100% safe for people and almost fully recyclable," Zanata told Reuters.

The technology, however, does not eliminate viruses and bacteria when they drop from the air onto surfaces or the floor. Nor can it prevent direct contagion when someone who is infected sneezes or talks loudly in the proximity of someone else.

Eltech K-Laser has received a patent from Italian authorities and is seeking to extend this globally.

The portable version of the invention is some 1.8 metres (5.9 ft) high and weighs about 25 kg (55 lb). The company said the technology can also be placed within air-conditioning units.

In the meantime, the first potential customers are lining up, including Germany's EcoCare, a service provider of testing and vaccination solutions.

"The company aims to license the technology for German and UAE markets," an EcoCare spokesperson said in an email to Reuters.

Reporting by Giselda Vagnoni; Editing by Crispian Balmer, William Maclean

Our Standards: The Thomson Reuters Trust Principles.

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Science, industry team up in Italy to zap virus with laser - Reuters

Synthetic auxotrophy remains stable after continuous evolution and in coculture with mammalian cells – Science Advances

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Abstract

Understanding the evolutionary stability and possible context dependence of biological containment techniques is critical as engineered microbes are increasingly under consideration for applications beyond biomanufacturing. While synthetic auxotrophy previously prevented Escherichia coli from exhibiting detectable escape from batch cultures, its long-term effectiveness is unknown. Here, we report automated continuous evolution of a synthetic auxotroph while supplying a decreasing concentration of essential biphenylalanine (BipA). After 100 days of evolution, triplicate populations exhibit no observable escape and exhibit normal growth rates at 10-fold lower BipA concentration than the ancestral synthetic auxotroph. Allelic reconstruction reveals the contribution of three genes to increased fitness at low BipA concentrations. Based on its evolutionary stability, we introduce the progenitor strain directly to mammalian cell culture and observe containment of bacteria without detrimental effects on HEK293T cells. Overall, our findings reveal that synthetic auxotrophy is effective on time scales and in contexts that enable diverse applications.

New safeguards are needed for the deliberate release of engineered microbes into the environment, which has promise for applications in agriculture, environmental remediation, and medicine (1). Genetically encoded biocontainment strategies enable attenuation of engineered live bacteria for diverse biomedical applications (24), including as potential vaccines (510), diagnostics (11), and therapeutics (1215). Auxotrophy, which is the inability of an organism to synthesize a compound needed for its growth, is an existing strategy for containment. However, foundational studies of auxotrophic pathogens demonstrated proliferation in relevant biological fluids (16) and reversion to prototrophy upon serial passaging (17, 18). Modern genome engineering strategies can prevent auxotrophic reversion, and auxotrophy has been a key component of microbial therapies that have reached advanced clinical trials. However, the ability for auxotrophs to access required metabolites within many host microenvironments, and after leaving the host, remains unaddressed. Auxotrophy may not be effective in scenarios where engineered living bacteria encounter metabolites from dead host cells (19) or invade host cells (20). Growth of double auxotrophs is supported in vivo by neoplastic tissue (13). Auxotrophy may also be insufficient for tight control of cell proliferation in environments rich with microbial sources of cross-feeding (21), such as gut, oral, skin, and vaginal microbiomes. Given that most naturally occurring microorganisms are auxotrophs (22), it is also unlikely that auxotrophy will limit the spread of an engineered microbe once it leaves the body and enters the environment.

Synthetic auxotrophy may overcome these hurdles by requiring provision of a synthetic molecule for survival of the engineered bacteria. This strategy was first implemented successfully in Escherichia coli by engineering essential proteins to depend on incorporation of a nonstandard amino acid (nsAA) (23, 24). We previously engineered E. coli strains for dependence on the nsAA biphenylalanine (BipA) by computer-aided redesign of essential enzymes in conjunction with expression of orthogonal translation machinery for BipA incorporation (23). Among several synthetic auxotrophs originally constructed, one strain harbored three redesigned, nsAA-dependent genesadenylate kinase (adk.d6), tyrosyl-tRNA synthetase (tyrS.d8), and BipA-dependent aminoacyl-tRNA synthetasefor aminoacylation of BipA (BipARS.d6). This BipA-dependent strain, dubbed DEP, exhibited undetectable escape throughout 14 days of monitoring at an assay detection limit of 2.2 1012 escapees per colony-forming unit (CFU) (23). Although this strain demonstrates effective biocontainment in 1-liter batch experiments, its precise escape frequency and long-term stability remained unexplored.

Here, we perform the first study of evolutionary stability of a synthetic auxotroph with the aid of automated continuous evolution. Continuous evolution better emulates scenarios where biocontainment may be needed by fostering greater genetic variability within a population. We posited that decreasing BipA concentrations would add selective pressure for adaptation or for escape, either of which would be enlightening. Adaptive laboratory evolution of DEP may improve its fitness in relevant growth contexts, as previously demonstrated for its nonauxotrophic but recoded ancestor, C321.A (25). We report that DEP maintains its inability to grow in the absence of synthetic nutrient, even after three parallel 100-day chemostat trials. In addition, we find evidence of adaptation, with evolved DEP isolates requiring 10-fold lower BipA concentration to achieve optimal growth than ancestral DEP (0.5 M rather than 5 M). We resequence evolved populations and perform allelic reconstruction in ancestral DEP using multiplex automatable genome engineering (MAGE), identifying alleles that partially restore the adaptive phenotype. Last, we advance this technology toward host-microbe coculture applications, demonstrating direct mixed culture of DEP and mammalian cells without the need for physical barriers or complex fluidics.

To perform continuous evolution of E. coli, we constructed custom chemostats for parallelized and automated culturing (Fig. 1A). Our design and construction were based on the eVOLVER system (26), an open-source, do-it-yourself automated culturing platform (figs. S1 to S4). By decreasing BipA concentration over time in our chemostats, we provide an initial mild selection for escape and steadily increase its stringency. This design is analogous to a morbidostat, where a lethal drug is introduced dynamically at sublethal concentrations to study microbial drug resistance (27), but with synthetic auxotrophy providing selective pressure. Our working algorithm for automated adjustment of BipA concentration as a function of turbidity is shown in Fig. 1B, and a representative image of our hardware is shown in Fig. 1C (see also fig. S5).

(A) Illustration of a smart sleeve connected to separate nonpermissive media and biphenylalanine (BipA; structure shown in blue) feed lines for automated adjustment of BipA concentration based on growth rate. Pumps and optics are integrated with Arduino controller hardware and Python software based on the eVOLVER do-it-yourself automated culturing framework. (B) Working algorithm for maintenance of cultures in continuous evolution mode. Criteria for lowering the BipA concentration are based on the difference in time elapsing between OD peaks (tpeak OD). Smaller time elapsed between OD peaks is indicative of higher growth rates, triggering decrease in BipA concentration when below a threshold value. (C) Representative configuration of hardware for parallelized evolution in triplicate, with three empty sleeves shown. Photo credit: Michael Napolitano, Harvard Medical School.

Our long-term culturing experiments featured two phases. The first phase included one chemostat (N = 1) that was inoculated with DEP for an 11-day incubation, with an initial concentration of BipA of 100 M and automated adjustment based on growth rate (Fig. 2A). Because we observed no colony formation when the outgrowth from this population was plated on nonpermissive media, we then began a second phase in replicate. We used our population grown for 11 days to inoculate three chemostats in parallel (N = 3) where BipA supply decreased automatically over the following 90 days from 100 M to nearly 100 nM. One controller provided identical BipA concentrations to all three vials at any given time. To determine whether the decrease in BipA supply was due to escape from dependence on BipA, we periodically performed escape assays. We continued to observe no escape, including when we seeded liter-scale cultures and plated the associated outgrowth on nonpermissive media. Evolved isolates were obtained after this procedure (fig. S6), and th
eir growth was characterized across BipA concentrations (Fig. 2B and fig. S7). At 0.5 to 1 M BipA, we observed growth of all evolved isolates and no growth of the ancestral DEP strain.

(A) Timeline for continuous evolution, with detection limits for escape frequency assays shown in parentheses. (B) Doubling times of progenitor and evolved synthetic auxotrophs as a function of BipA concentration, normalized to the doubling time of DEP at 100 M BipA. Error bars represent the SD across technical triplicates within the same experiment.

To identify the causal alleles contributing to decreased BipA requirement of all three evolved isolates, we performed whole-genome sequencing and mutational analysis. We expected that mutations in auxotrophic markers or orthogonal translation machinery associated with aminoacylation of BipA would be observed. However, no variants were detected in the plasmid-expressed orthogonal translation machinery (aminoacyl-tRNA synthetase and tRNA) reference sequence. Instead, in all three evolved isolates, variants were observed in three nonessential genes, all of which are implicated in molecular transport: acrB, emrD, and trkH (Fig. 3A). AcrB and EmrD are biochemically and structurally well-characterized multidrug efflux proteins (28), and TrkH is a potassium ion transporter (29). These exact mutations have no precedent in the literature to our knowledge. Because they are missense mutations or in-frame deletions, it is unclear whether they cause loss of function or altered function (table S1). Because permissive media contain four artificial targets of efflux (BipA, l-arabinose, chloramphenicol, and SDS), mutations that confer a selective advantage during continuous evolution could disable BipA/l-arabinose efflux, improve chloramphenicol/SDS efflux, or affect transport of these or other species more indirectly. Given the strong selective pressure enforced by decreasing BipA concentration, we hypothesize that mutations observed are more likely to affect BipA transport. We also observed mutations in all evolved populations to the 23S ribosomal RNA (rRNA) gene rrlA (table S2). 23S rRNA mutations have been found to enhance tolerance for D-amino acids (30) and -amino acids (31). However, 23S rRNA mutations could also be related to increased tolerance of chloramphenicol (32).

(A) List of alleles identified through next-generation sequencing. Sequencing results originally obtained during the project identified this EmrD allele as a 33-bp deletion, which was then reconstructed in the experiment shown in (B). However, resequencing performed at the end of the project identified the allele as a 39-bp deletion and was confirmed by Sanger sequencing. A repetitive GGCGCG nucleotide sequence corresponding to G323-A324 and G336-A337 creates ambiguity about the precise positional numbering of the deletion. However, the three possible 13amino acid deletions (323335, 324336, and 325337) result in the same final protein sequence. (B) Effect of reconstructed allele in DEP progenitor on doubling time as a function of BipA concentration, normalized to the doubling time of DEP at 100 M BipA. Error bars represent the SD across technical triplicates within the same experiment.

To learn how identified transporter alleles may contribute to increased growth rates at low BipA concentration, we performed allelic reconstruction in the progenitor DEP strain using MAGE (33). Among four mutants that we generated in DEP, we observed growth of all mutants at 2 M BipA, a condition in which progenitor DEP could not grow (Fig. 3B and fig. S8). Furthermore, only emrD mutants exhibited near-normal growth at 1 M BipA. To investigate possible differential sensitivity of strains that contain reconstructed alleles to other media components of interest (SDS, l-arabinose, tris buffer, and chloramphenicol), we varied the concentration of these components and measured doubling times (fig. S9). We observed no significant deviation in doubling time from DEP in any of these cases. These results collectively suggest that observed transporter alleles are linked to BipA utilization.

The unobservable escape of DEP even after 100 days of evolution encouraged us to explore the possibility of an improved in vitro model for host-microbe interactions. In vitro models allow direct visualization and measurement of cells and effectors during processes such as pathogenesis (34). They are more relevant than animal studies for several human cell-specific interactions due to biological differences across animal types (35, 36). A nonpathogenic E. coli strain engineered to express heterologous proteins could be particularly useful for studying or identifying virulence factors and disease progression. However, an obstacle associated with coculture of microbial and mammalian cells is microbial takeover of the population. Approaches used to address this are bacteriostatic antibiotics (37), semipermeable Transwell membranes (3840), microcarrier beads (41), microfluidic cell trapping (42), peristaltic microfluidic flow (43, 44), and microfluidic perfusion (45). However, the use of a well-characterized synthetic auxotroph capable of limited persistence could offer a superior alternative for spatiotemporal control of microbial growth, especially for studying longer duration phenomena such as chronic infection or wound healing. Our study demonstrates how temporal control can be achieved by removal of BipA; we anticipate that spatial control could be achieved by patterning BipA onto a variety of solid surfaces with limited diffusion, such as a skin patch.

We investigated mammalian cell culture health, growth, and morphology after simple transient exposure to a hypermutator variant of DEP that we engineered by inactivating mutS during allelic reconstruction (DEP*). The use of DEP* rather than DEP is yet another form of a stress test to increase opportunity for escape under coculture conditions. We directly cocultured adherent human cell line human embryonic kidney (HEK) 293T with either no bacteria, nonauxotrophic E. coli DH5, or DEP* overnight (24 hours). HEK293T cells were cultured in selection media that allow only growth of desired but not contaminant strains while selecting for bacterial plasmid maintenance. After coculture, we washed cells and replenished cells with media varying in inclusion of BipA and/or an antibiotic cocktail (penicillin/streptomycin/amphotericin B). We continued incubation and imaged cells at days 2, 4, and 7 after initial coincubation. HEK293T cells contain a copy of mCherry integrated into the AAVS1 locus, and they appear red. DH5 and DEP* were transformed with Clover green fluorescent protein before coculture and appear green.

Compared to the control culture where bacteria were not added (Fig. 4A), HEK293T cells cocultured with DH5 display visible bacterial lawns with no attached human cells in the absence of the antibiotic cocktail at all days of observation (Fig. 4B). In the presence of antibiotic, cocultures containing DH5 sharply transition from bacterial overgrowth to apparent bacterial elimination (Fig. 4C). In contrast, cells cocultured with DEP* in the absence of BipA exhibited similar morphology to the control at all days of observation and no detectable bacteria by fluorescence microscopy on day 7, without the need for antibiotics to achieve bacterial clearance (Fig. 4D). Thus, DEP* addition was not detrimental to HEK293T cells in the absence of BipA, and DEP* remains biocontained and cannot survive because of cross-feeding. Clearance of bacterial cells from human cells appears to occur faster for DEP* when not provided BipA (Fig. 4D) than for DH5 when provided with the antibiotic cocktail (Fig. 4C).

Bacteria were added to HEK293T cell cultures and coincubated for 24 hours before washing and replenishing media. HEK293T cells express mCherry, whereas bacterial cells express Clover green protein marker. Images were taken at days 2, 4, and 7 after coincubation. (A) Untreated HEK293T cells. (B) HEK293T with commercial E. coli DH5 in the absence of antibiotic cocktail. (C) HEK293T with DH5 in presence of antibioti
c cocktail. (D) HEK293T and DEP* (mismatch repair inactivated to create hypermutator phenotype) in the absence of BipA. (E) HEK293T cells and DEP* in the presence of BipA. (F) HEK293T and DEP* in the absence of BipA until day 2 [identical at this point to condition in (D)], and then 100 M BipA was added to this condition daily until day 7.

To learn how the synthetic auxotroph behaves when supplied its essential nutrient in these coculture settings, we tested DEP* cocultures with continual resupply of 100 M BipA. Here, DEP* proliferates and in turn decreases proliferation and viability of HEK293T cells (Fig. 4E). A bacterial lawn begins to form on day 2, and at later times, human cell debris is overtaken by DEP*. This demonstrates that DEP* is fully capable of taking over the coculture if supplied with BipA. Replicates for these experiments can be found in figs. S10 to S12.

Given that DEP* grows in cocultures when BipA is provided, we sought to understand whether it could be rescued by readdition of BipA after multiple days of withholding. The possible time scale of reemergence influences applications where the duration of bacterial activity would need to be prolonged and/or repeated via limited BipA introduction while remaining contained. We find that coculturing DEP* with HEK293T cells for 2 days in the absence of BipA followed by the addition of BipA at day 2 does not rescue the DEP* growth (Fig. 4F and fig. S13). Human cells still grow and look morphologically similar to untreated cells, and bacteria are not visible. To look at analogous questions for nonauxotrophic E. coli, we removed antibiotics after 2 days of coculturing and do not observe bacterial rescue (fig. S13). We also investigated whether bacterial clearance could be delayed by the addition of antibiotic after some growth of DH5. DH5 cells grown in the absence of the antibiotic cocktail for 2 days before addition of the cocktail and maintenance to day 7 result in bacterial lawns (fig. S13, A and D). This demonstrates that antibiotic cocktails ordinarily used in mammalian cell culture maintenance can become ineffective beyond a certain amount of nonauxotrophic bacterial growth, whereas synthetic auxotrophy is subject to fewer and different constraints.

To further investigate the persistence of progenitor DEP and its evolved descendants, we performed BipA readdition studies in Lennox lysogeny broth (LB-Lennox) monoculture. Within 7 hours of BipA removal, DEP cell populations that are harvested from midexponential or stationary phases can be reactivated upon delayed BipA addition with unperturbed growth kinetics after a highly tunable lag phase (fig. S14). Further studies are ongoing to investigate the amount of time after which BipA reintroduction can recover growth of synthetic auxotrophs under different contexts.

We have shown that synthetic auxotrophy can exhibit long-term stability and function in unique contexts, enabling reliable control of microbial proliferation. Recent work has also shown that the escape rate and fitness of multiple synthetic auxotrophs can be improved by increasing the specificity of nsAA incorporation machinery (46). Collectively, these engineering and characterization efforts advance synthetic auxotrophy as a powerful safeguard for basic and applied research when using engineered microbes.

Cultures for general culturing, growth rate assays, biocontainment escape assays, MAGE, and fluorescent protein assays were prepared in LB-Lennox medium [bacto tryptone (10 g/liter), sodium chloride (5 g/liter), and yeast extract (5 g/liter)] supplemented with chloramphenicol (15 g/ml), 0.2% (w/v) l-arabinose, 20 mM tris-HCl buffer, 0.005% SDS, and variable concentration of L-4,4-biphenylalanine (BipA). Unless otherwise indicated, all cultures were grown in 96-well deep plates in 300 l of culture volumes at 34C and 400 rpm. The above media are permissive for growth of the synthetic auxotroph. Nonpermissive media are identically formulated as permissive media except for BipA, which is not included.

Construction of appropriate fluidics and chambers followed the eVOLVER framework (26) (figs. S1 and S2). The following components were included: (i) fluidics and chambers (reactor vial, inlet and outlet lines, filters, pumps, stirrers, and inlet and outlet reservoirs); (ii) light source and detector (LED and photodiode); (iii) controller hardware (circuit and microprocessors); and (iv) controller software (Arduino for controlling tasks, Raspberry Pi for computing tasks, and Python code for programming tasks) (full build of materials included in table S3). Briefly, our apparatus consisted of a custom smart sleeve (fig. S3), with the following modifications: Each vial was constructed without temperature control and was supplied by two media pumps (one for permissive media and another for nonpermissive media) and connected to one waste pump. All pumps were RP-Q1 from Takasago Fluidics, each driven off a standard N power MOSFET (metal oxide semiconductor field-effect transistor) with an Arduino controlling the gate. Like the eVOLVER system, we installed a stirring fan underneath each sleeve that consisted of magnets attached to a computer fan. By including a small stir bar within each reactor vial, we enabled efficient mixing of 1-ml working volumes. To enable automated measurement of turbidity [optical density (OD)], we used a 605-nm LED (LO Q976-PS-25) and an OPT101P-J photodiode detector. We mounted the LED and detector on custom printed circuit boards mounted to the vial sleeve to enable easier construction and better control of ambient light leakage into the light path (fig. S4). To monitor turbidity within each vial and to control pump arrays in response, we constructed printed circuit board designs in Gerber format as is standard for circuit fabrication. We attached an Arduino Mega microcontroller with an analog-digital converter and directed it using a PyMata script (47).

Chemostats were operated by automated maintenance of culture OD within a specified parameter range within exponential growth phase (20 to 80% of dynamic range) depending on linearity of photodiode measurements. Constant fixed dilutions of permissive media were used to decrease OD until desired equilibrium of cell growth and dilution rates. This resulted in a sawtooth curve (27), where time between peaks is recorded as a proxy for growth rate. Our program gradually decreased the ratio of permissive to nonpermissive media as step functions, with a specified number of dilution cycles allowed to elapse before the next decrease to provide time for acclimation. Time between OD peaks lengthened as strain fitness decreased. Once a threshold difference between ancestral peak-to-peak time and current peak-to-peak time was passed, the ratio of permissive to nonpermissive media remained fixed. This allowed cells to evolve until peak-to-peak time returns to ancestral values, which initiated the next phase of decrease in BipA concentration. To assess the quality of our continuous evolution process, we paused chemostat trials on a weekly basis for strain storage, strain evaluation, chemostat cleaning, and investigation of contamination.

Growth assays were performed by plate reader with blanking as previously described (25). Overnight cultures were supplemented with different BipA concentrations depending on the strain. The DEP progenitor strain was grown in permissive media containing 100 M BipA, and evolved DEP strains DEP.e3, DEP.e4, and DEP.e5 were grown in permissive media containing 1 M BipA. Saturated overnight cultures were washed twice in LB and resuspended in LB. Resuspended cultures were diluted 100-fold into three 150-l volumes of permissive media. BipA concentrations used in this assay were 0, 0.001, 0.01, 0.1, 0.5, 1, 10, and 100 M. Cultures were incubated in a flat-bottom 96-well plate (34C, 300 rpm). Kinetic growth (OD600) was monitored in a Biotek Eon H1 microplate spectrophotometer reader at 5-min intervals for 48 hours. The doubling times across technical replicates were calculated as previously indicated. We refer to these as technical replica
tes because although triplicate overnight cultures were used to seed triplicate experiment cultures, the overnight cultures were most often seeded from one glycerol stock.

Escape assays were performed as previously described with minor adjustments to decrease the lower detection limit for final evolved populations (23, 46). Strains were grown in permissive media and harvested in late exponential phase. Cells were washed twice with LB and resuspended in LB. Viable CFU were calculated from the mean and SEM of three technical replicates of 10-fold serial dilutions on permissive media. Twelve technical replicates were plated on noble agar combined with nonpermissive media in 500-cm2 BioAssay Dishes (Thermo Fisher Scientific 240835) and monitored daily for 4 days. If synthetic auxotrophs exhibited escape frequencies above the detection limit (lawns) on nonpermissive media, escape frequencies were calculated from additional platings at lower density. The SEM across technical replicates of the cumulative escape frequency was calculated as previously indicated.

Genomic DNA was obtained from evolved populations and ancestral clone using the Wizard Genomic DNA purification kit (Promega). Sequencing libraries were prepared as described in Baym et al. (48). Sequencing was performed using a NextSeq instrument, producing 75base pair (bp), paired-end reads. Resulting data were aligned to the E. coli C321.delA nonauxotrophic but recoded reference sequence (GenBank no. CP006698.1) and the sequence of the plasmid encoding nsAA incorporation machinery. The Millstone software suite was used to identify variants, provide measures of sequencing confidence, and predict their likelihood of altering gene function (49). Genomic variants of low confidence, low sequence coverage, or presence in the ancestral strain were discarded, prioritizing variants observed in three nonessential genes that encode membrane proteins: acrB, emrD, and trkH.

Subsequent genomic sequencing was performed on genomic DNA extracted from the evolved populations and ancestral clone using the DNeasy Blood and Tissue Kit (Qiagen). Genomic DNA was then sent to the Microbial Genome Sequencing Center (MiGS) in Pittsburgh, PA. Variants were identified through the variant calling service from MiGS.

MAGE (33) was used to inactivate the endogenous mutS gene in the DEP strain. Overnight cultures were diluted 100-fold into 3 ml of LB containing chloramphenicol, BipA, l-arabinose, and tris-HCl buffer and grown at 34C until midlog. The genome-integrated lambda Red cassette in this C321.A-derived strain was induced in a shaking water bath (42C, 300 rpm, 15 min), followed by cooling the culture tube on ice for at least 2 min. The cells were made electrocompetent at 4C by pelleting 1 ml of culture (8000 rcf, 30 s) and washing thrice with 1 ml of ice-cold 10% glycerol. Electrocompetent pellets were resuspended in 50 l of dH2O containing the desired DNA; for MAGE oligonucleotides, 5 M of each oligonucleotide was used. Allele-specific colony polymerase chain reaction (PCR) was used to identify desired colonies resulting from MAGE as previously described (50). Oligonucleotides used for MAGE and for allele-specific colony PCR are included in table S4.

This assay was performed using a similar protocol as described in the Measurement of doubling times section. The cultures for DEP and its single mutants were grown overnight in 100 M BipA. Then, cultures were diluted 100 in the media specified. Those conditions include standard media conditions and single component changes: 0% SDS, 0.01% SDS, 0.02% (w/v) arabinose, 0 mM tris-HCl, and chloramphenicol (30 g/ml). The cultures were grown in triplicate for each condition and in a SpectraMax i3 plate reader, shaking at 34C for 24 hours. The OD600 was measured about every 5 min. The doubling times were then calculated as previously described.

HEK293T cells containing one copy of mCherry marker (red) integrated into the AAVS1 locus were grown at 40 to 50% confluency in DMEM (Dulbeccos modified Eagles medium) high-glucose medium (Thermo Fisher Scientific, catalog no. 11965175) with 10% inactivated fetal bovine serum (FBS; Thermo Fisher Scientific, catalog no. 10082147), 100 MEM NEAA (nonessential amino acids; Thermo Fisher Scientific, catalog no. 11140050), and 100 diluted anti-anti cocktail [antibiotic-antimycotic: penicillin (10,000 U/ml), streptomycin (10,000 g/ml), and Gibco amphotericin B (25 g/ml); Thermo Fisher Scientific, catalog no. 15240112). Commercially acquired E. coli DH5 bacteria were used as control to the E. coli DEP mutS or DEP* strain. A plasmid containing Clover (green marker) containing a UAA stop codon compatible with the biocontained strain DEP, and under the selection marker ampicillin was transformed into both DH5 and DEP* strains to visualize them with the mammalian cells (red). BipA-dependent auxotroph DEP* bacteria were grown to an OD of 0.6 in LB medium supplemented with 1% l-arabinose, 100 M BipA, carbenicillin (100 g/ml), and chloramphenicol (25 g/ml) and then washed three times with 1 phosphate-buffered saline (PBS). DEP* culture conditions with l-arabinose, carbenicillin, and chloramphenicol supplements did slightly affect HEK293T early cell growth compared to untreated cells, although insufficient to affect conclusions drawn from these experiments. DH5 strain was grown to an OD of 0.6 with carbenicillin (100 g/ml). The pellet of 10-ml bacterial cell culture was resuspended in mammalian cell medium as described above without any antibiotics and anti-anti, and split equally among all conditions and their replicates. Auxotroph bacteria are added to HEK293T cells plated in pretreated 12-well plates in 2 ml of mammalian cell medium. The coculture is incubated overnight before the medium that contains the bacterial cells is removed. HEK293T cells were washed three times with 1x PBS (Thermo Fisher Scientific, catalog no. 10010023) and replenished with fresh media as conditions indicate. Media were replaced and added fresh to all conditions daily for 7 days. Imaging of cells was done with the inverted microscope Nikon Eclipse TS100 at days 2, 4, and 7 after initial coculture at 200 magnification.

Conditions:

Control: HEK293T grown in regular 10% FBS media with anti-anti and NEAA as described above.

DH5: HEK293T cells cocultured with this strain in mammalian cell media supplemented with carbenicillin (100 g/ml) to maintain plasmid during growth and absence of anti-anti.

DH5; anti-anti (antibiotic cocktail): HEK293T cells cocultured with this strain in mammalian cell media supplemented with carbenicillin (100 g/ml) to maintain plasmid during growth and presence of anti-anti cocktail.

DH5; anti-anti after day 2: HEK293T cells cocultured with this strain in mammalian cell media supplemented with carbenicillin (100 g/ml) to maintain plasmid during growth and absence of anti-anti cocktail. At 48 hours, anti-anti added and maintained to day 7.

DH5; anti-anti; no anti-anti after day 2: HEK293T cells cocultured with this strain in mammalian cell media supplemented with carbenicillin (100 g/ml) to maintain plasmid during growth and presence of anti-anti until day 2. After day 2, no anti-anti added and maintained to day 7.

DEP*: HEK293T cells cocultured with the biocontained strain in media supplemented with l-arabinose, chloramphenicol (25 g/ml), and carbenicillin (100 g/ml) to maintain bacteria and green marker. No bipA or anti-anti was added.

DEP*; bipA: HEK293T cells cocultured with the biocontained strain in media supplemented with l-arabinose, chloramphenicol (25 g/ml), and carbenicillin (100 g/ml) to maintain bacteria and green marker. One hundred micromolar bipA and no anti-anti added.

DEP*; bipA after day 2: HEK293T cells cocultured with the biocontained strain in media supplemented with l-arabinose, chloramphenicol (25 g/ml), and carbenicillin (100 g/ml) to maintain bacteria and green marker. No bipA or anti-anti added. At 48 hours, bipA at 100 M concentration added and maintained to day 7.

DEP*; anti-anti: HEK293T cells cocultured with the biocontaine
d strain in media supplemented with anti-anti, l-arabinose, chloramphenicol (25 g/ml), and carbenicillin (100 g/ml) to maintain bacteria and green marker. No bipA added.

DEP*; bipA; anti-anti: HEK293T cells cocultured with the biocontained strain in media supplemented with anti-anti, l-arabinose, chloramphenicol (25 g/ml), and carbenicillin (100 g/ml) to maintain bacteria and green marker. One hundred micromolar bipA added.

Persistence was evaluated by two kinds of assays: plate reader and colony count. For the plate reader case, DEP, DEP.e3, DEP.e4, and DEP.e5 cultures were grown overnight in permissible media conditions with 100 M BipA. For cells harvested at midexponential phase, the cultures were diluted 100 and grown to that state. Both stationary-phase and midexponential-phase cultures were then washed twice with LB media and resuspended in the original volume of nonpermissible media containing all specified media components except BipA. The resuspended cultures were then diluted 100 into nonpermissible media in triplicate for each time point to be tested. The specified concentration of BipA was then added back to those cultures at the specified time points. Typically, the BipA readdition occurred at 10 or 5 M concentrations and at hourly or daily intervals. The cultures were then incubated with shaking in SpectraMax i3 plate readers in a flat, clear-bottom 96-well plate with breathable and optically transparent seal for an upward of 84 hours at 34C. Approximately every 5 min, the OD600 was measured to determine cell growth kinetics.

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Synthetic auxotrophy remains stable after continuous evolution and in coculture with mammalian cells - Science Advances